{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T03:01:53Z","timestamp":1781060513067,"version":"3.54.1"},"reference-count":66,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2024,11,14]],"date-time":"2024-11-14T00:00:00Z","timestamp":1731542400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"AIST (Japan)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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 (PPAR\u03b3 and PPAR\u03b1). 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.<\/jats:p>","DOI":"10.3390\/ijms252212256","type":"journal-article","created":{"date-parts":[[2024,11,14]],"date-time":"2024-11-14T10:47:53Z","timestamp":1731581273000},"page":"12256","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Molecular Insights into the Inhibition of Lipid Accumulation in Hepatocytes by Unique Extracts of Ashwagandha"],"prefix":"10.3390","volume":"25","author":[{"given":"Dongyang","family":"Li","sequence":"first","affiliation":[{"name":"AIST-INDIA DAILAB, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba 305-8565, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanlin","family":"Han","sequence":"additional","affiliation":[{"name":"AIST-INDIA DAILAB, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba 305-8565, Japan"},{"name":"Graduate School of Science and Technology, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8577, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixin","family":"Sun","sequence":"additional","affiliation":[{"name":"AIST-INDIA DAILAB, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba 305-8565, Japan"},{"name":"Graduate School of Science and Technology, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8577, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huayue","family":"Zhang","sequence":"additional","affiliation":[{"name":"AIST-INDIA DAILAB, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba 305-8565, Japan"},{"name":"Graduate School of Science and Technology, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8577, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren","family":"Yoshitomi","sequence":"additional","affiliation":[{"name":"AIST-INDIA DAILAB, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba 305-8565, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunil C.","family":"Kaul","sequence":"additional","affiliation":[{"name":"AIST-INDIA DAILAB, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba 305-8565, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8248-5192","authenticated-orcid":false,"given":"Renu","family":"Wadhwa","sequence":"additional","affiliation":[{"name":"AIST-INDIA DAILAB, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba 305-8565, Japan"},{"name":"Graduate School of Science and Technology, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8577, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1055\/a-2289-9600","article-title":"The Potential Pharmacological Effects of Natural Product Withaferin A in Cancer: Opportunities and Challenges for Clinical Translation","volume":"90","author":"Devabattula","year":"2024","journal-title":"Planta Med."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Kashyap, V.K., Peasah-Darkwah, G., Dhasmana, A., Jaggi, M., Yallapu, M.M., and Chauhan, S.C. 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