Molecular Insights into the Inhibition of Lipid Accumulation in Hepatocytes by Unique Extracts of Ashwagandha – PubMed Black Hawk Supplements
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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…
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Molecular Insights into the Inhibition of Lipid Accumulation in Hepatocytes by Unique Extracts of Ashwagandha
Dongyang Li et al. Int J Mol Sci. .
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.
Keywords: Ashwagandha; CARF expression; lipogenesis; regulation; steatosis; stress; treatment; withanolides.
Conflict of interest statement
The authors declare no conflict of interest.
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References
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- Kaul S.C., Wadhwa R. Science of Ashwagandha: Preventive and Therapeutic Potentials. Springer; Cham, Switzerland: 2017.
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- Cavaleri F., Chattopadhyay S., Palsule V., Kar P.K., Chatterjee R. Study of Drug Targets Associated With Oncogenesis and Cancer Cell Survival and the Therapeutic Activity of Engineered Ashwagandha Extract Having Differential Withanolide Constitutions. Integr. Cancer Ther. 2024;23:15347354231223499. doi: 10.1177/15347354231223499. – DOI – PMC – PubMed
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Grants and funding
The study is supported by grants from AIST (Japan).
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