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J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Non-alcoholic fatty liver disease (NAFLD) is a prevalent metabolic disorder that can progress to non-alcoholic steatohepatitis (NASH), in which lipotoxicity, oxidative stress, apoptosis, and impaired autophagy contribute to liver injury. 14-Deoxy-11,12-didehydroandrographolide (deAND), a bioactive diterpenoid from Andrographis paniculata, has shown anti-inflammatory and antioxidant activities, but its role in NASH-associated lipotoxicity remains unclear. This study investigated the protective effects and underlying mechanisms of deAND using palmitic acid (PA)-treated AML12 hepatocytes and a choline-deficient, L-amino acid-defined, high-fat-diet (CDAHFD)-induced mouse model of NASH. In AML12 cells, PA impaired autophagic flux and reduced the expression of the mitophagy-associated proteins PINK1 and Parkin and increased p62, LC3-II, reactive oxygen species production, and apoptotic signaling. deAND treatment restored autophagic flux and increased PINK1 and Parkin expression, enhanced antioxidant defense-related proteins, including HO-1, GCLM, and GPX2, and reduced oxidative stress and apoptosis. The protective effects of deAND were attenuated by autophagy inhibitors, supporting the involvement of autophagy regulation. In CDAHFD-fed mice, deAND reduced hepatic steatosis, inflammation, fibrosis, apoptosis, and autophagy dysregulation. These findings suggest that deAND alleviates lipotoxic liver injury by restoring autophagic homeostasis and reducing oxidative stress.<\/jats:p>","DOI":"10.3390\/ijms27177567","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T13:20:43Z","timestamp":1787577643000},"page":"7567","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["14-Deoxy-11,12-didehydroandrographolide Attenuates Lipotoxicity and Non-Alcoholic Steatohepatitis Through Restoration of Autophagy and Reduction in Oxidative Stress"],"prefix":"10.3390","volume":"27","author":[{"given":"Chia-Wen","family":"Lo","sequence":"first","affiliation":[{"name":"Department of Nutrition, College of Medical and Health Care, Hungkuang University, Taichung 433, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yen-Chih","family":"Chen","sequence":"additional","affiliation":[{"name":"Sports Medicine Division, Department of Orthopedics, Kuang Tien General Hospital, Taichung 433, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai-Li","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Chung Shan Medical University, Taichung 402, Taiwan"},{"name":"Department of Nutrition, Chung Shan Medical University Hospital, Taichung 402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chien-Chun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Chung Shan Medical University, Taichung 402, Taiwan"},{"name":"Department of Nutrition, Chung Shan Medical University Hospital, Taichung 402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chong-Kuei","family":"Lii","sequence":"additional","affiliation":[{"name":"Department of Nutrition, China Medical University, Taichung 406, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsin-Hua","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Nutrition, China Medical University, Taichung 406, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Chieh","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Sports Medicine, China Medical University, Taichung 406, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-Chen","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Health and Nutrition Biotechnology, Asia University, Taichung 413, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7611-5515","authenticated-orcid":false,"given":"Haw-Wen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Nutrition, China Medical University, Taichung 406, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Nassir, F. 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