{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T17:26:24Z","timestamp":1784913984889,"version":"3.55.0"},"reference-count":38,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2022,12,20]],"date-time":"2022-12-20T00:00:00Z","timestamp":1671494400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100012176","name":"Project 211","doi-asserted-by":"publisher","award":["CPU2022QZ20"],"award-info":[{"award-number":["CPU2022QZ20"]}],"id":[{"id":"10.13039\/501100012176","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["2632021ZD03"],"award-info":[{"award-number":["2632021ZD03"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81872899"],"award-info":[{"award-number":["81872899"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81903625"],"award-info":[{"award-number":["81903625"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81903626"],"award-info":[{"award-number":["81903626"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20190563"],"award-info":[{"award-number":["BK20190563"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:sec><jats:title>Background and purpose<\/jats:title><jats:p>Liver fibrosis is a critical risk factor for the progression from chronic liver injury to hepatocellular carcinoma. Clinically, there is a lack of therapeutic drugs for liver fibrosis. Previous studies have confirmed that GL\u2010V9, a newly synthesized flavonoid derivative, exhibits anti\u2010inflammatory activity, but whether it has anti\u2010hepatic fibrosis actions remains unclear. This study aimed to investigate the anti\u2010fibrotic activities and potential mechanisms of GL\u2010V9.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental approach<\/jats:title><jats:p>Bile duct ligation (BDL) and carbon tetrachloride (CCl<jats:sub>4<\/jats:sub>) challenges were used to assess the anti\u2010fibrotic effects of GL\u2010V9 in vivo. Mouse primary hepatic stellate cells (pHSCs) and the human HSC line LX2 also served as a liver fibrosis model in vitro. Cellular functions and molecular mechanism were analysed using senescence\u2010associated beta\u2010galactosidase staining, real\u2010time PCR, western blotting, immunofluorescence, and co\u2010immunoprecipitation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key results<\/jats:title><jats:p>GL\u2010V9 attenuated hepatic histopathological injury and collagen accumulation, as well as decreasing the expression of fibrotic genes in vivo. GL\u2010V9 promoted senescence and inhibited the expression of fibrogenic genes in HSCs in vitro. Mechanistic studies revealed that GL\u2010V9 induced senescence by upregulating GATA4 expression in HSCs. Further studies confirmed that GL\u2010V9 stabilized GATA4 by promoting autophagic degradation of P62.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and implications<\/jats:title><jats:p>GL\u2010V9 exerted potent anti\u2010fibrotic effects both in vivo and in vitro by stabilizing GATA4, thereby promoting the senescence of HSCs, and by avoiding its activation and ultimately inhibiting liver fibrosis. This action indicated that the flavonoid GL\u2010V9 is a potential therapeutic candidate for the treatment of liver fibrosis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.15997","type":"journal-article","created":{"date-parts":[[2022,12,2]],"date-time":"2022-12-02T01:42:33Z","timestamp":1669945353000},"page":"1072-1089","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["The flavonoid GL\u2010V9 alleviates liver fibrosis by triggering senescence by regulating the transcription factor GATA4 in activated hepatic stellate cells"],"prefix":"10.1111","volume":"180","author":[{"given":"Jiawei","family":"Zhao","sequence":"first","affiliation":[{"name":"State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Department of Physiology, School of Basic Medicine and Clinical Pharmacy China Pharmaceutical University  24 Tongjiaxiang Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongsheng","family":"Bai","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Department of Physiology, School of Basic Medicine and Clinical Pharmacy China Pharmaceutical University  24 Tongjiaxiang Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Qi","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Department of Physiology, School of Basic Medicine and Clinical Pharmacy China Pharmaceutical University  24 Tongjiaxiang Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wangjia","family":"Cao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Department of Physiology, School of Basic Medicine and Clinical Pharmacy China Pharmaceutical University  24 Tongjiaxiang Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaying","family":"Du","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Department of Physiology, School of Basic Medicine and Clinical Pharmacy China Pharmaceutical University  24 Tongjiaxiang Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyang","family":"Gu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Department of Physiology, School of Basic Medicine and Clinical Pharmacy China Pharmaceutical University  24 Tongjiaxiang Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Zhou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Department of Physiology, School of Basic Medicine and Clinical Pharmacy China Pharmaceutical University  24 Tongjiaxiang Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Gao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Department of Physiology, School of Basic Medicine and Clinical Pharmacy China Pharmaceutical University  24 Tongjiaxiang Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lulu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, School of Pharmacy Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Zhao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Department of Physiology, School of Basic Medicine and Clinical Pharmacy China Pharmaceutical University  24 Tongjiaxiang Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4981-5281","authenticated-orcid":false,"given":"Na","family":"Lu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Department of Physiology, School of Basic Medicine and Clinical Pharmacy China Pharmaceutical University  24 Tongjiaxiang Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,12,20]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15541"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15537"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14112"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2021.1997051"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29275"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI24282"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.343129.120"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14153"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27005"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-018-1642-9"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00013.2007"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09295-7"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature16187"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.05.015"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510260503"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2018.02.001"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2017.05.007"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2008.10.020"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2019.09.028"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2015.1121361"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa5612"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-020-00372-7"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.3181\/0707-MR-190"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.06.049"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2011.08.054"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15178"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.4161\/auto.27163"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14768"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.05.039"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2015.017"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000410"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9040875"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.07.030"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1663"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2015.02.039"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2017.38"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2017.1375640"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules25215033"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.15997","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bph.15997","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.15997","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T19:35:27Z","timestamp":1692732927000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bph.15997"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,20]]},"references-count":38,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2023,4]]}},"alternative-id":["10.1111\/bph.15997"],"URL":"https:\/\/doi.org\/10.1111\/bph.15997","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,20]]},"assertion":[{"value":"2022-05-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-11-23","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-12-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}