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SIRT1/IGFBPrP1/TGF β1 axis involved in cucurbitacin B ameliorating concanavalin A‐induced mice liver fibrosis
Author(s) -
Yang Li,
Ao Qinfang,
Zhong Qingmei,
Li Wen,
Li Wenhong
Publication year - 2020
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/bcpt.13446
Subject(s) - concanavalin a , fibrosis , sirtuin 1 , masson's trichrome stain , blot , transforming growth factor , resveratrol , endocrinology , staining , western blot , chemistry , medicine , biochemistry , downregulation and upregulation , pathology , in vitro , gene
The present study investigated the improving effect of cucurbitacin B on liver fibrosis induced by concanavalin A in mice and explored its possible mechanism. AST, ALT and TB were detected by kits. ELISA was performed to detect the levels of IL 5, IL 6, IL 13 and TNF‐α in serum. Haematoxylin‐eosin (HE) staining and Masson's trichrome staining were used to evaluate pathological changes. Western blotting was performed to observe expression levels of sirtuin (SIRT) 1, insulin‐like growth factor binding protein‐related protein 1 (IGFBPrP1) and TGF β1. The activity of SIRT 1 also was detected. Results showed that cucurbitacin B could effectively improve the abnormal liver function, inhibit liver fibrosis and suppress releases of inflammatory factors in mice induced by concanavalin A. Furthermore, cucurbitacin B could down‐regulate the expressions of TGF β1 and IGFBPrP1, increase the expression and activity of SIRT 1. Interestingly, when SIRT1 activity was inhibited by EX 527, a selective inhibitor of SIRT 1, the preventive effect of cucurbitacin B was significantly attenuated. Taken together, the above results showed that cucurbitacin B could significantly suppress releases of inflammatory cytokines and improve liver fibrosis induced by concanavalin A in mice, and those may be achieved through SIRT1/IGFBPrP1/TGF β1 axis.