{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T05:18:38Z","timestamp":1788153518749,"version":"build-2803163510"},"reference-count":27,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82274081"],"award-info":[{"award-number":["82274081"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["82274081"],"award-info":[{"award-number":["82274081"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Objectives: This study focuses on exploring the mechanism by which Schisandrin B (Sch B) regulates metabolic dysfunction-associated steatotic liver disease (MASLD) mice induced by a high-fat methionine\u2013choline-deficient (MCD) diet through the activation of peroxisome proliferator-activated receptor \u03b3 (PPAR\u03b3). Methods: Male C57BL\/6 mice were fed a high-fat MCD diet for 8 weeks to establish a mouse MASLD model, and the effects of Sch B on MASLD and the mechanisms were investigated. PPAR\u03b3 overexpression (OE) was induced by adeno-associated virus (AAV) administration via intrahepatic portal vein injection in mice, and a negative control (NC-OE) was also established. Body weight; wet liver weight; hepatic index; serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-\u03b1 (TNF-\u03b1), interleukin-6 (IL-6), and interleukin-1\u03b2 (IL-1\u03b2); and hepatic triglyceride (TG) levels were measured in the mice. The histopathology and lipid deposition were observed by hematoxylin and eosin (H&amp;E) staining and Oil Red O staining, while the fibrosis was assessed using Masson staining. Western blot was employed to detect the expression levels of PPAR\u03b3, sterol regulatory element-binding protein 1c (SREBP-1c), carnitine palmitoyltransferase 1A (CPT1A), transforming growth factor \u03b21 (TGF-\u03b21), \u03b1-smooth muscle actin (\u03b1-SMA), collagen type I (collagen I), Smad family members 2\/3 (Smad2\/3), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (p38), and extracellular signal-regulated kinase 1\/2 (ERK1\/2), along with the phosphorylation activation status of these kinases. Results: It was confirmed that Sch B caused effects similar to those induced by PPAR\u03b3 overexpression, reducing the hepatic index, AST, and ALT levels while alleviating lipid accumulation and fibrosis; and upregulating PPAR\u03b3 and CPT1A while inhibiting SREBP-1c; and the phosphorylation of the TGF-\u03b2\/Smad and MAPK pathways were involved in the mechanisms. Conclusions: Sch B can alleviate high-fat MCD-induced MASLD by activating PPAR\u03b3 in mice.<\/jats:p>","DOI":"10.3390\/ph19091367","type":"journal-article","created":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T18:33:52Z","timestamp":1787942032000},"page":"1367","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Schisandrin B Targets the PPAR\u03b3-MAPK Signaling Axis to Ameliorate High-Fat MCD Diet-Induced MASLD in Mice"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-1199-0775","authenticated-orcid":false,"given":"Xi-Yuan","family":"Feng","sequence":"first","affiliation":[{"name":"School of Pharmacy, Beihua University, Jilin 132013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Gao","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Beihua University, Jilin 132013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei-Long","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Beihua University, Jilin 132013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Ze","family":"Li","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Beihua University, Jilin 132013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Li","family":"Cui","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Beihua University, Jilin 132013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng-Yang","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Beihua University, Jilin 132013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi-Hong","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Beihua University, Jilin 132013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8750-6404","authenticated-orcid":false,"given":"He","family":"Li","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Beihua University, Jilin 132013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-Mei","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Beihua University, Jilin 132013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6417-0813","authenticated-orcid":false,"given":"Jing-Hui","family":"Sun","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Beihua University, Jilin 132013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1002\/hep.28431","article-title":"Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes","volume":"64","author":"Younossi","year":"2016","journal-title":"Hepatology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1016\/j.metabol.2015.12.012","article-title":"The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD)","volume":"65","author":"Buzzetti","year":"2016","journal-title":"Metabolism"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1038\/s41591-018-0104-9","article-title":"Mechanisms of NAFLD development and therapeutic strategies","volume":"24","author":"Friedman","year":"2018","journal-title":"Nat. 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