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| Tripterygium wilfordii protects against an animal model of autoimmune hepatitis | |
Zhang,Ting; Rao,Qianru; Dai,Manyun; Zhao,Qi ; Li,Fei
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| 2023 | |
| Source Publication | JOURNAL OF ETHNOPHARMACOLOGY
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| ISSN | 1872-7573 |
| Volume | 309Pages:116365 |
| Abstract | Ethnopharmacological relevance: Tripterygium wilfordii tablets (TWT) is widely used to treat autoimmune diseases such as rheumatoid arthritis. Celastrol, one main active ingredient in TWT, has been shown to produce a variety of beneficial effects, including anti-inflammatory, anti-obesity, anti-cancer, and immunomodulatory. However, whether TWT could protect against Concanavalin A (Con A)-induced hepatitis remains unclear.The aim of the study: This study aims to investigate the protective effect of TWT against Con A-induced hepatitis and elucidate the underlying mechanism.Materials and methods: Metabolomic analysis, pathological analysis, biochemical analysis, qPCR and Western blot analysis and the Pxr-null mice were used in this study.Results: The results indicated that TWT and its active ingredient celastrol could protect against Con A-induced acute hepatitis. Plasma metabolomics analysis revealed that metabolic perturbations related to bile acid and fatty acid metabolism induced by Con A were reversed by celastrol. The level of itaconate in the liver was increased by celastrol and speculated as an active endogenous compound mediating the protective effect of celastrol. Administration of 4-octanyl itaconate (4-OI) as a cell-permeable itaconate mimicker was found to attenuate Con A-induced liver injury through activation of the pregnane X receptor (PXR) and enhancement of the transcription factor EB (TFEB)-mediated autophagy.Conclusions: Celastrol increased itaconate and 4-OI promoted activation of TFEB-mediated lysosomal autophagy to protect against Con A-induced liver injury in a PXR-dependent manner. Our study reported a protective effect of celastrol against Con A-induced AIH via an increased production of itaconate and upregulation of TFEB. The results highlighted that PXR and TFEB-mediated lysosomal autophagic pathway may offer promising therapeutic target for the treatment of autoimmune hepatitis. |
| Keyword | Tripterygium wilfordii tablets Celastrol Concanavalin A Autophagy TFEB PXR PREGNANE-X-RECEPTOR CHOLESTATIC LIVER-INJURY CELASTROL PROTECTS AUTOPHAGY OBESITY DYSFUNCTION DOMAIN |
| Subject Area | Plant Sciences ; Pharmacology & Pharmacy ; Integrative & Complementary Medicine |
| DOI | 10.1016/j.jep.2023.116365 |
| Indexed By | SCI |
| WOS ID | WOS:000956588000001 |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | http://ir.kib.ac.cn/handle/151853/75501 |
| Collection | 中国科学院昆明植物研究所 |
| Recommended Citation GB/T 7714 | Zhang,Ting,Rao,Qianru,Dai,Manyun,et al. Tripterygium wilfordii protects against an animal model of autoimmune hepatitis[J]. JOURNAL OF ETHNOPHARMACOLOGY,2023,309:116365. |
| APA | Zhang,Ting,Rao,Qianru,Dai,Manyun,Zhao,Qi,&Li,Fei.(2023).Tripterygium wilfordii protects against an animal model of autoimmune hepatitis.JOURNAL OF ETHNOPHARMACOLOGY,309,116365. |
| MLA | Zhang,Ting,et al."Tripterygium wilfordii protects against an animal model of autoimmune hepatitis".JOURNAL OF ETHNOPHARMACOLOGY 309(2023):116365. |
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| 1-s2.0-S037887412300（13950KB） | 期刊论文 | 出版稿 | 开放获取 | CC BY-NC-SA | View Download | |
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