{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T06:10:05Z","timestamp":1754028605780,"version":"3.41.2"},"reference-count":60,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p><jats:italic>Isodon lophanthoides<\/jats:italic>, a core botanical drug in Yao ethnomedicine, has traditionally been used to treat jaundice-type hepatitis and cholecystitis. However, its therapeutic potential and mechanisms against liver fibrosis remain largely unexplored.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The metabolites of <jats:italic>I. lophanthoides<\/jats:italic> water extract (ILW) were characterized by ultra-performance liquid chromatography (UPLC) and UPLC coupled with quadrupole time-of-flight mass spectrometry (Q-TOF\/MS). A carbon tetrachloride (CCl<jats:sub>4<\/jats:sub>)-induced liver fibrosis mouse model was employed to evaluate the anti-fibrotic effects of ILW. An integrated multi-omics approach encompassing transcriptomics, proteomics, and metabolomics was used to elucidate the underlying mechanisms, further supported by Western blotting, targeted metabolite quantification, and enzyme-linked immunosorbent assay (ELISA).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Thirty-two metabolites were identified in ILW. Among them, the concentrations of caffeic acid, rosmarinic acid, schaftoside, and isoschaftoside were determined to be 1.10, 5.13, 0.12, and 0.18\u00a0mg\u00b7g<jats:sup>-1<\/jats:sup>, respectively. ILW treatment significantly reduced serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), procollagen type III (PC-III), collagen type IV (COL-IV), laminin (LN), and hyaluronic acid (HA) in liver fibrotic mice. Histopathological analyses showed that ILW significantly alleviated liver inflammation, collagen deposition, and fibrosis. Multi-omics analysis revealed that ILW\u2019s anti-fibrotic effects are linked to modulation of purine metabolism and inhibition of the nuclear factor kappa-B (NF-\u03baB) signaling pathway. High-dose ILW lowered hepatic levels of adenine, adenosine monophosphate (AMP), and inosine monophosphate (IMP), while increasing adenosine, hypoxanthine, and N<jats:sup>6<\/jats:sup>-methyladenosine (m6A). Furthermore, high-dose and medium-dose ILW downregulated key NF-\u03baB-related proteins, including toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), phosphorylated NF-\u03baB, transforming growth factor beta 1 (TGF-\u03b21), tumor necrosis factor-alpha (TNF-\u03b1), interleukin-6 (IL-6), and interleukin-1 beta (IL-1\u03b2).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>ILW exerts protective effects against liver fibrosis by attenuating inflammation, fibrosis, and liver damage through modulation metabolism modulation and NF-\u03baB pathway inhibition. These findings provide a scientific basis for the traditional use of <jats:italic>I. lophanthoides<\/jats:italic> in liver-related disorders.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphar.2025.1630927","type":"journal-article","created":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T05:33:19Z","timestamp":1754026399000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Isodon lophanthoides alleviates liver fibrosis via modulation of purine metabolism and NF-\u03baB signaling pathway: insights from multi-omics analysis"],"prefix":"10.3389","volume":"16","author":[{"given":"Kuikui","family":"Chen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Liang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong","family":"Tan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaohua","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaojiao","family":"Pan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhonghui","family":"Guo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wentao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zongxi","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,8,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"757","DOI":"10.3390\/nu17050757","article-title":"Isoschaftoside in fig leaf tea alleviates nonalcoholic fatty liver disease in mice via the regulation of macrophage polarity","volume":"17","author":"Abe","year":"2025","journal-title":"Nutrients"},{"key":"B2","doi-asserted-by":"publisher","first-page":"14","DOI":"10.5152\/tjg.2018.17330","article-title":"Liver fibrosis","volume":"29","author":"Ayd\u0131n","year":"2018","journal-title":"Turk J. 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