{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T17:15:27Z","timestamp":1779297327230,"version":"3.51.4"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Jiangsu Province Traditional Chinese Medicine Science and Technology Development Program","award":["MS2022007"],"award-info":[{"award-number":["MS2022007"]}]},{"name":"Jiangsu Province Traditional Chinese Medicine Science and Technology Development Program","award":["QN202303"],"award-info":[{"award-number":["QN202303"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Hepatotoxicity associated with Isoniazid (INH) and Rifampicin (RIF) is one of the major impediments in antituberculosis therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>We aimed to investigate the protective effects of the cornel iridoid glycoside (CIG) on liver injury caused by INH and RIF in vivo and in vitro.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Liver injury model was induced by INH and RIF (150\u00a0mg\/kg). Then the mice were orally administered with CIG (50, 100, and 200\u00a0mg\/kg) and silymarin (100\u00a0mg\/kg) for 2\u00a0weeks. HepG2 cells were treated with 0.1\u00a0mg\/ml INH and 0.2\u00a0mg\/ml RIF to establish injury model. Blood samples and cell lysis were used for biochemical analysis and western blot assay. Liver tissues were harvested for histological examination.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Treatment of CIG significantly restored liver function, reduced the levels of inflammatory factors, enhanced the antioxidant activity, and alleviated lipid metabolism disorder compared with the model group in vivo. CIG restored cell viability and activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) in vitro. Furthermore, CIG inhibited the protein expression of JAK\/STAT pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>CIG is effective in preventing INH and RIF-induced hepatotoxicity in vivo and in vitro. These findings provide scientific basis for the clinical application of cornel in treating liver injury.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jpp\/rgag047","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T11:42:01Z","timestamp":1777030921000},"source":"Crossref","is-referenced-by-count":0,"title":["Protective effect of cornel iridoid glycoside against isoniazid- and rifampicin- induced liver injury via regulating JAK\/STAT pathway"],"prefix":"10.1093","volume":"78","author":[{"given":"Jia","family":"Liu","sequence":"first","affiliation":[{"name":"School of Chinese Medicine, Nanjing University of Chinese Medicine , Nanjing 210023 ,","place":["PR China"]},{"name":"Department of Cardiology, Jingjiang Hospital of Traditional Chinese Medicine , Jingjiang 214504 ,","place":["PR China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao","family":"Han","sequence":"additional","affiliation":[{"name":"School of Chinese Medicine, Nanjing University of Chinese Medicine , Nanjing 210023 ,","place":["PR China"]},{"name":"Department of Pharmacy, Dongtai Hospital of Traditional Chinese Medicine , Dongtai 224299 ,","place":["PR China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yumei","family":"Li","sequence":"additional","affiliation":[{"name":"School of Chinese Medicine, Nanjing University of Chinese Medicine , Nanjing 210023 ,","place":["PR China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingfeng","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Beigang Street community health Service center, Zhonglou District , Changzhou 213023 ,","place":["PR China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aiwu","family":"Hang","sequence":"additional","affiliation":[{"name":"School of Chinese Medicine, Nanjing University of Chinese Medicine , Nanjing 210023 ,","place":["PR China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0530-9687","authenticated-orcid":false,"given":"Yanxia","family":"Ma","sequence":"additional","affiliation":[{"name":"School of Chinese Medicine, Nanjing University of Chinese Medicine , Nanjing 210023 ,","place":["PR China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinjun","family":"Shan","sequence":"additional","affiliation":[{"name":"Department of Chinese Medicine Processing, Medical Metabolomics Center, School of Pharmacy, Nanjing University of Chinese Medicine , Nanjing 210023 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fengming","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Medicine, Nanjing University of Chinese Medicine , Nanjing 210023 ,","place":["PR China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2026,5,20]]},"reference":[{"key":"2026052012515850900_ref1","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1002\/hep.32689","article-title":"AASLD practice guidance on drug, herbal, and dietary supplement-induced liver injury","volume":"77","author":"Fontana","year":"2023","journal-title":"Hepatology"},{"key":"2026052012515850900_ref2","doi-asserted-by":"crossref","first-page":"2230","DOI":"10.1053\/j.gastro.2019.02.002","article-title":"Incidence and Etiology of drug-induced liver injury in mainland China","volume":"156","author":"Shen","year":"2019","journal-title":"Gastroenterology."},{"key":"2026052012515850900_ref3","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1007\/s12664-024-01643-w","article-title":"Incidence and risk factors of antituberculosis drug-induced liver injury in India: a systematic review and meta-analysis","volume":"44","author":"Kumar","year":"2025","journal-title":"Indian J Gastroenterol"},{"key":"2026052012515850900_ref4","doi-asserted-by":"crossref","first-page":"40","DOI":"10.14218\/JCTH.2018.00052","article-title":"Mitochondrial damage and Drp1 overexpression in rifampicin- and isoniazid-induced liver injury cell model","volume":"7","author":"Li","year":"2019","journal-title":"J Clin Transl Hepatol"},{"key":"2026052012515850900_ref5","doi-asserted-by":"crossref","first-page":"115134","DOI":"10.1016\/j.taap.2020.115134","article-title":"Pyridoxal isonicotinoyl hydrazone inhibition of FXR is involved in the pathogenesis of isoniazid-induced liver injury","volume":"402","author":"Zhang","year":"2020","journal-title":"Toxicol Appl Pharmacol"},{"key":"2026052012515850900_ref6","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1038\/nm.3104","article-title":"Human PXR modulates hepatotoxicity associated with rifampicin and isoniazid co-therapy","volume":"19","author":"Li","year":"2013","journal-title":"Nat Med"},{"key":"2026052012515850900_ref7","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1016\/j.apsb.2016.07.014","article-title":"Isoniazid metabolism and hepatotoxicity","volume":"6","author":"Wang","year":"2016","journal-title":"Acta Pharm Sin B"},{"key":"2026052012515850900_ref8","doi-asserted-by":"crossref","first-page":"115709","DOI":"10.1016\/j.jpba.2023.115709","article-title":"The identification of key metabolites and mechanisms during isoniazid\/rifampicin-induced neurotoxicity and hepatotoxicity in a mouse model by HPLC-TOF\/MS-based untargeted urine metabolomics","volume":"236","author":"Song","year":"2023","journal-title":"J Pharm Biomed Anal"},{"key":"2026052012515850900_ref9","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1111\/j.1440-1746.2007.05207.x","article-title":"Antituberculosis drug-induced hepatotoxicity: concise up-to-date review","volume":"23","author":"Tostmann","year":"2008","journal-title":"J Gastroenterol Hepatol"},{"key":"2026052012515850900_ref10","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1186\/s12944-020-01231-9","article-title":"Phytochemical analysis and evaluation of hepatoprotective effect of Maytenus royleanus leaves extract against anti-tuberculosis drug induced liver injury in mice","volume":"19","author":"Shabbir","year":"2020","journal-title":"Lipids Health Dis"},{"key":"2026052012515850900_ref11","doi-asserted-by":"crossref","first-page":"633447","DOI":"10.3389\/fphar.2021.633447","article-title":"Active components and pharmacological effects of Cornus officinalis: literature review","volume":"12","author":"Gao","year":"2021","journal-title":"Front Pharmacol"},{"key":"2026052012515850900_ref12","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.brainresbull.2010.07.003","article-title":"Neuroprotective effect of morroniside on focal cerebral ischemia in rats","volume":"83","author":"Wang","year":"2010","journal-title":"Brain Res Bull"},{"key":"2026052012515850900_ref13","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1002\/ptr.5529","article-title":"The Hypoglycemic and synergistic effect of Loganin, Morroniside, and Ursolic acid isolated from the fruits of Cornus officinalis","volume":"30","author":"He","year":"2016","journal-title":"Phytother Res"},{"key":"2026052012515850900_ref14","doi-asserted-by":"crossref","DOI":"10.1016\/j.jff.2021.104488","article-title":"An iridoid glycoside from Cornus officinalis balances intestinal microbiome disorder and alleviates alcohol-induced liver injury","volume":"82","author":"Han","year":"2021","journal-title":"J Funct Foods"},{"key":"2026052012515850900_ref15","doi-asserted-by":"crossref","first-page":"2145843","DOI":"10.1080\/19490976.2022.2145843","article-title":"Lactobacillus johnsonii alleviates colitis by TLR1\/2-STAT3 mediated CD206(+) macrophages(IL-10) activation","volume":"14","author":"Jia","year":"2022","journal-title":"Gut Microbes"},{"key":"2026052012515850900_ref16","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.etap.2018.05.006","article-title":"Hepatoprotective effect of lawsone on rifampicin-isoniazid induced hepatotoxicity in in vitro and in vivo models","volume":"61","author":"Darvin","year":"2018","journal-title":"Environ Toxicol Pharmacol"},{"key":"2026052012515850900_ref17","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.jhep.2006.01.037","article-title":"Oxidative stress inhibits IFN-alpha-induced antiviral gene expression by blocking the JAK-STAT pathway","volume":"45","author":"Di Bona","year":"2006","journal-title":"J Hepatol"},{"key":"2026052012515850900_ref18","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1007\/s40265-017-0701-9","article-title":"JAK-STAT Signaling as a target for inflammatory and autoimmune diseases: current and future prospects","volume":"77","author":"Banerjee","year":"2017","journal-title":"Drugs."},{"key":"2026052012515850900_ref19","doi-asserted-by":"crossref","first-page":"1037814","DOI":"10.3389\/fphar.2022.1037814","article-title":"Mechanisms of isoniazid and rifampicin-induced liver injury and the effects of natural medicinal ingredients: a review","volume":"13","author":"Zhuang","year":"2022","journal-title":"Front Pharmacol"},{"key":"2026052012515850900_ref20","doi-asserted-by":"crossref","first-page":"e72058","DOI":"10.1371\/journal.pone.0072058","article-title":"Protective effects of metallothionein on isoniazid and rifampicin-induced hepatotoxicity in mice","volume":"8","author":"Lian","year":"2013","journal-title":"PLoS One"},{"key":"2026052012515850900_ref21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cld.2016.08.001","article-title":"Drug metabolism in the liver","volume":"21","author":"Almazroo","year":"2017","journal-title":"Clin Liver Dis"},{"key":"2026052012515850900_ref22","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1111\/j.1365-2958.2006.05467.x","article-title":"Mechanisms of action of isoniazid","volume":"62","author":"Timmins","year":"2006","journal-title":"Mol Microbiol"},{"key":"2026052012515850900_ref23","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1007\/s11095-010-0144-4","article-title":"Suppression of the inflammatory cascade is implicated in resveratrol chemoprevention of experimental hepatocarcinogenesis","volume":"27","author":"Bishayee","year":"2010","journal-title":"Pharm Res"},{"key":"2026052012515850900_ref24","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1002\/hep.32538","article-title":"Intestinal peroxisome proliferator-activated receptor \u03b1-fatty acid-binding protein 1 axis modulates nonalcoholic steatohepatitis","volume":"77","author":"Yan","year":"2023","journal-title":"Hepatology"},{"key":"2026052012515850900_ref25","doi-asserted-by":"crossref","first-page":"5424","DOI":"10.1016\/j.bmcl.2015.09.003","article-title":"Protective effects of the bioactive natural product N-trans-Caffeoyldopamine on hepatotoxicity induced by isoniazid and rifampicin","volume":"25","author":"Wu","year":"2015","journal-title":"Bioorg Med Chem Lett"},{"key":"2026052012515850900_ref26","doi-asserted-by":"crossref","first-page":"455","DOI":"10.4196\/kjpp.2012.16.6.455","article-title":"Protective effect of ECQ on rat reflux esophagitis model","volume":"16","author":"Jang","year":"2012","journal-title":"Korean J Physiol Pharmacol"},{"key":"2026052012515850900_ref27","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/s11010-013-1864-7","article-title":"Lack of liver injury in Wistar rats treated with the combination of isoniazid and rifampicin","volume":"387","author":"Metushi","year":"2014","journal-title":"Mol Cell Biochem"},{"key":"2026052012515850900_ref28","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1093\/toxsci\/kfw213","article-title":"Dual role of epidermal growth factor receptor in liver injury and regeneration after acetaminophen overdose in mice","volume":"155","author":"Bhushan","year":"2017","journal-title":"Toxicol Sci"},{"key":"2026052012515850900_ref29","doi-asserted-by":"crossref","first-page":"201","DOI":"10.5455\/jice.20140916011549","article-title":"Protective effect of cornel iridoid glycoside in D-galactosamine\/tumor necrosis factor-\u03b1-injured L02 hepatocytes and its mechanism","volume":"3","author":"Jiang","year":"2014","journal-title":"Journal of intercultural ethnopharmacology"},{"key":"2026052012515850900_ref30","doi-asserted-by":"crossref","first-page":"31185","DOI":"10.1074\/jbc.M110.107805","article-title":"Regulation of MRP2\/ABCC2 and BSEP\/ABCB11 expression in sandwich cultured human and rat hepatocytes exposed to inflammatory cytokines TNF-{alpha}, IL-6, and IL-1{beta}","volume":"285","author":"Diao","year":"2010","journal-title":"J Biol Chem"},{"key":"2026052012515850900_ref31","first-page":"4653","article-title":"Targeted anti-interleukin-6 monoclonal antibody therapy for cancer: a review of the rationale and clinical evidence","volume":"9","author":"Trikha","year":"2003","journal-title":"Clin Cancer Res"}],"container-title":["Journal of Pharmacy and Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jpp\/article-pdf\/78\/5\/rgag047\/68346770\/rgag047.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jpp\/article-pdf\/78\/5\/rgag047\/68346770\/rgag047.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T16:52:09Z","timestamp":1779295929000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jpp\/article\/doi\/10.1093\/jpp\/rgag047\/8688272"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5]]},"references-count":31,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5,2]]}},"URL":"https:\/\/doi.org\/10.1093\/jpp\/rgag047","relation":{},"ISSN":["2042-7158"],"issn-type":[{"value":"2042-7158","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,5]]},"published":{"date-parts":[[2026,5]]},"article-number":"rgag047"}}