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In the course of screening for cell differentiation inducers from botanical sources, the methanol extract of Withania somnifera L. (Dun.) showed activity. From the aerial parts of the plant, sixteen withanolides, including three new compounds, 14, 15 and 16, were isolated and their structures elucidated to be (20S,22R)-4β,5β,6α,27-tetrahydroxy-1-oxo-witha-2,24-dienolide, (20R,22R,24S,25R)-4β,20β-dihydroxy-5β,6β-epoxy-3β-methoxy-1-oxo-withanolide and 3-O-[β-D-glucopyranosyl(1→6)-β-D-glucopyranosyl]-(20S,22R)-1α,3β-dihydroxywitha-5,24-dienolide, respectively, from the spectral data. Of these withanolides, 1, 2, 3 and 4 showed potent cell differentiation inducing activity against M1 cells. The most potent compound, 3, showed more potent activity than dexamethasone, the positive control. These active compounds have the same partial structure of the AB ring part, having a 4β-hydroxy-5β,6β-epoxy-2-en-1-one moiety.

Solanaceae, Withania somnifera, withanolide, cell differentiation inducer, M1 cell

Publication DOI: 10.1248/cpb.47.1646
Journal NLM ID: 0377775
Publisher: Pharmaceutical Society Of Japan
Institutions: School of Bioresources, Hiroshima Prefectural University, 562 Nanatsukacho, Shobara-shi, Hiroshima 727-0023, Japan, School of Pharmaceutical Sciences, University of Shizuoka, 52-1, Yada, Shizuoka-shi 422-8526, Japan
Methods: 13C NMR, 1H NMR, TLC, HPLC, CD, phagocytosis assay, HR-FAB-MS

Glycowithanolides, consisting of equimolar concentrations of sitoindosides VII-X and withaferin A, isolated from the roots of Withania somnifera Dunal, have been reported to have an antioxidant effect in the rat brain frontal cortex and striatum. In the present study, the effect of 10 days of oral administration of these active principles, in graded doses (10, 20 and 50 mg/kg), was noted on iron overload (FeSO4, 30 mg/kg, i.p.) induced hepatotoxicity in rats. Apart from hepatic lipid peroxidation (LPO), the serum enzymes, alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase, were assessed as indices of hepatotoxicity. Silymarin (20 mg/kg, p.o.) was used for comparison. Iron overload induced marked increase in hepatic LPO and serum levels of the enzymes, which was attenuated by WSG in a dose-related manner, and by silymarin. The results indicate that the reported use of WS in Ayurveda for hepatoprotection against heavy metals and other environmental toxins, may be due the antioxidant action of WSG.

Hepatoprotection, lipid peroxidation, Withania somnifera, glycowithanolides, iron-induced hepatotoxicity

NCBI PubMed ID: 11054855
Publication DOI: 10.1002/1099-1573(200011)14:7<568::aid-ptr663>3.0.co;2-q
Journal NLM ID: 8904486
Publisher: Chichester: Wiley
Correspondence: Bhattacharya SK
Institutions: Drug Research and Development Centre, Calcutta, India, Department of Pharmacology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India
Methods: biological assays, extraction, HPTLC

Hepatoprotection, lipid peroxidation, Withania somnifera, glycowithanolides, iron-induced hepatotoxicity