Traditional Chinese medicine Pien-Tze-Huang ameliorates LPS-induced sepsis through bile acid-mediated activation of TGR5-STAT3-A20 signalling
10.1016/j.jpha.2023.12.005
- Author:
Li BEI
1
;
Zhang YONG
;
Liu XINYUAN
;
Zhang ZIYANG
;
Zhuang SHUQING
;
Zhong XIAOLI
;
Chen WENBO
;
Hong YILIN
;
Mo PINGLI
;
Lin SHUHAI
;
Wang SHICONG
;
Yu CHUNDONG
Author Information
1. State Key Laboratory of Cellular Stress Biology,School of Life Sciences,Xiamen University,Xiamen,361102,China
- Keywords:
Pien Tze Huang;
Bile acids;
Sepsis;
Inflammation;
TGR5;
STAT3-A20 signalling
- From:
Journal of Pharmaceutical Analysis
2024;14(4):601-614
- CountryChina
- Language:Chinese
-
Abstract:
Pien Tze Huang(PZH),a class-1 nationally protected traditional Chinese medicine(TCM),has been used to treat liver diseases such as hepatitis;however,the effect of PZH on the progression of sepsis is un-known.Here,we reported that PZH attenuated lipopolysaccharide(LPS)-induced sepsis in mice and reduced LPS-induced production of proinflammatory cytokines in macrophages by inhibiting the acti-vation of mitogen-activated protein kinase(MAPK)and nuclear factor-kappa B(NF-κB)signalling.Mechanistically,PZH stimulated signal transducer and activator of transcription 3(STAT3)phosphory-lation to induce the expression of A20,which could inhibit the activation of NF-κB and MAPK signalling.Knockdown of the bile acid(BA)receptor G protein-coupled bile acid receptor 1(TGR5)in macrophages abolished the effects of PZH on STAT3 phosphorylation and A20 induction,as well as the LPS-induced inflammatory response,suggesting that BAs in PZH may mediate its anti-inflammatory effects by acti-vating TGR5.Consistently,deprivation of BAs in PZH by cholestyramine resin reduced the effects of PZH on the expression of phosphorylated-STAT3 and A20,the activation of NF-κB and MAPK signalling,and the production of proinflammatory cytokines,whereas the addition of BAs to cholestyramine resin-treated PZH partially restored the inhibitory effects on the production of proinflammatory cytokines.Overall,our study identifies BAs as the effective components in PZH that activate TGR5-STAT3-A20 signalling to ameliorate LPS-induced sepsis.
