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The development of ALD is largely driven by oxidative stress, inflammation, and apoptosis. Shikonin (SKN) is a natural extract possessing both antioxidant and anti\u2010inflammatory properties. This study investigated the protective effects of SKN against ALD in an in\u00a0vivo rat model of ALD induced by daily gavage with 52% alcohol for 6\u2009weeks. Following this, SKN was administered, and its antioxidant, anti\u2010inflammatory, and anti\u2010apoptotic properties were examined. Results demonstrated that SKN treatment inhibited the alcohol\u2010induced increase of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total cholesterol (TC), triglycerides (TG), lipopolysaccharide (LPS), reactive oxygen species (ROS), interleukin\u20101\u03b2 (IL\u20101\u03b2), tumor necrosis factor\u2010\u03b1 (TNF\u2010\u03b1), and interleukin\u20106 (IL\u20106) in serum and liver tissue, while enhancing the anti\u2010inflammatory factor IL\u201010. Moreover, SKN mitigated alcohol\u2010induced histological changes in liver tissues. In addition, the administration of SKN led to the restoration of hepatic superoxide dismutase (SOD) levels while reducing malondialdehyde (MDA) levels. Western blot revealed that SKN notably decreased Keap1 expression and elevated the expression of Nrf2 and HO\u20101 proteins, thereby enhancing the antioxidant capacity. In addition, SKN mitigated inflammation by inhibiting the TLR4\/MyD88\/NF\u2010\u03baB pathway. Furthermore, SKN administration inhibited the expression of Bax and Caspase3, while upregulating the anti\u2010apoptotic protein Bcl\u20102, thereby reducing hepatocyte injury through the inhibition of apoptosis. Overall, these results indicated that SKN could ameliorate ALD by mitigating oxidative stress, apoptosis, and inflammation, positioning it as a promising natural extract for preventing and treating ALD.<\/jats:p>","DOI":"10.1002\/fsn3.71064","type":"journal-article","created":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T05:04:33Z","timestamp":1759986273000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Shikonin Ameliorates Alcohol\u2010Associated Liver Disease by Reducing Oxidative Stress, Apoptosis, and Inflammation"],"prefix":"10.1002","volume":"13","author":[{"given":"Haining","family":"Gan","sequence":"first","affiliation":[{"name":"Guangdong Provincial Second Hospital of Traditional Chinese Medicine (Guangdong Provincial Engineering Technology Research Institute of Traditional Chinese Medicine)  Guangzhou China"},{"name":"Guangdong Provincial Key Laboratory of Research and Development in Traditional 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