Molecular Insights into the Inhibition of Lipid Accumulation in Hepatocytes by Unique Extracts of Ashwagandha
Li D, Han H, Sun Y, Zhang H, Yoshitomi R, Kaul SC, Wadhwa R
International journal of molecular sciences · 2 citations
Review labels
Neutral facts our review recorded about how this study was done. They describe method, never whether we like the result.
How it was studied
- Design
- In vitro/mechanistic study (classified by our AI screen)
- Studied in
- Cells or lab samples
- Main outcome
- Mechanisms only
Who paid for it
- Funding
- Independent funding
- Government
- National Institute of Advanced Industrial Science and Technology
- Government
- AIST (Japan)
Based on 2 listed funder(s) and full-text disclosure statement.
Publication
- Published
- 2024-11-14 · Int J Mol Sci · vol. 25 · issue 22 · p. 12256
- Publisher
- Multidisciplinary Digital Publishing Institute
- Cited
- 3 citations · more than 74% of similar papers · 0.8× the field average
- References
- 67 works
- Access
- Open access (journal) · CC-BY
- Research areas
- Liver Disease Diagnosis and Treatment · Drug-Induced Hepatotoxicity and Protection · Phytochemicals and Medicinal Plants
- Keywords
- Withaferin A, Withanolide, Lipogenesis, Chemistry, Peroxisome, Steatosis, Biochemistry, Fatty acid synthase, Oxidative stress, Fatty acid, Nonalcoholic fatty liver disease, Fatty liver, Lipid metabolism, Peroxisome proliferator-activated receptor, Pharmacology, Withania somnifera, Biology, Receptor, Internal medicine, Endocrinology, Medicine
- MeSH
- hepatocytes, humans, withania, fatty acids, nonesterified, plant extracts, oxidative stress, lipogenesis, lipid metabolism, withanolides, hep g2 cells, non-alcoholic fatty liver disease
7 authors
From JP
- Dongyang LiNational Institute of Advanced Industrial Science and Technology
- Hanlin HanUniversity of Tsukuba; National Institute of Advanced Industrial Science and Technology
- Yixin SunUniversity of Tsukuba; National Institute of Advanced Industrial Science and Technology
- Huayue ZhangUniversity of Tsukuba; National Institute of Advanced Industrial Science and Technology
- Ren YoshitomiNational Institute of Advanced Industrial Science and Technology
- Sunil C. KaulNational Institute of Advanced Industrial Science and Technology
Abstract
We investigated the effect of purified withanolides and extracts derived from Ashwagandha on steatosis, the abnormal accumulation of fat that can lead to non-alcoholic fatty liver disease (NAFLD). Collaborator of ARF (CARF, also known as CDKN2AIP, a protein that regulates hepatic lipid metabolism, fat buildup, and liver damage) was used as an indicator. Six withanolides (Withaferin A, Withanone, Withanolide B, Withanoside IV, Withanoside V, and Withanostraminolide-12 deoxy) reversed the decrease in CARF caused by exposure to free fatty acids (FFAs) in liver-derived cells (HepG2 hepatocytes). After analyzing the effects of these withanolides on CARF mRNA and protein levels, FFA accumulation, protein aggregation, and oxidative and DNA damage stresses, we selected Withaferin A and Withanone for molecular analyses. Using the palmitic-acid-induced fatty acid accumulation stress model in Huh7 cells, we found a significant reduction in the activity of the key regulators of lipogenesis pathways, including sterol regulatory element-binding protein-1c (SREBP-1c), fatty acid synthase (FASN), and peroxisome proliferator-activated receptors (PPARγ and PPARα). This in vitro study suggests that low, non-toxic doses of Withaferin A, Withanone, or Ashwagandha extracts containing these withanolides possess anti-steatosis and antioxidative-stress properties. Further in vivo and clinical studies are required to investigate the therapeutic potential of these Ashwagandha-derived bioactive ingredients for NAFLD.
Abstract via Europe PMC. Copyright remains with the authors or publisher (CC BY).
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