{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:40:22Z","timestamp":1791823222197,"version":"4.3.4"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T00:00:00Z","timestamp":1771804800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013078","name":"Natural Science Research Project of Guizhou Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013078","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005329","name":"Natural Science Foundation of Guizhou Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013055","name":"Guizhou Provincial Youth Science and Technology Talents Growth Project","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013055","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009619","name":"Science and Technology Bureau, Guiyang Municipal Government","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017957","name":"Health Commission of Guizhou Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100017957","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>The liver, as the central metabolic hub of the body, is highly susceptible to diet-induced injury. The increasing prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) highlights the urgent need for effective clinical interventions. Currently, there are no specific therapeutics for MASLD, and dietary patterns are closely associated with its pathogenesis, making the exploration of natural bioactive compounds a promising strategy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this study, we identified acetylshikonin (AS), a component derived from traditional Chinese medicine (TCM), as a core bioactive agent targeting MASLD via a cross-screening strategy of MASLD-related TCM formulas. Male mouse models of MASLD were induced by a high-fat and high-cholesterol (HFHC) diet or carbon tetrachloride (CCl4) and treated with AS (600 mg\/kg, gavage) for six consecutive weeks. In vitro experiments were conducted on Hepa1-6 and HCCLM3 hepatocytes stimulated with palmitic acid\/oleic acid (PA\/OA, 1:2). Integrated network pharmacology, molecular docking, and thermal shift assays were applied to explore the underlying mechanism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In vivo results showed that AS markedly attenuated hepatic steatosis (assessed by triglyceride and total cholesterol levels) and liver fibrosis (evaluated by collagen deposition). In vitro, AS suppressed intracellular lipid accumulation (validated by Oil Red O staining and lipid quantification) and inflammatory responses (assessed by pro-inflammatory cytokine expression) in the stimulated hepatocytes. Mechanistically, AS downregulated the transcriptional expression of key genes involved in lipid metabolism (Ppar\u03b3 and Srebp1c), inflammation (Tnf\u03b1 and Ccl2), and fibrosis (Col1a1 and Acta2) pathways. Integrated analyses confirmed peroxisome proliferator-activated receptor \u03b3 (PPAR\u03b3) as the core direct target of AS. Western blotting demonstrated that AS reduced PPAR\u03b3 protein expression, and its lipid-lowering effect was synergistically enhanced when combined with the PPAR\u03b3 antagonist GW9662.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>This is the first study to definitively confirm that AS exerts therapeutic effects on diet-induced MASLD by targeting the PPAR\u03b3 signaling pathway, thereby reducing hepatic lipid deposition, alleviating inflammation, and ameliorating liver fibrosis progression. Our findings provide novel experimental evidence supporting the use of natural products in MASLD treatment and lay a theoretical foundation for the application of AS in the health management of diet-related liver diseases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1735481","type":"journal-article","created":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T05:27:23Z","timestamp":1771824443000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Acetylshikonin mitigates diet-induced MASLD by targeting PPAR\u03b3-mediated metabolic dysfunction"],"prefix":"10.3389","volume":"17","author":[{"given":"Ling","family":"Ou","sequence":"first","affiliation":[{"name":"GuiZhou University Medical College","place":["Guiyang, Guizhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Endoscopy and Digestive System, Guizhou Provincial People\u2019s Hospital","place":["Guiyang, Guizhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayang","family":"Liu","sequence":"additional","affiliation":[{"name":"GuiZhou University Medical College","place":["Guiyang, Guizhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyan","family":"Tai","sequence":"additional","affiliation":[{"name":"GuiZhou University Medical College","place":["Guiyang, Guizhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinghan","family":"Chai","sequence":"additional","affiliation":[{"name":"GuiZhou University Medical College","place":["Guiyang, Guizhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqiong","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, The First People\u2019s Hospital of Yunnan Province","place":["Kunming, Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Li","sequence":"additional","affiliation":[{"name":"GuiZhou University Medical College","place":["Guiyang, Guizhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lirong","family":"Tan","sequence":"additional","affiliation":[{"name":"GuiZhou University Medical College","place":["Guiyang, Guizhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Cao","sequence":"additional","affiliation":[{"name":"GuiZhou University Medical College","place":["Guiyang, Guizhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Zhu","sequence":"additional","affiliation":[{"name":"GuiZhou University Medical College","place":["Guiyang, Guizhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1186\/1475-2875-13-190","article-title":"Screening and hit evaluation of a chemical library against blood-stage Plasmodium falciparum","volume":"13","author":"Avery","year":"2014","journal-title":"Malar. 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