{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T12:33:43Z","timestamp":1768912423343,"version":"3.49.0"},"reference-count":45,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T00:00:00Z","timestamp":1757980800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003819","name":"Natural Science Foundation of Hubei Province","doi-asserted-by":"publisher","award":["2024AFD221"],"award-info":[{"award-number":["2024AFD221"]}],"id":[{"id":"10.13039\/501100003819","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytotherapy Research"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>\n<jats:styled-content style=\"fixed-case\">\n<jats:italic>Foeniculum vulgare<\/jats:italic>\n<\/jats:styled-content> root bark (FVRB), a traditional ethnomedicine, demonstrates hepatoprotective properties and has been clinically employed in managing liver fibrosis. As volatile oils represent principal bioactive constituents of FVRB, the therapeutic potential of <jats:styled-content style=\"fixed-case\">\n<jats:italic>F. vulgare<\/jats:italic>\n<\/jats:styled-content> root bark volatile oil (FVRBO) against liver fibrosis remains unelucidated. This study investigates the antifibrotic mechanisms of FVRBO through integrated in\u00a0vitro and in\u00a0vivo approaches. The FVRBO was extracted using the steam distillation method, and the content of its main components was determined by gas chromatography. Liver fibrosis models were established using CCl<jats:sub>4<\/jats:sub>\u2010induced mice and TGF\u2010\u03b21\u2010induced JS\u20101 cells. Antifibrotic efficacy was validated through significant downregulation of fibrotic markers and inflammatory cytokines. Integrated transcriptomic and metabolomic analyses revealed FVRBO's mechanism. The principal constituents of FVRBO were quantified as dillapiole, apiole, and myristicin, with the extraction method demonstrating consistent stability. In\u00a0vivo, FVRBO significantly attenuated CCl<jats:sub>4<\/jats:sub>\u2010induced liver injury in mice, as evidenced by decreased liver and spleen indices, reduced serum ALT and AST levels, attenuated inflammatory infiltration, and suppressed collagen deposition in hepatic tissue. In\u00a0vitro, FVRBO effectively inhibited TGF\u2010\u03b2\u2010induced JS\u20101 cell activation and downregulated fibrotic markers at mRNA and protein levels. Integrated transcriptomic\u2010metabolomic analysis revealed FVRBO exerts antifibrotic efficacy by regulating the glycolysis pathway and suppressing the expression of HK2, PKM2, and LDHA. FVRBO exerts antifibrotic effects by modulating the glycolytic pathway and its associated gene expression. This study provides mechanistic evidence for FVRBO as a phytopharmaceutical candidate and establishes a foundation for developing natural\u2010product\u2010based anti\u2010fibrotic therapeutics.<\/jats:p>","DOI":"10.1002\/ptr.70050","type":"journal-article","created":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T15:30:27Z","timestamp":1758036627000},"page":"4934-4949","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Investigating the Antifibrotic Action of <scp><i>Foeniculum vulgare<\/i><\/scp> Root Bark Volatile Oil Through the HK2\/PKM2\/LDHA Pathway"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-8296-9764","authenticated-orcid":false,"given":"Kehong","family":"Ming","sequence":"first","affiliation":[{"name":"Hubei Provincial Engineering Technology Research Center for Chinese Medicine Processing, School of Pharmacy Hubei University of Chinese Medicine  Wuhan 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