title: Hypoglycemic activity of withanolides and elicitated Withania somnifera.
abstract: Withania somnifera, known in India as Asghawhanda, is used traditionally to treat many medical problems including diabetes and has demonstrated therapeutic activity in various animal models as well as in diabetic patients. While much of W. somnifera's therapeutic activity is attributed to withanolides, their role in the anti-diabetic activity of W. somnifera has not been adequately studied. In the present study, we evaluated the anti-diabetic activity of W. somnifera extract and purified withanolides, as well as the effect of various elicitors on this activity. W. somnifera leaf and root extracts increased glucose uptake in myotubes and adipocytes in a dose dependent manner, with the leaf extract more active than the root extract. Leaf but not root extract increased insulin secretion in basal pancreatic beta cells but not in stimulated cells. Six withanolides isolated from W. somnifera were tested for anti-diabetic activity based on glucose uptake in skeletal myotubes. Withaferin A was found to increase glucose uptake, with 10μM producing a 54% increase compared with control, suggesting that withaferin A is at least partially responsible for W. somnifera's anti-diabetic activity. Elicitors applied to the root growing solutions affected the physiological state of the plants, altering membrane leakage or osmotic potential. Methyl salicylate and chitosan increased withaferin A content by 75% and 69% respectively, and extracts from elicited plants increased glucose uptake to a higher extent than non-elicited plants, demonstrating a correlation between increased content of withaferin A and anti-diabetic activity.
authors: Judea Regional Research and Development Center, Kiryat Arba, Israel. Electronic address: jonathangorelick@gmail.com.
authors: Jonathan
authors: J
authors: Gorelick
authors: Institute of Soil Water and Environmental Sciences, Volcani Center, POB 6, 50-250, Israel.
authors: Rivka
authors: R
authors: Rosenberg
authors: Judea Regional Research and Development Center, Kiryat Arba, Israel.
authors: Avinoam
authors: A
authors: Smotrich
authors: Institute for Drug Research, Hebrew University Medical Faculty, Jerusalem 91120, Israel. Electronic address: lumirh@ekmd.huji.ac.il.
authors: Lumír
authors: L
authors: Hanuš
authors: Institute of Soil Water and Environmental Sciences, Volcani Center, POB 6, 50-250, Israel. Electronic address: Nirit@agri.gov.il.
authors: Nirit
authors: N
authors: Bernstein
mesh_terms: D009327:4-Chloro-7-nitrobenzofurazan / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D048271:Chitosan / Q000494:pharmacology; D003847:Deoxyglucose / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D007194:India; D007557:Israel; D015394:Molecular Structure; D012459:Salicylates / Q000494:pharmacology; D032341:Withania / Q000737:chemistry*; D054358:Withanolides / Q000494:pharmacology*
chemical_list: D007004:Hypoglycemic Agents; D012459:Salicylates; D054358:Withanolides; D048271:Chitosan; D003847:Deoxyglucose; D009327:4-Chloro-7-nitrobenzofurazan; C098340:2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose; C009684:withaferin A; C033069:methyl salicylate
keywords: Elicitation; Glucose uptake; Withaferin A; Withania somnifera; Withanolide