Withasomniferol D, a New Anti-Adipogenic Withanolide from the Roots of Ashwagandha (Withania somnifera)

Abstract

Withania somnifera (Solanaceae), well-known as ‘Indian ginseng’ or ‘Ashwagandha’, is a medicinal plant that is used in Ayurvedic practice to promote good health and longevity. As part of an ongoing investigation for bioactive natural products with novel structures, we performed a phytochemical examination of the roots of W. somnifera employed with liquid chromatography–mass spectrometry (LC/MS)-based analysis. The chemical analysis of the methanol extract of W. somnifera roots using repeated column chromatography and high-performance liquid chromatography under the guidance of an LC/MS-based analysis resulted in a new withanolide, withasomniferol D (1). The structure of the newly isolated compound was elucidated by spectroscopic methods, including one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR) and high-resolution (HR) electrospray ionization (ESI) mass spectroscopy, and its absolute configuration was established by electronic circular dichroism (ECD) calculations. The anti-adipogenic activities of withasomniferol D (1) were evaluated using 3T3-L1 preadipocytes with Oil Red O staining and quantitative real-time polymerase chain reaction (qPCR). We found that withasomniferol D (1) inhibited adipogenesis and suppressed the enlargement of lipid droplets compared to the control. Additionally, the mRNA expression levels of adipocyte markers Fabp4 and Adipsin decreased noticeably following treatment with 25 μM of withasomniferol D (1). Taken together, these findings provide experimental evidence that withasomniferol D (1), isolated from W. somnifera, exhibits anti-adipogenic activity, supporting the potential application of this compound in the treatment of obesity and related metabolic diseases.

Protective Effects of Withagenin A Diglucoside from Indian Ginseng (Withania somnifera) against Human Dermal Fibroblast Damaged by TNF-α Stimulation

“…To date, more than 40 withanolides have been isolated from W. somnifera , including novel withanolides [ 17 ] as well as withanolide glycosides with β-D-glucopyranose linked at C-3 or C-27 [ 17 ]. According to our recent studies on W. somnifera roots, we reported bioactive new withanolides, namely withasilolides A–F [ 18 ] and withasomniferol D [ 19 ], which exhibit significant cytotoxicity against human cancer cells and anti-adipogenic activity. Specifically, a few withanolide glycosides have been reported in the group of withanolides, and a recent study reported that withanolide glycosides (withanosides I–XI) were found to show anti-Alzheimer, anti-stress, and neuroprotective activities [ 20 ].…”

Recent Advancements in Extraction Techniques of Ashwagandha (Withania somnifera) with Insights on Phytochemicals, Structural Significance, Pharmacology, and Current Trends in Food Applications

“…Similarly, flavonoid content was higher in leaves (43.51 ± 0.346 mg/g) than in stem (42.82 ± 1.189 mg/g) and root (39.13 ± 0.607 mg/g) extract . Another antiadipogenic withanolide was isolated from the root of WS via reflux extraction with 80% aqueous methanol . The dried root and fruits of WS were homogenized separately at room temperature with methanol:water (8:2) to yield 19% and 22% extractive yields, respectively .…”

In Silico Study on the Interactions, Molecular Docking, Dynamics and Simulation of Potential Compounds from Withania somnifera (L.) Dunal Root against Cancer by Targeting KAT6A

“…Taxonomical evidence states that W. somnifera is known to have a rich source of compound classes called withanolides. These classes of compounds are known to show diverse pharmacological effects, which include anti-inflammatory, hepatoprotective, antitumor, antimicrobial, anti-diabetic and immunosuppressive activities [ 19 , 20 , 21 ]. Studies have shown that withanolides from the roots of W. somnifera are known to have an inhibitory action on the transcription signal and signal transducer in human breast cells [ 22 ].…”