Dingwu Li, Jianing Chen, Chenhui Ye, Bingru Lin, Tiantian Zhang, Qingxia Chen, Chaohui Yu, Xingyong Wan
{"title":"Celastrol通过抑制Notch/骨桥蛋白信号通路改善西方饮食/四氯甲烷诱导的非酒精性脂肪性肝炎的纤维化。","authors":"Dingwu Li, Jianing Chen, Chenhui Ye, Bingru Lin, Tiantian Zhang, Qingxia Chen, Chaohui Yu, Xingyong Wan","doi":"10.1016/j.phymed.2025.156369","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Celastrol was recently identified as a potential treatment for obesity and hepatic steatosis. However, whether Celastrol effectively suppresses the nonalcoholic fatty liver disease (NAFLD) stage remains unknown. This study aimed to evaluate the role of Celastrol in the progression from simple steatosis to nonalcoholic steatohepatitis (NASH) and fibrosis.</p><p><strong>Methods: </strong>C57BL/6 mice were fed a Western diet combined with a weekly low-dose injection of CCl<sub>4</sub> (WD/CCl<sub>4</sub>) for 16 weeks to establish NASH models. The effects of Celastrol on NASH were further explored through histopathological assessments, immunoblotting, and in vitro analyses.</p><p><strong>Results: </strong>Celastrol treatment effectively attenuated hepatic steatosis and fibrosis in WD/CCl<sub>4</sub>-induced NASH models, in which Notch2 was downregulated by Celastrol in a posttranscriptional manner. In vitro experiments revealed that Notch2 suppression in Celastrol-treated hepatocytes further decreased osteopontin (OPN) levels, inhibiting hepatic stellate cells (HSCs) activation. Moreover, the protective effects of Celastrol on NASH progression were abolished in Notch2-overexpressing mice.</p><p><strong>Conclusion: </strong>This study demonstrated the protective effects of Celastrol on NASH-related liver fibrosis by modulating Notch/OPN signaling, providing fresh insights into the potential application of Celastrol in NASH treatment.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"137 ","pages":"156369"},"PeriodicalIF":6.7000,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Celastrol ameliorates fibrosis in Western diet/tetrachloromethane-induced nonalcoholic steatohepatitis by suppressing Notch/osteopontin signaling.\",\"authors\":\"Dingwu Li, Jianing Chen, Chenhui Ye, Bingru Lin, Tiantian Zhang, Qingxia Chen, Chaohui Yu, Xingyong Wan\",\"doi\":\"10.1016/j.phymed.2025.156369\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Celastrol was recently identified as a potential treatment for obesity and hepatic steatosis. However, whether Celastrol effectively suppresses the nonalcoholic fatty liver disease (NAFLD) stage remains unknown. This study aimed to evaluate the role of Celastrol in the progression from simple steatosis to nonalcoholic steatohepatitis (NASH) and fibrosis.</p><p><strong>Methods: </strong>C57BL/6 mice were fed a Western diet combined with a weekly low-dose injection of CCl<sub>4</sub> (WD/CCl<sub>4</sub>) for 16 weeks to establish NASH models. The effects of Celastrol on NASH were further explored through histopathological assessments, immunoblotting, and in vitro analyses.</p><p><strong>Results: </strong>Celastrol treatment effectively attenuated hepatic steatosis and fibrosis in WD/CCl<sub>4</sub>-induced NASH models, in which Notch2 was downregulated by Celastrol in a posttranscriptional manner. In vitro experiments revealed that Notch2 suppression in Celastrol-treated hepatocytes further decreased osteopontin (OPN) levels, inhibiting hepatic stellate cells (HSCs) activation. Moreover, the protective effects of Celastrol on NASH progression were abolished in Notch2-overexpressing mice.</p><p><strong>Conclusion: </strong>This study demonstrated the protective effects of Celastrol on NASH-related liver fibrosis by modulating Notch/OPN signaling, providing fresh insights into the potential application of Celastrol in NASH treatment.</p>\",\"PeriodicalId\":20212,\"journal\":{\"name\":\"Phytomedicine\",\"volume\":\"137 \",\"pages\":\"156369\"},\"PeriodicalIF\":6.7000,\"publicationDate\":\"2025-02-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Phytomedicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.phymed.2025.156369\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/6 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Phytomedicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.phymed.2025.156369","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/6 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
Celastrol ameliorates fibrosis in Western diet/tetrachloromethane-induced nonalcoholic steatohepatitis by suppressing Notch/osteopontin signaling.
Background: Celastrol was recently identified as a potential treatment for obesity and hepatic steatosis. However, whether Celastrol effectively suppresses the nonalcoholic fatty liver disease (NAFLD) stage remains unknown. This study aimed to evaluate the role of Celastrol in the progression from simple steatosis to nonalcoholic steatohepatitis (NASH) and fibrosis.
Methods: C57BL/6 mice were fed a Western diet combined with a weekly low-dose injection of CCl4 (WD/CCl4) for 16 weeks to establish NASH models. The effects of Celastrol on NASH were further explored through histopathological assessments, immunoblotting, and in vitro analyses.
Results: Celastrol treatment effectively attenuated hepatic steatosis and fibrosis in WD/CCl4-induced NASH models, in which Notch2 was downregulated by Celastrol in a posttranscriptional manner. In vitro experiments revealed that Notch2 suppression in Celastrol-treated hepatocytes further decreased osteopontin (OPN) levels, inhibiting hepatic stellate cells (HSCs) activation. Moreover, the protective effects of Celastrol on NASH progression were abolished in Notch2-overexpressing mice.
Conclusion: This study demonstrated the protective effects of Celastrol on NASH-related liver fibrosis by modulating Notch/OPN signaling, providing fresh insights into the potential application of Celastrol in NASH treatment.
期刊介绍：
Phytomedicine is a therapy-oriented journal that publishes innovative studies on the efficacy, safety, quality, and mechanisms of action of specified plant extracts, phytopharmaceuticals, and their isolated constituents. This includes clinical, pharmacological, pharmacokinetic, and toxicological studies of herbal medicinal products, preparations, and purified compounds with defined and consistent quality, ensuring reproducible pharmacological activity. Founded in 1994, Phytomedicine aims to focus and stimulate research in this field and establish internationally accepted scientific standards for pharmacological studies, proof of clinical efficacy, and safety of phytomedicines.
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