Anti-apoptotic potential of several antidiabetic medicinal plants of the eastern James Bay Cree pharmacopeia in cultured kidney cells(Article)(Open Access)

BMC Complementary and Alternative MedicineOpen AccessVolume 18, Issue 1, 30 January 2018, Article number 37 Li, S.a,bEmail Author, Pasquin, S.aEmail Author, Eid, H.M.a,b,cEmail Author, Gauchat, J.-F.aEmail Author, Saleem, A.dEmail Author, Haddad, P.S.a,bEmail Author View Correspondence (jump link) aUniversité de Montréal, Department of Pharmacology and Physiology, Downtown Postal Station, P.O. Box 6128, Montreal, QC H3C 3J7, Canada bNatural Health Products and Metabolic Diseases Laboratory, CIHR Team in Aboriginal Antidiabetic Medicines and Montreal Diabetes Research Center, CRCHUM, Montreal, Canada cBeni-Suef University, Department of Pharmacognosy, Faculty of Pharmacy, Beni-Suef, 62514, Egypt View additional affiliations Abstract View references (97) Background: Our team has identified 17 Boreal forest species from the traditional pharmacopeia of the Eastern James Bay Cree that presented promising in vitro and in vivo biological activities in the context of type 2 diabetes (T2D). We now screened the 17 plants extracts for potential anti-apoptotic activity in cultured kidney cells and investigated the underlying mechanisms. Methods: MDCK (Madin-Darnby Canine Kidney) cell damage was induced by hypertonic medium (700 mOsm/L) in the presence or absence of maximal nontoxic concentrations of each of the 17 plant extracts. After 18 h' treatment, cells were stained with Annexin V (AnnV) and Propidium iodide (PI) and subjected to flow cytometry to assess the cytoprotective (AnnV-/PI-) and anti-apoptotic (AnnV+/PI-) potential of the 17 plant extracts. We then selected a representative subset of species (most cytoprotective, moderately so or neutral) to measure the activity of caspases 3, 8 and 9. Results: Gaultheria hispidula and Abies balsamea are amongst the most powerful cytoprotective and anti-apoptotic plants and appear to exert their modulatory effect primarily by inhibiting caspase 9 in the mitochondrial apoptotic signaling pathway. Conclusion: We conclude that several Cree antidiabetic plants exert anti-apoptotic activity that may be relevant in the context of diabetic nephropathy (DN) that affects a significant proportion of Cree diabetics. © 2018 The Author(s). SciVal Topic Prominence Topic: Hypoglycemic Agents | Pharmacopoeias as Topic | medicinal plant Prominence percentile: 43.861 Author keywords Aboriginal traditional medicineAnnexin VCaspaseDiabetic nephropathyMDCK cellsPropidium iodide Indexed keywords EMTREE drug terms: Abies balsamea extractbenzyloxycarbonylvalylalanylaspartyl fluoromethyl ketonecaspase 3caspase 8caspase 9cytoprotective agentGaultheria hispidula extractlipocortin 5plant extractunclassified drugantidiabetic agentcaspaseplant extractpropidium iodideprotective agent EMTREE medical terms: Abies balsameaantiapoptotic activityArticlecell protectioncontrolled studydrug activityenzyme activityenzyme inhibitionflow cytometryGaultheriaGaultheria hispidulalimit of quantitationMDCK cell linemitochondrionsignal transductiontraditional medicineanimalapoptosisCanadachemistrydiabetic nephropathydogdrug effectsMDCK cell linemedicinal plantmetabolismtraditional medicine MeSH: AnimalsAnnexin A5ApoptosisCanadaCaspasesDiabetic NephropathiesDogsHypoglycemic AgentsMadin Darby Canine Kidney CellsMedicine, TraditionalPlant ExtractsPlants, MedicinalPropidiumProtective Agents Chemicals and CAS Registry Numbers: caspase 3, 169592-56-7; caspase 8; caspase 9, 180189-96-2; lipocortin 5, 111237-10-6; caspase, 186322-81-6; propidium iodide, 25535-16-4; Annexin A5; Caspases; Hypoglycemic Agents; Plant Extracts; Propidium; Protective Agents Funding details Funding sponsor Funding number Acronym OP2–144645 CTP-79855 Canadian Institutes of Health Research See opportunities by CIHR CIHR Funding text Team Grants from the Canadian Institutes of Health Research (CIHR Team in Aboriginal Antidiabetic Medicines; CTP-79855 and OP2–144645) to Pierre S. Haddad and collaborators funded these studies. ISSN: 14726882 CODEN: BCAMC Source Type: Journal Original language: English DOI: 10.1186/s12906-018-2104-1 PubMed ID: 29378549 Document Type: Article Publisher: BioMed Central Ltd. References (97) View in search results format All View all 97 references 1 Polonsky, K.S. The past 200 years in diabetes (2012) New England Journal of Medicine, 367 (14), pp. 1332-1340. Cited 120 times. http://www.nejm.org/doi/pdf/10.1056/NEJMra1110560 doi: 10.1056/NEJMra1110560 View at Publisher 2 Ozougwu, J.C., Obimba, K.C., Belonwu, C.D., Unakalamba, C.B. The pathogenesis and pathophysiology of type 1 and type 2 diabetes mellitus (2013) J Physiol Pathophysiol, 4, pp. 46-57. Cited 71 times. 3 Tan, K.T., Cheah, J.S. Pathogenesis of type 1 and type 2 diabetes mellitus. (1990) Annals of the Academy of Medicine Singapore, 19 (4), pp. 506-511. Cited 5 times. 4 Hall, J.E., Guyton, A.C. Guyton and hall textbook of medical physiology (2011) . Cited 696 times. 12th ed. Philadelphia: Elsevier 5 Wild, S., Roglic, G., Green, A., Sicree, R., King, H. Global Prevalence of Diabetes: Estimates for the year 2000 and projections for 2030 (2004) Diabetes Care, 27 (5), pp. 1047-1053. Cited 9733 times. doi: 10.2337/diacare.27.5.1047 View at Publisher 6 Amos, A.F., McCarty, D.J., Zimmet, P. The rising global burden of diabetes and its complications: Estimates and projections to the year 2010 (1997) Diabetic Medicine, 14 (12 SUPPL.5), pp. S7-S85. Cited 1476 times. 7 King, H., Aubert, R.E., Herman, W.H. Global burden of diabetes, 1995-2025: Prevalence, numerical estimates, and projections (1998) Diabetes Care, 21 (9), pp. 1414-1431. Cited 4583 times. http://care.diabetesjournals.org/ doi: 10.2337/diacare.21.9.1414 View at Publisher 8 King, H., Rewers, M. Global estimates for prevalence of diabetes mellitus and impaired glucose tolerance in adults (1993) Diabetes Care, 16 (1), pp. 157-177. Cited 828 times. doi: 10.2337/diacare.16.1.157 View at Publisher 9 Ekoe, J.-M., Thouez, J.-P., Petitclerc, C., Foggin, P.M., Ghadirian, P. Epidemiology of obesity in relationship to some chronic medical conditions among Inuit and Cree Indian populations in New Quebec, Canada (1990) Diabetes Research and Clinical Practice, 10 (SUPPL. 1), pp. S17-S27. Cited 11 times. doi: 10.1016/0168-8227(90)90135-G View at Publisher 10 Hegele, R.A., Cao, H., Harris, S.B., Hanley, A.J.G., Zinman, B. The hepatic nuclear factor-1α G319S variant is associated with early- onset type 2 diabetes in Canadian Oji-Cree (1999) Journal of Clinical Endocrinology and Metabolism, 84 (3), pp. 1077-1082. Cited 120 times. 11 Nachar, A., Vallerand, D., Musallam, L., Lavoie, L., Badawi, A., Arnason, J., Haddad, P.S. The action of antidiabetic plants of the Canadian James bay Cree traditional pharmacopeia on key enzymes of hepatic glucose homeostasis (Open Access) (2013) Evidence-based Complementary and Alternative Medicine, 2013, art. no. 189819. Cited 17 times. doi: 10.1155/2013/189819 View at Publisher 12 NEEL, J.V. Diabetes mellitus: a "thrifty" genotype rendered detrimental by "progress"? (1962) American journal of human genetics, 14, pp. 353-362. Cited 2083 times. 13 Young, T.K., Reading, J., Elias, B., O'Neil, J.D. Type 2 diabetes mellitus in Canada's First Nations: Status of an epidemic in progress (2000) CMAJ, 163 (5), pp. 561-566. Cited 292 times. View at Publisher 14 Kuzmina, E., Lejeune, P., Dannenbaum, D., Torrie, J.E. Cree diabetes information system (CDIS) 2009 annual report (2010) . Cited 7 times. 3rd ed. Cree Board of Health and Social Services of James Bay: Montréal 15 Obesity, G.D. The eating habits of the aboriginal population (2008) Health Rep, 19, pp. 21-35. 16 Hanley, A.J.G., Harris, S.B., Mamakeesick, M., Goodwin, K., Fiddler, E., Hegele, R.A., Spence, J.D., (...), Zinman, B. Complications of type 2 diabetes among aboriginal Canadians: Prevalence and associated risk factors (Open Access) (2005) Diabetes Care, 28 (8), pp. 2054-2057. Cited 49 times. doi: 10.2337/diacare.28.8.2054 View at Publisher 17 Ritz, E., Orth, S.R. Nephropathy in patients with type 2 diabetes mellitus (1999) New England Journal of Medicine, 341 (15), pp. 1127-1133. Cited 549 times. doi: 10.1056/NEJM199910073411506 View at Publisher 18 Fineberg, D., Jandeleit-Dahm, K.A.M., Cooper, M.E. Diabetic nephropathy: Diagnosis and treatment (2013) Nature Reviews Endocrinology, 9 (12), pp. 713-723. Cited 60 times. doi: 10.1038/nrendo.2013.184 View at Publisher 19 Adler, A.I., Stratton, I.M., Neil, H.A.W., Yudkin, J.S., Matthews, D.R., Cull, C.A., Wright, A.D., (...), Holman, R.R. Association of systolic blood pressure with macrovascular and microvascular complications of type 2 diabetes (UKPDS 36): Prospective observational study (2000) British Medical Journal, 321 (7258), pp. 412-419. Cited 1481 times. View at Publisher 20 Stratton, I.M., Adler, A.I., Neil, H.A.W., Matthews, D.R., Manley, S.E., Cull, C.A., Hadden, D., (...), Holman, R.R. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): Prospective observational study (2000) British Medical Journal, 321 (7258), pp. 405-412. Cited 5497 times. View at Publisher 21 Diabetes, H.S.L. renal tubular cell apoptosis (2013) World J Diabetes, 4, pp. 27-30. 22 Kumar, D., Robertson, S., Burns, K.D. Evidence of apoptosis in human diabetic kidney (2004) Molecular and Cellular Biochemistry, 259 (1-2), pp. 67-70. Cited 101 times. doi: 10.1023/B:MCBI.0000021346.03260.7e View at Publisher 23 Sanchez-Niñ O, M.D., Sanz, A.B., Lorz, C., Gnirke, A., Rastaldi, M.P., Nair, V., Egido, J., (...), Ortiz, A. BASP1 promotes apoptosis in diabetic nephropathy (2010) Journal of the American Society of Nephrology, 21 (4), pp. 610-621. Cited 47 times. http://jasn.asnjournals.org/cgi/reprint/21/4/610 doi: 10.1681/ASN.2009020227 View at Publisher 24 Horio, M., Ito, A., Matsuoka, Y., Moriyama, T., Orita, Y., Takenaka, M., Imai, E. Apoptosis induced by hypertonicity in Madin Darley canine kidney cells: Protective effect of betaine (2001) Nephrology Dialysis Transplantation, 16 (3), pp. 483-490. Cited 57 times. http://ndt.oxfordjournals.org/ doi: 10.1093/ndt/16.3.483 View at Publisher 25 Fraser, M.-H., Cuerrier, A., Haddad, P.S., Arnason, J.T., Owen, P.L., Johns, T. Medicinal plants of Cree communities (Québec, Canada): Antioxidant activity of plants used to treat type 2 diabetes symptoms (2007) Canadian Journal of Physiology and Pharmacology, 85 (11), pp. 1200-1214. Cited 34 times. http://article.pubs.nrc-cnrc.gc.ca/RPAS/RPViewDoc?_handler_=HandleInitialGet&calyLang=eng&journal=cjpp&volume=85&articleFile=y07-108.pdf doi: 10.1139/Y07-108 View at Publisher 26 Haddad, P.S., Musallam, L., Martineau, L.C., Harris, C., Lavoie, L., Arnason, J.T., Foster, B., (...), Badawi, A. Comprehensive evidence-based assessment and prioritization of potential antidiabetic medicinal plants: A case study from Canadian eastern James Bay Cree traditional medicine (Open Access) (2012) Evidence-based Complementary and Alternative Medicine, 2012, art. no. 893426. Cited 16 times. doi: 10.1155/2012/893426 View at Publisher 27 Harbilas, D., Martineau, L.C., Harris, C.S., Adeyiwola-Spoor, D.C.A., Saleem, A., Lambert, J., Caves, D., (...), Haddad, P.S. Evaluation of the antidiabetic potential of selected medicinal plant extracts from the Canadian boreal forest used to treat symptoms of diabetes: Part II (2009) Canadian Journal of Physiology and Pharmacology, 87 (6), pp. 479-492. Cited 53 times. http://article.pubs.nrc-cnrc.gc.ca/RPAS/rpv?hm=HInit&calyLang=eng&journal=cjpp&volume=87&afpf=y09-029.pdf doi: 10.1139/Y09-029 View at Publisher 28 Spoor, D.C.A., Martineau, L.C., Leduc, C., Benhaddou-Andaloussi, A., Meddah, B., Harris, C., Burt, A., (...), Haddad, P.S. Selected plant species from the Cree pharmacopoeia of northern Quebec possess anti-diabetic potential (2006) Canadian Journal of Physiology and Pharmacology, 84 (8-9), pp. 847-858. Cited 77 times. doi: 10.1139/Y06-018 View at Publisher 29 Erkan, E., Devarajan, P., Schwartz, G.J. Apoptotic response to albumin overload: Proximal vs. distal/collecting tubule cells (2005) American Journal of Nephrology, 25 (2), pp. 121-131. Cited 20 times. doi: 10.1159/000084888 View at Publisher 30 Hizoh, I., Haller, C. Radiocontrast-induced renal tubular cell apoptosis: Hypertonic versus oxidative stress (2002) Investigative Radiology, 37 (8), pp. 428-434. Cited 114 times. doi: 10.1097/00004424-200208000-00003 View at Publisher 31 Terada, Y., Inoshita, S., Hanada, S., Shimamura, H., Kuwahara, M., Ogawa, W., Kasuga, M., (...), Marumo, F. Hyperosmolality activates Akt and regulates apoptosis in renal tubular cells (Open Access) (2001) Kidney International, 60 (2), pp. 553-567. Cited 64 times. doi: 10.1046/j.1523-1755.2001.060002553.x View at Publisher 32 Yoshida, T., Yoshino, J., Hayashi, M., Saruta, T. Identification of a renal proximal tubular cell-specific enhancer in the mouse 25-hydroxyvitamin D 1α-hydroxylase gene (Open Access) (2002) Journal of the American Society of Nephrology, 13 (6), pp. 1455-1463. Cited 11 times. doi: 10.1097/01.ASN.0000013885.23734.CA View at Publisher 33 Zhang, B., Suzuki, J.S., Nishimura, N., Tohyama, C. Difference in cadmium cytotoxicity in two kidney cell lines (LLC-PK1 and MDCK) with special reference to metallothionein (1995) Toxicology in Vitro, 9 (5), pp. 765-767,769-772. Cited 14 times. doi: 10.1016/0887-2333(95)00055-D View at Publisher 34 Shang, N., Saleem, A., Musallam, L., Walshe-Roussel, B., Badawi, A., Cuerrier, A., Arnason, J.T., (...), Haddad, P.S. Novel approach to identify potential bioactive plant metabolites: Pharmacological and metabolomics analyses of ethanol and hot water extracts of several Canadian medicinal plants of the cree of eeyou istchee (Open Access) (2015) PLoS ONE, 10 (8), art. no. e0135721. Cited 10 times. http://www.plosone.org/article/fetchObject.action?uri=info:doi/10.1371/journal.pone.0135721&representation=PDF doi: 10.1371/journal.pone.0135721 View at Publisher 35 Yong, Y., Saleem, A., Guerrero-Analco, J.A., Haddad, P.S., Cuerrier, A., Arnason, J.T., Harris, C.S., (...), Johns, T. Larix laricina bark, a traditional medicine used by the Cree of Eeyou Istchee: Antioxidant constituents and in vitro permeability across Caco-2 cell monolayers (2016) Journal of Ethnopharmacology, 194, pp. 651-657. Cited 2 times. www.elsevier.com/locate/jethpharm doi: 10.1016/j.jep.2016.10.054 View at Publisher 36 Eid, H.M., Ouchfoun, M., Saleem, A., Guerrero-Analco, J.A., Walshe-Roussel, B., Musallam, L., Rapinski, M., (...), Haddad, P.S. A combination of (+)-catechin and (-)-epicatechin underlies the in vitro adipogenic action of Labrador tea (Rhododendron groenlandicum), an antidiabetic medicinal plant of the Eastern James Bay Cree pharmacopeia (2016) Journal of Ethnopharmacology, 178, pp. 251-257. Cited 6 times. www.elsevier.com/locate/jethpharm doi: 10.1016/j.jep.2015.12.021 View at Publisher 37 Harris, C.S., Asim, M., Saleem, A., Haddad, P.S., Arnason, J.T., Bennett, S.A.L. Characterizing the cytoprotective activity of Sarracenia purpurea L., a medicinal plant that inhibits glucotoxicity in PC12 cells (Open Access) (2012) BMC Complementary and Alternative Medicine, 12, art. no. 245. Cited 9 times. http://www.biomedcentral.com/1472-6882/12/245 doi: 10.1186/1472-6882-12-245 View at Publisher 38 Shang, N., Guerrero-Analco, J.A., Musallam, L., Saleem, A., Muhammad, A., Walshe-Roussel, B., Cuerrier, A., (...), Haddad, P.S. Adipogenic constituents from the bark of Larix laricina du Roi (K. Koch; Pinaceae), an important medicinal plant used traditionally by the Cree of Eeyou Istchee (Quebec, Canada) for the treatment of type 2 diabetes symptoms (2012) Journal of Ethnopharmacology, 141 (3), pp. 1051-1057. Cited 12 times. doi: 10.1016/j.jep.2012.04.002 View at Publisher 39 Nachar, A., Saleem, A., Arnason, J.T., Haddad, P.S. Regulation of liver cell glucose homeostasis by dehydroabietic acid, abietic acid and squalene isolated from balsam fir (Abies balsamea (L.) Mill.) a plant of the Eastern James Bay Cree traditional pharmacopeia (2015) Phytochemistry, 117, pp. 373-379. Cited 6 times. http://www.journals.elsevier.com/phytochemistry/ doi: 10.1016/j.phytochem.2015.07.001 View at Publisher 40 Guerrero-Analco, J.A., Muhammad, A., Saleem, A., Martineau, L.C., Musallam, L., Eid, H.M. Bioactive phytochemicals from Canadian boreal Forest species used traditionally by eastern James Bay Cree aboriginals to treat diabetes mellitus (2014) Phytochemicals - biosynthesis, function and application, 44, pp. 57-84. Jetter R, editor. New York: Springer International Publishing 41 UYEO, S., OKADA, J., MATSUNAGO, S. SELENIUM DEHYDROGENATION OF ABIESLACTONE. (Open Access) (1964) Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan, 84, pp. 453-457. Cited 2 times. doi: 10.1248/yakushi1947.84.5_453 View at Publisher 42 Steglich, W., Klaar, M., Zechlin, L., Hecht, H.J. Abietospiran, the Triterpene from the Bark of the White Fir (Abies alba) (1979) Angewandte Chemie International Edition in English, 18 (9), pp. 698-698. Cited 14 times. doi: 10.1002/anie.197906981 View at Publisher 43 Baxter, H., Harborne, J.B., Moss, G.P. Phytochemical Dictionary: A Handbook of Bioactive Compounds from Plants (1999) . Cited 520 times. 2nd ed. London et Philadelphia: Taylor & Francis: CRC press 44 Manville, J.F., Kriz, C.D. Juvabione and its analogues. IV. Isolation, identification, and occurrence of juvabione, juvabiol, and epijuvabiol from the whole wood of Abies lasiocarpa (Open Access) (1977) Canadian Journal of Chemistry, 55 (13), pp. 2547-2553. Cited 18 times. doi: 10.1139/v77-351 View at Publisher 45 Gray, P.S., Mills, J.S. The isolation of abienol from Canada Balsam, the Oleoresin of Abies balsamea (L.) Mill (1964) Journal of the Chemical Society (Resumed), pp. 5815-5818. Cited 16 times. 46 Ryabinin, A.A. Journal of general chemistry of the Union of Soviet Socialist Republics (1962) 1st ed. New York: Consultants Bureau Enterprises 47 Saleem, A., Harris, C.S., Asim, M., Cuerrier, A., Martineau, L., Haddad, P.S., Arnason, J.T. A RP-HPLC-DAD-APCI/MSD method for the characterisation of medicinal Ericaceae used by the Eeyou Istchee Cree First Nations (Open Access) (2010) Phytochemical Analysis, 21 (4), pp. 328-339. Cited 23 times. http://www3.interscience.wiley.com/cgi-bin/fulltext/123270716/PDFSTART doi: 10.1002/pca.1203 View at Publisher 48 Teresa JdP, J.G. Urones, Basabe P (1977) Llanos A Anales de Quim, 73, p. 463. 49 Phytochemical, L.-Z. Studies on flavonoids and other compounds of juniper fruits (1980) Pol J Chem, 54, pp. 213-219. Cited 7 times. 50 Baker, W., Finch, A.C.M., Ollis, W.D., Robinson, K.W. The Structures of the Naturally Occurring Biflavonyls (1963) Journal of the Chemical Society (Resumed), pp. 1475-1477. Cited 24 times. 51 Nakanishi, T., Iida, N., Inatomi, Y., Murata, H., Inada, A., Murata, J., Lang, F.A., (...), Tanaka, T. Neolignan and flavonoid glycosides in Juniperus communis var. depressa (2004) Phytochemistry, 65 (2), pp. 207-213. Cited 68 times. http://www.journals.elsevier.com/phytochemistry/ doi: 10.1016/j.phytochem.2003.10.025 View at Publisher 52 Weinges, K., Göritz, K., Nader, F. (1968) Justus Liebigs Annalen der Chemie, 715 (1), pp. 164-171. Cited 80 times. doi: 10.1002/jlac.19687150118 53 Thomas, A.F., Ozainne, M. "Junionone" [1-(2,2-dimethylcyclobutyl)but-1-en-3-one], the first vegetable monocyclic cyclobutane monoterpenoid (1973) Journal of the Chemical Society, Chemical Communications, (19), p. 746. Cited 20 times. doi: 10.1039/C39730000746 View at Publisher 54 Kagawa, K., Tokura, K., Uchida, K., Kakush, H., Shiki, T., Kikuch, J., Nakai, H., (...), Subed, L. Platelet Aggregation Inhibitors in a Bhutanese Medicinal Plant, Shug Chher (Open Access) (1993) Chemical and Pharmaceutical Bulletin, 41 (9), pp. 1604-1607. Cited 22 times. doi: 10.1248/cpb.41.1604 View at Publisher 55 Arya, V.P., Erdtman, H., Kubota, T. Chemistry of the natural order cupressales-41. The structure and stereochemistry of communic acid (1961) Tetrahedron, 16 (1-4), pp. 255-263. Cited 21 times. doi: 10.1016/0040-4020(61)80076-8 View at Publisher 56 Hinge, V.K., Wagh, A.D., Paknikar, S.K., Bhattacharyya, S.C. Terpenoids-LXXI. Constituents of Indian black dammar resin (1965) Tetrahedron, 21 (11), pp. 3197-3203. Cited 15 times. doi: 10.1016/S0040-4020(01)96937-6 View at Publisher 57 Schneider, I., Gibbons, S., Bucar, F. Inhibitory activity of Juniperus communis on 12(S)-HETE production in human platelets (2004) Planta Medica, 70 (5), pp. 471-474. Cited 17 times. doi: 10.1055/s-2004-818980 View at Publisher 58 Arya, V.P., Enzell, C., Erdtman, H., Kubota, T. Communic acid, a new Diterpene acid from Juniperus Communis L. (1961) Acta Chem Scand, 15, pp. 225-226. Cited 8 times. 59 Thomas, A.F. 1, 4‐Dimethylcyclohex‐3‐enyl Methyl Ketone, a monoterpenoid with a novel skeleton (1973) Helvetica Chimica Acta, 56 (5), pp. 1800-1802. Cited 10 times. doi: 10.1002/hlca.19730560541 View at Publisher 60 Yannai, S. Dictionary of food compounds (2004) . Cited 41 times. With CD-ROM: additives, flavors, and ingredients. 2 ed. Chapman & Hall/CRC: Boca Raton 61 Teresa, J.D.P., Barrero, A.F., Feliciano, A.S., Bellido, I.S. (1977) Anales de Quim, 73, p. 568. Cited 3 times. 62 Little, C.H.A., Andrew, D.M., Silk, P.J., Strunz, G.M. (1979) Phytochemistry, 18 (7), pp. 1219-1220. Cited 7 times. doi: 10.1016/0031-9422(79)80139-9 63 Williams, A.H. Dihydrochalcones; Their occurrence and use as indicators in chemical plant taxonomy [42] (1964) Nature, 202 (4934), pp. 824-825. Cited 23 times. doi: 10.1038/202824b0 View at Publisher 64 Wilkins, C.K., Bohm, B.A. (1976) Can J Bot, 54, p. 2133. Cited 66 times. 65 Braekman, J.C., Nyembo, L., Bourdoux, P., Kahindo, N., Hootele, C. (1974) Phytochemistry, 13 (11), pp. 2519-2528. Cited 25 times. doi: 10.1016/S0031-9422(00)86930-7 66 Manners, G.D., Swan, E.P. Stilbenes in the barks of five canadian Picea species (1971) Phytochemistry, 10 (3), pp. 607-610. Cited 21 times. doi: 10.1016/S0031-9422(00)94705-8 View at Publisher 67 Nozzolillo, C., Isabelle, P., Andersen, Ø.M., Abou-Zaid, M. Anthocyanins of jack pine (Pinus banksiana) seedlings (2002) Canadian Journal of Botany, 80 (7), pp. 796-801. Cited 18 times. doi: 10.1139/b02-056 View at Publisher 68 Rowe, J.W., Bower, C.L., Wagner, E.R. Extractives of jack pine bark: Occurrence of cis- and trans-pinosylvin dimethyl ether and ferulic acid esters (1969) Phytochemistry, 8 (1), pp. 235-241. Cited 32 times. doi: 10.1016/S0031-9422(00)85819-7 View at Publisher 69 Vermes, B., Chari, V.M., Wagner, H. Structure Elucidation and Synthesis of Flavonol Acylglycosides. III.. The synthesis of tiliroside (1981) Helvetica Chimica Acta, 64 (6), pp. 1964-1967. Cited 24 times. doi: 10.1002/hlca.19810640630 View at Publisher 70 Farkas, L., Vermes, B., Nógrádi, M. (1974) Chemische Berichte, 107 (5), pp. 1518-1525. Cited 9 times. doi: 10.1002/cber.19741070512 71 Abou-zaid, M.M., Nozzolillo, C. Flavonol glycosides from needles of Pinus banksiana (1991) Biochemical Systematics and Ecology, 19 (3), pp. 237-240. Cited 6 times. doi: 10.1016/0305-1978(91)90007-M View at Publisher 72 Bower, C.L., Rowe, J.W. Extractives of jack pine bark: Occurrence of (+)-13-epimanoyl oxide and related labdane diterpenes (1967) Phytochemistry, 6 (1), pp. 151-153. Cited 21 times. doi: 10.1016/0031-9422(67)85024-6 View at Publisher 73 Carman, R.M., Duffield, A.R. (+)-α-Bisabolol and (+)-Anymol. A Repetition of the Synthesis from the Limonene 8, 9-Epoxides (1989) Australian Journal of Chemistry, 42 (11), pp. 2035-2039. Cited 19 times. doi: 10.1071/CH9892035 View at Publisher 74 Tanaka, H., Ichino, K., Ito, K. Dihydrochalcones from lindera umbellata (1984) Phytochemistry, 23 (5), pp. 1198-1199. Cited 17 times. doi: 10.1016/S0031-9422(00)82646-1 View at Publisher 75 HILLIS, W.E., ORMAN, H.R. The extractives of New Zealand Nothofagus species (Open Access) (1962) Journal of the Linnean Society of London, Botany, 58 (371), pp. 175-184. Cited 11 times. doi: 10.1111/j.1095-8339.1962.tb00891.x View at Publisher 76 Harborne, J.B., Williams, C.A. Leaf survey of flavonoids and simple phenols in the genus Rhododendron (1971) Phytochemistry, 10 (11), pp. 2727-2744. Cited 45 times. doi: 10.1016/S0031-9422(00)97273-X View at Publisher 77 Hörhammer, L., Wagner, H., Reinhardt, H. (1965) Die Naturwissenschaften, 52 (7), p. 161. Cited 10 times. doi: 10.1007/BF00609279 78 Terahara, N., Takeda, Y., Nesumi, A., Honda, T. Anthocyanins from red flower tea (Benibana-cha), Camellia sinensis (2001) Phytochemistry, 56 (4), pp. 359-361. Cited 20 times. doi: 10.1016/S0031-9422(00)00359-9 View at Publisher 79 Kolodziej, H. The first natural biflavonoid with flavanol and dihydroflavonol constituent units coupled at the B-ring (1987) Journal of the Chemical Society, Chemical Communications, (3), pp. 205-206. Cited 8 times. doi: 10.1039/C39870000205 View at Publisher 80 Emiko, E.-F.-G.-I.N., Nishioka, I., Hayashi, K. Isolation and structures of Procyanidins (condensed tannins) from Rhaphiolepis Umbellata (1986) Agric Biol Chem, p. 50. Haddad, P.S.; Université de Montréal, Department of Pharmacology and Physiology, Downtown Postal Station, P.O. Box 6128, Montreal, QC, Canada; email:pierre.haddad@umontreal.ca © Copyright 2018 Elsevier B.V., All rights reserved.