Tuesday, 31 July 2018
Pablo F. Gómez, Creating Knowledge and Healing in the Early Modern Atlantic Pablo F. Gómez , , Chapel Hill : University of North Carolina Press , 2017 . Pp. 314. $29.95. ISBN 978 1 4696 3087 8. Paul F Ramírez Social History of Medicine, Volume 31, Issue 3, 1 August 2018, Pages 648–649, https://doi.org/10.1093/shm/hky042 Published: 03 June 2018 Cite Permissions Share [Privacy Badger has replaced this AddThis button.] Among the healers featured in this study of Caribbean healing over the seventeenth century (ca. 1580–1720) is Antonio Congo, an African-born slave who lived in Spain, New Spain, Santo Domingo and Curaçao before settling in Cartagena de Indias. A free healer, Congo referred to herbs and other products of the natural world as his ‘offspring’; cast coins received in payment on the floor of his shack to appease the spirits of the Amerindians interred underneath; and communed with nature, witnessed by a crowd commanding a tropical storm into submission sometime around 1680. For this he was denounced to the Inquisition’s office in Cartagena and his experiences entered...
Monday, 30 July 2018
J Microbiol Biotechnol. 2016 Jan;26(1):61-5. doi: 10.4014/jmb.1508.08095. Kim MS1, Shin WC2, Kang DK3, Sohn HY1. Author information 1 Department of Food and Nutrition, Andong National University, Andong 760-749, Republic of Korea. 2 Research Institute, Kooksoondang Brewery Co, Ltd., Seongnam 460-120, Republic of Korea. 3 Gyeongsangbukdo Agricultural Research & Extension Services, Daegu 702-708, Republic of Korea. Abstract From the lees of bokbunja wine (LBW) made from Rubus coreanus Miquel, we have identified six compounds (1: trans-4-hydroxycinnamic acid; 2: trans-4-hydroxy-3-methoxycinnamic acid; 3: 3,4-dihydroxycinnamic acid; 4: 4-hydroxy-3-methoxybenzoic acid; 5: 3,5-dimethoxy-4- hydroxybenzoic acid; and 6: 3,5-dimethoxy-4-hydroxycinnamic acid (sinapic acid)) through silica gel chromatography and UHPLC-MS. The compounds 1-6 showed strong anticoagulation and platelet aggregation inhibitory activities without hemolytic effect against human red blood cells. To date, this is the first report of the in vitro anti-thrombosis activity of sinapic acid. Our results suggest that different cinnamic and benzoic acid derivatives are closely linked to the anti-thrombosis activity of LBW, and sinapic acid could be developed as a promising anti-thrombosis agent. KEYWORDS: Anti-thrombosis Activity; Rubus coreanus MIQ; Sinapic Acid; lees of bokbunja wine PMID: 26387815 DOI: 10.4014/jmb.1508.08095 [Indexed for MEDLINE] Free full text
Glob Chang Biol. 2018 Feb;24(2):e485-e495. doi: 10.1111/gcb.13899. Epub 2017 Oct 11. Boulanger V1, Dupouey JL2, Archaux F3, Badeau V2, Baltzinger C3, Chevalier R3, Corcket E4, Dumas Y3, Forgeard F5, Mårell A3, Montpied P2, Paillet Y3, Picard JF2, Saïd S6, Ulrich E1. Author information 1 Office National des Forêts, Département Recherche, Développement et Innovation, Fontainebleau, France. 2 INRA - Université de Lorraine, UMR 1137 Ecologie et Ecophysiologie Forestières, Champenoux, France. 3 Irstea, UR EFNO, Domaine des Barres, Nogent-sur-Vernisson, France. 4 Université de Bordeaux, UMR1202 BioGeCo, Allée Geoffroy St-Hilaire, Pessac Cedex, France. 5 Laboratoire d'Ecologie Végétale, Université de Rennes I, Rennes Cedex, France. 6 Office National de la Chasse et de la Faune sauvage, DRE Unité, Ongulés sauvages, Birieux, France. Abstract Large wild ungulates are a major biotic factor shaping plant communities. They influence species abundance and occurrence directly by herbivory and plant dispersal, or indirectly by modifying plant-plant interactions and through soil disturbance. In forest ecosystems, researchers' attention has been mainly focused on deer overabundance. Far less is known about the effects on understory plant dynamics and diversity of wild ungulates where their abundance is maintained at lower levels to mitigate impacts on tree regeneration. We used vegetation data collected over 10 years on 82 pairs of exclosure (excluding ungulates) and control plots located in a nation-wide forest monitoring network (Renecofor). We report the effects of ungulate exclusion on (i) plant species richness and ecological characteristics, (ii) and cover percentage of herbaceous and shrub layers. We also analyzed the response of these variables along gradients of ungulate abundance, based on hunting statistics, for wild boar (Sus scrofa), red deer (Cervus elaphus) and roe deer (Capreolus capreolus). Outside the exclosures, forest ungulates maintained higher species richness in the herbaceous layer (+15%), while the shrub layer was 17% less rich, and the plant communities became more light-demanding. Inside the exclosures, shrub cover increased, often to the benefit of bramble (Rubus fruticosus agg.). Ungulates tend to favour ruderal, hemerobic, epizoochorous and non-forest species. Among plots, the magnitude of vegetation changes was proportional to deer abundance. We conclude that ungulates, through the control of the shrub layer, indirectly increase herbaceous plant species richness by increasing light reaching the ground. However, this increase is detrimental to the peculiarity of forest plant communities and contributes to a landscape-level biotic homogenization. Even at population density levels considered to be harmless for overall plant species richness, ungulates remain a conservation issue for plant community composition. KEYWORDS: biodiversity; biotic homogenization; exclosure; large herbivores; species richness; temperate forest; vegetation cover; vegetation monitoring Comment in Are ungulates in forests concerns or key species for conservation and biodiversity? Reply to Boulanger et al. (DOI: 10.1111/gcb.13899). [Glob Chang Biol. 2018] The role of ungulates in nowadays temperate forests. A response to Fløjgaard et al. (DOI:10.1111/gcb.14029). [Glob Chang Biol. 2018]
Egyptian Propolis compared to Nanohydroxyapatite graft in Treatment of Grade II furcation defects in dogs.
J Periodontol. 2018 May 26. doi: 10.1002/JPER.17-0685. [Epub ahead of print] Zohery AA1, Meshri SM1, Madi MI2, Rehim SSAE3, Nour ZM4. Author information 1 Assistant lecturer, Department of Oral Medicine, Periodontology, Oral Diagnosis and Radiology, Faculty of Dentistry, Alexandria University, Alexandria, Egypt. 2 Assistant professor, Department of preventive dental sciences, College of dentistry, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia. 3 Professor, Department of Oral Biology, Faculty of Dentistry, Alexandria University, Alexandria, Egypt. 4 Professor, Department of Oral Medicine, Periodontology, Oral Diagnosis and Radiology Department, Faculty of Dentistry, Alexandria University, Alexandria, Egypt. Abstract BACKGROUND: Complementary and alternative medicine approaches are gaining ground in everyday practice. Propolis is a bee product that has been suggested to have bone regenerative effects. This study was conducted to compare the effectiveness of Egyptian propolis with nanohydroxyapatite graft on furcation defect regeneration in Mongrel dogs. METHODS: A split mouth design was utilized in 6 clinically healthy mongrel dogs. A total of 24 grade II furcation defects were surgically created in mandibular third and fourth premolars. The defects on the right side were filled with nanohydroxyapatite graft and covered with collagen membrane, while on the left side the defects were filled with propolis and also covered with collagen membrane. The dogs were sacrificed after one and three months. Segments containing the defects were prepared for histological evaluation. RESULTS: The histological evaluation after one month revealed newly formed bone in both treatment groups. However, after three months, the bone trabeculae appeared thinner in the collagen/nanohydroxyapatite group than in the collagen/propolis group. The histomorphometric evaluation showed a significant increase in bone height as well as bone surface area for the collagen/propolis group compared to collagen/nanohydroxyapatite group. CONCLUSIONS: Both Egyptian propolis and nanohydroxyapatite graft material showed favorable periodontal regenerative effect. Propolis showed increased cellular proliferative ability that could be beneficial in reducing the healing period needed after periodontal therapy. This article is protected by copyright. All rights reserved. © 2018 American Academy of Periodontology. KEYWORDS: Antioxidant; Bone graft; Furcation; Nanohydroxyapatite; Propolis; Regeneration
Clin Dermatol. 2018 May - Jun;36(3):369-375. doi: 10.1016/j.clindermatol.2018.03.014. Epub 2018 Mar 21. Rabinovich L1, Kazlouskaya V2. Author information 1 Department of Dermatology, SUNY Downstate Medical Center, Brooklyn, NY. Electronic address: email@example.com. 2 Department of Dermatology, SUNY Downstate Medical Center, Brooklyn, NY. Abstract Topical sunscreens are the mainstay for protection from ultraviolet (UV) radiation. With skin cancer rates on the rise and great interest in reversing or preventing the effects of photoaging, new molecules with potential to defend against UV damage have received a great deal of attention. Specifically, there is a growing interest in herbal substances that offer protection against the damaging effects of UV rays. Herbal substances may work as adsorbents of the UV rays and antioxidants and potentially have few side effects. Many of them have shown the potential to protect from UV rays in in vitro studies and animal models; however, only a limited number of human studies were conducted which we discuss in the current review. Among the most studied herbal substances that have proven photoprotective activity are green tea extract, carotenoids, and Polypodium leucotomos extract (PLE). They have been shown to increase minimal erythema dose and improve signs of photodamage. PLE has been shown to be helpful in holistic treatment of several conditions, including polymorphous light eruption, solar urticaria, and melasma; it also may be used as an adjuvant to the UVB treatment of vitiligo and photodynamic therapy of actinic keratosis. PMID: 29908579 DOI: 10.1016/j.clindermatol.2018.03.014
J Pers Soc Psychol. 2018 Jan;114(1):52-74. doi: 10.1037/pspi0000108. Epub 2017 Sep 18. . Sezer O1, Gino F2, Norton MI3. Author information 1 Department of Organizational Behavior, Kenan-Flagler Business School, University of North Carolina at Chapel Hill. 2 Department of Negotiation, Organizations & Markets, Harvard Business School. 3 Department of Marketing, Harvard Business School. Abstract Self-presentation is a fundamental aspect of social life, with myriad critical outcomes dependent on others' impressions. We identify and offer the first empirical investigation of a prevalent, yet understudied, self-presentation strategy: humblebragging. Across 9 studies, including a week-long diary study and a field experiment, we identify humblebragging-bragging masked by a complaint or humility-as a common, conceptually distinct, and ineffective form of self-presentation. We first document the ubiquity of humblebragging across several domains, from everyday life to social media. We then show that both forms of humblebragging-complaint-based or humility-based-are less effective than straightforward bragging, as they reduce liking, perceived competence, compliance with requests, and financial generosity. Despite being more common, complaint-based humblebrags are less effective than humility-based humblebrags, and are even less effective than simply complaining. We show that people choose to deploy humblebrags particularly when motivated to both elicit sympathy and impress others. Despite the belief that combining bragging with complaining or humility confers the benefits of each strategy, we find that humblebragging confers the benefits of neither, instead backfiring because it is seen as insincere. (PsycINFO Database Record. PMID: 28922000 DOI: 10.1037/pspi0000108
Sunday, 29 July 2018
https://recipes.hypotheses.org/11019 24/07/2018 laurencetotelin By Matthew Phillpott The Roman emperor Augustus is said to have asked the Roman orator, poet, and politician, Publius Vedius Pollio, how to live a long life. Pollio answered that ‘applying the Muse water within, and anointing oil without the body’ would help to keep him free of sickness. Whether Augustus took up Pollio’s advice is not mentioned. Indeed, Thomas Hill was little interested in exploring the story further when he took it from Pliny the Elder’s The Natural History in the 1560s as part of his small treatise on beekeeping, A Pleasant Instruction of the Perfect ordering of Bees (London, 1568). Drawing of Thomas Hill from his The Art of Gardening (1568). The story’s purpose, as an opening passage of his twenty-ninth chapter, was meant only to introduce Muses water (otherwise called Melicrate by the Greeks or more commonly, Hydromel), and to suggest that it is a drink containing various health benefits. Hill went on to explain that the Muses water can ‘ease the passage of wind or breath, soften the belly’ and cure poisoning by Henbane. He then gave a recipe; Let eight times so much water be mixed unto your honey prepared which boil or seethe so long, until no more foam arises to be skimmed off, then taking it from the fire, preserve to your use. Hill provides no more detail than that, but he does go on in the next chapter to give a recipe for Oenomel – ‘a sweet wine made with honey’ – that he says is ‘not only for the preservation of health but also to expel the torment of sickness’. Hill advises his readers that the best Oenomel is made of ‘old and tart wine’ with ‘the best purified honey’. His recipe; Take one gallon and a quart of wine and mix it with half a gallon and a pint of the best honey. There are more recipes in Hill’s treatise on beekeeping. There are several that describes a distillation of the honey, and another that describes the making of a Honey Quintessence. Hill’s manual was the first handbook published in English about beekeeping, and it was attached to the very first handbook on gardening (The Profitable Art of Gardening), also produced by Hill. The purpose was a simple one: to bring the knowledge of ancient authorities such as Aristotle, Pliny the Elder, and Virgil, to a modern audience as a means of providing ‘their knowledge and experience’ for the profit of ‘poor husbandmen’ and the better wealth of England more generally. It seems likely that the recipes for Hydromel and Oenomel were common knowledge and all Hill did here was to cite an authority for something that was already known (he cited Paul Aegina – a 7th-century Greek physician – and Pedanius Dioscorides – a 1st-century Greek physician and botanist). The recipes for distillation and Quintessence were more advanced and might well have been one of the earliest published recipes for these drinks in the English language (although again, the general principles were likely well known).* By including recipes in his book, Hill emphasises the benefits of beekeeping for his readers but also makes the manual useful beyond those strictly interested in managing a swarm of bees. Landowners or their land managers, who purchased the book to improve the gardens, might equally pass the knowledge of honey recipes to others in gentry households. It would be fascinating to discover if any manuscript recipe books from this period contained references to Hill’s honeyed-drinks or whether any copy of Hill’s books contains annotations or bookmarks related to the recipes. At the very least, by initialising the genre of beekeeping manuals in England, Hill provided precedence in terms of the structure of content, if not in detail. Many of the beekeeping manuals published in the seventeenth-century also contained recipes for honeyed-drinks and many followed a similar structure to the one that Hill provided, even where they disagreed with many of his claims. How many people followed the recipes, however, is another question entirely. * Quintessence was described by Andreas Vesalius in 1551 in a book called A compendious declaration of the excellent virtues of a certain lately invented oil, called for the worthiness thereof oil imperial. He described the Quintessence as ‘nothing else but aqua vitae’ (i.e. distilled wine), and does not mention honey. In 1559, Konrad Gesner’s The Treasure of Euonymus included a much more detailed description of types of Quintessence as drawn out of wine made from a variety of wood, fruits, flowers, oats, leaves, seeds, stones, metals, flesh, and spices. There is a brief mention of honey quintessence, but not a specific recipe for it. I have yet to find any other English printed work before 1568 that describes Honey Quintessence in any kind of detail. Matthew Phillpott lives in the United Kingdom and undertook studies in early modern history at Hull and Sheffield. He now works at the School of Advanced Study, University of London, and in addition investigates early modern printed materials for ideas about knowledge, history, culture, health, and food. He has recently started a new website to talk more about his research into bee culture in the early modern period called Early Modern Bees.
Molecules. 2018 Jul 18;23(7). pii: E1767. doi: 10.3390/molecules23071767. Kosakowska O1, Bączek K2, Przybył JL3, Pióro-Jabrucka E4, Czupa W5, Synowiec A6, Gniewosz M7, Costa R8, Mondello L9,10, Węglarz Z11. Author information 1 Laboratory of New Herbal Products, Department of Vegetable and Medicinal Plants, Faculty of Horticulture, Biotechnology and Landscape Architecture, Warsaw University of Life Sciences SGGW, 02-776 Warsaw, Poland. firstname.lastname@example.org. 2 Laboratory of New Herbal Products, Department of Vegetable and Medicinal Plants, Faculty of Horticulture, Biotechnology and Landscape Architecture, Warsaw University of Life Sciences SGGW, 02-776 Warsaw, Poland. email@example.com. 3 Laboratory of New Herbal Products, Department of Vegetable and Medicinal Plants, Faculty of Horticulture, Biotechnology and Landscape Architecture, Warsaw University of Life Sciences SGGW, 02-776 Warsaw, Poland. firstname.lastname@example.org. 4 Laboratory of New Herbal Products, Department of Vegetable and Medicinal Plants, Faculty of Horticulture, Biotechnology and Landscape Architecture, Warsaw University of Life Sciences SGGW, 02-776 Warsaw, Poland. email@example.com. 5 Laboratory of New Herbal Products, Department of Vegetable and Medicinal Plants, Faculty of Horticulture, Biotechnology and Landscape Architecture, Warsaw University of Life Sciences SGGW, 02-776 Warsaw, Poland. firstname.lastname@example.org. 6 Division of Food Biotechnology and Microbiology, Department of Biotechnology, Microbiology and Food Evaluation, Faculty of Food Sciences, Warsaw University of Life Sciences SGGW, 02-776 Warsaw, Poland. email@example.com. 7 Dipartimento di Scienze Biomediche, Odontoiatriche, e Delle Immagini Morfologiche e Funzionali (BIOMORF), University of Messina, 98122 Messina, Italy. firstname.lastname@example.org. 8 Dipartimento di Scienze Biomediche, Odontoiatriche, e Delle Immagini Morfologiche e Funzionali (BIOMORF), University of Messina, 98122 Messina, Italy. email@example.com. 9 Dipartimento di Scienze Chimiche, Biologiche, Farmaceutiche ed Ambientali (ChiBioFarAm), University of Messina, 98122 Messina, Italy. firstname.lastname@example.org. 10 Chromaleont s.r.l., a Start-Up of the University of Messina, 98122 Messina, Italy. email@example.com. 11 Laboratory of New Herbal Products, Department of Vegetable and Medicinal Plants, Faculty of Horticulture, Biotechnology and Landscape Architecture, Warsaw University of Life Sciences SGGW, 02-776 Warsaw, Poland. firstname.lastname@example.org. Abstract Roseroot (Rhodiola rosea L.) belongs to plants revealing adaptogenic properties, which are attributed to the presence of specific phenolic compounds and are reflected mainly as antioxidant activity. The aim of the present study was to determine the antioxidant and antibacterial activity of various products obtained from R. rosea (underground organs as well as their aqueous and ethanolic dry extracts) in relation to the chemical profiles of phenolic and essential oil compounds. The chemical profiles were determined by High-performance Liquid Chromatography with a diode-array detector (HPLC-DAD) and Gas chromatography-mass spectrometry (GC-MS), antioxidant activity by (1,1-Diphenyl-2-picrylhydrazyl) Scavenging Capacity Assay (DPPH), (2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulphonic acid)) Scavenging Capacity Assay (ABTS) and Ferric Reducing Antioxidant Power Assay (FRAP) and antimicrobial properties were expressed as minimum inhibitory concentration (MIC) and minimum bacterial concentration (MBC) values following the broth microdilutions method. The results show that the investigated samples differed in terms of their chemical compositions and biological activities. The extracts were more abundant in phenolic compounds (salidroside, tyrosol, and rosavin derivatives) in comparison to dried underground organs. The content of the determined phenolics in the analyzed extracts was affected by the solvent used for extraction. The ethanolic extract was characterized by the highest content of these substances in comparison to the aqueous one and the dried raw material, especially with regard to rosavin (969.71 mg/100 g). In parallel, this extract showed the strongest antioxidant and antibacterial activity. However, dried R. rosea underground organs also revealed strong antibacterial effects against, for example, Staphylococcus strains. KEYWORDS: antibacterial activity; antioxidant power; dry extracts; essential oil; geraniol; rosavins; roseroot; salidroside; underground organs PMID: 30022015 DOI: 10.3390/molecules23071767 Free full text
The pilot studies for the development of the combined methods of rehabilitation of the patients as exemplified by the application of phyto- and physiotherapeutic modalities
Vopr Kurortol Fizioter Lech Fiz Kult. 2018;95(3):63-68. doi: 10.17116/kurort201895363. . [Article in Russian; Abstract available in Russian from the publisher] Babaskina LI1, Babaskin DV1, Pavlova AV1. Author information 1 I.M. Sechenov First Moscow State Medical University, Moscow, Russia. Abstractin English, Russian Under the modern market conditions, the process of development of the methods for the combined rehabilitation of the patients is becoming increasingly more complicated. For the reduction of potential risks and leveling the factors responsible for the uncertain market situation influencing the creation of new methods, it is necessary to carry out the full-scale pilot studies with the use of the marketing analysis methods. The objective of the present work was to create and elaborate the rationale for the graphological structure (the scheme) of the process of exploratory research with a view to the development of the combined rehabilitation methods as exemplified by phyto- and physiotherapeutic modalities. The work is based on the application of the existing approaches to the structural, comparative, systemic, and situational analyses. The proposed graphological structure (scheme) of the exploratory research process consists of 6 stages. Its distinctive features are as follows: a fractional stage by stage evaluation of a variety of issues including the study of physical factors, characteristic of the means of herbal medicine with special reference to the mechanisms of their production and application under the current market conditions, monitoring the marketing environment with the constant focus on the trends and behavior of the target market, the parallel pursuing of serial studies with the application of the iterative procedures; the use of the previously created data bank to expand medical services at the stages of development and maturation of the life cycle, the evaluation of the possibility of establishment of the industry of parapharmaceutical products. KEYWORDS: development of new methods; exploratory research; marketing; methods of rehabilitation; physiotherapy; phytotherapy PMID: 29985383 DOI: 10.17116/kurort201895363
Future Sci OA. 2018 Feb 1;4(4):FSO283. doi: 10.4155/fsoa-2017-0124. eCollection 2018 Apr. Andrade JM1,1, Faustino C2,2, Garcia C1,1, Ladeiras D1,1, Reis CP2,3,2,3, Rijo P1,2,1,2. Author information 1 CBIOS - Research Center for Biosciences & Health technologies, Universidade Lusófona de Humanidades e Tecnologias, Campo Grande 376, 1749-024 Lisboa, Portugal. 2 iMed.ULisboa - Research Institute for Medicines, Faculdade de Farmácia da Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal. 3 Biophysics & Biomedical Engineering Institute (IBEB), Faculdade de Ciências da Universidade de Lisboa, Campo Grande, 1749-016 Lisbon, Portugal. Abstract The worldwide interest in the use of medicinal plants has been growing, and its beneficial effects being rediscovered for the development of new drugs. Based on their vast ethnopharmacological applications, which inspired current research in drug discovery, natural products can provide new and important leads against various pharmacological targets. This work pioneers an extensive and an updated literature review on the current state of research on Rosmarinus officinalis L., elucidating which compounds and biological activities are the most relevant. Therefore, a search was made in the databases PubMed, ScienceDirect and Web of Science with the terms 'rosemary', 'Rosmarinus officinalis', 'rosmarinic acid' 'carnosol' and 'carnosic acid', which included 286 articles published since 1990 about rosemary's pharmacological activities and their isolated compounds. According to these references, there has been an increasing interest in the therapeutic properties of this plant, regarding carnosic acid, carnosol, rosmarinic acid and the essential oil. The present manuscript provides an updated review upon the most reported activities on R. officinalis and its active constituents. KEYWORDS: Rosmarinus officinalis; biologic activity; carnosic acid; carnosol; essential oil; rosemary; rosmarinic acid PMID: 29682318 PMCID: PMC5905578 DOI: 10.4155/fsoa-2017-0124 Free PMC Article
Applied Pediatric Integrative Medicine: What We Can Learn from the Ancient Teachings of Sebastian Kneipp in a Kindergarten Setting.
Children (Basel). 2018 Jul 26;5(8). pii: E102. doi: 10.3390/children5080102. Eckert M1, Anheyer M2. Author information 1 Kinderkrankenhaus St. Marien, 84036 Landshut, Germany. email@example.com. 2 Elisabeth Krankenhaus, 45138 Essen, Germany. firstname.lastname@example.org. Abstract Pediatric integrative medicine focuses on the whole child and the environment in which the child grows up during the treatment of a child's illness. Nowadays, many different treatment modalities are applied even in children, and doctors need to know about them and, ideally, be able to apply different approaches in the process of treating a child themselves. The program Pediatric Integrative Medicine in Residency (PIMR) already provides residents with several tools to provide this kind of service for the child. In our PIMR pilot program in Germany, we chose to diversify our knowledge about treatment and prevention options by visiting a Kneipp-certified kindergarten in Germany. The philosophy of Sebastian Kneipp focuses on five pillars of health, which incorporate aspects of prevention, self-awareness, self-responsibility, and consciousness of health by means of hydrotherapy, herbal medicine, exercise, nutrition, and lifestyle-medicine. These are being taught to the children during the early years they spend in kindergarten, and represent integral parts of integrative medicine. Integration of Kneipp-based health programs within a kindergarten setting can work well and provides an effective means of early prevention education in childhood. KEYWORDS: Kneipp; PIMR; kindergarten
Andrographis paniculata (Chuān Xīn Lián) for symptomatic relief of acute respiratory tract infections in adults and children: A systematic review and meta-analysis
PLoS One. 2017 Aug 4;12(8):e0181780. doi: 10.1371/journal.pone.0181780. eCollection 2017. . Hu XY1, Wu RH2, Logue M1, Blondel C3, Lai LYW1, Stuart B1, Flower A1, Fei YT2, Moore M1, Shepherd J4, Liu JP2, Lewith G1. Author information 1 Primary Care and Population Sciences, Aldermoor Health Centre, Southampton, United Kingdom. 2 Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China. 3 AgroParisTech, Paris Institute of Technology for Life, Food and Environmental Sciences, Paris, France. 4 Southampton Health Technology Assessments Centre (SHTAC), Faculty of Medicine, University of Southampton, Southampton, United Kingdom. Abstract INTRODUCTION: Antimicrobial resistance (AMR) is a substantial threat to public health. Safe and effective alternatives are required to reduce unnecessary antibiotic prescribing. Andrographis Paniculata (A. Paniculata, Chuān Xīn Lián) has traditionally been used in Indian and Chinese herbal medicine for cough, cold and influenza, suggesting a role in respiratory tract infections (RTIs). This systematic review aimed to evaluate the clinical effectiveness and safety of A. Paniculata for symptoms of acute RTIs (ARTIs). MATERIALS AND METHODS: English and Chinese databases were searched from their inception to March 2016 for randomised controlled trials (RCTs) evaluating oral A. Paniculata without language barriers (Protocol ID: CRD42016035679). The primary outcomes were improvement in ARTI symptoms and adverse events (AEs). A random effects model was used to pool the mean differences and risk ratio with 95% CI reported. Methodological quality was evaluated using the Cochrane risk of bias tool; two reviewers independently screened eligibility and extracted data. RESULTS: Thirty-three RCTs (7175 patients) were included. Most trials evaluated A. Paniculata (as a monotherapy and as a herbal mixture) provided commercially but seldom reported manufacturing or quality control details. A. Paniculata improved cough (n = 596, standardised mean difference SMD: -0.39, 95% confidence interval CI [-0.67, -0.10]) and sore throat (n = 314, SMD: -1.13, 95% CI [-1.37, -0.89]) when compared with placebo. A. Paniculata (alone or plus usual care) has a statistically significant effect in improving overall symptoms of ARTIs when compared to placebo, usual care, and other herbal therapies. Evidence also suggested that A. Paniculata (alone or plus usual care) shortened the duration of cough, sore throat and sick leave/time to resolution when compared versus usual care. No major AEs were reported and minor AEs were mainly gastrointestinal. The methodological quality of included trials was overall poor. CONCLUSIONS: A. Paniculata appears beneficial and safe for relieving ARTI symptoms and shortening time to symptom resolution. However, these findings should be interpreted cautiously owing to poor study quality and heterogeneity. Well-designed trials evaluating the effectiveness and potential to reduce antibiotic use of A. Paniculata are warranted. PMID: 28783743 PMCID: PMC5544222 DOI: 10.1371/journal.pone.0181780 [Indexed for MEDLINE] Free PMC Article
The final conference program for ISE 2018 is now available on the conference webpage under “Program” tab and at the following direct links: https://docs.wixstatic.com/ugd/da15ce_e7067515795f46d4816c06cb6f82b34c.pdf [Organized Sessions] https://docs.wixstatic.com/ugd/da15ce_2fc0593d93f74563834224073d53f798.pdf [Thematic Sessions composed of individually volunteered papers] https://docs.wixstatic.com/ugd/da15ce_d0654829d4d345debe308ec4cf004e77.pdf [Poster Sessions] https://docs.wixstatic.com/ugd/da15ce_35a036ea72244de69625b25987be87ac.pdf [Panel Discussions] https://docs.wixstatic.com/ugd/da15ce_012a140f34894003b7217c666a745ef5.pdf [List of Presenters] https://docs.wixstatic.com/ugd/da15ce_287c051f23624a9bb2ba500fe807da9e.pdf [Book Launches] Scheduling for each individual abstract approved for ISE 2018 Belem +30 is also available through the online platform (for those who have registered) using the link https://icongresso.fadesp.itarget.com.br/estacao/index/login/evento/2. Sign in to your profile, open the "Abstract” area and then click on the small calendar icon beside each abstract submitted to view the date, time, and room for all submissions. See you all in Belém! —— Glenn H. Shepard Jr. email: email@example.com firstname.lastname@example.org Organizing committee for "Belém +30" XVI Congress of the International Society of Ethnobiology https://www.ise2018belem.com ISE 2018 secretariat: Instituto Amazônico de Agriculturas Familiares/ INEAF – UFPA Universidade Federal do Pará – Campus Básico. Rua Augusto Correa, nº 01 – Guamá. CEP: 66075-110. Belém, Pará Tel: (91) 3201-7913; email: email@example.com
Saturday, 28 July 2018
http://www.herbmed.org/Sponsored/kratomsubcat.html Evidence for Efficacy (Human Data) Clinical Trials No Records Observational Studies/Case Reports A case was presented of management of kratom overdose and withdrawal in a young man. Diep 2018 Elevation of serum prolactin, hypogonadism, and low serum testosterone were associated with kratom cessation in a 42-year-old man. LaBryer 2018 Regular kratom users reported moderate pain experiences during kratom cessation, and 46% experienced sleep problems; however, the withdrawal effects were considered negligible, as compared to those reported for opioid analgesics. Singh 2018 Regular kratom consumption over prolonged periods (>2 years) was not associated with impaired testosterone levels, hematological and biochemical parameters. Singh 2018 In a study involving social media status of kratom and cannabis in Thailand, no negative information on kratom was found between April and November 2015. Thaikla 2018 Mitragynine, among other drugs, was identified in antemortem and postmortem specimens from a deceased victim of drug overdose. Walsh 2018 Results of an anonymous online survey of 10,000 kratom users, conducted using resources from the American Kratom Association, are presented. Grundmann 2017 Introducing… Kratom. [No abstract] Pizarro-Osilla 2017 Kratom use was characterized in persons enrolled in a drug rehabilitation program. Among the 500 respondents, 20.8% reported lifetime kratom use, with the majority of kratom-users using it as a substitution for other opioid drugs. Smith 2017 Recent developments in the legal status, pharmacology, and adverse potential of kratom are reviewed. Prozialeck 2016 The observed pattern of Mitragyna speciosa consumption in a northern Malaysian town includes daily use by 88% of the respondents (91% response rate), the mean age of 28.3 years old when starting using, and a reverse association of education level with the ability to "quit." Ahmad 2012 A survey of "legal highs" available at UK-based websites showed kratom as one of the top 5 products. Schmidt 2011 The cross-sectional survey of active users in Malaysia showed that the use of kratom (ketum, krathom) for the management of opioid withdrawal symptoms is more popular than previously acknowledged. Vicknasingam 2010 Mitragynine was detected in the urine of 0.9% of a random selection of Thai drivers. Ingsathit 2009 A case of self-treatment of opioid withdrawal and chronic pain with Mitragyna speciosa is reported, also involving a tonic-clonic seizure when kratom was co-administered with modafinil. Boyer 2008 Kratom (krathom) was one of the most commonly illicit drugs used by high-school students in Thailand in 2002-2004. Assanangkornchai 2007 An increase in the incidence of self-treatment of opioid withdrawal with Mitragyna sp. (kratom) was deduced from the number of mentions of the plant on a website that facilitates online purchase of opioid analgesics. Boyer 2007 Ex-kratom consumption was found to be a significant factor affecting the level of energy drink consumption in Thai Chonburi Province. Pichainarong 2004
Re: Korean Red Ginseng May Reduce Genotoxicity and Improve Quality of Life in Patients with Epithelial Ovarian Cancer receiving Chemotherapy
PDF (Download) Korean Red Ginseng (Panax ginseng, Araliaceae) Epithelial Ovarian Cancer Adjuvant Chemotherapy Date: 06-30-2018 HC# 111758-595 Kim HS, Kim M-K, Lee M, Kwon B-S, Suh DH, Song YS. Effect of red ginseng on genotoxicity and health-related quality of life after adjuvant chemotherapy in patients with epithelial ovarian cancer: a randomized, double blind, placebo-controlled trial. Nutr. July 2017; 9(7):772. doi: 10.3390/nu9070772. Epithelial ovarian cancer (EOC) has no effective screening method for early detection, and it is often detected at advanced states. As a consequence, the survival rate is low. Patients diagnosed with EOC have a poor health-related quality of life (HRQL), which is worsened by chemotherapy. Complementary and alternative medicines are being evaluated to help improve HRQL in these patients. Korean red ginseng (Panax ginseng, Araliaceae) root contains ginsenosides that may reduce genotoxic effects of chemotherapy. Also, studies show that Korean red ginseng may improve fatigue and cognition, thereby improving quality-of-life. The purpose of this randomized, double-blind, placebo-controlled study was to evaluate the effect of Korean red ginseng on genotoxicity and HRQL in patients with EOC undergoing chemotherapy. Women (n = 30, mean age 52.9 years in the placebo group and 55.9 years in the ginseng group) with EOC participated in this study from April 2012 to November 2014 at Seoul National University Hospital in Seoul, Korea. Included patients were older than 20 years; received six cycles of adjuvant taxane- and platinum-based chemotherapy after cytoreductive surgery; had a complete or partial response after chemotherapy; and completed the treatment within 8 weeks prior to entering the study. Excluded patients had a history of smoking, a chronic disease, recurrent cancer requiring more intensive treatment, previous radiotherapy, and a history of hypersensitivity to ginseng. Patients received either placebo or 3000 mg/day (2 capsules 3x/day) Korean red ginseng (prepared for the study from 6-year-old root) for 12 weeks. At baseline and at 12 weeks, blood was drawn to evaluate toxicity (white blood cells [WBC], hemoglobin, platelet counts, neutrophil counts, lymphocyte counts, alanine aminotransferase [ALT] levels, aspartate aminotransferase [AST] levels, bilirubin levels, alkaline phosphatase [ALP] levels, blood urea nitrogen [BUN], and creatinine). Genotoxicity was evaluated by measuring binucleated cell (BN) index and micronuclei (MN) yield. HRQL was evaluated using the European Organization for Research and Treatment of Cancer QLQ-C30 (EORTC QLQ-C30), the Brief Fatigue Inventory (BFI), the Brief Pain Inventory (BPI), the Hospital Anxiety and Depression Scale (HADS), and the Sleep Scale from the Medical Outcome Study (MOS-SS). Progression-free survival (PFS) was measured and defined as the time from the date of diagnosis to the date of cancer recurrence. Overall survival was measured and defined as the time from the date of diagnosis to the date of cancer-related death or end of the study. Baseline characteristics were similar between groups (P > 0.05). Treatment compliance was excellent, with > 90% compliance rate. There was no significant difference for either group in the BN index (P > 0.05) when comparing the beginning to the end of the trial. However, Korean red ginseng significantly decreased MN yield from week 0 to 12 (P = 0.038). There were no significant changes in either group for lymphocyte and platelet counts, bilirubin, ALP, BUN, and creatinine levels (P > 0.05 for all). Both the Korean red ginseng group and the placebo group had significant increases in WBC (P = 0.008 for both), neutrophils (P = 0.030 for both), and hemoglobin (P < 0.001 and P = 0.001, respectively). AST (P = 0.010) and ALT (P = 0.009) levels significantly increased over time in the Korean red ginseng group but not the placebo group. There were no significant differences between groups for the incidence of any adverse events (AE; P = 1.000 for all). For the Korean red ginseng group’s EROTC QLQ-C30 results, emotional score (P = 0.027), fatigue (P = 0.012), nausea and vomiting (P = 0.004), and dyspnea (P = 0.021) scores were significantly improved at week 12 compared with baseline. In contrast, the placebo group did not have significant improvements on these same EROTC QLQ-C30 parameters (P > 0.05 for all). On the BFI, for the Korean red ginseng group, worst fatigue score (P = 0.026), interference score (P = 0.014), and enjoyment of life score (P = 0.035) were significantly improved at week 12 compared with baseline. In contrast, the placebo group did not have significant changes on these BFI parameters (P > 0.05 for all). On the HADS, anxiety was significantly lower at week 12 compared with baseline in the Korean red ginseng group (P = 0.015), but not in the placebo group (P = 0.119). On the MOS-SS, daytime somnolence score was significantly improved at week 12 compared with baseline in the Korean red ginseng group (P = 0.043), but not in the placebo group (P = 0.342). There were no significant differences between groups on mean PFS (P = 0.448) and mean overall survival(P = 0.478). The authors conclude that Korean red ginseng is safe and may reduce genotoxicity and improve HRQL in patients with EOC receiving chemotherapy. The decrease in MN in the Korean red ginseng group indicates that Korean red ginseng may reduce additional genetic mutations. Low MN is related to improved survival in cancer patients. The authors hypothesize that oxidative stress and inflammation induced by chemotherapy may reduce HRQL, and Korean red ginseng may benefit the patient by decreasing both. The limitations of this study are the small population size and relatively short duration. Large-scale clinical studies are needed to better estimate the effects of Korean red ginseng on many of these outcomes. The authors declare no conflicts of interest. —Heather S. Oliff, PhD
Re: Meta-analysis Finds Chaste Tree Effective for Premenstrual Syndrome, but Published Research Is Heterogeneous; More High-quality Studies Are Needed
Chaste Tree (Vitex agnus-castus; Lamiaceae) Premenstrual Syndrome Systematic Review/Meta-analysis Date: 06-30-2018 HC# 111763-595 Verkaik S, Kamperman AM, van Westrhenen R, Schulte PFJ. The treatment of premenstrual syndrome with preparations of Vitex agnus-castus: a systematic review and meta-analysis. Am J Obstet Gynecol. August 2017;217(2):150-166. doi: 10.1016/j.ajog.2017.02.028. Premenstrual syndrome (PMS) is the occurrence of physical and psychological symptoms during the luteal phase of the menstrual cycle and continuing into the first few days of menstruation. Symptoms include headache, edema, breast or abdominal pains, anxiety, depression, agitation, and aggression. Mild symptoms of these types are normal for many women, but in 5-8% of women, they can be severe and may be characterized as premenstrual dysphoric disorder (PMDD). While there are many hypotheses as to the cause of PMS and PMDD, none have been scientifically proven. The most common pharmaceutical treatment prescribed is selective serotonin reuptake inhibitors (SSRIs). These can have many undesired side effects such as anxiety, weight gain, nausea, sexual dysfunction, and more. Chaste tree (VAC; Vitex agnus-castus; Lamiaceae) fruit is among the alternative remedies commonly used to treat PMS symptoms. The goal of this systematic review and meta-analysis was to determine the efficacy and tolerability of chaste tree in the treatment of PMS and/or PMDD. Ten databases were searched including MEDLINE, Embase, Web of Science, PubMed, and Google Scholar, using search terms such as "premenstrual syndrome," "PMS," and variations, as well as "vitex," "chaste tree," and other common names in multiple languages. The search was updated in January of 2016. Clinical studies of women of reproductive age diagnosed with PMS or PMDD were considered. Included studies were randomized controlled trials that used any dose or preparation of chaste tree, with either a placebo or pharmacotherapy comparator and a minimal duration of two menstrual cycles. Studies using homeopathic preparations of chaste tree or combination treatments were excluded. Outcomes data preferred for meta-analysis were those based on validated scales. Discontinuation rates, adverse events, and satisfaction were also analyzed. Risk of bias was assessed for each trial using the Cochrane Risk of Bias Tool, and potential publication bias was determined using a funnel plot and Egger test. After title and abstract screening of 395 articles, 38 articles were selected and the full-text was assessed for eligibility. Seventeen randomized controlled trials were ultimately included in the qualitative analysis, 14 of which were also included in the quantitative analysis; sufficient data were not available for the other three. Eight articles were written in English, four in Farsi, three in Italian, and two in Turkish. The authors report using a translator as necessary to interpret these. Ten articles were placebo controlled and nine were comparator controlled, with comparators including the SSRI, fluoxetine, an oral contraceptive, pyridoxine, magnesium, and St. John's wort (Hypericum perforatum, Hypericaceae) or vitamin E. Two trials compared chaste tree to both an oral contraceptive and a placebo. Most studies were double-blind, though two were single-blind and blinding was not adequately explained in two others. Seven preparations of VAC were specified in 11 studies. Six preparations were extracts and one was capsules containing ground dried berries. Six studies did not specify the preparation. In 10 of the studies that used a placebo control, , VAC was found to be superior in all but one.. The one negative study used ground berries, where all others used extracts. VAC was found to be superior for relieving PMS symptoms in studies comparing it to pyridoxine, magnesium, St. John's wort, or vitamin E. VAC was compared to oral contraceptives in three studies and was found to be comparable. VAC was compared to fluoxetine in two studies. In one study, VAC was comparable to fluoxetine. In the other, fluoxetine was superior for some components of the Hamilton depression rating scale. The authors rated only two studies as having a low risk of bias, six were considered to have a moderate risk of bias and nine a high risk, with reporting incomplete for all studies. The pooled effect of VAC vs. placebo for all PMS symptom was large (Hedges g -1.21; Hedges g; 95% confidence interval [CI], -1.53 to -0.88; I2, 91%). Meta-analyses of studies separately reporting depressive symptoms (n=5) and anxiety symptoms (n=2) also showed a large effect. There was no significant difference between the efficacy of VAC and either oral contraceptives or fluoxetine, but fewer adverse events occurred with VAC than with either of these comparators. Adverse events in placebo-controlled studies were mild and not substantially different from placebo, and the products were considered well-tolerated. Dropout rates varied greatly among studies but did not differ for VAS vs. placebo. Heterogeneity among studies was very high, and both the funnel plot and Egger tests suggested the possibility of publication bias. Smaller studies reported larger effect sizes, leading to the suspicion that small studies with negative results might exist that have not been published. Among analyses of heterogeneity, it should be noted that double-blind studies reported greater effects than single-blinded or poorly described studies (P<0.05); although, studies suspected of reporting bias also reported greater effects (P value not stated), and those using commercial products reported greater effects than those using custom-made products (P=0.036). The authors conclude that while the meta-analysis shows a large pooled effect for VAC in placebo-controlled trials, they are not convinced a definitive conclusion can be drawn on its effectiveness due to the high risk of bias, high heterogeneity, and risk of publication bias. There is a clear need for high-quality research of appropriate duration and adequate number of subjects. The authors suggest these be conducted using standardized extracts, and could include both superiority trials vs. placebo and non-inferiority trials with SSRIs and oral contraceptives as comparators. The first author works for a biotechnology corporation that does not presently work on drugs for PMS/PMDD and was not involved in the study. The other authors report no potential conflicts. —Erin Smith, MSc., CCH
HerbalEGram: Volume 14, Issue 5, May 2017 Editor’s Note: Each month, HerbalEGram highlights a conventional food and briefly explores its history, traditional uses, nutritional profile, and modern medicinal research. We also feature a nutritious recipe for an easy-to-prepare dish with each article to encourage readers to experience the extensive benefits of these whole foods. With this series, we hope our readers will gain a new appreciation for the foods they see at the supermarket and frequently include in their diets. The basic materials for this series were compiled by dietetic interns from Texas State University (TSU) in San Marcos and the University of Texas at Austin (UT) through the American Botanical Council’s (ABC’s) Dietetic Internship Program, led by ABC Education Coordinator Jenny Perez. We would like to acknowledge Perez, ABC Special Projects Director Gayle Engels, and ABC Chief Science Officer Stefan Gafner, PhD, for their contributions to this project. By Hannah Baumana and Monica Silvab a HerbalGram Associate Editor b ABC Dietetics Intern (TSU, 2017) Overview The caper (Capparis spinosa, Capparaceae) bush is a small, salt-tolerant shrub with trailing, thorny branches and thick, fleshy leaves. Caper has a deep root system and trailing vines that grow seven to 10 feet tall.1 The semi-prostrate branches have ovate, petiolate leaves arranged opposite of each other. The flowers are pink or white with three petals and numerous stamens. Caper is a deciduous, dicotyledonous plant that produces distinctive flower buds, which have a life span of 24 to 36 hours after opening.1,2 Caper’s edible shoots are considered a vegetable, and its processed buds are considered a culinary herb.1 The tender shoots emerge in the spring, while the flower buds are harvested from mid-May to mid-August. Each plant produces hundreds of flowers each season. When pickled in vinegar or brine, the immature flower buds form capric acid, which is responsible for caper’s unique, salty-sour flavor.2,3 Once the flower blooms and is pollinated, it produces a fruit two to three inches in length and one-half to three-quarters of an inch in diameter. Caper fruits start out green, but turn purple when ripe. Each fruit contains 200 to 300 seeds.1 The fruit of the caper bush is also harvested, but not commonly used.2 Currently, capers are cultivated commercially in northern Africa, Spain, and Italy. Caper plants in Cyprus, Greece, and Turkey are grown for domestic use and not for export. The United States imports more than $20 million of processed capers annually.1 Caper plants that are two to three years old produce about two pounds of buds in a year, while plants older than four years may produce more than 20 pounds of buds annually.1 Phytochemicals and Constituents Macronutrients are found in capers in very small amounts. One tablespoon (8.6 grams) of pickled capers has two calories, half a gram of carbohydrates, and minute amounts of protein and fat. An important micronutrient to consider when eating capers is sodium. One tablespoon of capers contains 202 milligrams of sodium, which is 8.5% of the recommended daily intake for a healthy adult.4,5 The flower bud also contains trace amounts of vitamins C and E. The concentration of vitamins can vary from plant to plant. The vitamin C content in capers cultivated in different regions in Tunisia, for example, ranged from 0.3 to 0.5 milligrams per 100 grams of capers.6 A number of bioactive compounds have been isolated from the flower buds of the caper bush. The pickling process has varying effects on the bioavailability of compounds due to different fermentation methods.7 Among the most investigated of these phytochemicals are flavonoids and antioxidants. Flavonoids from capers reportedly have cytotoxic, anti-inflammatory, antidiabetic, and antiparasitic properties.7,8 Rutin (quercetin-3-O-rutinoside) is the most abundant flavonoid in fresh and pickled caper buds.7 Simple water extractions high in rutin have been shown to reduce inflammation and arrest cell growth in cancer cells, as well as kill intestinal parasites in animals.8,9 Caper flower buds also contain quercetin-3-O-rhamnosylrutinoside, a derivative of quercetin.6 Quercetin, another well-studied flavonoid, is formed from rutin during the pickling process.7 Quercetin can inhibit inflammation and cancer cell growth in the same way as rutin.9 Quercetin has also shown immune-health benefits. Kaempferol 3-O-rhamnosylrutinoside, another flavonoid identified in an aqueous extract, has proven antiparasitic properties.8 The flower bud of the caper bush also contains antioxidants such as carotenoids, tocopherols, ascorbic acid, and a newly identified antioxidant, cappariside, a small organic acid.6,10 Antioxidants eliminate free radicals that cause damage to body tissues and DNA, and have been implicated in the prevention of cancer, kidney damage, and heart disease, as well as protection against prescription drug-induced toxicity.11 The antioxidant effects of flower bud preparations have been shown to be more potent than those of the antioxidants in isolation.8 Historical and Commercial Uses The unopened flower buds of the caper bush are commercially known as capers.2 Capers are used as a condiment in salads and sauces, or with meat or fish. They are also used in cosmetics and medicines. Archeological evidence for the historical use of capers as a food and medicine exists among many ancient cultures.12 The earliest known evidence of caper consumption was found in the Mesolithic soil layer of an excavation site in Syria, potentially dating back to 9000 BCE. Nearby ancient peoples may have been using capers in 7500 BCE as evidenced by mineralized seeds found in the Franchthi cave, a Stone Age cave in the Greek Peloponnesian peninsula. Dried seeds found in the Nahal Hemar cave in Israel may have been used as early as 6000 BCE. In China, fresh clumps of capers and plant parts were preserved in entombed containers that are almost 3,000 years old. There is also evidence of Egyptian consumption of capers from 275 BCE to 600 CE. Historical medicinal uses of capers ranged from expelling bad odor spirits in ancient Arabic cultures to treating paralysis in ancient Xinjiang, China.12 In addition to the buds, the root bark, fruit, and aerial parts of the caper bush were used in traditional remedies. Countries in the native range of caper, including Iran, Iraq, and Syria, used every part of the caper bush for a variety of ailments. As the cultivation and use of capers spread, the Greeks, Egyptians, and Chinese incorporated the caper bush into their traditional medicine practices. Capers contain phytochemicals that can inhibit inflammation, which supports caper’s usages as a cleanser and pain reliever.9,12 In ancient Chinese, Greek, and Arabic cultures, the root bark was mixed with vinegar or honey and applied topically to treat skin conditions such as ulcers and white spots associated with vitiligo.12 Similarly, the root was consumed as a treatment for inflammation and lacerations of the mouth, spleen, stomach, and intestines. In ancient Egypt, the root was used to reduce the pain of a scorpion sting. In ancient Greece and China, the caper bush was regarded for its drying properties and was used as an expectorant in treating wet cough and asthma.12 Ancient Romans boiled caper root and root bark in oil and used it as an anthelmintic (digestive tract parasitic worm expeller). Likewise, in the 12th century, the Egyptians used the root to cleanse and dry the stomach. Current medicinal usages are a testament to caper’s efficacy for treating different ailments. In the Middle East, indigenous groups still use capers as a so-called “blood purifier” and diuretic, to relieve stomach discomfort, treat kidney stones, improve liver function, and treat eczema.13 In Ayurveda, one of the traditional medicine systems of India, caper is used to treat paralysis and tremors, as well as edema, gout, and rheumatism.14 The root bark is still used to stimulate the menstrual cycle, as an expectorant, and to treat paralysis, rheumatism, spleen conditions, and toothaches.15 Modern Research Commercial capers are not frequently studied for their medicinal properties. However, some research has been conducted on the bioactive compounds in the flower buds. A recent study investigated the antiparasitic effect of a caper bud extract against Haemonchus contortus, a common parasite in cows and sheep. The large number of eggs and short life span of H. contortus allows the parasite to adapt quickly to its environment.16 Parasite infestations can result in large economic losses in the animal production industry, and current treatments include chemotherapy and vaccinations, which pose a safety concern.17 Researchers compared the caper extract to a commonly prescribed antiparasitic drug albendazole. The flower bud extract (50 mg/mL) was almost twice as effective as albendazole (1 mg/mL) at killing parasites in sheep and inhibited the hatching of parasitic eggs more than the leaf extract.8 The caper bud has also been studied for its anti-inflammatory and cytotoxic properties. A recent study investigated the potential of capers to inhibit nuclear factor-kappa B (NF-κB), a transcription factor that controls inflammation and cell growth. Mutations that impact its activation may lead to uncontrolled cell growth, one of the conditions that can cause a proliferation of cancer cells.18 For this reason, NF-κB is a therapeutic target for pancreatic, renal, and thyroid cancer treatments.18-20 In one in vitro study, researchers tested an aqueous extract of the flower bud and leaves, which were selected for their high levels of phenolic compounds, on human adenocarcinoma cells. The caper extract successfully inhibited the inflammation mechanism, and arrested cell growth in a dose-dependent manner.9 Additionally, a caper flower bud extract has been studied for its ability to treat liver toxicity in animals. Rats were exposed to two different liver toxins: carbon tetrachloride, a known carcinogen that has been used as a commercial refrigerant, propellant, and solvent; and paracetamol, also known as acetaminophen, a pain-relieving drug that can induce liver failure in sufficiently high doses.21 Compared to control, the caper extract resulted in a significant reductions in carbon tetrachloride-induced and paracetamol-induced liver toxicity. Nutrient Profile4 Macronutrient Profile: (Per 1 tablespoon pickled capers, drained) 2 calories 0.2 g protein 0.4 g carbohydrate 0.1 g fat Secondary Metabolites: (Per 1 tablespoon pickled capers, drained) Provides small amounts of: Vitamin K: 2.1 mcg (2.6% DV) Dietary Fiber: 0.3 g (1.2% DV) Provides trace amounts of: Magnesium: 3 mg (0.8% DV) Vitamin C: 0.4 mg (0.7% DV) Iron: 0.1 mg (0.6% DV) Riboflavin: 0.01 mg (0.6% DV) Folate: 2 mcg (0.5% DV) Vitamin E: 0.1 mg (0.5% DV) Manganese: 0.007 mg (0.4% DV) Calcium: 3 mg (0.3% DV) Niacin: 0.06 mg (0.3% DV) Vitamin A: 12 IU (0.2% DV) Phosphorus: 1 mg (0.1% DV) Potassium: 3 mg (0.1% DV) Thiamin: 0.002 mg (0.1% DV) Vitamin B6: 0.002 mg (0.1% DV) DV = Daily Value as established by the US Food and Drug Administration, based on a 2,000-calorie diet. Recipe: Lemon Capellini with Capers Adapted from Ina Garten22 Ingredients: 1 pound dried capellini pasta 1/3 cup of extra virgin olive oil Zest and juice of two lemons 1/4 cup capers, drained Salt and pepper to taste Directions: Cook pasta according to package directions. Before draining, reserve 1/4 cup of pasta cooking water. Drain pasta and return to pot off the heat. Toss the cooked pasta with olive oil, lemon juice, salt, and pepper, adding pasta water a tablespoon at a time until a thin sauce forms. Discard any remaining pasta water. Add capers and lemon zest and toss once more to combine. Serve immediately. References Kontaxis DG. Specialty Crop: Capers. Davis, CA: University of California Cooperative Extension; 2012. Available at: http://sfp.ucdavis.edu/pubs/SFNews/DecJan97-98/capers_148/. Accessed April 17, 2017. Van Wyk, BE. Food Plants of the World: An Illustrated Guide. Portland, OR: Timber Press; 2005. National Geographic Society. Edible: An Illustrated Reference to the World’s Food Plants. Washington DC: National Geographic Society; 2008. Basic Report: 02054, Capers, canned. United States Department of Agriculture Agricultural Research Service website. Available at: https://ndb.nal.usda.gov/ndb/foods/show/303. Accessed April 6, 2017. Appendix 7. Nutritional Goals for Age-Sex Groups Based on Dietary Reference Intakes and Dietary Guidelines Recommendations. In: Dietary Guidelines for Americans 2015-2020. 8th ed. Washington DC: US Department of Health and Human Services and US Department of Agriculture; 2015. Tlili N, Khaldi A, Triki S, Munné-Bosch S. Phenolic compounds and vitamin antioxidants of caper (Capparis spinosa). Plant Foods Hum Nutr. 2010;65(3):260-265. Nabavi SF, Maggi F, Daglia M, Habtemariam S, Rastrelli L, Nabavi SM. Pharmacological effects of Capparis spinosa L. Phyother Res. 2016;30:1733-1744. Akkari H, B’chir F, Hajaji S, et al. Potential anthelmintic effect of Capparis spinosa (Capparidaceae) as related to its polyphenolic content and antioxidant activity. Veterinární Medicína. 2016;61(6):308-316. Kulisic-Bilusic T, Schmöller I, Schnäbele K, Siracusa L, Ruberto G. The anticarcinogenic potential of essential oil and aqueous infusion from caper (Capparis spinosa L.). Food Chem. 2012;132(1):261-267. Yang T, Wang C, Liu H, Chou G, Cheng X, Wang Z. A new antioxidant compound from Capparis spinosa. Pharm Biol. 2010;48(5):589-594. Kaur CK, Kapoor HC. Antioxidants in fruits and vegetables — the millennium’s health. International Journal of Food Science and Technology. 2001;36(7):703-725. Jiang HE, Li X, Ferguson DK, Wang YF, Liu CJ, Li CS. The discovery of Capparis spinosa L. (Capparidaceae) in the Yanghai tombs (2800 years b.p.), NW China, and its medicinal implications. J Ethnopharmacol. 2007;113(3):409-420. Sher H, AlMutairi K, Mansoor M. Study on the ethnopharmaceutical values and traditional uses of Capparis spinosa L. African Journal of Pharmacy and Pharmacology. 2012;6(16):1255-1259. Nadkarni K. Indian Materia Medica. Vol 1. Bombay, India: Bombay Popular Prakashan; 1976. Duke J. Duke’s Handbook of Medicinal Plants of the Bible. Boca Raton, FL: CRC Press; 2008. Emery DL, Hunt PW, Le Jambre LF. Haemonchus contortus: the then and now, and where to from here? Int J Parasitol. 2016;46(12):755-769. Kebede B, Sori T, Kumssa B. Review on current status of vaccines against parasitic diseases of animals. J Veterinar Sci Techno. 2015;7(3):27. Tunçel D. Role of NF-kappa b in the approach to pancreatic ductal adenocarcinoma. Archives Medical Review Journal. 2015;24(4):565-577. Li X, Abdel-Mageed AB, Mondal D, Kandil E. The nuclear factor kappa-B signaling pathway as a therapeutic target against thyroid cancers. Thyroid. 2013;23(2):209-218. Peri S, Devarajan K, Yang DH, Knudson AG, Balachandran S. Meta-analysis identifies NF-kappaB as a therapeutic target in renal cancer. PLoS One. 2013;8(10):e76746. Chhaya G, Mishra SH. Antihepatotoxic activity of p-methoxy benzoic avid from Capparis spinosa. J Ethnopharmacol. 1999;66:187-192. Garten I. Lemon capellini with caviar. Food Network Magazine. Available at: www.foodnetwork.com/recipes/ina-garten/lemon-capellini-with-caviar. Accessed April 6, 2017.
Inhibitory potentials of phenolic-rich extracts from Bridelia ferruginea on two key carbohydrate-metabolizing enzymes and Fe2+-induced pancreatic oxidative stress
April 2018Journal of integrative medicine 16(3) DOI: 10.1016/j.joim.2018.04.006 Afolabi Olakunle BAfolabi Olakunle BOmotade OloyedeOmotade OloyedeAgunbiade Shadrach Oludare Abstract OBJECTIVE: The current study was designed to evaluate the various antioxidant potentials and inhibitory effects of phenolic-rich leaf extracts of Bridelia ferruginea (BF) on the in vitro activities of some key enzymes involved in the metabolism of carbohydrates. METHODS: In this study, BF leaf free and bound phenolic-rich extracts were used. We quantified total phenolic and flavonoid contents, and evaluated several antioxidant activities using assays for ferric reducing antioxidant power, total antioxidant activity (phosphomolybdenum reducing ability), 1,1-diphenyl-2-picrylhydrazyl and thiobarbituric acid reactive species. Also, extracts were tested for their ability to inhibit α-amylase and α-glucosidase activity. RESULTS: The total phenolic and total flavonoid contents in the free phenolic extract of BF were significantly greater than in the bound phenolic extract. Also, all the antioxidant activities considered were significantly greater in the free phenolic extract than in the bound phenolic extract. In the same vein, the free phenolic-rich extract had a significantly higher percentage inhibition against α-glucosidase activity (IC50 = 28.5 µg/mL) than the bound phenolic extract (IC50 = 340.0 µg/mL). On the contrary, the free phenolic extract (IC50 = 210.0 µg/mL) had significantly lower inhibition against α-amylase than the bound phenolic-rich extract (IC50 = 190.0 µg/mL). CONCLUSION: The phenolic-rich extracts of BF leaves showed antioxidant potentials and inhibited two key carbohydrate-metabolizing enzymes in vitro.
James Wong @Botanygeek 20h20 hours ago More The smell of the air after a storm is caused by Geosmin: A chemical released by dead soil bacteria. Humans are hyper sensitive to it, capable of detecting at a concentration of 5 parts per trillion. It's theorised in our evolutionary past this helped us seek out water.
Friday, 27 July 2018
Pesticidal plants as a possible alternative to synthetic acaricides in tick control: A systematic review and meta-analysis
Elsevier Industrial Crops and Products Available online 27 July 2018 In Press, Corrected ProofWhat are Corrected Proof articles? Industrial Crops and Products Author links open overlay panelOlubukola TolulopeAdenubiadAroke ShahidAhmedaFolorunso OludayoFasinabLyndy JoyMcGawaJacobus NicolaasEloffaVinnyNaidooac a Phytomedicine Programme, Department of Paraclinical Sciences, Faculty of Veterinary Sciences, University of Pretoria, Onderstepoort, 0110, South Africa b Department of Veterinary Tropical Diseases, Faculty of Veterinary Sciences, University of Pretoria, Onderstepoort, 0110, South Africa c Biomedical Research Centre, Faculty of Veterinary Sciences, University of Pretoria, Onderstepoort, 0110, South Africa d Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine, Federal University of Agriculture, PMB 2240, Alabata, Abeokuta, Ogun State, Nigeria Received 10 August 2017, Revised 20 May 2018, Accepted 22 June 2018, Available online 27 July 2018. https://doi.org/10.1016/j.indcrop.2018.06.075 Get rights and content Highlights • Ticks cause enormous stock losses globally and transmit human and animal diseases. • Chemical acaricides are expensive and many ticks are increasingly resistant. • Rural farmers have been using plant extracts to control ticks for many centuries. • One of the most useful chemical acaricide classes, pyrethroids discovered from plant. • We summarize work reported in international databases in this meta-analyis. Abstract Ticks are a large group of parasitic arthropods which transmit pathogens to animals and humans, causing great economic losses. Chemical-based antitick measures include the use of pyrethroids, carbamates, organophosphates, formamidines and macrocyclic lactones, which all have associated costs, resistance-development and environmental hazards. Some plant-based alternatives may have good efficacy, low toxicity and reduced environmental impacts. A review of published scientific articles was conducted for medicinal plants with in vitro tick repellent or acaricidal activities against immature and adult stages of ticks. Veterinary databases (All Databases, CAB Abstracts and Global Health, PubMed, Web of Science, BIOSIS Citation Index, Science Direct, Current Content Connect and Google Scholar) were used. The search words were “acaricidal”, “tick repellent”, “medicinal plants”, “phytochemical constituents” and “antitick assays”. To investigate correlations, meta-analysis was conducted using the Fixed-effect model in an Excel programme.The different plant parts, extractants used and their efficacies, where available are listed. Extracts of some species including Azadirachta indica, Gynandropsis gynandra, Lavandula angustifolia, Pelargonium roseum and Cymbopogon species have good acaricidal and larvicidal effects with 90–100% efficacy, comparable to those of currently used synthetic acaricides. Bioassays used in the determination of repellent, acaricidal, larvicidal, inhibition of oviposition and hatchability include tick climbing repellency, Petri dish, larval packet and immersion tests amongst others. Using a total of 1 428, 1 924, 574, 281 and 68 events, the median efficiency value for acaricidal, larvicidal, egg hatching inhibition, inhibition of oviposition, repellency, acaricidal effects of the Lamiaceae and Asteraceae families were 80.12 (CI95%: 79.20–81.04), 86.05 (CI95%: 85.13–86.97), 83.39 (CI95%: 82.47–84.31), 53.01 (CI95%: 52.08–53.93), 92.00 (CI95%: 91.08–92.93), 80.79 (CI95%: 79.87–81.71) and 48.34% (CI95%: 47.42–49.26) respectively. Among the 26 isolated active compounds identified, some such as azadirachtin, carvacrol, linalool, geraniol and citronellal and their potential uses are discussed. While plant species used in ethnoveterinary medicine hold vast potential as parasiticides, the variations in testing methodologies and assay conditions make comparison among studies very problematic. The standardization of components, extraction techniques and experimental design is urgently required to fully explore their potential. Abbreviations Cl-Chloride CNSCentral Nervous System ConcConcentration DDTDichlorodiphenyltrichloroethane DEETN,N-Diethyl-meta-toluamide ECEffective concentration FigFigure GABAγ- Aminobutyric acid GluClGlutamate-gated chloride LCLethal concentration LDLethal dose MEVMedian efficiency value NDNot determined Picaridin1-Piperidinecarboxylic acid 2-(2-hydroxyethyl)-1-methylpropylester PMDPara-menthane-3,8-diol SS2201S,2S-2-Methylpiperidinyl-3-cyclohexene-1-carboxamide Keywords Antitick Acaricide Tick repellent Phytochemical Livestock Plant extract 1. Introduction Ticks are a diverse group of haematophagous arthropods, with at least 898 recognized species, distributed among three families: Argasidae (194 species), Ixodidae (703 species) and Nuttalliellidae (1 species) (Norval et al., 2004). They parasitize a wide range of hosts, and are ranked closely with mosquitoes in their capacity to transmit disease agents of importance (protozoa, bacteria, rickettsia and viruses) to livestock, domestic animals and humans (Sonenshine et al., 2002). Ticks are the most economically important ectoparasites and the most widespread species include Amblyomma testudinarium, Dermacentor auratus, Haemaphysalis bispinosa, Rhipicephalus (Boophilus) microplus, Ixodes acutitarsus, Ixodes ovatus, Nosomma monstrosum, Rhipicephalus haemaphysaloides, Rhipicephalus sanguineus and Rhipicephalus turanicus (Mans and Neitz, 2004). Economic loss caused by ticks and tick-borne diseases in cattle is estimated to be more than 7 billion USD worldwide (Zahir et al., 2010). Tick control programmes are largely based on the use of commercially available ectoparasiticides such as the organochlorines, organophosphates, pyrethroids and more recently, the insect growth regulators and isoxazolines on or in the animals or in the environment (de Oliveira et al., 2012; McTier et al., 2016) (Table 1). Limiting exposure to tick-infested areas and the use of repellents is also considered effective in preventing ticks and tick-borne diseases in companion animals and humans (Cisak et al., 2012). At present, the most commonly used repellents include N, N-diethyl-meta-toluamide (DEET) and 1-piperidinecarboxylic acid 2-(2-hydroxyethyl)-1-methylpropylester (picaridin) (Table 2). Table 1. Classes of acaricides and their mechanisms of action. Class of acaricide and examples Site and mechanism of action Chemical Structure LC50 (mg/ml) References Arsenicals: arsenic trioxide, potassium arsenite, dihydro-1, 3, 2,-dithiarsenol-2ylmercapto-acetic acid In the citric acid cycle, they inhibit pyruvate dehydrogenase and by competing with phosphate, uncouple oxidative phosphorylation, thus inhibiting energy-linked reduction of nicotinamide adenine dinucleotide, mitochondrial respiration and adenosine triphosphate synthesis leading to death Arsenic trioxide – Klaassen and Watkins (2003)a Organochlorines: benzenehexachloride, dichlorodiphenyltrichloroethane (DDT), lindane, aldrin, dieldrin, toxaphene, endosulphan, methoxychlor, hexachlorocyclohexane Binding at the picrotoxinin site in the gamma aminobutyric acid (GABA) chloride (Cl−) ionophore complex which inhibits Cl- flux into the nerve causing hyperexcitation and death DDT 36.8 Lawrence and Casida (1984)a, Camerino (2015)b Organophosphates: coumaphos, chlorfenvinphos, diazinon, parathion, malathion, diaxanthion, oxinothiophos Act at the synapse of nerve junctions and inhibit the activity of acetylcholinesterase irreversibly. Acetylcholinesterase breaks down the neurotransmitter acetylcholine, which carries impulses across the synapse from one nerve cell to another. Cholinesterase inhibition results in continuous nerve discharges leading to paralysis and death Coumaphos 0.39 Barthold and Schier (2005)a, Singh et al. (2014)b Carbamates: carbaryl, aldicarb, carbofuran, ethienocarb, fenobuacrb, oxamyl, propoxur Reversibly inhibits the activity of acetylcholinesterase. Cholinesterase inhibition results in continuous nerve discharges leading to paralysis and death Propoxur 0.039 Barthold and Schier (2005)a, Camerino (2015)b Formamidines: amitraz, chlordimeform, clenpyrin, chloromethiuron Competes with octopamine for its receptor site, guanosine diphosphate is replaced with guanosine triphosphate, inducing the production of cyclic adenosine monophosphate leading to inhibition of attachment and ultimately blood feeding with eventual death Amitraz 0.001 Beugnet and Franc (2012)a, Malan (2015)b Pyrethroids: cypermethrin, permethrin, deltamethrin They block sodium ion movement along the axon of the nerve fibre. This stimulates repetitive nerve discharges that lead to paralysis and death Cypermethrin 0.005 Shafer et al. (2005)a, Singh et al. (2014)b Macrocyclic lactones: avermectins (ivermectin, eprinomectin, selamectin, doramectin, abamectin) milbemycins Bind to GABA and glutamate-gated chloride channels (GluCl) thereby opening chloride channels in nerves, resulting in disruption of activity and loss of function in these cells leading to paralysis and death Ivermectin 0.61 Raymond and Sattelle (2002)a, Rodriguez-Vivas et al. (2017)b Phenylpyrazoles: fipronil, pyriprole Binds to the allosteric sites of GABAA and GluCl channels of the parasites as an antagonist (non-competitive inhibition). This prevents the opening of Cl− channels normally encouraged by GABA, reducing the Cl− ability to lower the neuron’s membrane potential. This results in an overabundance of neurons reaching action potential, CNS toxicity via over-stimulation and eventual death Fipronil 0.00053 Cole et al. (1993)a, Ravindran et al. (2014)b Spinosyns: Spinosad (mixture of spinosyn A and D), spinetoram Primarily targets binding sites on nicotinic acetylcholine receptors of the parasite’s nervous system leading to disruption of neurotransmission, paralysis and death Spinosyn A, R=H Spinosyn D, R = CH3 Spinosad 0.11 Bacci et al. (2016)a, Kovendan et al. (2012)b *Insect growth regulators: azadirachtin, methoprene, diflubenzuron, fluazuron Bears a structural resemblance to the moulting hormone, 20-hydroxyecdsyone, thus interrupting moulting, metamorphosis and development of the female reproductive system. Ticks which survive are unable to produce a progeny Azadirachtin 5 Beckage et al. (2000)a, Al‐Rajhy et al. (2003)b Isoxazolines: afoxolaner, fluralaner, sarolaner, lotilaner, CPD I Non-competitive GABA receptor antagonists, bind to Cl− channels in nerve and muscle cells blocking the transmission of neuronal channels, paralysis and death Fluralaner 0.28 McTier et al. (2016)a Williams et al. (2015)b a Reference for synthetic acaricide and mechanism of action. b Reference for LC50; LC50-Lethal concentration killing 50% of the population. * Demonstrates tick growth regulator activity. Table 2. Insect/Tick repellents and their mechanisms of action. Tick repellent Site and mechanism of action Chemical Structure References N, N-diethyl-meta-toluamide (DEET) Blocks the olfactory receptors for 1-octen-3-ol, a volatile constituent of sweat and breath. A protein, ionotropic receptor 40a, has also been identified as a putative DEET receptor Kain et al. (2013) 1-piperidinecarboxylic acid 2-(2-hydroxyethyl)-1-methylpropylester (Picaridin) The receptors, CquiOR136•CquiOrco and odorant binding protein 1 have been identified Drakou et al. (2017) Para-menthane-3,8-diol (PMD) ND Van Langenhove and Paul (2014) Ethyl butylactyloaminopropionate (IR3535) Has a dual effect on olfactory receptors, both inhibiting (antagonism) and activating them (agonism), thus, the arthropod can no longer detect attractant cues from a host Bohbot and Dickens (2012) 1S,2S-2-methylpiperidinyl-3-cyclohexene-1-carboxamide (SS220) Modality for repellent activity is olfactory Carroll et al. (2005) Racemic 2-methylpiperidinyl-3-cyclohexene-1-carboxamide (AI3-37220) Ionotropic receptor 40a could be a putative receptor Kain et al. (2013) The sale and procurement of ectoparasiticides accounted for 22% of the annual veterinary market of 872 million ZAR (73 million USD) in 2003 in South Africa (Peter et al., 2005). In other countries such as Kenya, Zambia, Zimbabwe, Nigeria, Tanzania and Uganda, the annual cost of importing ectoparasiticides had been estimated at 16 million, 10 million, 9.3 million, 30 million, 26 million and 26 million USD respectively (Kaaya and Hassan, 2000). The global parasiticide market was valued at 6 509.1 million USD in 2013. This is expected to reach 8 918.1 million USD by 2019 growing at a rate of 5.4% (www.marketsandmarkets.com). Commercial repellents and/or acaricidal agents are available for use on companion animals, livestock and humans, in different formulations, including tablets, sprays, soaps, shampoos, powders, impregnated collars, dip solutions, pour-on and spot-on applications (Gassel et al., 2014). Appropriate use of these chemicals is beneficial in controlling ticks, but improper application and misuse may lead to poisoning of humans and animals, emergence of resistant strains, issues of drug residues in animal food products (meat and milk) as well as environmental hazards (Babar et al., 2012). To overcome these obstacles, the development of an effective and environmentally friendly alternative of low toxicity to replace the synthetic agents is required. Research and Development orientated towards alternative methods of tick control that are consistent with the principles of sustainable agriculture, includes the use of tick antigens as vaccines (Shahein et al., 2013), entomopathogenic fungi (Nana et al., 2015, 2016) and plant-based alternatives (Benelli et al., 2017a,b). Plants have long provided mankind with a source of medicinal agents, with natural products once serving as the major provider of all therapeutic drugs (Balandrin et al., 1993). Many plant secondary metabolites are synthesized to provide protection against pathogens, predators and pests. These agents act in one or more of the following ways: counteraction of growth regulatory hormones, anti-feeding effects, inhibition of egg development, disruption of mating and sexual communication, inhibition of chitin formation and repellent action (Benelli et al., 2016b). It should be kept in mind that plant-produced chemicals that deter invertebrates and vertebrates primarily target herbivores and not blood feeders, such as ticks. Probably because of their shared arthropod lineage with herbivorous insects, ticks are also susceptible to some plant-produced deterrents. For example, the pyrethrins, which are a class of organic compounds derived from the dried flower heads of Chrysanthemum cinerariifolium (Trev.) Vis, have been used for centuries for their acaricidal and tick repellent properties (Dhang and Sanjayan, 2014). They also provide a structural backbone for the synthetic pyrethroids which are components of many household, agricultural and industrial insecticides (Dhang and Sanjayan, 2014). In some countries, plant-based ectoparasitic formulations are commercially available (Freitag and Kells, 2013). MyggA® Natural (Bioglan, Lund, Sweden), contains 30% of Corymbia citriodora (Hook.) oil with a minimum of 50% para-menthane-3,8-diol (PMD); Citriodiol®, manufactured by Citrefine International Limited, UK contains 64% PMD; Economist®, a natural alternative to permethrin, which contains pyrethrins and d-limonene, obtained from Citrus species is available in South Africa; BioUD®, with the active ingredient 7.75% 2-undecanone, originally derived from Lycopersicon hirsutum subsp glabratum C.H. Mull (wild tomato plants), registered by the United States Environmental Protection Agency in 2007 and TT-4302 (Guardian®Wilderness; Tyratech, Inc. Morrisville, NC, U.S.A) containing 5% geraniol (Bissinger et al., 2009, 2016). In an attempt to find safe and efficient compound(s) with tick repellent and/or acaricidal properties, research on plant extracts used traditionally in tick control has grown in recent years as seen in many reviews (Atanasov et al., 2015; Adenubi et al., 2016; Benelli et al., 2016b; Pavela et al., 2016; Katz and Baltz, 2016; Benelli and Lukehart, 2017; Benelli et al., 2017a,b). Renewed interest in natural compounds derived from plants and microorganisms to develop non-synthetic medications for the veterinary industry using newer methodologies such as combinatorial chemistry, computational biology and high throughput screening, could yield new repellents/acaricides (Sparks et al., 2016). Tick repellents or acaricides with mechanisms of action targeting previously unexplored metabolic pathways can be developed that may overcome multi-acaricide resistant populations. The market for plant-based tick repellents and acaricides is extremely promising considering the high level of synthetic acaricide consumption (Borges et al., 2011). Plant-based products could be useful for organic livestock production as well as providing alternatives for controlling resistant strains. As prevention of contamination of food and the environment is one of the sustainable development goals to transform our world, it is essential to invest in developing a pharmaceutical phytotherapy industry, with interdisciplinary approaches towards finding solutions to the menace caused by ticks and tick-borne diseases. In this review, we provide information from selected studies that include plant species used in traditional veterinary medicine globally for tick infestation as repellents or acaricides, including those with antifeedant and growth-inhibition properties. Plant species cited are reviewed for efficacy, bioactive constituents and possible mechanism of action to validate their traditional use in animal health. We have summarized and harmonized the most important results of the tests of plant extract efficacy against different tick species and life stages (eggs, larvae, nymphs or adults), To investigate correlations, meta-analysis was conducted. Plant species and compounds therein showing very good efficacy are highlighted. Bioactive products based on plant extracts or isolated compounds may constitute prototypes for the development of promising alternatives to chemical acaricides. 2. Materials and methods The keywords used to collect relevant literature for the review were: “tick repellent”, “acaricidal”, “medicinal plants”, “isolated compounds” and “antitick assays”. Veterinary databases (All Databases, CAB Abstracts and Global Health, PubMed, Web of Science, BIOSIS Citation Index, Science Direct, Current Content Connect and Google Scholar) were searched. Specifically, the plant species tested, the effective concentrations and concentration killing 50% of the population (LC50), extractants, possible mechanism of action, species and life stage of ticks targeted, type of bioassay used and compounds isolated were considered. 2.1. Selection criteria applied to published results The selected papers focusing on in vitro tick repellent and/or acaricidal efficacy of plant extracts as listed in the Web of Science database, complied with at least one of the four criteria listed below: (1) Efficacy for the evaluation of larvae, nymph and adult mortalities and/or tick repellency higher than 60%. (2) Efficacy for the evaluation of growth inhibition estimated. (3) The LC50 (acaricidal) and/or EC50 (repellency) estimated. (4) Compounds isolated from the plant extracts. 2.2. Meta-analysis applied to published results Data for plant extracts with tick repellent and/or acaricidal properties was extracted and compiled from peer reviewed journals obtained from the databases mentioned above. The data was quality-checked through data filtration to remove duplicates and harmonized into a single Microsoft Excel® spreadsheet. All concentrations (including LC50/EC50) were harmonized and expressed as mg/ml. Filtered data was coded for use in a Microsoft Excel® programme, including: the plant name, part(s) of the plants used and family; acaricidal activity, larvicidal activity, inhibition of oviposition, egg hatching inhibition and repellency effects; assay type employed and further in vivo studies (if any). The number of events, sample sizes and outcomes were calculated based on the data. Data was analysed using fixed-effect model (precision-based estimates) in the Meta-analyses software on Excel and comparison between individual studies was calculated in WinPepi v11.24 (Neyeloff et al., 2012). Outputs were generated as percentage of acaricidal, larvicidal, inhibition of oviposition, egg hatching inhibition and repellency effects of the plants or of specific families with 95% confidence intervals. Cumulative events with measures of central tendencies were also produced in forest plots. 3. Results 3.1. Plant species with repellent potential In total, 27 plant species from 18 families were represented (Table 3). The family with the highest frequency was: Asteraceae (15%), followed by Lamiaceae (11%). The Cleomaceae, Poaceae, Rutaceae and Verbenaceae had 7% representation each while the other families were represented by 1 plant species (4%) each (Table 3). Most of the studies used essential oils from the aerial parts of the plants (63%). This was followed by ethanol extracts (22%), methanol and hexane extracts (7%). The leaf was the most used part, followed by the aerial parts, fruits, flowers and drupes in one study. About 56% of the studies used nymphs to test for repellency, 37% used adults while 7% used larvae. Tick climbing repellency, fingertip repellency, vertical filter paper and Petri dish repellency assays were commonly employed. Duration of repellency ranged from 1 h to 35 h (Lavandula angustifolia Mill.) and active phytochemicals include eugenol, β-caryophyllene, linalool, carvacrol, 1, 8-cineole, myrcene and geraniol (Table 3, Table 6). Only 1 study progressed to in vivo validation of in vitro studies. Table 3. Plant species evaluated for repellent activity and their possible bioactives. Plant family and species Common name Plant part/ Extractant Tick repellent bioassay, tick species and life stage studied Conc. (mg/ml) Effect (%) EC50 (mg/ml) Some active isolated compounds References Asparagaceae Convallaria majalis L. Lily of the valley L (EO) PDR using nymphal I. ricinus 100 67 ND Convallamaroside Nartowska et al. (2004)b, Thorsell et al. (2006)a Asteraceae Ageratum conyzoides (L.) L Billy-goat weed L (EtOH) FR using nymphal A. cajennense 1.1 85 0.21 Stigmasterol, β-sitosterol, precocene II, ageratochromene Soares et al. (2010)a, Kumar et al. (2016)b Artemisia abrotanum L. Southern wormwood L (EO) PDR using adult I. ricinus 100 69.1 ND Coumarin, thujyl alcohol, cinnamyl aldehyde, α-copaene, eugenol, eucalyptol Tunón et al. (2006)a, b Artemisia absinthium L. Absinthe wormwood L (EO) FVR using nymphal I. ricinus 100 78.1 ND Sabinene, thujenol, linalool, geranyl acetate Sabinene, thujenol, linalool, geranyl acetate Jaenson et al. (2005)a, b Tagetes minuta L. Southern marigold AP (EO) TCR using adult H. marginatum rufipes – – 0.07 Cis-ocimene, β-ocimene, 3-methyl-2-(-2-methyl-2-butenyl)-furan, 2-butanone, dihydrotagetone, cis-tagetone Nchu et al. (2012) Makang’a (2012)b Bignoniaceae Kigelia africana (Lam.) Benth Sausage tree Fr (MeOH) FR using larvae R. appendiculatus 0.25 76 ND Kiglin, 6-methoxymellein, stigmasterol, lapachol Gabriel and Olubunmi (2009)b, Opiro et al. (2013)a Burseraceae Commiphora holtziana Engl. Myrrh Re (HX) PDR using larvae R. (B.) microplus 10 80 ND Germacrene-D, δ-elemene, β-bourbonene β-selinene, β-elemene, γ-elemene, α-cubebene Birkett et al. (2008)a, b Caryophyllaceae Dianthus caryophyllus L. Carnation Fl (EO) PDR using nymphal I. ricinus 100 100 ND 2-Phenyl-ethanol, eugenol, geraniol, coumarin, α-pinene, β-citronellol Tunón et al. (2006)a, b Chenopodiaceae Dysphania ambrosioides (L.) Mosyakin & Clemants (formerly Chenopodium ambrosioides L.) Wormseed L (EtOH) FR using nymphal A. cajennense 2.2 100 0.51 Ascaridole, 2-carene, ρ-cymene, isoascaridole, α-terpinene Soares et al. (2010)a, Chu et al. (2011)b Cleomaceae (previously Capparaceae) Cleome gynandra L. (syn. Gynandropsis gynandra (L.) Briq.) Cat’s whiskers AP (EO) TCR using adult R. appendiculatus 0.1 98.9 ND Carvacrol, transphytol, linalool, trans-2-methylcyclopentanol, β-caryophyllene Lwande et al. (1999)a, b Cleome monophylla L. Single-leaved cleome AP (EO) TCR using adult R. appendiculatus 0.1 89.9 ND Terpenolene, 1-α-terpeneol, 2-dodecanone, α-humulene, β-humulene, n-Pentacosane Ndungu et al. (1995)a, b Cupressaceae Chamaecyparis nootkatensis (D. Don) Spach (formerly Cupressus nootkatensis D. Don) Alaska yellow cedar AP (EO) FVR using nymphal I. scapularis – – 0.48 Nootkatone, valencene-13-ol, nootkatone 1, 10- epoxide, carvacrol Dietrich et al. (2006)a, b Ericaceae Rhododendron tomentosum (Stokes) H. Harmaja (formerly Ledum palustre L.) Rhododendron tomentosum Harmaja Marsh Labrador tea L (EO) FVR using nymphal I. ricinus 100 95.1 ND Myrcene, palustrol, 2,6-dimethyl-1,5,7-octatriene-3-ol, 2-methyl-6-methylene-1,7-octadiene-3-one (myrcenone), alloaromadendrene, ledol, p-cymene, β-caryophyllene Jaenson et al. (2005)a, b Fabaceae Senna (Cassia) didymobotrya (Fresen.) Irwin & Barneby African senna AP (MeOH) FR using larval R. appendiculatus 0.25 87.6 ND Anthraquinones, terpenoids, flavonoids, phenolic compounds, tannins Opiro et al. (2013)a, Alemayehu et al. (2015)b Geraniaceae Pelargonium graveolens L'Her Rose geranium L (EO) VFP using nymphal A. americanum 0.10 90 ND Citronellol, geraniol, 10-epi-γ-eudesmol Tabanca et al. (2013)a, b Lamiaceae Lavandula angustifolia Mill. (syn. L. officinalis Chaix ex Vill.) English lavender AP (EO) TCR using adult H. marginatum rupifes 200 100 ND Linalool, borneol, camphor, eucalyptol Mkolo and Magano (2007)a, Fadia et al. (2015)b Mentha pulegium L. Squaw mint AP (EtOH) FR using nymphal A. cajennense 1.1 85 0.45 1α, 6βdimethyl-5β-hydroxy-4β-(prop-1-en-2-yl)-decahydronaphthalen-2-one, 1-(O-β-D-glucopyranosyl)-2,7-dimethyloct-5-en-3-one Soares et al. (2010)a, Ibrahim (2013)b Ocimum suave (Wild) Wild basil L (EO) TCR using adult R. appendiculatus – – 0.24 1,8-cineole, linalool, pinene, eugenol, camphor, methyl chavicol, ocimene, terpinene, limonene Mwangi et al. (1995)a, b, Pandey et al. (2014)b Lauraceae Lindera melissifolia (Walter) Blume Pondberry D (EO) TCR using nymphal A. americanum 0.83 74 0.67 β-caryophyllene, α-humulene, germacrene D, β-elemene Oh et al. (2012)a, b Meliaceae Melia azedarach L. Chinaberry tree Fr (HX) FR using nymphal A. cajennense – – 2.22 3,7,11,15- tetramethyl-2-hexadecen-1-ol, carotene, rhodoxanthin, meliatoxin, melianone, meliantriol, nimbolidin A, nimbolidin B Soares et al. (2010)a, Krishnaiah and Prashanth (2014)b Myrtaceae Syzygium aromaticum (L.) Merr. & L.M. Perry (syn. Eugenia caryophyllata Thunb.) Cloves EO PDR using nymphal I. ricinus 100 68 ND Carvacrol, thymol, eugenol, cinnamaldehyde Chaieb et al. (2007)b, Thorsell et al. (2006)a Poaceae Cymbopogon nardus (L.) Rendle Citronella grass AP (EtOH) FR using nymphal A. cajennense 0.28 100 0.09 Linalool, citronellal Soares et al. (2010)a, Avoseh et al. (2015)b Cymbopogon nardus (L.) Rendle EO PDR using nymphal I. ricinus 100 89 ND Thorsell et al. (2006)a Rutaceae Ruta graveolens L. Rue AP (EtOH) FR using nymphal A. cajennense – – 4.14 2-undecanone, 2-nonanone, α-limonene, 5, 6-diethenyl-1-methyl-cyclohexane Soares et al. (2010)a, Haddouchi et al. (2013)b Spiranthera odoratissima A. St.- Hil. Manaca L (EtOH) FR using nymphal A. cajennense – – 8.43 Dictamine, γ-fagarine, skimmianine, 1-methyl-2-phenylquinolin-4-one, limonexic acid, limonin Soares et al. (2010)a, Terezan et al. (2010)b Verbenaceae Callicarpa americana L. American beautyberry EO FR using nymphal A. cajennense 1.0 85 0.1 Callicarpenal, intermedeol Soares et al. (2010)a, b Lippia javanica (Burm. f.) Spreng. Lemon bush AP (EO) TCR using adult H. marginatum rupifes 53 69.2 ND Myrcene, 1,8-cineole, dyhrodrotagetone, ipsenone, bicycle(3.1.1)heptanes-2-one, 2-butanone Magano et al. (2011)a, b Plant parts: AP- Aerial parts; L- Leaves; D- Drupes; Fl- Flowers; Fr- Fruit; Re- Resin. Plant peparations: EO- Essential Oil; EtOH- Ethanolic extract; MeOH- Methanolic extract; HX- Hexane extract. Ticks: A - Amblyomma; H.- Hyalomma; I.- Ixodes; R.- Rhipicephalus. Test type: FR- Fingertip Repellency; TCR- Tick Climbing Repellency; PDR- Petri Dish Repellency; FVR- Falcon Vial Repellency; VFP- Vertical Filter Paper Repellency. Others: Syn. - Synonym; ND- Not determined yet; Conc.- Concentration; EC50 - Effective concentration 50. a Reference for repellent activity. b Reference for isolated compounds. 3.2. Plant species with acaricidal and growth inhibitory potential In total, 55 plant species from 22 families had activities that were in line with the criteria we set (Table 4). The families with the highest frequencies were: Lamiaceae (20%), Asteraceae (13%), Rutaceae and Fabaceae (9%) and Solanaceae (7%). The Meliaceae and Poaceae had 6% representation each, Euphorbiaceae and Piperaceae had 4% representation each while the remaining 13 plant families were represented by 1 plant species each (2%) (Table 4). Table 4. Plant species evaluated for their acaricidal and growth inhibitory activities and their possible bioactives. Plant family and species Common name Plant part/Extractant Acaricidal bioassay, tick species and life stage studied Conc.* (mg/ml) Effect (%) IO (%) EHI (%) Some active isolated compounds Mechanism of action References Acanthaceae Andrographis paniculata (Burm.f) Nees King of bitters L (MeOH) APT using field adult Haemaphysalis bispinosa 3(0.33) 100 ND ND Andrographolide, andrograpine, panicoline, paniculide-A, B, C ND Elango and Rahuman (2011)a, Hossain et al. (2014)b Amaryllidaceae Allium sativum L. Garlic C (MeOH) AIT using field EF R. (B.) microplus 100 80 85.8 100 Allicin, alliin ND Hughes and Lawson (1991)b, Shyma et al. (2014)a, C (DCM) CB using lab-reared adult H. marginatum rufipes 240 (59) 100 ND ND ND Nchu et al. (2005)a Annonaceae Annona squamosa L. Sugar apple FP (Aq) AIT using field adult Haemaphysalis bispinosa 2(0.44) 100 ND ND 1H- cycloprop[e]azulen-7-ol decahydro-1,1,7-trimethyl-4-methylene-[1ar-(1aα,4aα, 7β, 7 a, β, 7bα)], retinal 9-cis- 3,17-dioxo-4-androsten-11alpha-yl hydrogen succinate, 1-naphthalenepentanol decahydro-5-(hydroxymethyl)-5,8a-dimethyl-y,2-bis(methylene)-(1α,4aβ,5α,8aα), 1-naphthalenemethanol decahydro −5-(5-hydroxy-3-methyl-3-pentenyl)- 1,4a-di methyl - 6-methylene -(1S-[1α, 4aα, 5α(E), 8aβ], (−)-spathulenol, podocarp-7-en-3-one13β-methyl-13-vinyl, 1-phenanthrene carboxaldehyde 7-ethenyl-1,2,3,4,4a,4,5,6,7,9,10,10a-dodecahydro-1,4a,7-trimethyl-[1R-(1α,4aβ.4bα,7β, 10aα)] ND Madhumitha et al. (2012)a, b Araceae Acorus calamus L. Sweet flag Rh (50%EtOH/DW) AIT using lab-reared EF R. (B.) microplus; in vivo 100 100 100 ND α-asarone, β-asarone ND Ghosh et al. (2011)a, b Apocynaceae Calotropis procera (Aiton) Dryand. Apple of Sodom LX (EtOH) AIT using field EF H. dromedarii (1.1) – ND ND Digitoxin, cardenolide Inhibition of Na+, K+-ATPase of ticks Al‐Rajhy et al. (2003)a, b Asteraceae Artemisia absinthium L. Absinthe wormwood AP (CH) AIT using field EF R. sanguineus 200 (88) 93.3 85.1 100 Artemisinin Reacts with the heme groups of the haemoglobin molecules digested by parasites, altering the cell structure and its functions, thus affecting growth and reproduction Godara et al. (2014)a, b Calea serrata Less. Snake herb AP (HX) AIT using field EF R. (B.) microplus 50 14.6 ND 100 Precocene II Interferes with tick oviposition, development and reproduction Ribeiro et al. (2011)a, b Eupatorium adenophorum Spreng. (syn. Ageratina adenophora) Sticky snakeroot AP (EtOH) AIT using field nymphal Haemaphysalis longicornis 1500 100 ND ND Quercetagetin 7-β-O-glucoside, 6-methoxykaempferol 7-methyl ether 3- β-O-glucoside, quercetagetin 4^-methy lether 7- β-O-glucoside, 6-hydroxykaempferol-7- β-O-glucoside, 6-methoxygenkwanin; umbelliferone; 3-(2^- β-O-pyranoglaucoside)-phenyl-2-trans-trans-propenoic acid, dotriacontanol. ND Li et al. (2008)b, Nong et al. (2013)a Matricaria (Chamomilla) chamomilla L. Chamolile Fl (EtOH) AIT using field EF R. (B.) annulatus 80 26.7 46.7 ND Angelic acid (2-meyhyl-2-butenoic acid), azolen, chamazulene (1,4-dimethyl-7-etazulene), α-bisablol, sineol, maricarin, matricin ND Pirali-Kheirabadi and Razzaghi-Abyaneh, (2007)a, b Tagetes erecta L. Mexican marigold L (AC) APT using field adult Haemaphysalis bispinosa 3 84 ND ND Benzaldehyde, limonene, linalool, myroxide, β-ocimene, phenylacetaldehyde, piperitone ND Elango and Rahuman (2011) Tagetes minuta L. Southern marigold AP (EO) NPT using lab-reared nymphal H. marginatum rufipes 0.10 60 ND ND Cis-ocimene, β-ocimene, 2-butanone, 3-methyl-2-(2-methyl-2-butenyl)-furan, piperitenone ND Nchu et al. (2012)a, b Tagetes patula L. French marigold AP (EtOH) AIT using lab-reared EF R. sanguineus 50 0 21.5 ND 50 - hydroxymethyl-5-(3-butene-1-ynil)-2,20 -bithiophene; methyl-5-[4-(3- methyl-1- oxobutoxy)-1-butynyl]-2,2’ bithiophene; cholesterol; β-sitosterol (24-R-stigmast-5- ene-3β-ol) (4); stigmasterol [24-(S)-stigmast-5,22E-dien- 3β-ol], lupeol, kaempferol, quercetina, patuletin-7-O-glucoside (patulitrin), patuletin, quercetagetin, quercetagetin-7-O-glucoside, luteolin ND Politi et al. (2012)a, b Bromeliaceae Ananas comosus (L.) Merr. Pineapple Sk (Aq) AIT using field EF R. (B.) microplus 500 59.4 39.1 33.3 Bromelain May be attributed to enzyme complex of bromelain which promote digestion of the cuticle and death of the parasite Domingues et al. (2013)a, b Caricaceae Carica papaya L. Pawpaw Sd (MeOH) AIT using field EF R. (B.) microplus 100 93.3 100 100 Papain, chymopapain, peptidase A, peptidase B, lysozyme ND Shyma et al. (2014)a, b Combretaceae Guiera senegalensis J.F.Gmel. Moshi medicine L (EtOH) AIT using field EF. H. anatolicum 150 100FI 100 100 (0.508%) Catechin, myricitrin, rutin, quartterin, 3,4,5-tri-O-galloylquinic acid Antifeedant property Osman et al. (2014)a, b Euphorbiaceae Jatropha curcas L. Barbados nut L (EtOH) AIT using field EF R. (B.) annulatus 100 0 10.1 90 Apigenin 7-O-β-D-neohesperidoside, apigenin 7-O-β-D-galactoside), orientin, vitexin, vicenin II, di-C-β-Dglucopyranoside-methylene-(8, 8’)-biapigenin Could be attributed to apigenin which can cause decrease in the level of active ecdysteroid by inhibiting the P450 enzyme, leading to decreased incorporation of free ecdysteriods into the eggs or interference with the uptake of modified egg yolk protein, itellin into the oocytes both being important for egg maturation and development Juliet et al. (2012)a, b Ricinus communis L. Castorbean L (EtOH) AIT using field EF R. (B.) microplus; in vivo 99 85 39 ND Quercetin, gallic acid, flavone, kaempferol, ricin Inhibition of the development and maturation of oocytes Ghosh et al. (2013)a, b Fabaceae Calpurnia aurea (Ait.) Benth Wild laburnum L (AC/DW) CB using lab-reared adult R. pulchellus 200 100 DA – – Calpurmenin, 13α-(2’-pyrrolecarboxylic acid) ester, virgiline, lupanine ND Zorloni et al. (2010)a, b Leucaena leucocephala (Lam.) de Wit White leadtree L (AC/DW) AIT using field EF R. (B.) microplus 192 0 7.3 29.0 Tannins, quercetin, caffeic acid, scopoletin High levels of tannins present probably responsible for activity Fernández-Salas et al. (2011)a, Von Son-de Fernex et al. (2015)b Lysiloma latisiliquum (L.) Benth. False tamarind L (AC/DW) AIT using field EF R. (B.) microplus 192 0 36.4 69.3 Tannins High levels of tannins present probably responsible for activity Fernández-Salas et al., (2011)a, b Piscidia piscipula (L.) Sarg. (Syn. Piscidia erythrina L.) Fishpoison tree L (AC/DW) AIT using field EF R. (B.) microplus 192 0 15.7 39.2 Tannins, 5,7-dihydroxylated isoflavones, coumaronochromones, 5-deoxyisoflavones High levels of tannins present probably responsible for activity Fernández-Salas et al. (2011)a, Tahara et al. (1993)b Pongamia glabra Vent. (Syn. Miliettia pinnata (L.) Panigrahi Pongam oiltree L (EtOH) AIT using field EF R. (B.) annulatus 100 17 13 50 Karinjin, pongamol, kaempferol, β-sitosterol ND Ravindran et al. (2017)a, b Hypericaceae Hypericum polyanthemum Klotzch ex Reichardt St. John’s wort AP (MeOH) AIT using field EF R. (B.) microplus 25 0 12.8 0 Benzopyrans Disturb the development process and reproduction Ribeiro et al. (2007)a, b Lamiaceae Anisomeles malabarica (L.) R. Br. Ex Sims Malabar catmint L (MeOH) APT using field adult Haemaphysalis bispinosa 3(0.72) 100 ND ND Anisomelic acid, ovatodiolide, pedalitin, acteoside, terniflorin ND Rao et al. (2012)b, Zahir et al. (2010)a Hesperozygis ringens (Benth.) Epling Pulegium L (EO) AIT using field EF R. (B.) microplus 50 ND 76.4 95 Pulegone, limonene, linalool, β-caryophyllene, bicyclogermacrene Due to chemosterilant effect of pulegone Ribeiro et al. (2010)a, b Hyptis verticillata Jacq. John Charles AP (EO) CB using field EF R. (B.) microplus 4 45 87.2 90 Cadina- 410(15)-dien-3-one (1), aromadendr-1(10)- en-9-one (squamulosone), viridiflorol, hexadecyl acetate ND Facey et al. (2005)a, Picking et al. (2013)b Leucas aspera (Willd.) Link Thumbai AP (EtOH) AIT using field EF R. (B.) annulatus 100 54.2 69.4 100 Nicotine, acacetin, apigenin Inhibit the action of prostaglandins Ravindran et al. (2011)a, b Leucas indica (L.) Sm – L (EtOH) AIT using field EF R. (B.) annulatus 500 66.7 55.2 0 Leucolactone, sitosterol, campesterol, stigmasterol, nicotine ND Divya et al. (2014)a, b Ocimum basilicum L. Great basil L (CH) AIT using field adult R. (B.) microplus 100 (55) 100 ND ND Linalool, (Z)-cinnamic acid methyl ester, cyclohexene, α- cadinol, 2,4-diisopropenyl-1-methyl-1-vinylcyclohexane, 3,5-pyridine-dicarboxylic acid, 2,6-dimethyl-diethyl ester, β-cubebene, guaia-1(10),11-diene, cadinene, (E)-cinnamic acid methyl ester, β-guaiene ND Zhang et al. (2009)b, Veeramani et al. (2014)a Origanum minutiflorum O. Schwarz & P.H. Davis Wild origanum AP (EO) VP using field adult R. turanicus 10 100 ND ND Carvacrol, p-cymene, borneol, γ-terpinene, myrcene, camphene, α-pinene, thymol ND Cetin et al. (2009a)a, b Origanum onites L. Turkish oregano L (EO) APT using field adult R.turanicus 250 (23) 100 ND ND Carvacrol, p-cymene, linalool, γ-terpinene, myrcene, camphene, α-pinene, thymol ND Coskun et al. (2008)a, b Satureja thymbra L. Savory AP (EO) VP using field adult H. marginatum rufipes 5 100 ND ND Carvacrol, γ-terpinene ND Cetin et al. (2009b)a, b Tetradenia riparia (Hochst.) Codd Ginger bush L (EO) AIT using field EF R. (B.) microplus 18 100 100 100 14-hydroxy-9-epi-cariophyllene, cismuurolol-5-en-4-a-ol, ledol, a-cadinol, limonene, fenchone ND Gazim et al. (2011)a, b Vitex negundo L. Five-leaved chaste tree L (EtOH) AIT using field EF R. (B.) microplus 50 (7.02) 53.9 100 Terpenoids, irridoids, steroids, phenolic compounds, lignane derivatives, amino acids, fatty acids, aliphatic alcohol ND Singh et al. (2014)a, b Meliaceae Azadirachta indica AJuss. Neem L (MeOH) AIT using field EF R. (B.) microplus 100 33.3 20.7 20 Azadirachtin, meliacarpin Anti-feedant effect and causes delay in the production of ecdysone Akhtar et al. (2008)b Shyma et al. (2014)a S, L, B (EtOH) AIT using lab-reared EF R. (B.) microplus; in vivo 80 (51) 80 ND ND Srivastava et al. (2008)a Carapa guianensis Aubl. Andiroba S (E)O) AIT using field EF R. (B.) microplus 6 ND ND 93.3 Palmtic acid, oleic acid, stearic acid, α-copaene ND de Souza Chagas et al. (2012)a, b Melia azedarach L. Chinaberry Fr (HX) AIT using field EF R. (B.) microplus 2 0 100 100 Azadirachtin, meliacarpin Due to alterations on the neuroendocrine system of the tick. Borges et al. (2003)a, Akhtar et al. (2008)b Myrtaceae Melaleuca alternifolia (Maiden & Betche) Cheel Narrow-leaved paperback L (EO) AIT using field EF R. (B.) microplus 50 ND 100 100 1, 8-cineole, terpinen-4-ol. ND Pazinato et al. (2014)a, b Syzygium aromaticum (L.) Merr & L.M. Perry Clove L (EO) AIT using field EF R. (B.) microplus 10 100 90.3 ND Eugenol, trans-β-caryophyllene ND Yessinou et al. (2016)a, b Papaveraceae Argemone mexicana L. Mexican poppy WP (EtOH) AIT using lab-reared EF R. (B.) microplus 100 90 65.5 ND Alkaloids, terpenoids, flavonoids, phenolics ND Ghosh et al. (2015)a, b Phytolaccaceae Petiveria alliacea L. Guinea henweed S (MeOH) AIT using field EF R. (B.) microplus 200 86.6 91 17 Benzyltrisulfide, benzyldisulfide ND Rosado-Aguilar et al. (2010)a, b Piperaceae Piper aduncum L. Spiked pepper L (EA) AIT using field EF R. (B.) microplus 100 22 46.78 ND Dillapiole, neorodiol, globulol, spathulenol, croweacin, apiole Alter development and metabolism producing physiological disturbances that may lead to inhibition of reproduction or death due to interference with feeding and growth Silva et al. (2009)a, b Piper tuberculatum Jacq. Painful pepper Fr (HX) AIT using field EF R. (B.) microplus 75 (18.4) 100 100 100 Piperine, piplartine ND da Silva Lima et al. (2014)a, b L (EA) AIT using field EF R. (B.) microplus (38) ND ND 81.7 ND de Souza Chagas et al. (2012)a, b Poaceae Cymbopogon citratus (DC.) Stapf Lemon grass L (EO) AIT using field EF R. (B.) microplus, in vivo 125 92 ND ND Citral ND Chungsamarnyart and Jiwajinda (1992)a, b Cymbopogon martini (Roxb.) W. Watson Ginger grass L (E)O) AIT using field EF R. (B.) microplus (29) ND ND 86.7 Geraniol, geranyl acetate, linalool, trans-ocimene, myrcene, β-caryophyllene ND de Souza Chagas et al. (2012)a, b Cymbopogon nardus (L.) Rendle Citronella grass L (EO) AIT using field EF R. (B.) microplus, in vivo 125 100 ND ND Citronellal, d-limonene ND Chungsamarnyart and Jiwajinda (1992)a, b Rutaceae Aegle marmelos (L.) Correa Golden apple L APT using field adult Haemaphysalis bispinosa 3(0.36) 100 ND ND Skimmiarepins A, Skimmiarepins C ND Elango and Rahuman, (2011)a, b Citrus hystrix DC. Kaffir lime FP (E)O) AIT using lab-reared EF R. (B.) microplus 200 80 ND ND Citronellal, β-pinene, sabinene ND Chungsamarnyart and Jansawan (1996)a, Sato et al. (1990)b Citrus maxima (Burm.) Merr. Pomelo FP (E)O) AIT using lab-reared EF R. (B.) microplus 200 100 ND ND d-limonene ND Chungsamarnyart and Jansawan (1996)a, b Citrus reticulata Blanco Tangerin FP (E)O) AIT using lab-reared EF R. (B.) microplus 100 100 ND ND d-limonene, geranial, neral, geranyl acetate, geraniol ND Chungsamarnyart and Jansawan (1996)a, Chutia et al. (2009)b Citrus sinensis (L.) Osbeck Sweet orange FP (E)O) AIT using lab-reared EF R. (B.) microplus 100 98.59 ND ND d-limonene, terpineol, 1,8-cineole, sinsetin ND Chungsamarnyart and Jansawan (1996)a, Favela-Hernández et al. (2016)b Solanaceae Capsicum frutescens L. Malagueta pepper Fr (EtOH) AIT using field EF R. (B.) microplus 50 10 25.3 84.6 Capsaicin, dihydrocapsaicin, pentadecanoic acid, hexadecanoic acid, octadecanoic acid Interference with the conversion of blood ingested by ticks in eggs Vasconcelos et al. (2014)a, b Datura stramonium L. Devil’s snare L (MeOH) AIT using field EF R. (B.) microplus 100 73.33 77.17 70 Scopolamine, hyoscyamine, meteloidine, atropine Similar to organophosphates Shyma et al. (2014)a, b Datura metel L. Devil’s trumpet Fr (EtOH) AIT using lab-reared EF R. (B.) microplus 90 100 100 ND Yangjinhualine A, megastigmane sesquiterpenes, alkaloids, glycosides ND Ghosh et al. (2015)a, b Kuang et al. (2008)b Withania somnifera (L.) Dunal Indian ginseng L (EtOH) AIT using field EF R. (B.) microplus 61 20 21.36 100 Isopelletierine, anaferine, withanolides, withaferins, sitoindoside VII, VIII, IX, X Due to the decreased levels of ecdysteroids leading to decreased incorporation of free ecdysteroids into the eggs necessary for oocyte maturation Singh et al. (2014)a, b Stemonaceae Stemona collinsae Craib. – R (MeOH) AIT using field engorged adult R. (B.) microplus, in vivo 250 100 ND ND Stemofoline, didehydrostemofoline, stemofurans A-K, dihydrostilbene Reduces tick attachment Pacher et al. (2002)b, Kongkiatpaiboon et al. (2014)a, b Verbernaceae Lippia sidoides Cham. Pepper-rosmarin L (EO) NPT using lab-reared nymphal R. sanguineus 19 96.1 ND ND Thymol, o-cymene, E-caryophyllene, myrcene Blocks the GABA receptors, impairing the flow of Cl- ions, leading to alterations on nerve impulses and death Gomes et al. (2014)a, b Plant parts: L- Leaves; S- Stem; B- Bark; R- Root; AP- Aerial parts; WP- Whole plant; Sd- Seed, Fl- Flowers; F- Fruit; FP- Fruit peel; Sk- Skin; C- Cloves; Rh- Rhizome. Extractant: EO- Essential Oil; EtOH- Ethanol; MeOH-Methanol; HX- Hexane; AC- Acetone; DW- Distilled Water; CH- Chloroform; Aq- Aqueous; DCM- Dichloromethane; EA- Ethyl acetate. Ticks: H.- Hyalomma; R.- Rhipicephalus. Test: IO- Inhibition of oviposition; EHI- Egg hatching inhibition; AIT- Adult Immersion Test; APT- Adult Packet Test; NPT- Nymphal Packet Test; CB- Contact Bioassay; VPB- Vapour Phase Bioassay. Others: EF- Engorged adult female; ND- Not determined yet; Conc. – Concentration. a Reference for acaricidal activity. b Reference for isolated compounds. * LC50 – Lethal concentration 50 in bracket; DA- decidedly affected (dead plus very weak). Rhipicephalus (Boophilus) microplus was the most studied tick and the adult immersion test was the most commonly employed method. Most of the studies used essential oils followed by ethanol extracts of the plants, as well as methanol, acetone, hexane, chloroform, water, dichloromethane and ethyl acetate extracts. Engorged female ticks obtained from the field were mostly used and 30% of the studies checked for growth inhibition. The bioactive compounds in the plants were evaluated in 93% of the studies while only 17% attempted to determine the mechanism of action of the plant extract or isolated compound. Active phytochemicals include geraniol, eugenol, β-caryophyllene, carvacrol, linalool, 1, 8-cineole, azadirachtin, thymol, nicotine and scopolamine (Table 4, Table 6). Only 5 of the studies progressed to in vivo experiments. 3.3. Plant species with larvicidal potential In total, 40 plant species from 19 families with larvicidal activity were found (Table 5). The family with the highest frequency was Lamiaceae (25%). This was followed by Asteraceae and Poaceae (10% each), Piperaceae (7.5%), Verbenaceae, Solanaceae, Amaryllidaceae (5% each). The other 12 plant families were represented by 1 plant species each (2.5%) (Table 5). Rhipicephalus (Boophilus) microplus larvae were also mostly studied and the average age was 14 days old. Most of the studies also used essential oils more than organic extracts. Active phytochemicals include geraniol, eugenol, β-caryophyllene, limonene, borneol, artemisinin and 1, 8-cineole (Table 5, Table 6). Table 5. Plant species evaluated for larvicidal activity using the Larval Packet or Larval Immersion Tests and their possible bioactives. Plant family and species Common name Plant part/Extractant Tick species and age of larvae Conc. (mg/ml) Effect (%) LC50 (mg/ml) Some active isolated compounds Mechanism of action References Acanthaceae Andrographis paniculata (Burm.f) Nees King of bitters L (MeOH) 7–14 days old LV R. (B.) microplus – – 0.2 Andrographolide, andrograpine, panicoline, paniculide-A, B, C ND Elango and Rahuman (2011)a, Hossain et al. (2014)b Amaryllidaceae Allium sativum L. Garlic C (MeOH) 12 days old LV R. (B.) microplus 100 69 ND Allicin, alliin ND Shyma et al. (2014)a EO 10 days old LV R. (B.) microplus 50 100 ND Allicin, diallyl trisulfide, diallyl disulphide, ajoene ND Martinez-Velazquez et al. (2011)a, Mikaili et al. (2013)b Bl (EO) 15 days old LV R. (B.) annulatus 50 100 ND Allicin, allin, dially disulfide, methyl alkyl disulphide, diallyl trisulfide Interaction with several glycosylated receptor proteins in the mid gut of the parasite leading to inhibition of nutrient absorption and death. Also gets accumulated into the haemolymph and ovarioles thereby interfering with development and reproduction Aboelhadid et al. (2013)a, b Allium cepa L. Onion Bl (EO) 15 days old LV R. (B.) annulatus 50 100 ND Dipropyl disulphide, methyl propyl disulphide, methyl propyl trisulphide Chemical reaction with thiol groups of various enzymes which affects the essential metabolism of cysteine proteinase activity involved in virulence of the parasite Aboelhadid et al., 2013a, b Annonaceae Annona squamosa L. Sugar apple FP (Aq) 14–21 days old LV R. (B.) microplus 2 100 0.5 1H- cycloprop[e]azulen-7-ol decahydro-1,1,7-trimethyl-4-methylene-[1ar-(1aα,4aα, 7β, 7 a, β, 7bα)], retinal 9-cis- 3,17-dioxo-4-androsten-11alpha-yl hydrogen succinate, 1-naphthalenepentanol decahydro-5-(hydroxymethyl)-5,8a-dimethyl-y,2-bis(methylene)-(1α,4aβ,5α,8aα), 1-naphthalenemethanol decahydro −5-(5-hydroxy-3-methyl-3-pentenyl)- 1,4a-di methyl - 6-methylene -(1S-[1α, 4aα, 5α(E), 8aβ], (−)-spathulenol, podocarp-7-en-3-one13β-methyl-13-vinyl, 1-phenanthrene carboxaldehyde 7-ethenyl-1,2,3,4,4a,4,5,6,7,9,10,10a-dodecahydro-1,4a,7-trimethyl-[1R-(1α,4aβ.4bα,7β, 10aα)] ND Madhumitha et al. (2012)a, b Apocynaceae Calotropis procera (Aiton) Dryand. Apple of Sodom AP 14 days old LV H. dromedarii – – 0.58 Digitoxin, cardenolide Inhibition of Na+, K+-ATPase of ticks Al‐Rajhy et al. (2003)a, b L (MeOH) 12 days old LV R. (B.) microplus 100 63.2 ND Shyma et al. (2014) Asteraceae Artemisia absinthium L. Absinthe wormwood AP (CH) 14 days old LV R. sanguineus – – 11 Artemisinin Reacts with the heme groups of the haemoglobin molecules digested by parasites, altering the cell structure and thus affect the growth and reproduction Godara et al. (2014)a, b Calea serrata Less Snakeherb AP 14 days old LV R. (B.) microplus 6.25 100 ND Precocene II, eupatoriochromene Interfere with tick oviposition, development and reproduction Ribeiro et al. (2011)a, b Eupatorium adenophorum Spreng. Sticky snake root AP (EtOH) 7–14 days old LV Haemaphysalis longicornis 1500 100 ND Cadinene sesquiterpenes ND Nong et al. (2013)a, b Tagetes patula L. French marigold AP (EtOH) LV R. sanguineus – – 7.43 50 - hydroxymethyl-5-(3-butene-1-ynil)-2,20 -bithiophene; methyl-5-[4-(3- methyl-1- oxobutoxy)-1-butynyl]-2,2’ bithiophene; cholesterol; β-sitosterol, stigmasterol, lupeol, kaempferol, quercetina, patuletin-7-O-glucoside (patulitrin), patuletin, quercetagetin, quercetagetin-7-O-glucoside, luteolin ND Politi et al. (2012)a, b Caricaceae Carica papaya L. Pawpaw Sd (MeOH) 12 days old LV R. (B.) microplus 100 82.2 ND Papain, chymopapain, peptidase A. peptidase B, lysozyme ND Shyma et al. (2014)a, b Combretaceae Guiera senegalensis J.F. Gmel Moshi medicine L (EtOH) 10-14 days old LV H. anatolicum 150 100 8 Catechin, myricitrin, rutin, quartterin ND Osman et al. (2014)a, b Euphorbiaceae Croton sphaerogynus Baill Croton L (DCM) 14-21 days old LV R. (B.) microplus 200 100 67 Abieta-8,11-diene-3-one, abieta-8,11,13-trien-12-ol, podocarp-7-ene,13-methyl-13-vinyl-3-one ND Righi et al. (2013)a, b Fabaceae Leucaena leucocephala (Lam.) de Wit White leadtree L (AC/DW) LV R. (B.) microplus 4.8 66.8 ND Tannins, quercetin, caffeic acid, scopoletin Tannins responsible confirmed by using a specific blocker, polyethylene glycol Fernández-Salas et al. (2011)a, b Hypericaceae Hypericum polyanthemum Klotzch ex Reichardt St. John’s wort AP (HX) 14 days old LV R. (B.) microplus 6.25 100 ND 6-isobutyryl-5,7-dimethoxy-2,2-dimethylbenzopyran, 7-hydroxy-6-isobutyryl-5-methoxy-2,2-dimethylbenzopyran and 5- hydroxy-6-isobutyryl-7-methoxy-2,2-dimethylbenzopyran Affect development and reproduction of the tick Ribeiro et al. (2007)a, b Lamiaceae Cunila angustifolia Benth. – AP (EO) 14 days old LV R. (B.) microplus 2.5 100 ND Sabinene, γ-terpinene, limonene ND Apel et al. (2009)a, b Cunila incana Benth. – AP (EO) 14 days old LV R. (B.) microplus 2.5 100 ND α-pinene, β-pinene, β-caryophyllene ND Apel et al. (2009)a, b, Agostini et al. (2010)b, Cunila spicata Benth. – AP (EO) 14 days old LV R. (B.) microplus 5 100 ND Menthofurane, borneol ND Apel et al. (2009)a, b Hesperozygis ringens (Benth.) Epling Pulegium L (EO) 14 days old LV R. (B.) microplus 0.62 100 0.26 Pulegone, limonene, linalool, β-caryophyllene, bicyclogermacrene Due to chemosterilant effect of pulegone Ribeiro et al. (2010)a, b Ocimum canum L. Camphor basil L (aq) LV H. a. anatolicum 0.03 96 0.02 α-thujene, myrcene, α-pinene, sabinene, α-phellandrene, α-terpinene, limonene, γ-terpinene, terpinolene, β-caryophyllene, trans-α-bergarmotene, α-caryophyllene, germacrene D,β-seliene, biocyclogermacrene, estragole, thymol, carvacrol ND Jayaseelan and Rahuman (2012)a, b Ocimum suave Willd (syn. Ocimum gratissimum, L.) Clove basil L (EO) LV R. appendiculatus; in vivo 2 100 0.2 Germacrene-D, β-caryophyllene, β-eudesmol, α-humulene ND Mwangi et al. (1995)a, Runyoro et al. (2010)b, Ocimum urticaefolium Roth – L (EO) 14–21 days old LV R. (B.) microplus 50 100 9 Eugenol, elemicin, β-bisabolene ND Hüe et al. (2015)a, b Rosmarinus officinalis L. Rosemary L 10 days old LV R. (B.) microplus 100 89 ND α-pinene, verbenone,1,8-cineole Martinez-Velazquez et al. (2011), Tetradenia riparia (Hochst.) Codd Ginger bush L (EO) 14–21 days old LV R. (B.) microplus 250 100 122 14-hydroxy-9-epi-cariophyllene, cismuurolol-5-en-4-a-ol, ledol, limonene, fenchone ND Gazim et al. (2011)a, b Copaifera reticulata Ducke Copaiba L (DMSO/DW) 14-21 days old LV R. (B.) microplus – – 1.6 Oleoresin ND de Freitas Fernandes and de Paula Souza (2007)a, b Meliaceae Melia azedarach L. Chinaberry Fr (HX) 7–21 days old LV R. (B.) microplus 2.5 98 ND Azadirachtin Due to alterations on the neuroendocrine system of the tick Borges et al., (2003)a, b Myrtaceae Corymbia citriodora (syn. Eucalyptus citriodora) (Hook.) K.D. Hill & L.A.S. Johnson Lemon-scented gum L (EO) LV Anocentor nitens 500 100 ND Citronellal ND Clemente et al. (2010)a, b Phytolaccaceae Petiveria alliacea L. Guinea henweed S (HX) 7-14 days old LV R. (B.) microplus 200 100 38.8 Benzyltrisulfide, benzyldisulfide ND Rosado-Aguilar et al. (2010)a, b Piperaceae Piper aduncum L. Spiked pepper L (HX) 14-21 days old LV R. (B.) microplus 20 70.4 9.3 Dillapiole, neorodiol, globulol, spathulenol, croweacin, apiole, β-ocimene ND Silva et al. (2009)a, b, Bernuci et al. (2016)b Piper mikanianum (Kunth) Steud. Betel leaf AP (EO) 14 days old LV R. (B.) microplus – – 2.33 Apiol, dillapiol, myristicin, limonene, bicyclogermacrene, β-caryophyllene, safrole, β-vetivone, (Z)-isoelemicin, (E)-asarone ND de BF Ferraz et al. (2010)a, b, Bernuci et al. (2016)b Piper tuberculatum Jacq. Painful pepper Fr (HX) LV R. (B.) microplus 0.12 100 0.04 Piplartine, piperine ND da Silva Lima et al. (2014)a, b, L (EO) 14-21 days old LV R. (B.) microplus – – 4.1 ND de Souza Chagas et al. (2012)a, b Poaceae Cymbopogon citratus (DC.) Stapf Lemon grass L (EO) LV R. (B.) microplus; in vivo 1:8 99 ND Citral ND Chungsamarnyart and Jiwajinda (1992)a, b, Cymbopogon martini (Roxb.) Wats. Ginger grass L (EO) 14-21 days old LV R. (B.) microplus – – 4.7 Geraniol, geranyl acetate, linalool, trans-ocimene, myrcene, β-caryophyllene ND de Souza Chagas et al. (2012)a, b Cymbopogon nardus (L.) Rendle Citronella grass L (EO) LV R. (B.) microplus; in vivo 1:8 94 ND Citronellal, d-limonene ND Chungsamarnyart and Jiwajinda (1992)a, b Melinis minutiflora P.Beauv Molasses grass L (EO) LV R. (B.) microplus 0.01% 100 ND Propionic acid, 1,8-cineole, butyric acid, phenylethyl alcohol, hexanal, 9-E-eicosene ND Prates et al., (1998)a, b Rutaceae Aegle marmelos (L.) Correa Golden apple L (MeOH) 7-14 days old LV R. (B.) microplus 2 100 0.13 Skimmiarepin A, skimmiarepin C ND Elango and Rahuman (2011)a, b Solanaceae Datura stramonium L. Devil’s snare L (MeOH) 12 days old LV R. (B.) microplus 100 71.8 ND Scopolamine, hyoscyamine, meteloidine, atropine, terpenoids, flavonoids May be similar to organophosphates Shyma et al. (2014)a, b Solanum trilobatum L. Purple fruited pea eggplant L (Aq) LV H. a. anatolicum 0.05 55 0.05 Solamarine, solaine, solasodine, glycoalkaloid, diosogenin, tomatidine ND Shahjahan et al. (2004)b, Rajakumar et al. (2014)a Verbenaceae Lippia graveolens Kunth Mexican oregano L 10 days old LV R. (B.) microplus 25 100 ND Thymol, carvacrol, p-cymene, γ-terpinene ND Martinez-Velazquez et al. (2011), Lippia sidoides Cham. Pepper-rosmarin L (EO) 15-21 days old LV A. cajennense 18.8 100 ND Thymol, o-cymene, myrcene, E-carophyllene ND Gomes et al. (2014)a, b Plant parts: L- Leaves; S- Stem; B- Bark; R- Root; Bl – bulb; AP- Aerial parts; Sd- Seed, Fl- Flowers; F- Fruit; FP- Fruit peel; Sk- Skin; C- Cloves. Extractant: EO- Essential Oil; EtOH- Ethanol; MeOH- Methanol; HX- Hexane; AC- Acetone; DW- Distilled Water; DMSO-Dimethyl sulphoxide; DCM- Dichloromethane. Ticks: A.- Amblyomma; H.- Hyalomma; R.- Rhipicephalus. Others: LV- Larvae; ND- Not determined; Conc.- Concentration; LC50 – Lethal concentration 50. a Reference for larvicidal activity. b Reference for isolated compounds. Table 6. The lethal concentration (LC50) of some known tick repellent and acaricidal compounds isolated from plants. Class of compound Compound Plant species LC 50 mg/ml (molar)a Chemical Structure and Formula Reference Monoterpene α-pinene (insecticidal, acaricidal) Plectranthus barbatus Andrews Rosmarinus officinalis L. Satureja myrtifolia (Boiss & Hohen.) Greuter & Burdet 0.032 (0.0002) C10H16 Govindarajan et al. (2016) β-pinene (repellent) Lindera melissifolia (Walt.) Blume Stylosanthes humilis Kunth Cleome monophyla L. Clausena anisata (Hook.f) ex. Benth Cannabis sativa L. 6.5 (0.047) C10H16 Ogendo et al. (2011) β-citronellol (acaricidal, repellent) Pelargonium graveolens L.Her. Dianthus caryophyllus L. 789 (4.73) C10H20O Pohlit et al. (2011) Borneol (insecticidal) Lavandula angustifolia Mill. Artemisia abrotanum L. Cunila spinate Benth. Origanum minutiflorum O. Schwarz & P.H. Davis 0.5 (0.0032) C10H18O Pohlit et al. (2011) Carvacrol (acaricidal) Chamaecyparis nootkatensis (D. Don) Spach Gynandropsis gynandra (L.) Briq. Origanum minutiflorum O. Schwarz & P.H. Davis Satureja thymbra L. Lippia gracilis Schauer 4.46 (0.029) C10H14O de Oliveira Cruz et al. (2013) Citronellal (acaricidal) Cymbopogon nardus (L.) Rendle Corymbia citriodora (Hook.) K.D. Hill & L.A.S. Johnson Citrus hystrix DC. 210 (1.36) C10H18O Pohlit et al. (2011) Elemol (repellent) Maclura pomifera (Raf.) C.K. Schneid. 0.005 C15H26O Pohlit et al. (2011) Eucalyptol (1,8-cineole) (acaricidal) Eupatorium adenophorum Spreng. Lippia javanica (Burm.f) Spreng. Ocimum species 0.51 (0.003) C10H18O Badawy et al. (2010) Geraniol (acaricidal, repellent) Pelargonium species Cymbopogon species Dianthus caryophyllus L. 178 (1.15) C10H18O Pohlit et al. (2011) Limonene (acaricidal) Citrus species Copaifera reticulata Ducke Hesperozygis ringens (Benth.) Epling Tetradenia riparia (Hochst.) Codd 0.26 (0.001) C10H16 Badawy et al. (2010) Linalool (acaricidal) Tagetes erecta L. Hesperozygis ringens (Benth.) Epling Ocimum basilicum L. Origanum onites L. Cymbopogon martini (Roxb.) W.Watson 0.50 (0.003) C10H18O Badawy et al. (2010) Myrcene (acaricidal) Origanum minutiflorum O. Schwarz & P.H. Davis Lippia javanica (Burm.f) Spreng. Salvia nilotica Juss. ex. Jacq. 0.55 (0.004) C10H16 Badawy et al. (2010) Pulegone (acaricidal) Mentha suaveolens Ehrh. 0.32 (0.002) C10H16O Pohlit et al. (2011) Tagetone (insecticidal) Tagetes species 0.001 C10H16O Gakuubi et al. (2016) Thymol (acaricidal) Thymus vulgaris L. Lippia sidoides Cham. Lippia gracilis Schauer Origanum. Minutiflorum O. Schwarz & P.H. Davis 5.50 (0.036) C10H140 de Oliveira Cruz et al. (2013) Diterpene Callicarpenal (repellent, acaricidal) Callicarpa americana L. 0.08 (0.0003) C16H26O Carroll et al. (2007) Sesquiterpene α-humulene (repellent) Lindera melissifolia (Walt.) Blume Stylosanthes humilis Kunth Cleome monophyla L. 4.82 (0.023) C15H24 Ogendo et al. (2011) β- caryophyllene Syzygium aromaticum (L.) Merr. & L.M. Perry Canabis sativum L. 0.04 (0.0001) C15H24 Govindarajan et al. (2016) Nootkatone (acaricidal) Chamaecyparis nootkatensis(D. Don) Spach Chrysopogon zizanioides (L.) Roberty Citrus grandis (L.) Osbeck 0.02 C15H22O Panella et al. (2005) Tetranotriterpenoid Azadirachtin (acaricidal) Azadirachta indica A.Juss Melia azedarach L. 5 (0.006) C35H14016 Giglioti et al. (2011) Naphthoquinone Plumbagin (acaricidal) Plumbago zeylanica L. 1.37 (0.007) C11H8O3 Annan et al. (2009) Organosulfur Allicin (insecticidal) Allium sativum L. 0.0002 C6H10OS2 Block (2004) Phenylpropanoid Eugenol (insecticidal, acaricidal) Ocimum species Artemisia species Plectranthus barbatus Andrews 0.025 (0.0001) C10H12O2 Govindarajan et al. (2016) Pyrethrin Pyrethrin I (acaricidal, insecticidal) Chrysanthemum species 0.0004 C21H28O3 Akhtar et al. (2008) Resin Oleoresin (acaricidal) Copaifera reticulata Ducke 1.57 (0.002) C18H27NO3 de Freitas Fernandes and de Paula Souza (2007) Steroidal glycoside Digitoxin (acaricidal) Calotropis procera (Aiton) Dyrand Digitalis purpurea L. 0.40 (0.0005) C41H64O13 Al‐Rajhy et al. (2003) a Molar concentration in brackets. 3.4. Meta-analyses of plant extracts with tick repellent and/or acaricidal properties Based on the meta-analyses, a total of 32, 33, 20, 24, 9, 9 and 4 plant species were evaluated separately for acaricidal, larvicidal, egg hatching inhibition, inhibition of oviposition and repellency of various plant extracts, including also the specific acaricidal effects of two selected plant families (Fig. 1, Fig. 2, Fig. 3, Fig. 4, Fig. 5, Fig. 6, Fig. 7). A total of 1 428 events were considered for acaricidal activities with a median efficiency value (MEV) of 80.12% (CI95%: 79.20–81.04; Fig. 1); while 1 924 events were considered for the larvicidal assays with a MEV of 86.05% (CI95%: 85.13–86.97; Fig. 2). For the egg hatching inhibition assays, a total of 574 events with a MEV of 83.39% (CI95%: 82.47–84.31; Fig. 3) while the inhibition of oviposition had the following values: MEV 53.01% (CI95%: 52.08–53.93) (Fig. 4). The repellency assays had MEV of 92.00% (CI95%: 91.08–92.93; Fig. 5) while the specific acaricidal effects of the two selected plant families (Lamiaceae and Asteraceae) with 281 and 68 events respectively was MEV of 80.79% (CI95%: 79.87–81.71; Fig. 6) and 48.34% (CI95%: 47.42–49.26; Fig. 7) respectively. Fig. 1 Download high-res image (396KB)Download full-size image Fig. 1. Meta-analyses of acaricidal effects of extracts of some plant species. 2-Acorus calamus (Sweet flag); 3-Anisomeles malabarica (Malabar catmint); 4-Allium sativum (Garlic); 5-Andrographis paniculata (King of bitters); 6-Artemisia absinthium (Absinthe wormwood); 7-Azadirachta indica (Neem); 8-Calotropis procera (Apple of Sodom); 9-Calpurnia aurea (Wild laburnum); 10-Capsicum frutescens (Malagueta pepper); 11-Carica papaya (Pawpaw); 12-Citrus maxima (Pomelo); 13-Citrus reticulata (Tangerin); 14-Citrus sinensis (Sweet orange); 15-Citrus hystrix (Kaffir lime); 16-Cymbopogon citratus (Lemon grass); 17-Cympobogon nardus (Citronella grass); 18-Datura stramonium (Devil’s snare); 19-Leucas aspera (Thumbai); 20-Leucas indica; 21-Matricaria chamomilla (Chamolile); 22-Melaleuca alternifolia (Narrow-leaved paperback); 23-Ocimum basilicum (Great basil); 24-Origanum onites (Turkish oregano); 26-Petiveria alliaceae (Guinea henweed); 27-Ricinus communis (Castor bean); 28-Satureja thymbra (Savory); 29-Tagetes erecta (Mexican marigold); 30-Tagetes patula (French marigold); 31-Tetradenia riparia (Ginger bush); 32-Piper aduncum (Spiked pepper); 33-Stemona collinsae; Red box on the x axis - Median efficiency value (MEV); Lines running perpendicular to the x-axis - Efficiency values of the various plant extracts; Error bars - 95% confidence interval. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article). Fig. 2 Download high-res image (253KB)Download full-size image Fig. 2. Meta-analyses of larvicidal effects of extracts of some plant species. 0-Allium sativum (Garlic); 1-Andrographis paniculata (King of bitters); 2-Artemisia absinthium (Absinthe wormwood); 3-Calea serrata (Snake herb); 4-Carica papaya (Pawpaw); 5-Citrus maxima (Pomelo); 6-Citrus reticulata (Tangerin); 7-Citrus sinensis (Sweet orange); 8-Citrus hystrix (Kaffir lime); 9-Croton sphaerogyrus (Croton); 10-Copaifera reticulata (Copiaba); 11-Cymbopogon citratus (Lemon grass); 12-Cympobogon nardus (Citronella grass); 13-Datura stramonium (Devil’s snare); 14-Eucalyptus citriodora (Lemon-scented gum); 15-Eupatorium adenophorum (Sticky snakeroot); 16-Guiera senegalensis (Moshi medicine); 17-Hypericum polyanthemum (St. John’s wort); 18- Leucanea leucocephala (White leadtree); 19-Licania tomentosa; 20-Lippia sidoides (Pepper-rosmarin); 21-Lysiloma latisiliquum (False tamarind); 22-Ocimum urticaefolium (Basil); 23-Petiveria alliaceae (Guinea henweed); 24-Piper tuberculatum (Painful pepper); 25-Piscidia piscipula (Fishpoison tree); 26-Simarouba versicolor (Bitter wood); 27- Solanum trilobatum (Nightshade); 28-Tagetes erecta (Mexican marigold); 29-Tagetes patula (French marigold); 30-Tetradenia riparia (Ginger bush); 31-Thymus vulgaris (Thyme); 32-Ocimum canum (Camphor basil); Red box on the x axis - Median efficiency value (MEV); Lines running perpendicular to the x-axis - Efficiency values of the various plant extracts; Error bars - 95% confidence interval. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article). Fig. 3 Download high-res image (307KB)Download full-size image Fig. 3. Meta-analyses of egg hatching inhibition effects of extracts of some plant species. 2-Anisomeles malabarica (Malabar catmint); 3-Allium sativum (Garlic); 4-Ananas comosus (Pineapple); 5-Artemisia absinthium (Absinthe wormwood); 6-Baccharis trimera; 7-Calea serrata (Snake herb); 8-Capsicum frutescens (Malagueta pepper); 9-Guiera senegalensis (Moshi medicine); 10-Jatropha curcas (Psychic nut); 11- Leucanea leucocephala (White leadtree); 12-Leucas aspera (Thumbai); 13-Leucas indica; 14-Lysiloma latisiliquum (False tamarind);15-Melaleuca alternifolia (Narrow-leaved paperback); 16-Petiveria alliaceae (Guinea henweed); 17-Piper tuberculatum (Painful pepper); 18-Piscidia piscipula (Fishpoison tree); 19-Tetradenia riparia (Ginger bush); 20-Vitex negundo (Five-leaved chaste tree); 21-Withania somnifera (Poison gooseberry); Red box on the x axis - Median efficiency value (MEV); Lines running perpendicular to the x-axis - Efficiency values of the various plant extracts; Error bars - 95% confidence interval. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article). Fig. 4 Download high-res image (535KB)Download full-size image Fig. 4. Meta-analyses of inhibition of oviposition effects of extracts of some plant species. 2-Acorus calamus (Sweet flag); 3-Allium sativum (Garlic); 4-Ananas comosus (Pineapple); 5-Artemisia absinthium (Absinthe wormwood); 6-Calea serrata (Snake herb); 7-Capsicum frutescens (Malagueta pepper); 8-Carica papaya (Pawpaw); 9-Datura stramonium (Devil’s snare); 10-Hypericum polyanthemumh (St John’s wort); 11-Jatropha curcas (Psychic nut); 12- Leucanea leucocephala (White leadtree); 13-Leucas indica; 14-Lysiloma latisiliquum (False tamarind);15-Matricaria chamomilla (Chamolile); 16-Melaleuca alternifolia (Narrow-leaved paperback); 17-Petiveria alliaceae (Guinea henweed); 18-Piper tuberculatum (Painful pepper); 19-Piscidia piscipula (Fishpoison tree); 20-Ricinus communis (Castor bean); 21-Tagetes patula (French marigold); 22-Tetradenia riparia (Ginger bush); 23-Vitex negundo (Five-leaved chaste tree); 24-Withania somnifera (Poison gooseberry); Red box on the x axis - Median efficiency value (MEV); Lines running perpendicular to the x-axis - Efficiency values of the various plant extracts; Error bars - 95% confidence interval. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article). Fig. 5 Download high-res image (243KB)Download full-size image Fig. 5. Meta-analyses of repellency effects of extracts of some plant species. 2-Cassia didymobotrya (African senna); 3-Gynandropsis gynandra (Cat’s whiskers); 4-Lavandula angustifolia (English lavender); 5-Lindera melissifolia (Pondberry); 6-Lippia javanica (Lemon bush); 7-Pelargonium graveolens (Rose geranium); 8-Ptaeroxylon obliquum (Sneezewood tree); 9-Tagetes minuta (Southern marigold); 10-Cleome monophylla (Single-leaved cleome); Red box on the x axis - Median efficiency value (MEV); Lines running perpendicular to the x-axis - Efficiency values of the various plant extracts; Error bars - 95% confidence interval. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article). Fig. 6 Download high-res image (254KB)Download full-size image Fig. 6. Meta-analyses of acaricidal effects of extracts of some plant species in the Lamiaceae family. 2-Anisomeles malabarica (Malabar catmint); 3-Leucas aspera (Thumbai); 4-Leucas indica; 5-Ocimum basilicum (Great basil); 6-Origanum minutiflorum (Wild origanum); 7-Origanum onites (Turkish oregano); 8-Satureja thymbra (Savory); 9-Tetradenia riparia (Ginger bush); 10-Vitex negundo (Five-leaved chaste tree); Red box on the x axis - Median efficiency value (MEV); Lines running perpendicular to the x-axis - Efficiency values of the various plant extracts; Error bars - 95% confidence interval. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article). Fig. 7 Download high-res image (141KB)Download full-size image Fig. 7. Meta-analyses of acaricidal effects of extracts of some plant species in the Asteraceae family. 2-Artemisia absinthium (Absinthe wormwood); 3-Matricaria chamomilla (Chamolile); 4-Tagetes erecta (Mexican marigold); 5-Tagetes patula (French marigold); Red box on the x axis - Median efficiency value (MEV); Lines running perpendicular to the x-axis - Efficiency values of the various plant extracts; Error bars - 95% confidence interval. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article). 4. Discussion The use of botanicals for the control of ticks has a long history as an important component of traditional medicine in Africa and Asia, where most resource-poor farmers use plant materials to treat endo- and ectoparasites of livestock (Mondal et al., 2013). Traditional knowledge about the use of these plants is transferred through successive generations, especially in rural communities. Knowledge about the use of individual plant species, however, varies between localities in Africa and scientific validation of their uses may increase the range of plant species available for tick control and reduce the burden substantially on those that are at risk of extinction (Nchu et al., 2012). Pesticidal plant research in veterinary parasitology is a recent area of research globally when compared with screening of plant extracts for the treatment of bacterial diseases. Plant extracts contain mixtures of substances that can act synergistically, in different ways, which makes the development of parasite resistance more difficult than normally occurs with single compound acaricides (Varma and Dubey, 1999). According to Katoch et al. (2007), the efficacy of a single plant can be enhanced by a judicious combination with another plant or active ingredient that has adjuvant properties. This combination of phytochemicals with different mechanisms of action usually lowers the LD50 of the product and hampers the development of resistance by the ticks. 4.1. Tick species studied Rhipicephalus (Boophilus) microplus (Canestrini 1887) (Acari, Ixodidae), a one-host tick, was the most commonly studied tick. This is linked to its wide distribution and importance as a cattle parasite. It portends a major threat to the cattle industry in tropical and subtropical areas with huge economic implications (Domínguez-García et al., 2010). Rhipicephalus (B.) microplus is responsible for severe losses caused by tick worry, blood loss, damage to hides, injection of toxins and is a vector for many tick-borne diseases. In Australia, the overall losses caused by this tick were estimated to be more than 100 million AUD (75 million USD) per annum and in South Africa, losses were projected at between 70–200 million ZAR (5.6–16 million USD) per annum (Peter et al., 2005). It is unclear whether the outcome of these experiments on a one-host tick can be applied to other species of ticks that infest animals and humans. 4.2. Repellency activity From our review also, 27 plant species from 18 families have been shown to have tick repellent activity but relatively little research has been conducted to determine how ticks detect repellents. Carroll et al. (2005) noted that most repellency assays for ticks do not discriminate between repellency via tactile chemoreception or sensory chemoreception. Olfactory sensilla can detect vaporized molecules and evidence suggests that olfaction is involved at least, in part in repellency (Bissinger and Roe, 2013). Nonetheless, very little is known about chemoreception in ticks at the molecular level. Chemoreception in both mammals and insects relies on several families of transmembrane receptors that detect volatile and non-volatile compounds. There are differences in the structures and functioning of the signalling mechanisms of these receptors (Silbering and Benton, 2010). The duration of protection of tick repellent compounds may vary depending on the mode of testing, the formulation of the product, the concentration of the active ingredient, the tick species tested, the developmental stage of the tick species, the fitness of the developmental stage and the absence of adaptation or resistance. Different concentrations of a substance can change the direction of the behavioural response. Unfortunately, in many of the papers reviewed, the concentrations of substances tested are not clearly stated. Another important consideration is that host-seeking ticks respond to host odours and other host cues. Most plant volatiles are generally emitted from the plants and not from tick hosts and as such, may mask the host odours thereby disrupting the host-seeking behaviour or disorientating the host-seeking ticks rather than acting as true repellents. For a repellent to be ideal, it should provide protection against many blood-feeding arthropods for at least eight hours, be non-toxic, non-irritating, odourless and non-greasy (Bissinger and Roe, 2010). Such a repellent is yet to be developed. 4.3. Acaricidal and growth inhibition activities In total, 55 plant species from 22 families had substantial acaricidal and growth inhibition properties. The families with the highest frequencies were: Lamiaceae (20%), Asteraceae (13%), Rutaceae and Fabaceae (9%) and Solanaceae (7%). Most of the studies used essential oils followed by ethanol, methanol, acetone, hexane, chloroform, water, dichloromethane and ethyl acetate extracts of the plants. The number of extracts does not neccesarily indicate which extracts had the highest activity, but rather which extracts were mainly used. The penetration of a parasiticide varies according to the thickness of the layer of lipids on the cuticle and the solubilizing ability of the active compound. This can vary according to the species and developmental phase of the parasite. Therefore, the susceptibility differences between the stages found in many of the studies can be related to the composition and/or thickness of the tick cuticle. The waxy layer only occurs after nymph ecdysis and is most pronounced in adult ticks. Therefore, toxic chemicals may be sequestered within the wax, hampering their efficacy (Sonenshine, 1993). A toxic physical effect through cuticle solubilization by the essential oils in plants cannot be excluded, although terpenes and phenylpropanoids are known to act on the octopaminergic receptor which acts as neurotransmitter, neurohormone and neuromodulator in invertebrates (Regnault-Roger, 2013). Another approach that could be relevant in the sustainable management of ticks is through the disruption of their life cycle by targeting immature stages. This may result in the reduction of tick infestations to low and controllable levels, hence reducing the tick population during favourable climatic conditions. Though some plant species such as Melaleuca alternifolia, Piper tubeculatum, Carica papaya, Guiera seneganlensis, Melia azedarach and Tetradenia riparia did not show high acaricidal mortality, they however caused 100% inhibition of oviposition and hatchability, thereby disrupting life stages of the ticks. The bioactive compound azadirachtin present in Azadirahta indica and Melia azedarach fruit extracts affects tick embryo development and moulting stages. Sheep which consumed feed containing Azadirachta indica fruit and kernel extracts had no noticeable signs of toxicity (Pohlit et al., 2011). This diet, however, negatively affected the ability of the American dog tick Dermacentor variabilis to feed on sheep blood with 4.35–4.81 μg/ml plasma levels of azadirachtin over 14 days. This implies that Azadirachta indica extracts as food additives may have applications in tick control for use in public health and veterinary applications. 4.4. Isolated compounds Plant essential oils are complex mixtures of natural, volatile organic compounds predominantly composed of terpenic hydrocarbons (myrcene, pinene, terpinene, limonene, p-cymene, α- and β-phellandrene), acyclic monoterpene alcohols (geraniol, linalool), monocyclic alcohols (menthol, 4-carvomenthol, terpineol, carveol, borneol), aliphatic aldehydes (citral, citronellal, perillaldehyde), aromatic phenols (carvacrol, thymol, safrol, eugenol) (Tabara et al., 2017), bicyclic alcohol (verbenol), monocyclic ketones (menthone, pulegone, carvone), bicyclic monoterpenic ketones (thujone, verbenone, fenchone), acids (citronellic acid, cinnamic acid) and esters (linalyl acetate) (Nerio et al., 2010). Different arthropod species respond quite differently to specific plant volatiles. Benzaldehyde and benzyl alcohol are toxic to the storage mite Tyrophagus putrescentiae Schranck but are, at lower concentrations, attractants to Amblyomma ticks (Yoder et al., 1998). Eucalyptol (1, 8-cineole), which is a characteristic leaf compound of the genus Eucalyptus, is repellent and toxic to most insects, but exhibits attractant activity for some insects belonging to different orders such as Coleoptera and Lepidoptera (Parra et al., 2009). Linalool, which is ubiquitously present in flowers and induced in wounded plant leaves, is repellent to blood-seeking Culex pipiens female mosquitoes (Choi et al., 2002), but is an attractant to the honey bee, Apis mellifera L. (Henning et al., 1992). Methyl salicylate, a volatile emitted from flowers and stressed plants, is also a component of the aggregation-attachment pheromone of Amblyomma ticks and Sarcoptes scabiei mites but is highly toxic to house dust mites, Dermatophagoides and Tyrophagus (Jaenson et al., 2005). Myrcene is repellent to R. appendiculatus and the maize weevil Sitophilus zeamais but highly toxic to many insects, including house flies, cockroaches and Culex mosquito larvae (Koul et al., 2008). In this review, approximately 26 isolated active compounds have been identified from plant essential oils with tick repellent and/or acaricidal properties. Compounds such as geraniol, 2-undecanone, limonene and azadirachtin already have important commercial applications in a variety of commercial products which are useful for tick control (Benelli et al., 2016a). Geraniol, a monoterpene alcohol found in many plants, is an active ingredient in many commercially available insect repellents and has repellent activity against ticks (Chen and Viljoen, 2010). Geraniol appears on the United States Environmental Protection Agency’s list of compounds that are exempt from federal regulation because they are considered demonstrably safe. Some other compounds such as plumbagin, nootkatone and eugenol, might be interesting as lead molecules for the development of effective repellents. 4.5. Meta-analyses From the meta-analyses results, the efficiency values of various plant extracts showed minimal to wide disparities compared to the MEV for each category. Approximately 63% and 69% of all the plant species evaluated for acaricidal and larvicidal assays respectively surpassed the MEV respectively. This means that there is huge potential for plant-based tick repellents, acaricides and larvicides among the evaluated plant species. 4.6. In vitro tick repellent and acaricidal bioassays One major shortfall in research for new plant-based tick repellents and acaricides is the lack of a standardized testing method (Adenubi et al., 2018). For the papers reviewed, a wide range of methods were employed for testing for tick repellency and acaricidal effects. Tick climbing repellency, Petri dish, larval packet, immersion tests amongst others were used. Studies differed in the time frame in which repellence or toxicity was evaluated, the species and life stages of ticks used, the concentration of active ingredients from crude plant extracts, fractions or essential oils, use of different solvents (extractants) and the use of animal host cues or not. These variations identified made comparing results from different authors difficult. This difficulty has been earlier reported by Bissinger and Roe (2010) and Benelli et al. (2017a,b). Very recently, major challenges for future research have been outlined by Benelli and Pavela (2018) and Adenubi et al. (2018). It becomes expedient to develop a standardized laboratory test as a means of obtaining easily comparable data. 4.7. In vivo tick repellent and acaricidal bioassays Difficulty in transposing the efficacy obtained from the laboratory to the field is one of the main obstacles of phytotherapy research in animal health (Borges et al., 2011). Moreover, toxicity studies to identify risks to animal and human health cannot be neglected. Only about 17% of the studies attempted to determine the mechanism of action of the plant extract or isolated compound tested, while only 5 of the studies progressed to in vivo experiments. Methods used to test for bioactivity in vitro should conform to minimum standards and where possible, should be confirmed with in vivo tests. This recommendation for in vivo use of the plant extracts depends on careful toxicological studies and pharmacokinetic investigations to ensure that standardized extracts are used (Cañigueral et al., 2008). Achieving significant efficacy and adequate residual periods in field conditions are the new challenges of this research area, since the acaricidal activity of various plant species has been well documented in vitro (de Souza Chagas et al., 2012). Very recently Nyahangare et al. (2018) found that a water-detergent oil root extract of Maerua edulis had higher activity in protecting cattle against ticks than Amitraz the commercially used acaricide. Alternatively, if facilities for in vivo studies are not available, a battery of in vitro bioassays designed to investigate potential mechanisms of action will also provide useful information. 4.8. Future potential With the identification of plant species having such great potential use in veterinary parasitology, further studies are necessary to isolate more active compounds, elucidate their mechanisms of action, side effects and formulation development to improve their efficacy and stability (Maia and Moore, 2011). Factors such as seasonality, circadian rhythm, plant age and development stage, temperature, water availability, ultraviolet radiation and soil nutrients, can affect the concentration of secondary metabolites especially volatile compounds in plants (Gobbo-Neto and Lopes, 2007). Formulations to protect the active compounds from environmental degradation (to maintain stability) and enable fast penetration into ticks are needed. Formulation plays a crucial role in extending the duration of efficacy of a repellent. For example, a polymer formulation of DEET and cream formulations of Picaridin and SS220 provided almost complete repellency to nymphal Amblyomma americanum for 12 h (Carroll et al., 2008). The plant-derived repellent, 2-undecanone provided 74% repellency against Dermacentor variabilis 2 h after application when unformulated compared to 98% repellency from 3 to 3.5 h after application when formulated in the product BioUD (Bissinger et al., 2011; Kimps et al., 2011). These studies should be conducted with experts in chemistry, pharmacology, pharmacy formulation, entomology and veterinary drug companies. This is necessary to determine the most appropriate adjuvant and develop formulation models that can be adapted based to the nature of the plant extract or bioactive compound isolated. Simple formulations based on plant extracts or essential oils, tend to have a short residual activity due to instability or volatility of the bioactive compounds. This may possibly be circumvented by a study of the main chemical constituents in each new harvest. Subsequently, dose adjustments could be recommended to farmers in accordance with this variation. Commercial formulations composed of one natural bioactive compound allow greater control of the efficacy and quality of raw materials. Also, in vivo efficacy studies (field trials) using formulated products are clearly essential and the economic feasibility of the products must be demonstrated. The standardization of components, extraction techniques, experimental design, mammalian toxicology profiling and excipient development, as well as further investigation into the residual activities and length of shelf-life of these plant species are required before their potential can be fully explored (Ellse and Wall, 2014). 4.9. Future research The focus of this publication was to do a meta-analysis of which plant extracts had high activities in different assays. Several questions and theories posed by us in this review may have been addressed/resolved in other manuscripts that we missed by the key words we used. For future purposes, some areas of research can be considered: 1) The probable differences in enantiomeric purity of essential oil components which are purchased and used in bioassays to confirm the active tick repellent and acaricidal activities in many of the references cited. 2) Deciphering the synergistic, suppressive and other interactions of the components of plant extracts and essential oils. In many of the papers reviewed herein, the active compounds isolated have lesser efficacies than the plant extracts and essential oils from which they were isolated. It remains unclear whether the compound in itself is more active or whether synergism (a cocktail of components) is responsible for the effects of the plant species. 3) Determining the mechanisms of action of the bioactives. 5. Conclusion The use of plant species in the control of veterinary ectoparasites is an exciting area which holds much potential for the future. The potential use of this knowledge by pastoral farmers using low level technology also requires serious attention, especially in developing countries. The overview presented in this work could be useful to scientists who are new in the field and should attract necessary funding for future research to present viable alternatives in overcoming the problem of acaricidal drug resistance. Conflict of interest The authors declare no conflict of interest. Acknowledgements The Phytomedicine Programme at University of Pretoria, the Schlumberger Faculty for the Future Foundation and the National Research Foundation of South AfricaIPPR95991 to JNE) provided funding. References Aboelhadid et al., 2013 S. Aboelhadid, A. Kamel, W. Arafa, K. Shokier Effect of Allium sativum and Allium cepa oils on different stages of Boophilus annulatus Parasitol. Res., 112 (2013), pp. 1883-1890 CrossRefView Record in Scopus Adenubi et al., 2016 O. Adenubi, F. Fasina, L. McGaw, J. Eloff, V. 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