Total alkaloids of Cocculus orbiculatus attenuate ulcerative colitis in mice via PINK1/parkin mitophagy pathway
10.3969/j.issn.1000-4718.2025.10.015
- VernacularTitle:大风藤总生物碱通过PINK1/parkin线粒体自噬通路减轻小鼠溃疡性结肠炎
- Author:
Qiling JIANG
1
;
Yanfei XU
;
Sha YANG
;
Pengrui ZHANG
;
Qiannan DONG
;
Hao WU
;
Xiao KANG
Author Information
1. 湖北恩施学院医学部,湖北 恩施 445000
- Publication Type:Journal Article
- Keywords:
total alkaloids of Cocculus orbiculatus;
ulcerative colitis;
mitophagy;
PINK1/parkin pathway
- From:
Chinese Journal of Pathophysiology
2025;41(10):2001-2008
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To investigate whether total alkaloids of Cocculus orbiculatus(COTA)attenuate ulcerative colitis(UC)in mice via PINK1/parkin mitophagy pathway.METHODS:Sixty C57BL/6 mice were randomly divided into normal control group,model group,positive drug mesalazine group,and low-,medium-and high-dose(0.162,0.324 and 0.486 g/kg)COTA groups,with 10 mice in each group.Except for normal control group,the mice in all groups were given free access to 3%dextran sulfate sodium(DSS)solution for 7 consecutive days to establish a UC model in mice,and were then treated with COTA or mesalazine via oral gavage.The general condition of the mice was observed,and the colon length and disease activity index(DAI)score were determined.Colon histopathological damage was observed by HE staining.The serum levels of interleukin-1β(IL-1β),IL-6 and tumor necrosis factor-α(TNF-α)were detected by ELISA.The pro-tein levels of PINK1,parkin,microtubule-associated protein 1 light chain 3(LC3),P62 and beclin-1 in colon tissues were determined by Western blot.The protein expression of LC3 and parkin was detected by immunofluorescence.RE-SULTS:Compared with normal control group,the mice in model group showed varying degrees of soft stools or bloody stools,decreased body weight(P<0.05),increased DAI score,shortened colon length(P<0.05),and obvious pathologi-cal damage in the colon tissue.The serum levels of IL-1β,IL-6 and TNF-α were elevated(P<0.05).The protein levels of parkin,PINK1,LC3-II and beclin-1 were significantly decreased(P<0.05),while P62 protein expression was in-creased(P<0.05).Immunofluorescence showed a small number of autophagosomes in the colon tissue.In contrast,com-pared with model group,the mice in total alkaloids of Cocculus orbiculatus groups exhibited increased body weight(P<0.05),decreased DAI score,increased colon length(P<0.05),and reduced levels of IL-1β,IL-6 and TNF-α(P<0.05).The protein levels of parkin,PINK1,LC3 and beclin-1 were elevated(P<0.05),while P62 expression was re-duced(P<0.05),with numerous autophagosomes visible in the colon tissue via immunofluorescence.CONCLUSION:Total alkaloids of Cocculus orbiculatus can enhance the expression of mitophagy-related proteins PINK1,parkin,LC3 and beclin-1,activate mitophagy,and reduce the expression of inflammatory factors,thereby attenuating the inflammatory re-sponse in the colon mucosa of DSS-induced UC mice.
