Identification of anti-adipogenic withanolides from the roots of Indian ginseng ( Withania somnifera ).

Background: Withania somnifera (Solanaceae), generally known as Indian ginseng, is a medicinal plant that is used in Ayurvedic practice for promoting health and longevity. This study aims to identify the bioactive metabolites from Indian ginseng and elucidate their structures.
Methods: Withanolides were purified by chromatographic techniques, including HPLC coupled with LC/MS. Chemical structures of isolated withanolides were clarified by analyzing the spectroscopic data from 1D and 2D NMR, and HR-ESIMS experiment. Absolute configurations of the withanolides were established by the application of NMR chemical shifts and ECD calculations. Anti-adipogenic activities of isolates were evaluated using 3T3-L1 preadipocytes with Oil Red O staining and quantitative real-time PCR (qPCR).
Results: Phytochemical examination of the roots of Indian ginseng afforded to the isolation of six withanolides ( 1 - 6 ), including three novel withanolides, withasilolides G-I ( 1 - 3 ). All the six compounds inhibited adipogenesis and suppressed the enlargement of lipid droplets, compared to those of the control. Additionally, the mRNA expression levels of Fabp4 and Adipsin , the adipocyte markers decreased noticeably following treatment with 25 μM of 1 - 6 . The active compounds ( 1 - 6 ) also promoted lipid metabolism by upregulating the expression of the lipolytic genes HSL and ATGL and downregulating the expression of the lipogenic gene SREBP1.
Conclusion: The results of our experimental studies suggest that the withasilolides identified herein have anti-adipogenic potential and can be considered for the development of therapeutic strategies against adipogenesis in obesity. Our study also provides a mechanistic rationale for using Indian ginseng as a potential therapeutic agent against obesity and related metabolic diseases.
Competing Interests: The authors declare no conflicts of interest.
(© 2021 The Korean Society of Ginseng. Publishing services by Elsevier B.V.)