{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T02:43:59Z","timestamp":1787971439193,"version":"build-2784847793"},"reference-count":43,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T00:00:00Z","timestamp":1690848000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81960767"],"award-info":[{"award-number":["81960767"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Basic Clin Pharma Tox"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In this study, we aimed to determine whether asiatic acid (AA) exerts any therapeutic effects on rifampicin (RFP)\u2010 and isoniazid (INH)\u2010induced liver injury and elucidate the underlying mechanisms. Briefly, liver injury in mice was induced via RFP and INH administration. We investigated the effects and potential action mechanisms of AA on liver injury using transcriptomics, metabolomics and various examinations. We found that AA significantly ameliorated the pathological changes in liver tissues and decreased the transaminase activity, inflammation and oxidative stress damage. Transcriptomics revealed 147 differentially expressed genes (DEGs) between the AA and model groups that were enriched in metabolic and mitogen\u2010activated protein kinase (<jats:italic>MAPK<\/jats:italic>) signalling pathways. Metabolomics revealed 778 differentially expressed metabolites between the AA and model groups. Furthermore, integrated transcriptomics and metabolomics analyses revealed strong correlations between DEGs and differentially expressed metabolites and indicated that AA regulates the sphingolipid metabolism by inhibiting the expression of delta 4\u2010desaturase, sphingolipid 1. Experimental results confirmed that AA inhibited the <jats:italic>MAPK<\/jats:italic> signalling pathway. In summary, AA inhibits inflammation and oxidative stress damage by regulating the sphingolipid metabolism pathway and blocking the <jats:italic>MAPK<\/jats:italic> signalling pathway, thereby relieving the RFP\/INH\u2010induced liver injury.<\/jats:p>","DOI":"10.1111\/bcpt.13909","type":"journal-article","created":{"date-parts":[[2023,6,6]],"date-time":"2023-06-06T21:03:29Z","timestamp":1686085409000},"page":"402-417","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Asiatic acid ameliorates rifampicin\u2010 and isoniazid\u2010induced liver injury in vivo by regulating sphingolipid metabolism and mitogen\u2010activated protein kinase signalling pathways"],"prefix":"10.1111","volume":"133","author":[{"given":"Wuchang","family":"Zhu","sequence":"first","affiliation":[{"name":"Pharmaceutical College Guangxi Medical University  Nanning China"},{"name":"Pharmacy Department The First Affiliated Hospital of Guangxi Medical 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