{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:59:05Z","timestamp":1785437945907,"version":"3.56.0"},"reference-count":61,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100015308","name":"Science and Technology Department of Xinjiang Uyghur Autonomous Region","doi-asserted-by":"publisher","award":["No.2024TSYCQNTJ0039"],"award-info":[{"award-number":["No.2024TSYCQNTJ0039"]}],"id":[{"id":"10.13039\/501100015308","id-type":"DOI","asserted-by":"publisher"}]},{"award":["No.2024TSYCQNTJ0039"],"award-info":[{"award-number":["No.2024TSYCQNTJ0039"]}],"id":[{"id":"https:\/\/ror.org\/02vtvez67","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The global incidence of nonalcoholic fatty liver disease (NAFLD) is rising, with no approved pharmacotherapy available. Medicinal plants offer a potential preventive strategy. Anacyclus pyrethrum root exhibits anti-inflammatory and glucose-regulating properties, but its role in NAFLD prevention is unclear. This study aims to investigate the preventive effect of Anacyclus pyrethrum root ethanol extract (APE) against NAFLD and its underlying mechanisms. The chemical composition of APE was analyzed by UHPLC-HRMS. Network pharmacology predicted the potential signaling pathways underlying its protective effects against NAFLD. In a 12-week high-fat diet mice model, APE treatment led to measurements of blood glucose, lipid profiles, liver function parameters, histopathological changes in liver and colon, and gut microbiota alterations via 16S rDNA sequencing. In animal experiments, APE lowered fasting and random blood glucose, total cholesterol, triglycerides, LDL-C, AST, ALT, and serum lipopolysaccharide while increasing HDL-C, and alleviated hepatic steatosis. Network pharmacology suggested APE acts via TLR, NF-\u03baB, and TNF pathways. In vivo, APE suppressed hepatic TLR4, MyD88, p-NF-\u03baB p65, the p-NF-\u03baB p65\/NF-\u03baB p65 ratio, and TNF-\u03b1\/IL-6 levels. Gut microbiota analysis showed increased Akkermansiaceae and decreased Desulfovibrionaceae. APE also upregulated intestinal Occludin and ZO-1, and downregulated intestinal TNF-\u03b1 and IL-6. APE prevents NAFLD progression, potentially by regulating gut microbiota, protecting the intestinal mucosal barrier, and inhibiting the LPS\/TLR4\/MyD88\/NF-\u03baB pathway.<\/jats:p>","DOI":"10.3390\/ijms27104398","type":"journal-article","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T16:27:56Z","timestamp":1778776076000},"page":"4398","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated Network Pharmacology and Gut Microbiota Analysis Reveals the Alcoholic Extract of Anacyclus pyrethrum Root Prevents Nonalcoholic Fatty Liver Disease via the LPS\/TLR4\/NF-\u03baB Pathway"],"prefix":"10.3390","volume":"27","author":[{"given":"Hao","family":"Yang","sequence":"first","affiliation":[{"name":"School of Pharmacy, Xinjiang Medical University, Urumqi 830017, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Xinjiang Medical University, Urumqi 830017, China"},{"name":"Xinjiang Key Laboratory of Uyghur Medical Research, Xinjiang Institute of Materia Medica, Urumqi 830004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinle","family":"Tang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Xinjiang Medical University, Urumqi 830017, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1797","DOI":"10.1097\/HEP.0000000000000323","article-title":"AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease","volume":"77","author":"Rinella","year":"2023","journal-title":"Hepatology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"S32","DOI":"10.3350\/cmh.2022.0365","article-title":"Global incidence and prevalence of nonalcoholic fatty liver disease","volume":"29","author":"Teng","year":"2023","journal-title":"Clin. 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