Effects of paeoniflorin on inflammation and fibrosis in db/db mice via regulating NLRP3 inflammasome pathway

Acta Universitatis Medicinalis Anhui 2022 11 v.57 1687-1693     font:big middle small

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Authors:Wang Anli; Zhu Qijin; Wu Yonggui; Xia Lingling

Keywords:paeoniflorin;diabetic liver injury;inflammation;fibrosis;NLRP3 signaling pathway

DOI:10.19405/j.cnki.issn1000-1492.2022.11.002

〔Abstract〕 Objective To investigate the effect of paeoniflorin(PF) on liver injury mediated by NLRP3 inflammasome pathway in db/db mice. Methods In this study, db/db mice were used as the mice model of type 2 diabetic while db/m mice were used as control group. The mice were randomly divided into six groups: db/m group,db/m+ PF group,db/db group,db/db + PF 25 mg/kg group,db/db + PF 50 mg/kg group,db/db + PF 100 mg/kg group. After 12 weeks of PF gavage,mouse serum samples were collected to detect the levels of alanine aminotransferase( ALT),aspartate aminotransferase( AST),total cholesterol( TC),triglyceride( TG) and free fat acid( FFA).HE staining,oil red O staining and Sirius red staining were used to observe the degree of pathological injury of liver. The expression of F4/80,α-SMA and Col Ⅲ protein was detected by immunohistochemistry. The expression of interleukin-1β( IL-1β), interleukin-18( IL-18), tumor necrosis factor-α( TNF-α), NOD-like receptor 3( NLRP3),apotpsis associated spck-like protein( ASC) and cysteinyl asparate specific proteinase-1( Caspase-1)was detected by Western blot. Results Compared with db/m group,the levels of serum ALT,AST,TC,TG and FFA increased in db/db group,and these indexes decreased after PF gavage. Compared with db/m group,histopathological examination of the liver revealed increased hepatic tissue lipid accumulation,inflammatory cell infiltration,and collagen deposition in db/db mice,and PF treatment reduced hepatic lipid accumulation,inflammatory cell infiltration,and collagen deposition. Meanwhile,compared with db/m group,the expression of proinflammatory cytokines( IL-1β,IL-18 and TNF-α),F4/80,α-SMA,Col Ⅲ,NLRP3,ASC and Caspase-1 protein in the liver of db/db mice increased,and the expression of these proteins decreased after gavage with PF. Conclusion PF inhibited the NLRP3 inflammatory pathway and attenuated liver inflammation and fibrosis in db/db mice.