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Monday 30 April 2018

SCIENTIFIC NAME: Malpighia glabra, M. emarginata, M. punicifolia COMMON NAME: acerola

http://www.herbmed.org/Sponsored/acerolasubcat.html

Food As Medicine: Coriander/Cilantro (Coriandrum sativum, Apiaceae)

HerbalEGram:Volume 12, Issue 6, June 2015 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 in San Marcos and the University of Texas at Austin 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 Jayda Seibertb a HerbalGram Assistant Editor b ABC Dietetics Intern (TSU, 2015) History and Traditional Use Range and Habitat Coriandrum sativum, known by the common names coriander and cilantro, is a bright green herbaceous member of the Apiaceae (or carrot) family. Often grown as an annual, it has thin, hollow stems that can reach several feet in height. The stems bear glossy, aromatic, dissected leaves, and pale pink or white flowers forming an umbel inflorescence.1,2,3 Coriander originated in the eastern Mediterranean region and western Asia, and is commonly cultivated in all parts of the world for its aromatic leaves and seeds. The leaves of the plant historically have been used in Asian, Indian, Mexican, Spanish-American, and Middle Eastern cuisine.2 Coriander seeds are globular and aromatic with a slightly bittersweet taste, and have a long history of use as an important culinary spice. Internationally, India is the largest producer, consumer, and exporter of coriander seed. Only 10-15% of total production is exported; the rest is consumed domestically.4 Phytochemicals and Constituents The seeds of the coriander plant contain different types of volatile oils with proven health benefits. Coriander seeds have 25% fatty oil content and are made up of a high amount of petroselenic acid, followed by lesser amounts of linoleic acid, an omega-6 essential fatty acid.5 Coriander seed oil contains 60–70% linalool, a terpenoid that is a powerful cellular antioxidant as well as the source of coriander’s pleasant smell. Spices and seeds represent an important source of fatty acids in the human diet, and insufficient intake can result in inflammation and symptoms of dermatitis.6 In addition to the essential oil, the seeds contain sugars, alkaloids, flavones, resins, tannins, anthraquinones, sterols, and fixed oils.7,8 An alcohol extract of coriander produced antioxidant action comparable to other commercial antioxidants. The leaves appear to have more antioxidant activity than the seeds, likely due to their phenolic content.8 Coriander leaves contain beneficial flavonoids, polyphenols, and phenolic acids. The polyphenols present include kampferol and quercetin, which have also been shown to have an antioxidant and anti-inflammatory effect. Phenolic acids include caffeic acid, protocathenic acid, glycitin, and vanillic acid.5 These secondary plant metabolites have attracted interest and study for their potential protective role against oxidative damage and its associated diseases, including coronary heart disease, stroke, and cancers.9 The leaves of the plant are high in vitamins A, K, and C, as well as calcium.2 Historical and Commercial Uses The coriander plant has a long history of use dating back to the Neolithic Age, around 7000 BCE.7 Mentions of coriander have been documented in ancient Indian Sanskrit texts, the Old Testament, and Egyptian papyrus scrolls.3 Coriandrum sativum has been cultivated in Greece since the second millennium BCE, its fragrant seeds used in perfumes and both the seeds and leaves used in cooking.8 In both traditional Chinese medicine and Ayurvedic medicine, the seeds are used as a digestive, carminative, or a stomachic.8 In Ayurvedic medicine, the seeds are combined with caraway (Carum carvi) and cardamom (Elettaria cardamomum) seeds or with caraway, fennel (Foeniculum vulgare), and anise (Pimpinella anisum) seeds in European medicine to treat digestive complaints.5,10 The leaves of C. sativum have been traditionally used for common digestive issues including gastrointestinal spasms, dyspepsia, and as an appetite stimulant.5 Coriander has been reported to act as a stomachic, carminative, and spasmolytic due to its high essential oil content.10 Leaf preparations were also ingested and applied externally to the chest to treat coughs and chest pains. The seeds of C. sativum have been used to treat gastrointestinal upset such as indigestion, vomiting, diarrhea, and dysentery; as an antispasmodic and expectorant for coughs and bronchitis; and topically as an anti-inflammatory ointment for arthritis and rheumatism and skincare and cosmetic products.5 In Iranian traditional medicine, coriander seed was primarily used to treat anxiety and insomnia. The traditional dose of seed powder is from 1 g to 5 g, three times per day. This translates to a 14-71 mg/kg dose, three times per day, for a 150-pound individual.8 Currently, coriander seed is used in medicinal teas in Germany and can be found in various laxative and carminative remedies. Coriander’s carminative and stimulant effects are noted in the British Herbal Pharmocopoeia and The German Commission E Monographs; Wichtl’s Herbal Drugs and Phytopharmaceuticals confirms coriander’s use as a stomachic, spasmolytic, and carminative agent, and also notes its hypolipidemic effects and insulin-like activity.11 The seeds are a common component of curry powder and many other spice mixtures. They also are used to flavor gin and other liquors, such as Chartreuse and Benedictine.2 Modern Research The seeds of the coriander plant have been shown to in many studies to decrease blood sugar and reduce insulin resistance.12-14 This effect likely is due to the flavonoids and polyphenols present in the seed. Studies also have shown that the seeds can lower cholesterol levels, making it beneficial for heart health. In several animal studies, coriander seed extract decreased LDL cholesterol, triglycerides, and total cholesterol in rats.12 The extract also increased HDL cholesterol (the “good” cholesterol).15 Constituents and phytochemicals present in coriander seeds make them a popular component of aromatherapy treatments. Linalool, the most abundant terpenoid in coriander seed oil, repressed stress-induced effects on rats when inhaled.16 Coriander seed extract also has been shown to have a mild sedative effect, and is being studied for its suitability to treat mild anxiety and insomnia. The extract increased sleep time in mice,17 and another study found that the seed extract acted to decrease anxiety and relax muscles when mice were exposed to a stressful environment, which researchers linked to the polyphenols quercetin and isoquercetin present in the extract.18 While results from animal studies are promising, the anxiolytic and calming properties of coriander seed and its potential to promote sleep in those with insomnia do not appear to have been clinically tested in humans. The leaves of the coriander plant have been shown to decrease symptoms in people with arthritis. Researchers link this antioxidant effect to the presence of vitamins A and C, phenolic acids, and polyphenols in the leaves.19 The leaves’ phenolic content, specifically ethanolic extract, has been shown to protect against liver damage in rats.20 The topical use of diluted essential oils obtained from coriander seeds appears to be well-tolerated and effective in treating superficial skin infections and oozing dermatitis associated with Streptococcus pyogenes. Using the standard agar dilution method, coriander seed oil also has been shown to inhibit Staphylococcus aureus, S. haemolyticus, Pseudomonas aeruginosa, Escherichia coli, and Listeria monocytogenes.8 Coriander leaf oil contains aldehydes effective against Candida spp., S. aureus, Salmonella typhi, Salmonella choleraesuis, and other bacteria. The use of cilantro or coriander leaf has been falsely promoted as an herb that can remove accumulated heavy metals, specifically mercury, from the body, a process known as “chelation.” However, no scientific or clinical evidence supports these claims.8 Some pre-clinical evidence does suggest that concomitant use of coriander leaf while consuming foods considered high in heavy metals can reduce the absorption of toxins and potential toxic effects, but does not support the theory that coriander can remove heavy metals already present in the body. Consuming coriander leaf-based pesto, salsa, or chutney at the same time as foods often laden with mercury, like seafood, could potentially decrease the absorption of heavy metals in the body. More research is needed to validate these findings and determine proper dosing.8 Nutrient Profile21 Macronutrient Profile: (Per 20 g [approx. nine sprigs] coriander) 5 calories 0.43 g protein 0.73 g carbohydrate 0.1 g fat Secondary Metabolites: (Per 20 g [approx. nine sprigs] coriander) Excellent source of: Vitamin K: 62 mcg (77.5% DV) Vitamin A: 1350 IU (27% DV) Good source of: Vitamin C: 5.4 mg (9% DV) Also provides: Potassium: 104 mg (3% DV) Folate: 12 mcg (3% DV) Dietary Fiber: 0.6 g (2.4% DV) Iron: 0.35 mg (1.94% DV) Vitamin E: 0.5 mg (1.67% DV) Vitamin B6: 0.03 mg (1.5%DV) Calcium: 13 mg (1.3% DV) Magnesium: 5 mg (1.25% DV) Niacin: 0.22 mg (1.1% DV) Phosphorus: 10 mg (1% DV) DV = Daily Value as established by the US Food and Drug Administration, based on a 2,000-calorie diet. Recipe: Cilantro-Mint Chutney This condiment does more than add a new dimension to a dish — it helps aid the digestion as well. Cilantro leaves, mint, ginger, and cumin all have traditional uses as carminative agents that soothe upset stomachs.22 Ingredients: 1 cup fresh mint leaves, chopped 1 cup fresh cilantro leaves, chopped 1 small green chili, such as serrano, stem and seeds removed (optional) ½-inch piece of fresh ginger, peeled and roughly chopped 1 teaspoon ground cumin 1-2 tablespoon fresh lemon juice, to taste 1-2 tablespoons of water, as needed Kosher or black salt, to taste Directions: 1. In a food processor, combine all ingredients except for salt and blend until the mixture forms a smooth paste. Add water to create a thinner consistency, if necessary. 2. Mix salt into chutney. Serve chutney on sandwiches, or with rice, lentils, potatoes, samosas, or potato chips. References Murray M. The Encyclopedia of Healing Foods. New York, NY: Atria Books; 2005. Van Wyk B-E. Food Plants of the World: An Illustrated Guide. Portland, OR: Timber Press; 2005. Teuscher E. Medicinal Spices: A Handbook of Culinary Herbs, Spices, Spice Mixtures and Their Essential Oils. Boca Raton: Taylor and Francis; 2006. Burark, SS. Coriander prices to remain stable during harvest. Maharana Pratap University of Agriculture and Technology – Udaipur website. Available here. Accessed May 21, 2015. Sahib NG, Anwar F, Gilani A, Hamid AA, Saari N, Alkharfy KM. Coriander (Coriandrum sativum L.): A potential source of high-value components for functional foods and nutraceuticals – a review. Phytotherapy Research. 2013(10):1439. Chow CK. Fatty Acids in Foods and Their Health Implications, 3rd ed. Boca Raton, FL: CRC Press; 2008. Aggarwal B. Healing Spices: How to Use 50 Everyday and Exotic Spices to Boost Health and Beat Disease. New York, NY: Sterling; 2011. Abascal K, Yarnell E. Cilantro — culinary herb or miracle medicinal plant? Altern Complement Ther. 2012;18(5):259-264. Robbins RJ. Phenolic acids in foods: an overview of analytical methodology. J Agric Food Chem. 2003;51(10):2866-2887. Blumenthal M, Goldberg A, Brinkmann J, eds. Herbal Medicine: Expanded Commission E Monographs. Austin, TX: American Botanical Council; Newton, MA: Integrative Medicine Communications; 2000. Wichtl M. Herbal Drugs and Phytopharmaceuticals: A Handbook for Practice on a Scientific Basis. Boca Raton, FL: CRC Press; 2004. Aissaoui A, Zizi S, Israili ZH, Lyoussi B. Hypoglycemic and hypolipidemic effects of Coriandrum sativum L. in meriones shawi rats. J Ethnopharmacol. 2011;137:652-661. Gray AM, Flatt PR. Insulin-releasing and insulin-like activity of the traditional anti-diabetic plant Coriandrum sativum (coriander). British Journal of Nutrition (United Kingdom). 1999;81(3):203-9. Srinivasan K. Plant foods in the management of diabetes mellitus: spices as beneficial antidiabetic food adjuncts. Int J Food Sci Nutr. 2005;56(6):399-414. Dhanapakiam P, Joseph JM, Ramaswamy VK, Moorthi M, Kumar AS. The cholesterol lowering property of coriander seeds (coriandrum sativum): Mechanism of action. J Environ Biol. 2008;29(1):53-56. Nakamura A, Fujiwara S, Matsumoto I, Abe K. Stress repression in restrained rats by (R)-(−)-linalool inhalation and gene expression profiling of their whole blood cells. J Agric Food Chem. 2009;57(12):5480–5485. Momin AH, Acharya SS, Gajjar AV. Coriandrum sativum — review of advances in phytopharmacology. International Journal of Pharmaceutical Sciences and Research. 2012,5:1233. Emamghoreishi M, Heldari-Hamedani G. Sedative-hypnotic activity of extracts and essential oil of coriander seeds. Iran J Med Sci. 2006;31(1):22-27. Rajeshwari CU, Siri S, Andallu B. Original article: Antioxidant and antiarthritic potential of coriander (Coriandrum sativum L.) leaves. e-SPEN Journal. 2012;7:e223-e228. Pandey A, Bigoniya P, Raj V, Patel KK. Pharmacological screening of Coriandrum sativum linn. for hepatoprotective activity. Journal of Pharmacy & Bioallied Sciences. 2011;3(3):435-441. Basic Report: 11165, Coriander (cilantro) leaves, raw. Agricultural Research Service, United States Department of Agriculture website. Available here. Accessed May 21, 2015. Grieve M. A Modern Herbal. 1931. Available here. Accessed May 21, 2015.

Re: Review on Stress Reduction from Rhodiola

Rhodiola (Rhodiola rosea, Crassulaceae) Stress Date: 04-13-2018 HC# 031841-590 Anghelescu I-G, Edwards D, Seifritz E, Kasper S. Stress management and the role of Rhodiola rosea: a review. Int J Psychiatry Clin Pract. January 11, 2018; [epub ahead of print]. doi: 10.1080/13651501.2017.1417442. Stress, a physiological reaction to threat or pressure, is mediated by hormones, cytokines, and catecholamines. If untreated, these signals can lead to chronic stress or "burnout." Stressors may be physical, emotional, environmental, external, or self-driven. The World Health Organization calls stress "the health epidemic of the 21st century." Stress-related conditions include depression; anxiety; diabetes; and cardiovascular, gastrointestinal, musculoskeletal, and neurological diseases. Treatment options include lifestyle modifications (exercise, relaxation, meditation, and diet changes), herbal remedies, and pharmacological therapy. However, most treatments address only a single symptom of stress. An ideal therapy would affect all relevant symptoms and have a good safety profile. The authors reviewed literature on several herbal and prescription treatments for stress. They found a significant amount of data on rhodiola (Rhodiola rosea, Crassulaceae) extract (RRE*) and outlined a comprehensive approach to stress using RRE. RRE is the main adaptogen** for stress according to the Committee on Herbal Medicinal Products (HMPC) of the European Medicines Agency (EMA). In vitro and in vivo, it was shown to normalize stress hormones, boost energy, and activate mitochondrial adenosine triphosphate (ATP) synthesis. Excess reactive oxygen species (ROS) in mitochondria damage cells. RRE's antioxidant and anti-inflammatory effects may counter such damage, and thus protect against heart and brain disorders. In rabbits under immobilization stress, stress hormones were significantly elevated in those that had received placebo but were virtually unchanged in those treated with RRE (1 mg/kg) for seven days before the stressor. Rats given RRE (50 mg/kg) swam significantly longer than untreated ones. Clinical studies of stress, burnout, and chronic fatigue syndrome (CFS) report RRE effective, safe, and well tolerated. Better mental work capacity, attention, task performance, and mood were seen with RRE, with fewer feelings of stress and anxiety. In a single-arm study, 101 adults with life-stress symptoms took open-label RRE (200 mg b.i.d.) for 28 days. Improvements in all outcomes, seen as soon as three days after treatment began, continued throughout the trial. In 81 students with mild anxiety due to stress who were randomly assigned to receive RRE or no treatment, the RRE group reported significant improvements in anxiety, stress, anger, confusion, vigor, and total mood at 14 days as compared with the untreated group. Studies with varied designs and populations report significant cognitive benefits in RRE-treated subjects over untreated or placebo groups. Effects in 56 healthy physicians on hospital night duty over two weeks of RRE use suggest relief of general fatigue in some stressful situations. In a double-blind, randomized clinical trial, 50 patients with CFS took 576 mg/d RRE or placebo for four weeks. Symptoms significantly improved in the active group over placebo. In an open-label, single-arm study of 101 patients with CFS, RRE use for up to eight weeks brought significant improvements in fatigue, mood, concentration, quality of life, and general well-being. Alleviation of burnout symptoms was reported by 330 German patients after using RRE for eight weeks. These almost universally reported improvements in stress and related conditions, coupled with RRE's safety and tolerability—it has no known adverse effects or herb-drug or drug-drug interactions—make it a strong choice to prevent and counter effects of stress. The study was funded by Dr. Willmar Schwabe GmbH & Co. KG; Karlsruhe, Germany. Author I-G Anghelescu has received consulting fees and/or honoraria from Schwabe, Boehringer Ingelheim, Otsuka, Janssen, Lundbeck, Lilly, Medice, Servier, and Trommsdorff. Author D. Edwards has received honoraria and support from Bayer, Besins, Pfizer, and Schwabe. Author E. Seifritz has received consulting fees and/or honoraria from Schwabe, Otsuka, Janssen, Lundbeck, Eli Lilly, Servier, Hoffmann La Roche, Vifor, Takeda, Sunovion, Pfizer, AstraZeneca, and Angelini. Author S. Kasper has received grants/research support, consulting fees, and/or honoraria from Angelini, AOP Orphan Pharmaceuticals AG, AstraZeneca, Eli Lilly, Janssen, KRKA-Pharma, Lundbeck, Neuraxpharm, Pfizer, Pierre Fabre, Schwabe, and Servier. —Mariann Garner-Wizard * Rhodiola is found in many herbal products, but only those using RRE WS® 1375 (Dr. Willmar Schwabe GmbH & Co. KG; Karlsruhe, Germany) had, at the time of writing, met standards of the Committee on Herbal Medicinal Products (HMPC) of the European Medicines Agency (EMA) to become registered medicinal drugs. ** Herbal adaptogens normalize body functions, strengthen systems affected by stress, and boost non-specific stress resistance.

Re: Safety of Ginkgo biloba Leaf Extract in the Elderly

PDF (Download) Ginkgo (Ginkgo biloba, Ginkgoaceae) Safety Elderly Date: 04-13-2018 HC# 031851-590 Bonassi S, Prinzi G, Lamonaca P, et al. Clinical and genomic safety of treatment with Ginkgo biloba L. leaf extract (IDN 5933/Ginkgoselect®Plus) in elderly: a randomised placebo-controlled clinical trial [GiBiEx]. BMC Complement Altern Med. 2018;18(1):22. doi: 10.1186/s12906-018-2080-5. Ginkgo (Ginkgo biloba, Ginkgoaceae) is one of the most widely used medicinal plants throughout the world, and ginkgo leaf extract is used frequently to treat cognitive decline. There is extensive research evaluating the efficacy and safety of ginkgo. Clinical studies show that the rate of adverse events in patients treated with ginkgo is similar to those treated with placebo. However, a technical report published by the US National Toxicology Program concluded that high doses of ginkgo caused liver and thyroid cancer in rodents. The Committee on Herbal Medicinal Products of the European Medicines Agency reported that "there is no proof for an increased cancer risk in patients taking ginkgo folium medicinal products at their approved posology … ." Also, the International Agency for Research on Cancer "reported that there is inadequate evidence in humans for the carcinogenicity of Ginkgo biloba extract." Despite the conclusions of international agencies, the safety of ginkgo needs to be further evaluated, according to the authors. Hence, the purpose of this multicenter, randomized, double-blind, placebo-controlled study was to evaluate the clinical and genomic safety of ginkgo in elderly patients. Patients (n = 66, aged ≥ 65 years) living in nursing homes in the San Raffaele network (2 in Rome, Italy, and 1 in Latina, Italy) participated in the study, conducted between June and November 2015. Excluded patients had a history of increased bleeding tendency, were receiving anticoagulant or antiplatelet drugs, had cognitive impairment, or had a life expectancy of < 1 year. Patients received either 240 mg/day ginkgo tablets (IDN 5933/Ginkgoselect®Plus; Indena SpA; Milan, Italy), divided into 120-mg doses, or placebo tablets (also prepared by Indena SpA), administered twice daily for 6 months. IDN 5933/Ginkgoselect®Plus is obtained by extracting dried ginkgo leaves using ethanol:water (70:30 per volume), and contains 24.3% flavone glycosides and 6.1% terpene lactones (2.9% bilobalide, 1.38% ginkgolide A, 0.66% ginkgolide B, and 1.12% ginkgolide C). At baseline and at study end, blood was drawn to evaluate liver injury by measuring levels of gamma-glutamyl transferase, alanine aminotransferase, and aspartate aminotransferase; DNA damage via the comet assay; and genomic instability via the micronucleus assay. A subgroup of 17 patients had additional assessments to evaluate the expression of c-myb, p53, and CTNNB1 (β-catenin) genes, which are modulated in early stages of liver carcinogenesis. Nineteen patients were discontinued from the study due to death (n = 1), developing acute pancreatitis with pre-existing chronic renal failure and/or being discharged (n = 10), admission to a hospital (n = 4), and discontinuing treatment (n = 4). Of the patients who completed the study, 27 were treated with ginkgo and 20 were treated with placebo. Baseline variables were similar between groups, and the baseline characteristics of those who discontinued versus completed the study were similar. One patient in the ginkgo group died due to acute pancreatitis. The medical staff concluded that the death was due to worsening of a multipathological condition and not ginkgo treatment. Neither group of patients reported specific symptoms that could be classified as adverse events resulting from this study. The incidence of patients with pathological levels of liver enzymes was low, and the rates were the same at baseline and study end. There was no significant difference between groups in genomic instability according to the micronucleus assay, even after adjusting for confounding variables (P value not significant). There was no significant difference between groups in DNA damage according to the comet assay, even after adjusting for confounding variables (P value not significant). There was no significant difference between groups in gene expression (P value not significant). The authors conclude that treatment with IDN 5933/Ginkgoselect®Plus did not have a higher risk than placebo in affecting genomic safety. This study used a variety of indexes that may predict the risk of developing cancer in subjects treated with a therapeutic dose of ginkgo. The authors used these indexes because it would be difficult to do an epidemiological analysis that would involve finding a population of long-term ginkgo users and monitoring hepatic cancer, which has long latency (time between exposure and symptoms), as a primary endpoint. This also explains why the study had a 6-month duration; the objective was to study early genomic risks, not cancer outcome. A limitation of this study is the relatively small sample size. However, the strengths of this study are that it used multiple endpoint measures, used an elderly population, and it was a randomized controlled study. The study was funded by Indena SpA. One of the authors (Bonassi) was supported by a grant from the Associazione Italiana per la Ricerca sul Cancro (AIRC; Milan, Italy); this author also received consulting fees from Indena SpA. The institutions of 4 of the authors (Bonassi, Prinzi, Lamonaca, and Paximadas) have received research grant support from Indena SpA. One of the authors (Malandrino) is employed by Indena SpA. —Heather S. Oliff, PhD

Sunday 29 April 2018

The foundation and consequences of gender bias in grant peer review processes

http://www.cmaj.ca/sites/default/files/additional-assets/site/press/cmaj.180188.pdf The foundation and consequences of gender bias in grant peer review processes Rosemary Morgan, Kate Hawkins and Jamie Lundine , 2018 Institution: RinGs This commentary accompanies a paper by Tamblyn and colleagues that presents evidence from a cross-sectional study that shows the presence of gender bias in the grant peer review process in Canadian health research funding. Notably, female applicants with past grant success rates equivalent to male applicants were given lower application scores by reviewers, and male applicants with less experience than female applicants were favoured and awarded grants at a higher rate. Gender bias within the research grant review process worldwide is a manifestation of historical and systemic gender bias within academic institutions and beyond. For many reasons, women are underrepresented in academic leadership; their research is less frequently cited than that of men; and they may enjoy less credit for their published work than their male coauthors. Efforts to overhaul processes of research grant peer review must go hand in hand with larger projects that aim to shift traditional gender norms in academia through institutional policies that recognize gender bias and act to counter it.

Saturday 28 April 2018

Recipes Project - Tales from the Archives: THEATRICAL COSMETICS: MAKING FACE, MAKING “RACE”

19/09/2017 Amanda Herbert In September 2016, The Recipes Project celebrated its fourth birthday. We now have over 500 posts in our archives and over 120 pages for readers to sift through. That’s a lot of material! (And thank you so much to our contributors for sharing such a wealth of knowledge on recipes.) But with so much material on the site, it’s easy for earlier pieces to be forgotten. So, the editors have decided that, every now and then, we’ll pull something out of the archives to share with our readers anew. This month I’d like to share a 2014 post by Jessica Clark. It offers a rich, revealing look into the ways that race and gender were performed, made, mocked, and manipulated in 19th and 20th c. British-American white theatre. It’s a timely and important piece. We hope that you enjoy this latest installment from our Recipes Project Archives, and if you have any posts that you’d like for us to revisit, please send in your nominations… AH (editor) ***** By Jessica Clark Dan Leno as “Sister Anne” in a 1901 Drury Lane production of Bluebeard. Wikimedia Commons. Dan Leno as “Sister Anne” in a 1901 Drury Lane production of Bluebeard. Wikimedia Commons. In the world of British theatre, nothing marks the holiday season like the annual pantomime. A traditional panto features all the requisite elements of family entertainment: a wicked villain, slapstick that delights both young and old, and, perhaps most importantly, the archetypal Dame, a male actor in female costume. While all panto characters wear some form of makeup, the pantomime Dame’s overdrawn brows, gaudy eye shadow, and exaggerated lips are especially emblematic of this particular theatrical form. Despite evoking feminine beauty traits, the Dame is embellished to the point of farce.[i] Theatrical makeup like that of the Dame has a long history in the Anglo world, dating back to Elizabethan productions on the south shore of the Thames.[ii] By the late nineteenth century, actors created their stage looks using greasepaint, a major development in modern theatrical makeup. Greasepaint was a German innovation created and refined by two different theatre men. Endeavoring to conceal the seam of his wig in the 1860s, Carl Baudin of the Leipziger Stadt Theatre first mixed a concoction of yellow ochre, zinc white, vermillion, and lard.[iii] By 1873, Ludwig Leichner, a Berlin chemist who moonlighted as an opera singer, marketed a stick greasepaint that would become ubiquitous in the theatre world.[iv] But what did theatrical performers use before the invention and marketing of commercial greasepaint? Actors relied on a range of time-honored techniques to provide coverage and illumination in the glare of nineteenth-century footlights. At times, common cosmetics were used to fashion looks for the stage: vermillion for rouging the cheeks, Indian ink for contouring the eyes or eyebrows, and violet powder for refining the complexion. But it was also possible to alter recipes for run-of-the-mill paints to make them suitable for the theatre. For example, “Rouge de Theatre” was created from “Rouge Vegetal” – a natural concoction of safflowers and carbonate of soda – by adding mucilage of gum tragacanth, which hardened the rouge into a dry, vivid powder.[v] Advertisement in Frank Castles’ _Drawing Room Monologues_(1887) 50. Image courtesy of Google Books. Advertisement in Frank Castles’ _Drawing Room Monologues_(1887) 50. Image courtesy of Google Books. In other cases, actors relied on ingredients better suited to the chemist’s laboratory than a dressing room. No actor’s makeup kit was without powders like dry whiting (finely powdered chalk), burnt umber (calcified brown earth used as a pigment), and fuller’s earth (a hydrous silicate of alumina).[vi] Actors mixed such powders with grease or lard to create vibrant unguents, which they applied to the face. By the mid-nineteenth century, enterprising businessmen sold these powders as part of elaborate “Make-Up Boxes,” but individual ingredients were as readily available at the local druggist. Frontispiece of S.J. Adair Fitzgerald’s _How to “Make-Up”_ (1901). Image courtesy of Archive.org Frontispiece of S.J. Adair Fitzgerald’s _How to “Make-Up”_ (1901). Image courtesy of Archive.org Yet, theatrical powders and paints were not merely used to brighten the cheeks and highlight the lips. English theatrical guides of the late nineteenth and early twentieth centuries highlight other, problematic cosmetic practices that were, until quite recently, common in the Anglo theatre tradition. White actors dominated the profession and relied on makeup to “transform” into characters of different ethnicities. Theatrical guides from the period foreground this history, offering detailed instructions on “making up” the Othered face. Guides included step-by-step processes for creating “the distinctive colorings of the English, Italians, Japanese, Indians, or Africans,” simultaneously eliding race, nationality, and ethnicity.[vii] Cosmetic recipes and techniques were key to fashioning these stereotyped “national” looks. To create “Indian” characters, for example, actors mixed lard with a pigment known as “Mongolian” to produce a light brown color for the face and hands (“Mulattoes may be treated in the same matter,” suggested one American author[viii]). To portray black characters, actors used lumps of burnt cork “as large as a hazel nut,” which were reduced with water and applied to the face with both hands.[ix] By the early twentieth century, the racial underpinnings of theatrical makeup was codified in commercial greasepaint sticks; the lightest shade was known as “No. 1: Very pale flesh color,” while Nos. 18 through 20 were characterized as “East Indian, Hindoos, Filipino, Malays, etc.,” “Japanese,” and “Negroes,” respectively.[x] Dan Leno as “Widow Twankey,” in an 1896 Drury Lane production of Aladdin. Wikimedia Commons. Dan Leno as “Widow Twankey,” in an 1896 Drury Lane production of Aladdin. Wikimedia Commons. Ultimately, theatre functioned as a site of fantasy in the modern Anglo world, whisking audiences away from the drudgery of daily life. Theatrical makeup was central to the construction of this fantasy, and actors became masters at creating illusion via powder and paint. At times, such illusions had the potential to challenge dominant social and gender norms, as in the case of the late-Victorian Dame with her penciled brows. However, as the creation of “national” looks suggests, theatrical makeup also functioned to reify essentialized notions of race and nationality circulating in the Anglo imperial world.[xi] [i] For recent work on the Victorian Dame, see Jim Davis, “’Slap On! Slap Ever!’: Victorian pantomime, gender variance, and cross-dressing,” New Theatre Quarterly 30.3 (August 2014): 218-230. [ii] Annette Drew-Bear, Painted Faces on the Renaissance Stage: the moral significance of face-painting conventions (London: Assoicated University Presses, 1994). [iii] Maurice Hageman, Hageman’s Make-up Book: grease-paints, their origin, use and application, a useful and up-to-date hand book on practical make-up, especially prepared for amateurs and professionals (Chicago: Dramatic Publishing Co, 1898) 11 and Encyclopædia Britannica Online, s. v. “stagecraft”, accessed 02 November 2014 . [iv] Geoffrey Jones, Beauty Imagined: a history of the global beauty industry (New York: Oxford University Press, 2010). For an excellent survey of the history of greasepaint, and cosmetics more generally, see James Bennett, “Greasepaint,” Cosmetics and Skin . [v] Richard S. Cristiani, Perfumery and Kindred Arts: a comprehensive treatise on perfumery (Philadelphia: H.C. Baird, 1877) 152. [vi] Definitions of these powders courtesy of The Oxford English Dictionary. [vii] Cavendish Morton, The Art of Theatrical Make-Up (London: 1909) 16. [viii] DeWitt’s How to Manage Amateur Theatricals (New York: DeWitt, 1880) 46. [ix] James Young, Making Up (London: M. Witmark & Sons, 1905) 85. [x] Young 12. [xi] On the acts themselves, see Jacqueline S. Bratton et al, Acts of Supremacy: the British Empire and the stage, 1790-1930 (Manchester: Manchester University Press, 1991), especially chapter 5; Martin Clayton and Bennett Zon, eds., Music and Orientalism in the British Empire, 1780s-1940s (Burlington: Ashgate, 2007); and Hazel Waters, Racism on the Victorian Stage: representation of slavery and the black character (Cambridge: Cambridge University Press, 2007). On music hall, see Penny Summerfield, “Patriotism and Empire: music-hall entertainment 1870-1914,” Imperialism and Popular Culture, ed. John M. Mackenzie (Manchester: Manchester University Press, 1986) 17-48. ***** Jessica Clark (B.A., Trent; M.A., York; M.A., Ph.D., Johns Hopkins) teaches British history at Brock University. Her interests include British cultural and social history, urban space and the lived environment, empire, and women, gender, and sexuality. Her research explores intersections of gender, class, and ethnicity in the modern British world via the history of beauty and appearance. Clark’s work appears in the Women’s History Review and the forthcoming Gender and Material Culture in Britain after 1600 (Palgrave 2015). She is currently revising a manuscript on the role of Victorian entrepreneurs in developing England’s early beauty industry. She is also working on a new project, “Imperial Beauty,” which investigates transnational commodity and cultural flows linking London-based beauty brokers and imperial markets in British India, the West Indies, and Australia.

Invasive alien plants - valuable elixir

https://www.researchgate.net/publication/324719913_Invasive_Alien_Plants-_Valuable_Elixir_with_Pharmacological_and_Ethnomedicinal_Attributes

Hematologic and serologic status of military working dogs given standard diet containing natural botanical supplements

Toxicology Reports Volume 5, 2018, Pages 343-347 open access Toxicology Reports Author links open overlay panelEunchaeLeeaJun-HaChoibHa-JeongJeongcSung-GuHwangdSangrakLeeaJae-WookOhb https://doi.org/10.1016/j.toxrep.2018.02.016 Department of Animal Bioscience and Technology, College of Animal Bioscience and Technology, Konkuk University, Seoul 05029, Republic of Korea b Department of Animal Biotechnology, College of Animal Bioscience and Technology, Konkuk University, Seoul 05029, Republic of Korea c Department of Companion Animal Science, Seojeong College, 1046-56, Hwahap-ro, Yangju-si, Gyeonggi-do, Republic of Korea d Korea Customs Service, Customs Border Control Training Institute 208, Yeongjonghaeanbuk-ro 1204, Incheon-si, Gyeonggi-do, Republic of Korea Received 20 April 2017, Revised 27 February 2018, Accepted 27 February 2018, Available online 8 March 2018. Get rights and content Under a Creative Commons license Highlights • The experiments with military working dogs (MWDs) as a special case were carried out. • Osteoarthritis is a common inflammatory disease in MWDs. • We evaluated a mixture of natural botanicals as a dietary supplement. • This supplementation had positive effects on hematological and serological values. • Results provided support for the development of a feed supplement for MWDs. Abstract The health of military working dogs (MWDs) deployed with Korean troops is of prime importance. The aim of our study was to investigate the hematologic and serologic status of Korean MWDs given natural botanical supplements. To do this, 11 natural botanicals were selected based on relevant references and combined to supplement MWDs. Throughout the 16-week experimental periods, there was no significant difference in body weights of individual dogs. The Hemoglobin (HGB), hematocrit (HCT), Mean Corpuscular Volume (MCV), and Mean Corpuscular Hemoglobin (MCH) values were slightly higher in the group given the supplement. On the other hand, the Mean Corpuscular Hemoglobin Concentration (MCHC) values were slightly lower. Changes in platelet, lymphocyte, and basophil counts were observed in the supplemented group. The median serum IL-6 level did not differ significantly between the supplemented and control groups. However, the mean serum C-reactive protein (CRP) value increased significantly from the start of supplementation to 8 weeks, and then decreased at 16 weeks. Taken together, our result suggests that the health condition of most MWDs supplemented with natural botanicals was gradually improved. Thus, this study may provide support for the development of a feed supplement for MWDs using natural botanicals. Graphical abstract Download high-res image (168KB)Download full-size image Previous article in issue Next article in issue Keywords Military working dog Natural botanicals Blood Serum Immunoassay C-reactive protein 1. Introduction Hundreds of military working dogs (MWDs) are currently deployed with Korean troops, including the Republic of Korea Army, Air Force, and Navy. These highly trained animals provide various services such as explosive, mine, and drug detection; security; and rescue. All MWDs are maintained in excellent physical condition with routine obstacle course work and specialty training. Most of these dogs work 8–12 h a day several times a week. They are fed a standard diet, and each dog’s weight is kept within standard limits established by the Korean Military Veterinary Services with the help of U.S. forces. The health and well-being of these MWDs are of prime importance. Nevertheless, one of the categories of diseases that threaten their health is joint-related diseases such as osteoarthritis (OA) [1]. Specially, OA is a condition that causes pain, inflammation, and stiffness in many joints and commonly occurs as a consequence of joint dysplasia [2]. Even though the genetic background of select pedigreed breeds, excessive exercise, nutritional imbalances, chronic inflammation, and aging are also linked to the development of OA [2–4]. These inflammatory disorders are often treated using non-steroidal anti-inflammatory drugs (NSAIDs) and disease-modifying anti-rheumatic drugs (DMARDs) [1,5,6]. However, these drugs for OA result in unwanted side effects and various studies are being conducted to overcome these problems. An American study have suggested that 10–20% of all MWD retirements from service are due to degenerative joint disease [7]. A few years later, Smith et al. reported that restricting dogs’ diets by 25% resulted in a significant delay in the onset of signs of hip arthritis [8]. This suggests a possibility for preventing disease by adjusting the dietary intake of MWDs. In this regard, botanical dietary factors are the subject of considerable interest in OA research [6,9]. As mentioned above, OA is primarily a pro-inflammatory disease. The role of inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and chemokines; inflammatory enzymes such as cyclooxygenase (COX)-2, and matrix metalloproteinases (MMPs); and adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) in the pathogenesis of arthritis is well documented [10–12]. The inflammatory mediators linked to OA have been shown to be regulated by the transcription factor nuclear factor-kB (NF-κB) [11]. Nutritional management of inflammation is important in maintaining health in dogs. According to previous studies, some natural botanicals contain bioactive components with anti-inflammatory action and, when included in the diet, may contribute to a reduction in pro-inflammatory response. There are data to support the anti-inflammatory effects and the efficacy of such bioactive molecules from botanicals [for review see [6]. Among them, methyl sulfonyl methane (MSM) is used as a dietary supplement because of its potential to reduce arthritic pain [13]. The seeds of safflower (Carthamus tinctorius L.) are known to be effective against bone diseases such as fracture and osteoporosis [14]. Cirsium japonicum is a wild perennial herb native to Asia, including Korea, and has been used as an antihemorrhagic and antihypertensive agent [15]. Brown marine algae are traditionally used as a food and medicinal herb in East Asia [16,17]. Turmeric (Curcuma longa) is extensively used as a spice, food preservative, and coloring agent in Asia. It has been used in traditional medicine for various diseases, including rheumatism [18]. Curcumin (diferuloylmethane), the main yellow bioactive component of turmeric, has been shown to have various biological effects including anti-inflammatory action [18–20]. Extract of the roots and stems of Acanthopanax senticosus (Syn. Eleutherococcus senticosus) has been reported to have pharmacological action against rheumatism and allergies [21,22]. Glucosamine (Glu) is an amino-monosaccharide and the building block of proteoglycans, the base substances of articular cartilage [13]. Chondroitin sulfate (CS), a polymer of repeating disaccharide units (galactosamine sulfate and glucuronic acid), is the predominant component of articular cartilage [13]. The combination of Glu and CS has been shown to protect against chemically induced synovitis in dogs [23] and to stimulate cartilage metabolism, resulting in the inhibition of cartilage degradation [24,25]. Hyaluronan (HA) is a major component of both synovial fluid and articular cartilage [26,27]. OA treatment with intra-articular HA is an alternative treatment to NSAIDs [28]. A high dietary intake of the antioxidant nutrient vitamin C (ascorbic acid) has been suggested to slow osteoarthritis disease progression [29,30]. Finally, vitamin E is well known for its chondroprotective effects [31]. Studies have reported that the dietary supplementation with Vitamin E reduces symptoms of OA in human patients [32]. Currently, a lot of effort and high-cost are invested to make one good MWD in Korean troops. However, life expectancy as a MWD is relatively short. Thus, if we can extend the health of MWD by natural botanical supplements, they will become even more valuable, especially in a divided country like Korea. To date, there have been no studies regarding joint inflammation-related serum factors in Korean MWDs. Therefore, the objective of this study was to investigate the hematologic and serologic status of MWDs fed a diet with a supplemental mixture of natural botanicals. For this study, 11 species of natural botanicals were selected based on scientific references and mixed. Along with hematologic analyses, C-reactive protein (CRP) and IL-6 concentrations were analyzed in the serum of MWDs fed a diet supplemented with the botanical mixture. 2. Materials and methods 2.1. MWD sources Military installations that submitted samples during the study period were Chuncheon Korea Army Base (CKAB), located in a mountainous area in the northwest; and Jinju Korea Air Force Base (JKAFB), located in the southern part of the Korean Peninsula. Age, breed, sex, and the date of sample collection were recorded. 2.2. Population characteristics A total of 24 MWDs were included in the study – 9 MWDs were from the CKAB; another 15 were from the southern region JKAFB (Table 1). There were 11 MWDs in the 1- to 4-year-old age group, 11 in the 5- to 8-year-old age group, and 2 in the 9- to 12-year-old age group. There were 21 dogs in the 20–30 kg group and 3 dogs in the >30 kg group. The breed distribution included 3 Labrador Retrievers and 21 German Shepherd Dogs. The sex distribution included 13 female dogs and 11 males. Fifteen German Shepherd MWDs (30–92 months old, mean body weight 26.0 ± 2.48 kg) from the JKAB, and six German Shepherd (10–109 months old, mean body weight 30.2 ± 3.96 kg) plus three Labrador Retriever MWDs (15–49 months old, mean body weight 27.4 ± 2.57 kg) from the CKAB were randomly assigned to be supplemented. Table 1. The summarizing details of the individual MWD. No. Sex Age (month) Breed Color Weight (kg) Military base Formulation 1 M 65 GSDa Wolf-gray 24.5 JKAFBc 1 2 M 85 GSD Black and tan 26.8 JKAFB 1 3 M 40 GSD Black 28.4 JKAFB 1 4 M 53 GSD Wolf-gray 22.4 JKAFB 1 5 F 89 GSD Wolf-gray 27.6 JKAFB 1 6 F 85 GSD Wolf-gray 22.1 JKAFB 1 7 F 92 GSD Black and tan 28.9 JKAFB 1 8 F 91 GSD Wolf-gray 27.0 JKAFB 2 9 F 65 GSD Wolf-gray 24.7 JKAFB 2 10 F 68 GSD Wolf-gray 28.7 JKAFB 2 11 F 64 GSD Wolf-gray 27.2 JKAFB 2 12 F 39 GSD Wolf-gray 27.0 JKAFB 2 13 F 42 GSD Wolf-gray 25.1 JKAFB 2 14 F 33 GSD Black and tan 28.8 JKAFB 2 15 F 30 GSD Black and tan 21.5 JKAFB 2 16 M 15 LRb Yellow 28.5 CKABd 1 17 F 10 GSD Black and tan 27.9 CKAB 1 18 M 61 GSD Black and tan 30.0 CKAB 1 19 M 88 GSD Black and tan 33.7 CKAB 1 20 M 109 GSD Black and tan 28.1 CKAB 1 21 M 50 LR Yellow 29.3 CKAB 2 22 M 50 LR Yellow 24.5 CKAB 2 23 F 10 GSD Black and tan 25.7 CKAB 2 24 M 110 GSD Black and tan 36.2 CKAB 2 a GSD: German shepherd dog. b LR: Labrador Retriever. c JKAFB: Jinju Korea Air Force Base. d CKAB: Chuncheon Korea Army Base. 2.3. Diet Based on a literature survey, a mixture of natural botanicals containing MSM, safflower seed, thistle, seaweed fusiforme, turmeric, Acanthopanax root bark, Glu HCl, CS, Hyaluronic acid, and Vitamin C/E was produced, and then given to MWDs as a dietary supplement; Individual botanicals are well-known in oriental medicine to be beneficial to human health. Assigned two groups of MWD were supplemented daily with 500 mg capsulated formulation diet for 0–16 weeks (Table 2). The basal diet met or exceeded the requirements for all essential nutrients (data not shown). Body weight was recorded at 0 and 16 weeks. The research protocol was approved by the Institutional Animal Care and Use Committee of Konkuk University in Seoul, Korea. One dog (No 15 in Table 1) was died of acute pneumonia in two months after starting the experiment. Table 2. Materials and formulations of supplements fed to MWD. Material Botanical name Main component Purity (%) Source Formulation 1 Formulation 2 Referenceb Content (%) Daily intake (mg/day) Content (%) Daily intake (mg/day) Pine organic sulfur/MSM Pinus densiflora Methyl sulfonyl methane 98 YBSH co., Korea 20.0 100 25.0 125 Arafa et al. [13] Safflower seed Carthamus tinctorius Linolenic acid – KTMa 10.0 50 9.0 45 Nordstrom et al. [14] Thistle Cirsium japonicum Silymarin – KTM 10.0 50 9.0 45 Dixit et al. [15] Seaweed fusiforme Hizikia fusiformis Fucoidan – KTM 10.0 50 9.0 45 Lee et al. [16] Turmeric Curcuma longa Curcumin – KTM 10.0 50 9.0 45 Chattopadhyay et al. [18] The root bark of Acanthopanax Acanthopanacis Coumarin – KTM 10.0 50 9.0 45 Hemshekhar et al. [22] – – Glucosamin hydrochloride 99 Hwail co., Korea 12.8 64 12.8 64 Arafa et al. [13] – – Chondrotin sulfate 99 Hwail co., Korea 5.0 25 5.0 25 Arafa et al. [13] – – Hyaluronic acid 99 Humedix co., Korea 2.0 10 2.0 10 Uitterlinden et al. [26] – – Vitamin C 20 Dalim co., Korea 10.0 50 9.4 47 Peregoy and Wilder [29] – – Vitamin E 100 Dalim co., Korea 0.2 1 0.8 4 Aslan et al. [31] Total 100.0 500.0 100.0 500.0 a KTM: Kyungdong traditional market, Korea. b The detailed information of individual component is referred. 2.4. Blood sample collection Whole-blood samples were collected from MWDs by a licensed veterinary officer at their home Korean military locations. Blood (5 mL) was collected from the cephalic vein of the foreleg into Z Serum Sep Clot Activator tube (Greiner Bio-One, Kremsmünster, Austria) and K2-EDTA whole blood collection tube (LP ITALIANA, Milano, Italy) at 0, 8, and 16 weeks, and then sent to the KNOTUS institute (Guri, Korea) for hematologic analysis. Serum was obtained within 2 h of blood sample collection via centrifugation at 2400 g for 5 min; serum was harvested, transferred to cryovials, and immediately frozen (−20 °C) and stored until analysis. 2.5. Hematologic analysis Blood analysis was performed on each sample by licensed medical technologists using an automated hematology analyzer (ABX MICROS 60, France) in the laboratory on the day of blood collection. Only samples without blood clots were analyzed. Hematological parameters included leukocyte subpopulations profile comprising total white blood cells (WBC) count and erythrocyte profile consisting of red blood cells (RBC) count; differential leukocyte counts (lymphocytes, monocytes, neutrophils, eosinophils, and basophils), and hemoglobin (HGB), hematocrit (HCT), platelet, mean cell volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC). 2.6. Enzyme-linked immunosorbent assay (ELISA) CRP and IL-6 are prognostic biomarkers in dog osteoarthritis [33,34]. The analyses of canine serum CRP and IL-6 were performed with commercially available canine-specific ELISA kits. CRP (PTX1) Dog ELISA Kits were purchased from Abcam (Cambridge, MA. USA). Canine IL-6 Quantikine ELISA Kits were purchased from R&D Systems (Minneapolis, MN. USA). All serum samples were analyzed in duplicate according to the manufacturer’s instructions. Serum levels of CRP and IL-6 were determined by sandwich ELISA using the combination of specific canine monoclonal and polyclonal antibodies. 2.7. Statistical analysis Data were analyzed using PROC MIXED of SAS package program (2002–2003, release. 9.3 version, SAS inc., Cary, NC, U.S.A.) with a complete randomized design. Model was, Yij = μ + Ti + Eij where μ was an average value, Ti was treatment value, and Eij was the error value. The experimental unit of this study is a military working dog and fixed effect was time (week) effect. The pair-wise comparison among treatments was conducted using CONTRAST statement. Statistical difference was accepted at p value of less than 0.05. All means are presented as least square means. 3. Results and discussion Based on a literature survey, two types of different formulation of natural botanical supplements containing MSM, safflower seed, thistle, seaweed fusiforme, turmeric, Acanthopanax root bark, Glu HCl, CS, Hyaluronic acid, and Vitamin C/E were prepared, and then given to MWDs as a dietary supplement. Individual botanicals are well-known in oriental medicine to be beneficial to human health. Table 2 shows detailed information of the supplement given to two groups of MWDs; Formulation one was used in the first group and formulation two was used in the second group. The overall compositions of the two formulations differ only slightly. A statistical analysis of results was done for results from formulation one and from formulation two. There were not statistically significant differences in the results from the different formulations. Therefore, the results from the two formulations were combined for presentation. After supplementation, the body weight of individual MWDs was not affected within the experimental period, suggesting that there was no direct relationship between natural botanicals and obesity. The hemogram analysis revealed some significant changes within and between the groups of MWDs from the start to the end of the study, though most values remained within the reference ranges (Table 3). The hemoglobin (HGB) and hematocrit (HCT) values were slightly increased in the MWD group (HGB: 0 vs 8, P = 0.006; HCT: 0 vs 8, <0.001, 0 vs 16, P = 0.008) given the supplement for 8 or 16 weeks. The platelet counts were significantly increased in this group (0 vs 16, P = 0.024) after they received the botanical supplement. The Mean Corpuscular Volume (MCV) and Mean Corpuscular Hemoglobin (MCH) values were slightly increased in the supplemented group (MCV: 0 vs 8, P < 0.001, 0 vs 16, P < 0.001; MCH: 0 vs 8, P = 0.006, 0 vs 16, P = 0.002). On the other hand, the Mean Corpuscular Hemoglobin Concentration (MCHC) values were slightly decreased in the supplemented group (0 vs 8, P = 0.008, 0 vs 16, P = 0.011). An increase in lymphocyte counts in the supplemented group (0 vs 8, p = 0.002) was observed. Neutrophil counts were slightly increased in that group during the same period (0 vs 8, <0.001). Basophil counts were significantly higher in the supplemented group (0 vs 8, P = 0.040, 0 vs 16, <0.001). Table 3. Blood hemogram results at start (baseline), 8 and 16 weeks in MWDs given natural botanical supplements. Week SEM1 P value 0 8 16 0 vs 8A 0 vs 16B CRP (μg/mL) 12.66 21.51 8.30 2.972 0.050 0.337 IL-6 (pg/ml) 31.50 31.34 26.95 8.338 0.990 0.718 WBC (103/mm3) 10.19 9.54 11.50 0.604 0.479 0.160 RBC (106/mm3) 7.14 7.06 6.83 0.151 0.700 0.158 HGB (g/dl) 15.82 17.00 16.37 0.284 0.006** 0.185 HCT (%) 42.34 50.38 47.20 1.155 <0.001*** 0.008** Platelet (103/mm3) 229.79 193.76 327.91 26.271 0.400 0.024* MCV (μm3) 59.25 71.46 71.40 0.558 <0.001*** <0.001*** MCH (pg) 22.17 24.12 24.33 0.379 0.006** 0.002** MCHC (g/dl) 36.50 33.81 33.93 0.580 0.008** 0.011* Lymphocyte (%) 19.92 11.42 22.97 1.586 0.002** 0.238 Monocyte (%) 6.63 41.20 4.69 12.934 0.270 0.951 Neutrophil (%) 66.00 78.14 62.80 2.027 <0.001*** 0.314 Eosinophil (%) 7.46 8.92 8.91 1.079 0.372 0.374 Basophil (%) 0.00 0.23 0.54 0.064 0.040* <0.001*** SEM1: Standard error mean. 0 vs 8A; Comparisons between the 0 week and 8 weeks. 0 vs 16B; Comparisons between the 0 week and 16 weeks. * p < 0.05. ** p < 0.01. *** p < 0.001. Leukocytosis is a typical inflammatory process that temporarily increases immature neutrophils and is considered a sign of acute infection [35]. Through hematologic analysis, we observed a reduction in neutrophil percentage by the end of the experiment, suggesting that the acute innate immune response is likely to be gradually stabilized by supplementation with these natural botanicals. In general, basophils are very rare in healthy dogs. When basophil numbers are higher than normal in dogs, it is often in conjunction with an increase in the number of eosinophils, which is associated with allergies [36]. However, we could not observe a change in eosinophil percentage during the experiment. Basophils are one of granulocytes containing histamines, a compound intimately involved in allergic and asthmatic reactions, in the cytoplasm. Therefore, further study is needed to determine what substance or substances caused the increase in the number of basophils in the MWDs supplemented with natural botanicals. From another point of view, it is presumed that increased basophil numbers may be due to internal parasites or fleas in dogs [37]. However, this is very unlikely in MWD because MWDs in CKAB and JKAFB are regularly prescribed internal and external parasites medications. Supplementation with natural botanicals resulted in increased circulating platelet counts by the end of the experiment. Several studies have reported that acute exercise results in a transient increase in platelet count caused by hemoconcentration and platelet release from the liver, lungs, and the spleen [38,39], and that the subsequent formation of platelet-leukocyte aggregates (PLAs) is, in part, due to increased platelet P-selectin is detected and increased [38]. Thus, an increase in platelets due to strenuous exercise may lead to the secretion of various inflammatory mediators involved in both innate and adaptive immune responses. CRP levels in healthy dogs (mean 5.5 ± 1.8 μg/mL) and in dogs with OA (mean 9.3 ± 1.2 μg/mL) have been reported in previous studies [40,41]. In our study, the mean serum CRP concentration in MWDs increased significantly from the start of the experiment (mean 12.66 ± 2.015 μg/mL; P = 0.0006) to 8 weeks (mean 21.51 ± 4.130 μg/mL; P = 0.051). Then, it was decreased at 16 weeks (mean 8.30 ± 2.770 μg/mL; P = 0.337) (Table 3). It has been established that increased CRP concentrations in the blood are strongly associated with acute inflammation in humans [42,43] and dogs [44,45]. It is still controversial as to whether the CRP level is a more reliable marker than neutrophil count to quantify the severity of infection in acute disease [44,46]. However, it has been stated that in patients with clinical evidence of inflammation, CRP elevation can be of diagnostic value [46]. Nakamura et al. showed that dogs with active polyarthritis had higher CRP values than dogs with inactive disease [47]. However, because in acute inflammatory response activated neutrophils are the first immune cells to migrate to the inflammation site, both CRP and neutrophils may be considered biomarkers. Our result shows that serum CRP level and neutrophil percentage were both significantly lower following botanical supplementation. Serum IL-6 levels have been reported for healthy dogs (8.0–11.4 pg/mL, median 9.2 pg/mL) and for dogs with OA (10.2–26.5 pg/mL, median 15 pg/mL) were reported [34]. In this study, the median serum IL-6 concentration of MWDs was high initially (mean 31.50 ± 11.865 pg/mL; P < 0.01), at 8 weeks (mean 31.34 ± 8.722 pg/mL; P = 0.990), and at 16 weeks (mean 26.95 ± 4.427 pg/mL; P = 0.718) (Table 3). There were no significant differences in serum IL-6 levels between the two groups. Cytokines play an important role as regulators of immune response [48], and thus cytokine profiles contribute to the effects of immunity level on many diseases [49]. In previous studies, IL-6 was shown to play a pro- or anti-inflammatory role in the pathophysiology of OA and, in some studies, was classed as a diagnostic and prognostic biomarker [50]. However, in our study, no change in serum IL-6 levels was observed. Taken together, our results suggest that the health of most of MWDs supplemented with the mixture of 11 natural botanicals was gradually improved. Thus, our results may be used as data in developing feed using natural botanicals as supplements for MWDs. However, further research is needed to fully evaluate the effects of natural botanicals on MWDs. Conflicts of interest All the authors declare that there are no conflicts of interest. Acknowledgements This research was supported by the Cooperative Research Program (Project No. PJ009577), Rural Development Administration, the Republic of Korea and partly by Konkuk University’s research support program for its faculty on sabbatical leave in 2015. References [1] K.J. Vince Canine hip dysplasia: surgical treatment for the military working dog US Army Med. Dep. J. (2007), pp. 44-50 View Record in Scopus [2] Y. Zhang, J.M. Jordan Epidemiology of osteoarthritis Clin. Geriatr. Med., 26 (2010), pp. 355-369 ArticleDownload PDFView Record in Scopus [3] J.M. Wahl, S.M. Herbst, L.A. Clark, K.L. Tsai, K.E. Murphy A review of hereditary diseases of the German shepherd dog J. Vet. Behav., 3 (2008), pp. 255-265 ArticleDownload PDFView Record in Scopus [4] R.C. Hill The nutritional requirements of exercising dogs J. Nutr., 128 (1998), pp. 2686S-2690S [5] J.S. Smolen, R. Landewe, J. Bijlsma, G. Burmester, K. Chatzidionysiou, M. Dougados, J. Nam, S. Ramiro, M. Voshaar, R. van Vollenhoven, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update Ann. Rheum. Dis., 76 (2017), pp. 960-977 CrossRefView Record in Scopus [6] D. Khanna, G. Sethi, K.S. Ahn, M.K. Pandey, A.B. Kunnumakkara, B. Sung, A. Aggarwal, B.B. Aggarwal Natural products as a gold mine for arthritis treatment Curr. Opin. Pharmacol., 7 (2007), pp. 344-351 ArticleDownload PDFView Record in Scopus [7] G.E. Moore, K.D. Burkman, M.N. Carter, M.R. Peterson Causes of death or reasons for euthanasia in military working dogs: 927 cases (1993–1996) J. Am. Vet. Med. Assoc., 219 (2001), pp. 209-214 CrossRefView Record in Scopus [8] G.K. Smith, E.R. Paster, M.Y. Powers, D.F. Lawler, D.N. Biery, F.S. Shofer, P.J. McKelvie, R.D. Kealy Lifelong diet restriction and radiographic evidence of osteoarthritis of the hip joint in dogs J. Am. Vet. Med. Assoc., 229 (2006), pp. 690-693 CrossRefView Record in Scopus [9] K.S. Panickar, D.E. Jewell The beneficial role of anti-inflammatory dietary ingredients in attenuating markers of chronic low-grade inflammation in aging Horm. Mol. Biol. Clin. Investig., 23 (2015), pp. 59-70 View Record in Scopus [10] M.B. Goldring, M. Otero Inflammation in osteoarthritis Curr. Opin. Rheumatol., 23 (2011), pp. 471-478 CrossRefView Record in Scopus [11] J.A. Roman-Blas, S.A. Jimenez NF-kappaB as a potential therapeutic target in osteoarthritis and rheumatoid arthritis Osteoarthritis Cartilage, 14 (2006), pp. 839-848 ArticleDownload PDFView Record in Scopus [12] M. Kapoor, J. Martel-Pelletier, D. Lajeunesse, J.P. Pelletier, H. Fahmi Role of proinflammatory cytokines in the pathophysiology of osteoarthritis Nat. Rev. Rheumatol., 7 (2011), pp. 33-42 CrossRefView Record in Scopus [13] N.M. Arafa, H.M. Hamuda, S.T. Melek, S.K. Darwish The effectiveness of Echinacea extract or composite glucosamine, chondroitin and methyl sulfonyl methane supplements on acute and chronic rheumatoid arthritis rat model Toxicol. Ind. Health, 29 (2013), pp. 187-201 CrossRefView Record in Scopus [14] D.C. Nordstrom, V.E. Honkanen, Y. Nasu, E. Antila, C. Friman, Y.T. Konttinen Alpha-linolenic acid in the treatment of rheumatoid arthritis. A double-blind, placebo-controlled and randomized study: flaxseed vs. safflower seed Rheumatol. Int., 14 (1995), pp. 231-234 View Record in Scopus [15] N. Dixit, S. Baboota, K. Kohli, S. Ahmad, J. Ali Silymarin: a review of pharmacological aspects and bioavailability enhancement approaches Indian J. Pharmacol., 39 (2007), pp. 172-179 CrossRefView Record in Scopus [16] D.G. Lee, S.Y. Park, W.S. Chung, J.H. Park, E. Hwang, G.T. Mavlonov, I.H. Kim, K.Y. Kim, T.H. Yi Fucoidan prevents the progression of osteoarthritis in rats J. Med. Food, 18 (2015), pp. 1032-1041 CrossRefView Record in Scopus [17] S.C. Jeong, Y.T. Jeong, S.M. Lee, J.H. Kim Immune-modulating activities of polysaccharides extracted from brown algae Hizikia fusiforme Biosci. Biotechnol. Biochem., 79 (2015), pp. 1362-1365 CrossRefView Record in Scopus [18] I. Chattopadhyay, K. Biswas, U. Bandyopadhyay, R.K. Banerjee Turmeric and curcumin: biological actions and medicinal applications Curr. Sci., 87 (2004), pp. 44-53 View Record in Scopus [19] S. Lev-Ari, L. Strier, D. Kazanov, O. Elkayam, D. Lichtenberg, D. Caspi, N. Arber Curcumin synergistically potentiates the growth-inhibitory and pro-apoptotic effects of celecoxib in osteoarthritis synovial adherent cells Rheumatology (Oxford), 45 (2006), pp. 171-177 CrossRefView Record in Scopus [20] K.Y. Chin The spice for joint inflammation: anti-inflammatory role of curcumin in treating osteoarthritis Drug Des. Dev. Ther., 10 (2016), pp. 3029-3042 CrossRefView Record in Scopus [21] Y. Takahashi, M. Tanaka, R. Murai, K. Kuribayashi, D. Kobayashi, N. Yanagihara, N. Watanabe Prophylactic and therapeutic effects of Acanthopanax senticosus Harms extract on murine collagen-induced arthritis Phytother. Res., 28 (2014), pp. 1513-1519 CrossRefView Record in Scopus [22] M. Hemshekhar, K. Sunitha, R.M. Thushara, M.S. Santhosh, M.S. Sundaram, K. Kemparaju, K.S. Girish Antiarthritic and antiinflammatory propensity of 4-methylesculetin, a coumarin derivative Biochimie, 95 (2013), pp. 1326-1335 ArticleDownload PDFView Record in Scopus [23] S.O. Canapp Jr., R.M. McLaughlin Jr., J.J. Hoskinson, J.K. Roush, M.D. Butine Scintigraphic evaluation of dogs with acute synovitis after treatment with glucosamine hydrochloride and chondroitin sulfate Am. J. Vet. Res., 60 (1999), pp. 1552-1557 View Record in Scopus [24] L. Lippiello, A. Idouraine, P.S. McNamara, S.C. Barr, R.M. McLaughlin Cartilage stimulatory and antiproteolytic activity is present in sera of dogs treated with a chondroprotective agent Canine Pract., 24 (1999), pp. 18-19 [25] K.A. Johnson, D.A. Hulse, R.C. Hart, D. Kochevar, Q. Chu Effects of an orally administered mixture of chondroitin sulfate, glucosamine hydrochloride and manganese ascorbate on synovial fluid chondroitin sulfate 3B3 and 7D4 epitope in a canine cruciate ligament transection model of osteoarthritis Osteoarthritis Cartilage, 9 (2001), pp. 14-21 ArticleDownload PDFView Record in Scopus [26] E.J. Uitterlinden, J.L. Koevoet, C.F. Verkoelen, S.M. Bierma-Zeinstra, H. Jahr, H. Weinans, J.A. Verhaar, G.J. van Osch Glucosamine increases hyaluronic acid production in human osteoarthritic synovium explants BMC Musculoskelet. Disord., 9 (2008), p. 120 [27] S. Ishizuka, E.B. Askew, N. Ishizuka, C.B. Knudson, W. Knudson 4-Methylumbelliferone diminishes catabolically activated articular chondrocytes and cartilage explants via a mechanism independent of hyaluronan inhibition J. Biol. Chem., 291 (2016), pp. 12087-12104 CrossRefView Record in Scopus [28] I. Uthman, J.P. Raynauld, B. Haraoui Intra-articular therapy in osteoarthritis Postgrad. Med. J., 79 (2003), pp. 449-453 CrossRefView Record in Scopus [29] J. Peregoy, F.V. Wilder The effects of vitamin C supplementation on incident and progressive knee osteoarthritis: a longitudinal study Public Health Nutr., 14 (2011), pp. 709-715 CrossRefView Record in Scopus [30] H. Padh Vitamin C: newer insights into its biochemical functions Nutr. Rev., 49 (1991), pp. 65-70 CrossRefView Record in Scopus [31] A. Aslan, V. Kirdemir, T. Atay, Y.B. Baykal, O. Aytekin, F.C. Aydogan The efficacy of intra-articular injection of hyaluronic acid with supplemental peroral vitamin E following arthroscopic debridement in the treatment of knee osteoarthritis: a prospective, randomized, controlled study Turk. J. Phys. Med. Rehabil., 58 (2012), pp. 199-203 CrossRefView Record in Scopus [32] R.K. Chaganti, I. Tolstykh, M.K. Javaid, T. Neogi, J. Torner, J. Curtis, P. Jacques, D. Felson, N.E. Lane, M.C. Nevitt, G. Multicenter Osteoarthritis Study High plasma levels of vitamin C and E are associated with incident radiographic knee osteoarthritis Osteoarthritis Cartilage, 22 (2014), pp. 190-196 ArticleDownload PDFView Record in Scopus [33] M. Sowers, M. Jannausch, E. Stein, D. Jamadar, M. Hochberg, L. Lachance C-reactive protein as a biomarker of emergent osteoarthritis Osteoarthritis Cartilage, 10 (2002), pp. 595-601 ArticleDownload PDFView Record in Scopus [34] A. Hillstrom, J. Bylin, R. Hagman, K. Bjorhall, H. Tvedten, K. Konigsson, T. Fall, M. Kjelgaard-Hansen Measurement of serum C-reactive protein concentration for discriminating between suppurative arthritis and osteoarthritis in dogs BMC Vet. Res., 12 (2016), p. 240 [35] A. Mantovani, M.A. Cassatella, C. Costantini, S. Jaillon Neutrophils in the activation and regulation of innate and adaptive immunity Nat. Rev. Immunol., 11 (2011), pp. 519-531 CrossRefView Record in Scopus [36] K.D. Stone, C. Prussin, D.D. Metcalfe IgE, mast cells, basophils, and eosinophils J. Allergy Clin. Immunol., 125 (2010), pp. S73-S80 ArticleDownload PDFView Record in Scopus [37] B.L. Blagburn, M.W. Dryden Biology, treatment, and control of flea and tick infestations Vet. Clin. North Am. Small Anim. Pract., 39 (2009), pp. 1173-1200 ArticleDownload PDFView Record in Scopus [38] S. Heber, I. Volf Effects of physical (In)activity on platelet function Biomed Res. Int., 2015 (2015), p. 165078 [39] K.G. Chamberlain, M. Tong, D.G. Penington Properties of the exchangeable splenic platelets released into the circulation during exercise-induced thrombocytosis Am. J. Hematol., 34 (1990), pp. 161-168 CrossRefView Record in Scopus [40] K. Otabe, T. Sugimoto, T. Jinbo, M. Honda, S. Kitao, S. Hayashi, M. Shimizu, S. Yamamoto Physiological levels of C-reactive protein in normal canine sera Vet. Res. Commun., 22 (1998), pp. 77-85 CrossRefView Record in Scopus [41] K. Hurter, D. Spreng, U. Rytz, P. Schawalder, F. Ott-Knusel, H. Schmokel Measurements of C-reactive protein in serum and lactate dehydrogenase in serum and synovial fluid of patients with osteoarthritis Vet. J., 169 (2005), pp. 281-285 ArticleDownload PDFView Record in Scopus [42] T.C. Klein, R. Doffinger, M.B. Pepys, U. Ruther, B. Kyewski Tolerance and immunity to the inducible self antigen C-reactive protein in transgenic mice Eur. J. Immunol., 25 (1995), pp. 3489-3495 CrossRefView Record in Scopus [43] E.A. Fagan, R.F. Dyck, P.N. Maton, H.J. Hodgson, V.S. Chadwick, A. Petrie, M.B. Pepys Serum levels of C-reactive protein in Crohn’s disease and ulcerative colitis Eur. J. Clin. Invest., 12 (1982), pp. 351-359 CrossRefView Record in Scopus [44] S. Yamamoto, K. Tagata, H. Nagahata, Y. Ishikawa, M. Morimatsu, M. Naiki Isolation of canine C-reactive protein and characterization of its properties Vet. Immunol. Immunopathol., 30 (1992), pp. 329-339 ArticleDownload PDFView Record in Scopus [45] S. Hayashi, T. Jinbo, K. Iguchi, M. Shimizu, T. Shimada, M. Nomura, Y. Ishida, S. Yamamoto A comparison of the concentrations of C-reactive protein and alpha1-acid glycoprotein in the serum of young and adult dogs with acute inflammation Vet. Res. Commun., 25 (2001), pp. 117-126 View Record in Scopus [46] S.A. Burton, D.J. Honor, A.L. Mackenzie, P.D. Eckersall, R.J. Markham, B.S. Horney C-reactive protein concentration in dogs with inflammatory leukograms Am. J. Vet. Res., 55 (1994), pp. 613-618 View Record in Scopus [47] M. Nakamura, M. Takahashi, K. Ohno, A. Koshino, K. Nakashima, A. Setoguchi, Y. Fujlno, H. Tsujimoto C-reactive protein concentration in dogs with various diseases J. Vet. Med. Sci., 70 (2008), pp. 127-131 CrossRefView Record in Scopus [48] I. Karlsson, R. Hagman, A. Johannisson, L. Wang, E. Karlstam, S. Wernersson Cytokines as immunological markers for systemic inflammation in dogs with pyometra Reprod. Domest. Anim., 47 (Suppl. 6) (2012), pp. 337-341 CrossRefView Record in Scopus [49] C.I. Westacott, M. Sharif Cytokines in osteoarthritis: mediators or markers of joint destruction? Semin. Arthritis Rheum., 25 (1996), pp. 254-272 ArticleDownload PDFView Record in Scopus [50] M. Attur, S. Krasnokutsky-Samuels, J. Samuels, S.B. Abramson Prognostic biomarkers in osteoarthritis Curr. Opin. Rheumatol., 25 (2013), pp. 136-144 CrossRefView Record in Scopus © 2018 The Author(s). Published by Elsevier B.V.

Friday 27 April 2018

Trees and plants used by First Nations assessed for modern dermatology

July 5, 2017 http://www.derm.city/single-post/2017/07/05/Trees-and-plants-used-by-First-Nations-assessed-for-modern-dermatology by Emily Innes-Leroux Compounds found in trees and plants used by the North American First Nations people to treat skin diseases have been identified as being potentially relevant to both cosmetic and medical dermatology. Drs. Sophia Colantonio and Jason K. Rivers conducted a review of some trees and plants used in traditional First Nations medicine, with currently used by Western medicine for cosmeceutical or therapeutic purposes. Their findings were published in a two-part series in The Journal of Cutaneous Medicine and Surgery: “Botanical With Dermatology Properties Derived From First Nations Healing Part 1—Trees” (Feb. 1, 2017) and “Part 2—Plants and Algae” (Dec. 19, 2016). “It is important to validate the traditional knowledge that is already there to hopefully help preserve it and also encourage both ecological conservation and cultural conservation,” said Dr. Colantonio, a dermatology resident at the University of Ottawa. “As well, instead of re-inventing the wheel, there are quite a few things that have been documented that we can look back on and then look forward to new treatments.” Dr. Colantonio became interested in First Nations healing when she studied program and took a course on ethnobotany. Also, for two summers, she lived in the Haida Gwaii islands in Northern British Columbia among the Haida First Nations people. She was researching the ancient murrelet seabird. Since there are over 2,700 medicinal plants that are used in traditional healing, the investigators relied on the recommendations from expert ethnobotanists (Dr. Thor Arnason, Dr. Jonathan Ferrier, and Dr. Nancy J. Turners) to narrow their focus. Only a sampling assessed The trees they included in the report were the Western red cedar, the white spruce, birch, balsam poplar, and black spruce. The plants they investigated included seaweed, witch hazel, bearberry, and mayapple. “We wanted to write one comprehensive paper, but owing to the wealth of material we had to present it as two manuscripts that highlighted only a few of the many trees and plants used for medicinal purposes. One could write a book on this topic,” said Dr. Rivers, clinical professor of dermatology at the University of British Columbia and medical director of Pacific Derm in Vancouver. “Our selection of the trees and plants discussed in our papers required they were based in part on those used by First Nations in North America and as well had pre-clinical and/or clinical studies that pertained to contemporary dermatology.” The authors used seven databases including Web of Knowledge, Pubmed, AMED, Natural Medicines Comprehensive Database, Natural Standard, Litt’s D.E.R.M. Databse, and Google Scholar. They searched for the plant name and its known active principal compound individually and in combination with “derm” and “skin.” Ethnobotany references and government databases were also consulted. Western red cedar: thujaplicin The Western red cedar has been used in traditional medicine to treat carbuncles, dandruff, wounds and veneral disease, according to the investigators. Pre-clinical trials have studied its antibacterial, antifungal, anti-oxidant, and antimelanoma role, as well as its potential for promoting hair growth and reducing UV-B damage to the skin. In an open-label pilot study of atopic dermatitis patients (n=43), the Western red cedar’s active principal compound b-thujaplicin led to symptomatic improvements and a reduced burden of S aureus. The investigators note that future applications for thujaplicin include its use as a hair growth agent and as a topical anti-microbial agent in the “Many years ago I was introduced to thujaplicin by members of the UBC forestry department. I became interested in this molecule because there was in vitro evidence that it could mitigate sun damage,” said Dr. Rivers. “To me it was quite interesting that this plant material, which had been used by First Nations for many years, had potential utility in the modern medical sphere.” Birch: belutin, betulinic acid “Birch bark is one that has quite a bit of research into it and its main active component is betulin, which has been used for [conditions] like [actinic keratosis], rare genetic conditions like epidermolysis bullosa, and it is used also for healing split-thickness skin grafts, so that one is a pretty exciting [tree],” said Dr. Colantonio. Another bioactive pentacyclic triterpenes found in birch bark is betulinic acid, noted the authors. The investigators stated that the principal compounds in these trees could theoretically be used in the management of psoriasis, actinic keratosis, epidermolysis bullosa, wound healing, melanoma, acne, rosacea, androgenetic alopecia, herpes simplex virus infections, and dandruff. They also have potential cosmetic uses such as for the reduction of wrinkles, skin lightening agents in cosmetics, and topical anti-aging preparations. “Future possibilities for many of these plant/tree derivatives include new antiaging, anti-inflammatory, anti-microbial, and even anticancer agents,” said Dr. Rivers. “On the flip side, there are many [compounds] used in cosmetics today where there are no clinical studies to support the claims,” he said. Bearberry: arbutin Bearberry contains arbutin, a skin-lightening derivative of hydroquinone with less toxic effects. While there is “growing interest” in using it for melasma and solar lentigines, there have been no clinical studies conducted on bearberry. Regarding the other plants, the authors concluded that “seaweed could be used in the treatment of acne and wrinkles. Witch hazel is an effective and well-tolerated treatment for minor skin injuries, inflammation, and diaper dermatitis . . . The mayapple contains podophyllotoxin, [which is already] a common treatment for condyloma accuminata, molluscum contagiosum, and recalcitrant palmoplantar warts.” “I think our research highlights that we have literally hundreds of different plants and trees available to us from which future medicinal treatments can be derived for a variety of different skin conditions,” said Dr. Rivers. “Here in Canada, many people have embraced traditional Chinese medicine, but to some degree we have forgotten the insights provided by the First Nations people. I think it is time we give them credit for putting us on a different path, a path that may lead to the development of many novel dermatologic agents.” He added, “We hope through our research we can raise awareness of the fact that people have this untapped pharmacopeia in our Canadian backyards.” Dr. Rivers is the founder of Riversol Skin Care Solutions Inc., a company that incorporates thujaplicin into its skin care line. Tags: First Nations Dr. Jason Rivers Botanical Western red cedar thujaplicin Birch Betulin Betulinic acid Cosmetic Dermatology Bearberry arbutin

Botanicals With Dermatologic Properties Derived From First Nations Healing: Part 1-Trees

J Cutan Med Surg. 2017 Jul/Aug;21(4):288-298. doi: 10.1177/1203475417690306. Epub 2017 Feb 2. Colantonio S1, Rivers JK2,3. Author information 1 1 Division of Dermatology, The Department of Medicine, University of Ottawa, ON, Canada. 2 2 Department of Dermatology & Skin Science, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada. 3 3 Pacific Dermaesthetics, Vancouver, BC, Canada. Abstract INTRODUCTION: First Nations people have a long history of working with medicinal plants used to treat skin diseases. The purpose was to assess the dermatologic therapeutic potential of western red cedar, white spruce, birch, balsam poplar, and black spruce. METHODS: Based on expert recommendations, 5 trees were selected that were used in First Nations medicine for cutaneous healing and have potential and/or current application to dermatology today. We searched several databases up to June 12, 2014. RESULTS: Western red cedar's known active principal compound, β-thujaplicin, has been studied in atopic dermatitis. White spruce's known active principal compound, 7-hydroxymatairesinol, has anti-inflammatory activity, while phase II clinical trials have been completed on a birch bark emulsion for the treatment of actinic keratoses, epidermolysis bullosa, and the healing of split thickness graft donor sites. Balsam poplar has been used clinically as an anti-aging remedy. Black spruce bark contains higher amounts of the anti-oxidant trans-resveratrol than red wine. DISCUSSION: North American traditional medicine has identified important botanical agents that are potentially relevant to both cosmetic and medical dermatology. This study is limited by the lack of good quality evidence contributing to the review. The article is limited to 5 trees, a fraction of those used by First Nations with dermatological properties. KEYWORDS: First Nations; botanicals; cosmeceuticals; therapeutics; trees

Botanicals With Dermatologic Properties Derived From First Nations Healing: Part 2-Plants and Algae

J Cutan Med Surg. 2017 Jul/Aug;21(4):299-307. doi: 10.1177/1203475416683390. Epub 2016 Dec 19. Colantonio S1, Rivers JK2. Author information 1 1 The Division of Dermatology, The Department of Medicine, University of Ottawa, Ontario, Canada. 2 2 The Department of Dermatology & Skin Science, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada. Abstract INTRODUCTION: Plants and algae have played a central role in the treatment of skin conditions in both traditional First Nations healing and in modern dermatology. The objective of this study was to examine the evidence supporting the dermatological use of seaweed, witch hazel, bearberry, and mayapple. METHODS: Four plants and algae used in traditional First Nations treatments of skin disease were selected based on expert recommendations. Several databases were searched to identify relevant citations without language restrictions. RESULTS: Seaweed has potential clinical use in the treatment of acne and wrinkles and may be incorporated into biofunctional textiles. Witch hazel is an effective and well-tolerated treatment of inflammation and diaper dermatitis. Bearberry leaves contain arbutin, a skin-lightening agent that is an alternative for the treatment of hyperpigmentation. Mayapple contains podophyllotoxin, a treatment for condyloma accuminata, molluscum contagiosum, and recalcitrant palmoplantar warts. DISCUSSION: Common plants and algae are replete with bioactive agents that may have beneficial effects on the skin. Further research will open the door to new and innovative products in the future. Limitations of this study include that the scope of our study is limited to 4 plants and algae, a small sample of the breadth of plants used by First Nations for dermatological treatments. KEYWORDS: First Nations; botanicals; cosmeceuticals; plants; therapeutics

Therapeutic Potential of Ursolic Acid to Manage Neurodegenerative and Psychiatric Diseases

CNS Drugs December 2017, Volume 31, Issue 12, pp 1029–1041 Authors Authors and affiliations Ana B. Ramos-HrybFrancis L. PaziniManuella P. KasterAna Lúcia S. RodriguesEmail author Ana B. Ramos-Hryb 1 Francis L. Pazini 1 Manuella P. Kaster 1 Ana Lúcia S. Rodrigues 1Email authorView author's OrcID profile 1.Department of Biochemistry, Center for Biological SciencesUniversidade Federal de Santa CatarinaFlorianópolisBrazil Leading Article First Online: 02 November 2017 135 Downloads 1 Citations Abstract Ursolic acid is a pentacyclic triterpenoid found in several plants. Despite its initial use as a pharmacologically inactive emulsifier in pharmaceutical, cosmetic and food industries, several biological activities have been reported for this compound so far, including anti-tumoural, anti-diabetic, cardioprotective and hepatoprotective properties. The biological effects of ursolic acid have been evaluated in vitro, in different cell types and against several toxic insults (i.e. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, amyloid-β peptides, kainic acid and others); in animal models of brain-related disorders (Alzheimer disease, Parkinson disease, depression, traumatic brain injury) and ageing; and in clinical studies with cancer patients and for muscle atrophy. Most of the protective effects of ursolic acid are related to its ability to prevent oxidative damage and excessive inflammation, common mechanisms associated with multiple brain disorders. Additionally, ursolic acid is capable of modulating the monoaminergic system, an effect that might be involved in its ability to prevent mood and cognitive dysfunctions associated with neurodegenerative and psychiatric conditions. This review presents and discusses the available evidence of the possible beneficial effects of ursolic acid for the management of neurodegenerative and psychiatric disorders. We also discuss the chemical features, major sources and potential limitations of the use of ursolic acid as a pharmacological treatment for brain-related diseases. This is a preview of subscription content, log in to check access. Notes Acknowledgements The authors thank Servier Medical Art for providing images for Figs. 2 and 3. Compliance with Ethical Standards Funding The authors acknowledge funding from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), #308723/2013-9 and #449436/2014-4, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, NENASC Project (PRONEX-FAPESC/CNPq) #1262/2012-9. Manuella P. Kaster and Ana Lúcia S. Rodrigues are CNPq Research Fellows. Conflict of interest Ana B. Ramos-Hryb, Francis L. Pazini, Manuella P. Kaster, and Ana Lúcia S. Rodrigues have no conflicts of interest directly relevant to the content of this article. References 1. Chin JH, Vora N. The global burden of neurologic diseases. Neurology. 2014;83(4):349–51.PubMedPubMedCentralCrossRefGoogle Scholar 2. Whiteford HA, Ferrari AJ, Degenhardt L, Feigin V, Vos T. The global burden of mental, neurological and substance use disorders: an analysis from the Global Burden of Disease Study 2010. PLoS One. 2015;10(2):e0116820.PubMedPubMedCentralCrossRefGoogle Scholar 3. Tang SW, Helmeste DM, Leonard BE. Neurodegeneration, neuroregeneration, and neuroprotection in psychiatric disorders. Mod Trends Pharmacopsychiatry. 2017;31:107–23.PubMedCrossRefGoogle Scholar 4. Liu J. Oleanolic acid and ursolic acid: research perspectives. J Ethnopharmacol. 2005;100(1–2):92–4.PubMedCrossRefGoogle Scholar 5. Shanmugam MK, Dai X, Kumar AP, Tan BK, Sethi G, Bishayee A. Ursolic acid in cancer prevention and treatment: molecular targets, pharmacokinetics and clinical studies. Biochem Pharmacol. 2013;85(11):1579–87.PubMedCrossRefGoogle Scholar 6. Wozniak L, Skapska S, Marszalek K. Ursolic acid: a pentacyclic triterpenoid with a wide spectrum of pharmacological activities. Molecules. 2015;20(11):20614–41.PubMedCrossRefGoogle Scholar 7. Kashyap D, Tuli HS, Sharma AK. Ursolic acid (UA): a metabolite with promising therapeutic potential. Life Sci. 2016;146:201–13.PubMedCrossRefGoogle Scholar 8. Liby KT, Yore MM, Sporn MB. Triterpenoids and rexinoids as multifunctional agents for the prevention and treatment of cancer. Nat Rev Cancer. 2007;7(5):357–69.PubMedCrossRefGoogle Scholar 9. Dzubak P, Hajduch M, Vydra D, Hustova A, Kvasnica M, Biedermann D, et al. Pharmacological activities of natural triterpenoids and their therapeutic implications. Nat Prod Rep. 2006;23(3):394–411.PubMedCrossRefGoogle Scholar 10. Gao LP, Wei HL, Zhao HS, Xiao SY, Zheng RL. Antiapoptotic and antioxidant effects of rosmarinic acid in astrocytes. Pharmazie. 2005;60(1):62–5.PubMedGoogle Scholar 11. Szakiel A, Paczkowski C, Pensec F, Bertsch C. Fruit cuticular waxes as a source of biologically active triterpenoids. Phytochem Rev. 2012;11(2–3):263–84.PubMedPubMedCentralCrossRefGoogle Scholar 12. Szakiel A, Pączkowski C, Huttunen S. Triterpenoid content of berries and leaves of bilberry Vaccinium myrtillus from Finland and Poland. J Agric Food Chem. 2012;60(48):11839–49.PubMedCrossRefGoogle Scholar 13. Jäger S, Trojan H, Kopp T, Laszczyk MN, Scheffler A. Pentacyclic triterpene distribution in various plants: rich sources for a new group of multi-potent plant extracts. Molecules. 2009;14(6):2016–31.PubMedCrossRefGoogle Scholar 14. Lee S, Kim BK, Cho SH, Shin KH. Phytochemical constituents from the fruits of Acanthopanax sessiliflorus. Arch Pharm Res. 2002;25(3):280–4.PubMedCrossRefGoogle Scholar 15. González-Trujano ME, Ventura-Martínez R, Chávez M, Díaz-Reval I, Pellicer F. Spasmolytic and antinociceptive activities of ursolic acid and acacetin identified in Agastache mexicana. Planta Med. 2012;78(8):793–6.PubMedCrossRefGoogle Scholar 16. Verano J, González-Trujano ME, Déciga-Campos M, Ventura-Martínez R, Pellicer F. Ursolic acid from Agastache mexicana aerial parts produces antinociceptive activity involving TRPV1 receptors, cGMP and a serotonergic synergism. Pharmacol Biochem Behav. 2013;110:255–64.PubMedCrossRefGoogle Scholar 17. Caligiani A, Malavasi G, Palla G, Marseglia A, Tognolini M, Bruni R. A simple GC-MS method for the screening of betulinic, corosolic, maslinic, oleanolic and ursolic acid contents in commercial botanicals used as food supplement ingredients. Food Chem. 2013;136(2):735–41.PubMedCrossRefGoogle Scholar 18. Hong SY, Jeong WS, Jun M. Protective effects of the key compounds isolated from Corni fructus against β-amyloid-induced neurotoxicity in PC12 cells. Molecules. 2012;17(9):10831–45.PubMedCrossRefGoogle Scholar 19. Tapondjou LA, Lontsi D, Sondengam BL, Choi J, Lee KT, Jung HJ, et al. In vivo anti-nociceptive and anti-inflammatory effect of the two triterpenes, ursolic acid and 23-hydroxyursolic acid, from Cussonia bancoensis. Arch Pharm Res. 2003;26(2):143–6.PubMedCrossRefGoogle Scholar 20. Rollinger JM, Kratschmar DV, Schuster D, Pfisterer PH, Gumy C, Aubry EM, et al. 11beta-Hydroxysteroid dehydrogenase 1 inhibiting constituents from Eriobotrya japonica revealed by bioactivity-guided isolation and computational approaches. Bioorg Med Chem. 2010;18(4):1507–15.PubMedCrossRefGoogle Scholar 21. Kim JH, Kim GH, Hwang KH. Monoamine oxidase and dopamine β-hydroxylase inhibitors from the fruits of Gardenia jasminoides. Biomol Ther (Seoul). 2012;20(2):214–9.PubMedPubMedCentralCrossRefGoogle Scholar 22. Prediger RD, Fernandes MS, Rial D, Wopereis S, Pereira VS, Bosse TS, et al. Effects of acute administration of the hydroalcoholic extract of mate tea leaves (Ilex paraguariensis) in animal models of learning and memory. J Ethnopharmacol. 2008;120(3):465–73.PubMedCrossRefGoogle Scholar 23. Chattopadhyay D, Arunachalam G, Mandal SC, Bhadra R, Mandal AB. CNS activity of the methanol extract of Mallotus peltatus (Geist) Muell Arg. leaf: an ethnomedicine of Onge. J Ethnopharmacol. 2003;85(1):99–105.PubMedCrossRefGoogle Scholar 24. Ibarra A, Feuillere N, Roller M, Lesburgere E, Beracochea D. Effects of chronic administration of Melissa officinalis L. extract on anxiety-like reactivity and on circadian and exploratory activities in mice. Phytomedicine. 2010;17(6):397–403.PubMedCrossRefGoogle Scholar 25. Shen D, Pan MH, Wu QL, Park CH, Juliani HR, Ho CT, et al. A rapid LC/MS/MS method for the analysis of nonvolatile antiinflammatory agents from Mentha spp. J Food Sci. 2011;76(6):C900–8.PubMedCrossRefGoogle Scholar 26. Vasconcelos MA, Royo VA, Ferreira DS, Crotti AE, Andrade e Silva ML, Carvalho JC, et al. In vivo analgesic and anti-inflammatory activities of ursolic acid and oleanoic acid from Miconia albicans (Melastomataceae). Z Naturforsch C. 2006;61(7–8):477–82.PubMedGoogle Scholar 27. Taviano MF, Miceli N, Monforte MT, Tzakou O, Galati EM. Ursolic acid plays a role in Nepeta sibthorpii Bentham CNS depressing effects. Phytother Res. 2007;21(4):382–5.PubMedCrossRefGoogle Scholar 28. Jothie Richard E, Illuri R, Bethapudi B, Anandhakumar S, Bhaskar A, Chinampudur Velusami C, et al. Anti-stress activity of Ocimum sanctum: possible effects on hypothalamic-pituitary-adrenal axis. Phytother Res. 2016;30(5):805–14.PubMedCrossRefGoogle Scholar 29. Chung YK, Heo HJ, Kim EK, Kim HK, Huh TL, Lim Y, et al. Inhibitory effect of ursolic acid purified from Origanum majorana L. on the acetylcholinesterase. Mol Cells. 2001;11(2):137–43.PubMedGoogle Scholar 30. Heo HJ, Cho HY, Hong B, Kim HK, Heo TR, Kim EK, et al. Ursolic acid of Origanum majorana L. reduces Abeta-induced oxidative injury. Mol Cells. 2002;13(1):5–11.PubMedGoogle Scholar 31. Jetter R, Schäffer S. Chemical composition of the Prunus laurocerasus leaf surface. Dynamic changes of the epicuticular wax film during leaf development. Plant Physiol. 2001;126(4):1725–37.PubMedPubMedCentralCrossRefGoogle Scholar 32. Machado DG, Cunha MP, Neis VB, Balen GO, Colla A, Bettio LE, et al. Antidepressant-like effects of fractions, essential oil, carnosol and betulinic acid isolated from Rosmarinus officinalis L. Food Chem. 2013;136(2):999–1005.PubMedCrossRefGoogle Scholar 33. Machado DG, Neis VB, Balen GO, Colla A, Cunha MP, Dalmarco JB, et al. Antidepressant-like effect of ursolic acid isolated from Rosmarinus officinalis L. in mice: evidence for the involvement of the dopaminergic system. Pharmacol Biochem Behav. 2012;103(2):204–11.PubMedCrossRefGoogle Scholar 34. Çulhaoğlu B, Yapar G, Dirmenci T, Topçu G. Bioactive constituents of Salvia chrysophylla Stapf. Nat Prod Res. 2013;27(4–5):438–47.PubMedCrossRefGoogle Scholar 35. González-Cortazar M, Maldonado-Abarca AM, Jiménez-Ferrer E, Marquina S, Ventura-Zapata E, Zamilpa A, et al. Isosakuranetin-5-O-rutinoside: a new flavanone with antidepressant activity isolated from Salvia elegans Vahl. Molecules. 2013;18(11):13260–70.PubMedCrossRefGoogle Scholar 36. Bahadori MB, Dinparast L, Valizadeh H, Farimani MM, Ebrahimi SN. Bioactive constituents from roots of Salvia syriaca L.: acetylcholinesterase inhibitory activity and molecular docking studies. S Afr J Bot. 2016;106:1–4.CrossRefGoogle Scholar 37. Kowalski R. Studies of selected plant raw materials as alternative sources of triterpenes of oleanolic and ursolic acid types. J Agric Food Chem. 2007;55(3):656–62.PubMedCrossRefGoogle Scholar 38. Novotny L, Abdel-Hamid ME, Hamza H, Masterova I, Grancai D. Development of LC-MS method for determination of ursolic acid: application to the analysis of ursolic acid in Staphylea holocarpa Hemsl. J Pharm Biomed Anal. 2003;31(5):961–8.PubMedCrossRefGoogle Scholar 39. Rowe EJ, Orr JE. Isolation of oleanolic acid and ursolic acid from Thymus vulgaris L. J Am Pharm Assoc Am Pharm Assoc. 1949;38(3 Pt. 1):122–4.Google Scholar 40. Chandramu C, Manohar RD, Krupadanam DG, Dashavantha RV. Isolation, characterization and biological activity of betulinic acid and ursolic acid from Vitex negundo L. Phytother Res. 2003;17(2):129–34.PubMedCrossRefGoogle Scholar 41. Leal AS, Wang R, Salvador JA, Jing Y. Synthesis of novel ursolic acid heterocyclic derivatives with improved abilities of antiproliferation and induction of p53, p21waf1 and NOXA in pancreatic cancer cells. Bioorg Med Chem. 2012;20(19):5774–86.PubMedCrossRefGoogle Scholar 42. Dar BA, Lone AM, Shah WA, Qurishi MA. Synthesis and screening of ursolic acid-benzylidine derivatives as potential anti-cancer agents. Eur J Med Chem. 2016;111:26–32.PubMedCrossRefGoogle Scholar 43. Wojciak-Kosior M. Separation and determination of closely related triterpenic acids by high performance thin-layer chromatography after iodine derivatization. J Pharm Biomed Anal. 2007;45(2):337–40.PubMedCrossRefGoogle Scholar 44. Shanmugam MK, Ong TH, Kumar AP, Lun CK, Ho PC, Wong PT, et al. Ursolic acid inhibits the initiation, progression of prostate cancer and prolongs the survival of TRAMP mice by modulating pro-inflammatory pathways. PLoS One. 2012;7(3):e32476.PubMedPubMedCentralCrossRefGoogle Scholar 45. Chen Q, Luo S, Zhang Y, Chen Z. Development of a liquid chromatography-mass spectrometry method for the determination of ursolic acid in rat plasma and tissue: application to the pharmacokinetic and tissue distribution study. Anal Bioanal Chem. 2011;399(8):2877–84.PubMedCrossRefGoogle Scholar 46. Wang XH, Zhou SY, Qian ZZ, Zhang HL, Qiu LH, Song Z, et al. Evaluation of toxicity and single-dose pharmacokinetics of intravenous ursolic acid liposomes in healthy adult volunteers and patients with advanced solid tumors. Expert Opin Drug Metab Toxicol. 2013;9(2):117–25.PubMedCrossRefGoogle Scholar 47. Zhu Z, Qian Z, Yan Z, Zhao C, Wang H, Ying G. A phase I pharmacokinetic study of ursolic acid nanoliposomes in healthy volunteers and patients with advanced solid tumors. Int J Nanomedicine. 2013;8:129–36.PubMedPubMedCentralGoogle Scholar 48. Qian Z, Wang X, Song Z, Zhang H, Zhou S, Zhao J, et al. A phase I trial to evaluate the multiple-dose safety and antitumor activity of ursolic acid liposomes in subjects with advanced solid tumors. Biomed Res Int. 2015;2015:809714.PubMedPubMedCentralGoogle Scholar 49. Shanmugam MK, Manu KA, Ong TH, Ramachandran L, Surana R, Bist P, et al. Inhibition of CXCR4/CXCL12 signaling axis by ursolic acid leads to suppression of metastasis in transgenic adenocarcinoma of mouse prostate model. Int J Cancer. 2011;129(7):1552–63.PubMedCrossRefGoogle Scholar 50. Pathak AK, Bhutani M, Nair AS, Ahn KS, Chakraborty A, Kadara H, et al. Ursolic acid inhibits STAT3 activation pathway leading to suppression of proliferation and chemosensitization of human multiple myeloma cells. Mol Cancer Res. 2007;5(9):943–55.PubMedCrossRefGoogle Scholar 51. Shan JZ, Xuan YY, Ruan SQ, Sun M. Proliferation-inhibiting and apoptosis-inducing effects of ursolic acid and oleanolic acid on multi-drug resistance cancer cells in vitro. Chin J Integr Med. 2011;17(8):607–11.PubMedCrossRefGoogle Scholar 52. Prasad S, Yadav VR, Sung B, Reuter S, Kannappan R, Deorukhkar A, et al. Ursolic acid inhibits growth and metastasis of human colorectal cancer in an orthotopic nude mouse model by targeting multiple cell signaling pathways: chemosensitization with capecitabine. Clin Cancer Res. 2012;18(18):4942–53.PubMedPubMedCentralCrossRefGoogle Scholar 53. Tokuda H, Ohigashi H, Koshimizu K, Ito Y. Inhibitory effects of ursolic and oleanolic acid on skin tumor promotion by 12-O-tetradecanoylphorbol-13-acetate. Cancer Lett. 1986;33(3):279–85.PubMedCrossRefGoogle Scholar 54. De Angel RE, Smith SM, Glickman RD, Perkins SN, Hursting SD. Antitumor effects of ursolic acid in a mouse model of postmenopausal breast cancer. Nutr Cancer. 2010;62(8):1074–86.PubMedCrossRefGoogle Scholar 55. Monteiro MC, Coleman MD, Hill EJ, Prediger RD, Maia CS. Neuroprotection in neurodegenerative disease: from basic science to clinical applications. Oxid Med Cell Longev. 2017;2017:2949102.PubMedPubMedCentralCrossRefGoogle Scholar 56. Shimohama S, Sawada H, Kitamura Y, Taniguchi T. Disease model: Parkinson’s disease. Trends Mol Med. 2003;9(8):360–5.PubMedCrossRefGoogle Scholar 57. Falkenburger BH, Saridaki T, Dinter E. Cellular models for Parkinson’s disease. J Neurochem. 2016;139(Suppl. 1):121–30.PubMedCrossRefGoogle Scholar 58. Tsai SJ, Yin MC. Antioxidative and anti-inflammatory protection of oleanolic acid and ursolic acid in PC12 cells. J Food Sci. 2008;73(7):H174–8.PubMedCrossRefGoogle Scholar 59. Keeney PM, Xie J, Capaldi RA, Bennett JP. Parkinson’s disease brain mitochondrial complex I has oxidatively damaged subunits and is functionally impaired and misassembled. J Neurosci. 2006;26(19):5256–64.PubMedCrossRefGoogle Scholar 60. Mortiboys H, Thomas KJ, Koopman WJ, Klaffke S, Abou-Sleiman P, Olpin S, et al. Mitochondrial function and morphology are impaired in parkin-mutant fibroblasts. Ann Neurol. 2008;64(5):555–65.PubMedPubMedCentralCrossRefGoogle Scholar 61. Yealland G, Battaglia G, Bandmann O, Mortiboys H. Rescue of mitochondrial function in parkin-mutant fibroblasts using drug loaded PMPC-PDPA polymersomes and tubular polymersomes. Neurosci Lett. 2016;630:23–9.PubMedPubMedCentralCrossRefGoogle Scholar 62. Zheng XY, Zhang HL, Luo Q, Zhu J. Kainic acid-induced neurodegenerative model: potentials and limitations. J Biomed Biotechnol. 2011;2011:457079.PubMedCrossRefGoogle Scholar 63. Shih YH, Chein YC, Wang JY, Fu YS. Ursolic acid protects hippocampal neurons against kainate-induced excitotoxicity in rats. Neurosci Lett. 2004;362(2):136–40.PubMedCrossRefGoogle Scholar 64. Santos CY, Snyder PJ, Wu WC, Zhang M, Echeverria A, Alber J. Pathophysiologic relationship between Alzheimer’s disease, cerebrovascular disease, and cardiovascular risk: a review and synthesis. Alzheimers Dement (Amst). 2017;7:69–87.PubMedPubMedCentralGoogle Scholar 65. Aarsland D, Creese B, Politis M, Chaudhuri KR, Ffytche DH, Weintraub D, et al. Cognitive decline in Parkinson disease. Nat Rev Neurol. 2017;13(4):217–31.PubMedCrossRefGoogle Scholar 66. Bredesen DE. Neurodegeneration in Alzheimer’s disease: caspases and synaptic element interdependence. Mol Neurodegener. 2009;4:27.PubMedPubMedCentralCrossRefGoogle Scholar 67. Takahashi RH, Nagao T, Gouras GK. Plaque formation and the intraneuronal accumulation of β-amyloid in Alzheimer’s disease. Pathol Int. 2017;67(4):185–93.PubMedCrossRefGoogle Scholar 68. Hane FT, Lee BY, Leonenko Z. Recent progress in Alzheimer’s disease research. Part 1: pathology. J Alzheimers Dis. 2017;57(1):1–28.PubMedCrossRefGoogle Scholar 69. Snow WM, Albensi BC. Neuronal gene targets of NF-κB and their dysregulation in Alzheimer’s disease. Front Mol Neurosci. 2016;9:118.PubMedPubMedCentralCrossRefGoogle Scholar 70. Wilkinson K, Boyd JD, Glicksman M, Moore KJ, El Khoury J. A high content drug screen identifies ursolic acid as an inhibitor of amyloid beta protein interactions with its receptor CD36. J Biol Chem. 2011;286(40):34914–22.PubMedPubMedCentralCrossRefGoogle Scholar 71. Yoon JH, Youn K, Ho CT, Karwe MV, Jeong WS, Jun M. p-Coumaric acid and ursolic acid from Corni fructus attenuated β-amyloid(25-35)-induced toxicity through regulation of the NF-κB signaling pathway in PC12 cells. J Agric Food Chem. 2014;62(21):4911–6.PubMedCrossRefGoogle Scholar 72. Chow VW, Mattson MP, Wong PC, Gleichmann M. An overview of APP processing enzymes and products. Neuromol Med. 2010;12(1):1–12.CrossRefGoogle Scholar 73. Bates KA, Verdile G, Li QX, Ames D, Hudson P, Masters CL, et al. Clearance mechanisms of Alzheimer’s amyloid-beta peptide: implications for therapeutic design and diagnostic tests. Mol Psychiatry. 2009;14(5):469–86.PubMedCrossRefGoogle Scholar 74. Vassar R. BACE1 inhibitor drugs in clinical trials for Alzheimer’s disease. Alzheimers Res Ther. 2014;6(9):89.PubMedPubMedCentralCrossRefGoogle Scholar 75. Youn K, Jun M. Inhibitory effects of key compounds isolated from Corni fructus on BACE1 activity. Phytother Res. 2012;26(11):1714–8.PubMedCrossRefGoogle Scholar 76. Coraci IS, Husemann J, Berman JW, Hulette C, Dufour JH, Campanella GK, et al. CD36, a class B scavenger receptor, is expressed on microglia in Alzheimer’s disease brains and can mediate production of reactive oxygen species in response to beta-amyloid fibrils. Am J Pathol. 2002;160(1):101–12.PubMedPubMedCentralCrossRefGoogle Scholar 77. Stewart CR, Stuart LM, Wilkinson K, van Gils JM, Deng J, Halle A, et al. CD36 ligands promote sterile inflammation through assembly of a Toll-like receptor 4 and 6 heterodimer. Nat Immunol. 2010;11(2):155–61.PubMedCrossRefGoogle Scholar 78. Birks J. Cholinesterase inhibitors for Alzheimer’s disease. Cochrane Database Syst Rev. 2006;1:CD005593.Google Scholar 79. Esch T, Stefano GB, Fricchione GL, Benson H. The role of stress in neurodegenerative diseases and mental disorders. Neuro Endocrinol Lett. 2002;23(3):199–208.PubMedGoogle Scholar 80. Smith SM, Vale WW. The role of the hypothalamic-pituitary-adrenal axis in neuroendocrine responses to stress. Dialog Clin Neurosci. 2006;8(4):383–95.Google Scholar 81. Morgan SA, Sherlock M, Gathercole LL, Lavery GG, Lenaghan C, Bujalska IJ, et al. 11beta-hydroxysteroid dehydrogenase type 1 regulates glucocorticoid-induced insulin resistance in skeletal muscle. Diabetes. 2009;58(11):2506–15.PubMedPubMedCentralCrossRefGoogle Scholar 82. Chapman K, Holmes M, Seckl J. 11β-hydroxysteroid dehydrogenases: intracellular gate-keepers of tissue glucocorticoid action. Physiol Rev. 2013;93(3):1139–206.PubMedPubMedCentralCrossRefGoogle Scholar 83. Singla RK, Scotti L, Dubey AK. In silico studies revealed multiple neurological targets for the antidepressant molecule ursolic acid. Curr Neuropharmacol. 2016 (Epub ahead of print).Google Scholar 84. Youdim MB, Edmondson D, Tipton KF. The therapeutic potential of monoamine oxidase inhibitors. Nat Rev Neurosci. 2006;7(4):295–309.PubMedCrossRefGoogle Scholar 85. Nyola A, Karpowich NK, Zhen J, Marden J, Reith ME, Wang DN. Substrate and drug binding sites in LeuT. Curr Opin Struct Biol. 2010;20(4):415–22.PubMedPubMedCentralCrossRefGoogle Scholar 86. Levin EY, Levenberg B, Kaufman S. The enzymatic conversion of 3,4-dihydroxyphenylethylamine to norepinephrine. J Biol Chem. 1960;235:2080–6.PubMedGoogle Scholar 87. Cunningham C, Campion S, Lunnon K, Murray CL, Woods JF, Deacon RM, et al. Systemic inflammation induces acute behavioral and cognitive changes and accelerates neurodegenerative disease. Biol Psychiatry. 2009;65(4):304–12.PubMedPubMedCentralCrossRefGoogle Scholar 88. Lu J, Zheng YL, Wu DM, Luo L, Sun DX, Shan Q. Ursolic acid ameliorates cognition deficits and attenuates oxidative damage in the brain of senescent mice induced by d-galactose. Biochem Pharmacol. 2007;74(7):1078–90.PubMedCrossRefGoogle Scholar 89. Lu J, Wu DM, Zheng YL, Hu B, Cheng W, Zhang ZF, et al. Ursolic acid improves high fat diet-induced cognitive impairments by blocking endoplasmic reticulum stress and IκB kinase β/nuclear factor-κB-mediated inflammatory pathways in mice. Brain Behav Immun. 2011;25(8):1658–67.PubMedCrossRefGoogle Scholar 90. Wang YJ, Lu J, Wu DM, Zheng ZH, Zheng YL, Wang XH, et al. Ursolic acid attenuates lipopolysaccharide-induced cognitive deficits in mouse brain through suppressing p38/NF-κB mediated inflammatory pathways. Neurobiol Learn Mem. 2011;96(2):156–65.PubMedCrossRefGoogle Scholar 91. Ennaceur A. Tests of unconditioned anxiety: pitfalls and disappointments. Physiol Behav. 2014;135:55–71.PubMedCrossRefGoogle Scholar 92. Vorhees CV, Williams MT. Assessing spatial learning and memory in rodents. ILAR J. 2014;55(2):310–32.PubMedPubMedCentralCrossRefGoogle Scholar 93. Li L, Zhang X, Cui L, Wang L, Liu H, Ji H, et al. Ursolic acid promotes the neuroprotection by activating Nrf2 pathway after cerebral ischemia in mice. Brain Res. 2013;1497:32–9.PubMedCrossRefGoogle Scholar 94. Wang Y, He Z, Deng S. Ursolic acid reduces the metalloprotease/anti-metalloprotease imbalance in cerebral ischemia and reperfusion injury. Drug Des Devel Ther. 2016;10:1663–74.PubMedPubMedCentralCrossRefGoogle Scholar 95. Wei H, Li L, Song Q, Ai H, Chu J, Li W. Behavioural study of the d-galactose induced aging model in C57BL/6J mice. Behav Brain Res. 2005;157(2):245–51.PubMedCrossRefGoogle Scholar 96. Lu J, Wu DM, Zheng YL, Hu B, Zhang ZF, Ye Q, et al. Ursolic acid attenuates d-galactose-induced inflammatory response in mouse prefrontal cortex through inhibiting AGEs/RAGE/NF-κB pathway activation. Cereb Cortex. 2010;20(11):2540–8.PubMedCrossRefGoogle Scholar 97. Zhang T, Su J, Guo B, Zhu T, Wang K, Li X. Ursolic acid alleviates early brain injury after experimental subarachnoid hemorrhage by suppressing TLR4-mediated inflammatory pathway. Int Immunopharmacol. 2014;23(2):585–91.PubMedCrossRefGoogle Scholar 98. Zhang T, Su J, Wang K, Zhu T, Li X. Ursolic acid reduces oxidative stress to alleviate early brain injury following experimental subarachnoid hemorrhage. Neurosci Lett. 2014;579:12–7.PubMedCrossRefGoogle Scholar 99. Ding H, Wang H, Zhu L, Wei W. Ursolic acid ameliorates early brain injury after experimental traumatic brain injury in mice by activating the Nrf2 pathway. Neurochem Res. 2017;42(2):337–46.PubMedCrossRefGoogle Scholar 100. Chen X, Guo C, Kong J. Oxidative stress in neurodegenerative diseases. Neural Regen Res. 2012;7(5):376–85.PubMedPubMedCentralGoogle Scholar 101. Wu DM, Lu J, Zhang YQ, Zheng YL, Hu B, Cheng W, et al. Ursolic acid improves domoic acid-induced cognitive deficits in mice. Toxicol Appl Pharmacol. 2013;271(2):127–36.PubMedCrossRefGoogle Scholar 102. Rai SN, Yadav SK, Singh D, Singh SP. Ursolic acid attenuates oxidative stress in nigrostriatal tissue and improves neurobehavioral activity in MPTP-induced Parkinsonian mouse model. J Chem Neuroanat. 2016;71:41–9.PubMedCrossRefGoogle Scholar 103. Brooks SP, Dunnett SB. Tests to assess motor phenotype in mice: a user’s guide. Nat Rev Neurosci. 2009;10(7):519–29.PubMedCrossRefGoogle Scholar 104. Nitta A, Itoh A, Hasegawa T, Nabeshima T. beta-Amyloid protein-induced Alzheimer’s disease animal model. Neurosci Lett. 1994;170(1):63–6.PubMedCrossRefGoogle Scholar 105. Takeda S, Sato N, Niisato K, Takeuchi D, Kurinami H, Shinohara M, et al. Validation of Abeta1-40 administration into mouse cerebroventricles as an animal model for Alzheimer disease. Brain Res. 2009;1280:137–47.PubMedCrossRefGoogle Scholar 106. Liang W, Zhao X, Feng J, Song F, Pan Y. Ursolic acid attenuates beta-amyloid-induced memory impairment in mice. Arq Neuropsiquiatr. 2016;74(6):482–8.PubMedCrossRefGoogle Scholar 107. Krishnan V, Nestler EJ. Animal models of depression: molecular perspectives. Curr Top Behav Neurosci. 2011;7:121–47.PubMedPubMedCentralCrossRefGoogle Scholar 108. Colla AR, Oliveira A, Pazini FL, Rosa JM, Manosso LM, Cunha MP, et al. Serotonergic and noradrenergic systems are implicated in the antidepressant-like effect of ursolic acid in mice. Pharmacol Biochem Behav. 2014;124:108–16.PubMedCrossRefGoogle Scholar 109. Marks DM, Pae CU, Patkar AA. Triple reuptake inhibitors: the next generation of antidepressants. Curr Neuropharmacol. 2008;6(4):338–43.PubMedPubMedCentralCrossRefGoogle Scholar 110. Trivedi MH, Fava M, Wisniewski SR, Thase ME, Quitkin F, Warden D, et al. Medication augmentation after the failure of SSRIs for depression. N Engl J Med. 2006;354(12):1243–52.PubMedCrossRefGoogle Scholar 111. Bodkin JA, Lasser RA, Wines JD Jr, Gardner DM, Baldessarini RJ. Combining serotonin reuptake inhibitors and bupropion in partial responders to antidepressant monotherapy. J Clin Psychiatry. 1997;58(4):137–45.PubMedCrossRefGoogle Scholar 112. Sharma H, Santra S, Dutta A. Triple reuptake inhibitors as potential next-generation antidepressants: a new hope? Future Med Chem. 2015;7(17):2385–406.PubMedPubMedCentralCrossRefGoogle Scholar 113. Skolnick P, Krieter P, Tizzano J, Basile A, Popik P, Czobor P, et al. Preclinical and clinical pharmacology of DOV 216,303, a “triple” reuptake inhibitor. CNS Drug Rev. 2006;12(2):123–34.PubMedCrossRefGoogle Scholar 114. Beer B, Stark J, Krieter P, Czobor P, Beer G, Lippa A, et al. DOV 216,303, a “triple” reuptake inhibitor: safety, tolerability, and pharmacokinetic profile. J Clin Pharmacol. 2004;44(12):1360–7.PubMedCrossRefGoogle Scholar 115. Ramos-Hryb AB, Cunha MP, Pazini FL, Lieberknecht V, Prediger RD, Kaster MP, et al. Ursolic acid affords antidepressant-like effects in mice through the activation of PKA, PKC, CAMK-II and MEK1/2. Pharmacol Rep. 2017. doi: 10.1016/j.pharep.2017.05.009. 116. Popoli M, Brunello N, Perez J, Racagni G. Second messenger-regulated protein kinases in the brain: their functional role and the action of antidepressant drugs. J Neurochem. 2000;74(1):21–33.PubMedCrossRefGoogle Scholar 117. Hettema JM. What is the genetic relationship between anxiety and depression? Am J Med Genet C Semin Med Genet. 2008;148C(2):140–6.PubMedCrossRefGoogle Scholar 118. Colla AR, Rosa JM, Cunha MP, Rodrigues AL. Anxiolytic-like effects of ursolic acid in mice. Eur J Pharmacol. 2015;758:171–6.PubMedCrossRefGoogle Scholar 119. Jeon SJ, Park HJ, Gao Q, Pena IJ, Park SJ, Lee HE, et al. Ursolic acid enhances pentobarbital-induced sleeping behaviors via GABAergic neurotransmission in mice. Eur J Pharmacol. 2015;762:443–8.PubMedCrossRefGoogle Scholar 120. Anderson KN, Bradley AJ. Sleep disturbance in mental health problems and neurodegenerative disease. Nat Sci Sleep. 2013;5:61–75.PubMedPubMedCentralCrossRefGoogle Scholar 121. Leung AY, Foster S. Encyclopedia of common natural ingredients used in food, drug and cosmetics. 2nd ed. New York: Wiley; 1996.Google Scholar 122. Xia Y, Wei G, Si D, Liu C. Quantitation of ursolic acid in human plasma by ultra performance liquid chromatography tandem mass spectrometry and its pharmacokinetic study. J Chromatogr B Analyt Technol Biomed Life Sci. 2011;879(2):219–24.PubMedCrossRefGoogle Scholar 123. Bang HS, Seo DY, Chung YM, Oh KM, Park JJ, Arturo F, et al. Ursolic acid-induced elevation of serum irisin augments muscle strength during resistance training in men. Korean J Physiol Pharmacol. 2014;18(5):441–6.PubMedPubMedCentralCrossRefGoogle Scholar 124. Wrann CD, White JP, Salogiannnis J, Laznik-Bogoslavski D, Wu J, Ma D, et al. Exercise induces hippocampal BDNF through a PGC-1α/FNDC5 pathway. Cell Metab. 2013;18(5):649–59.PubMedPubMedCentralCrossRefGoogle Scholar 125. Moon HS, Dincer F, Mantzoros CS. Pharmacological concentrations of irisin increase cell proliferation without influencing markers of neurite outgrowth and synaptogenesis in mouse H19-7 hippocampal cell lines. Metabolism. 2013;62(8):1131–6.PubMedPubMedCentralCrossRefGoogle Scholar 126. Hussain H, Green IR, Ali I, Khan IA, Ali Z, Al-Sadi AM, et al. Ursolic acid derivatives for pharmaceutical use: a patent review (2012–2016). Expert Opin Ther Pat. 2017;27(9):1061–72.PubMedCrossRefGoogle Scholar 127. Zhao W, Zhang H, Wang H, Tang X, Wu J. Caffeoyl substituted pentacyclic triterpene derivative and use thereof. Google Patents; 2014.Google Scholar 128. Ting A, Milne JC, Jirousek MR, Bemis JE, Vu CB. Fatty acid triterpene derivatives and their uses. Google Patents; 2012.Google Scholar 129. Kuang C, Xiao Y, Hondmann D. Nutritional composition containing a neurologic component of ursolic acid. Google Patents; 2015.Google Scholar Copyright information © Springer International Publishing AG 2017 About this article CrossMark Cite this article as: Ramos-Hryb, A.B., Pazini, F.L., Kaster, M.P. et al. CNS Drugs (2017) 31: 1029. https://doi.org/10.1007/s40263-017-0474-4