Huazhuo Jiedu Prescription Treats Ulcerative Colitis by Inhibiting Excessive Mitophagy via PINK1/Parkin Signaling Pathway
10.13422/j.cnki.syfjx.20242238
- VernacularTitle:基于PINK1/Parkin信号通路介导线粒体自噬探讨化浊解毒方治疗溃疡性结肠炎的作用机制
- Author:
Haofeng ZHANG
1
;
Jinye ZHOU
1
;
Ziwei LIU
1
;
Yican WANG
1
;
Yirui CHENG
1
;
Zheng ZHI
2
;
Qian YANG
2
;
Bolin LI
2
Author Information
1. Hebei University of Chinese Medicine， Shijiazhuang 050091， China
2. Hebei Provincial Hospital of Traditional Chinese Medicine， Shijiazhuang 050011， China
- Publication Type:Journal Article
- Keywords:
Huazhuo Jiedu prescription;
ulcerative colitis;
mitophagy;
PTEN-induced putative kinase 1 （PINK1）;
Parkin protein
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2025;31(11):182-189
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the mechanism of Huazhuo Jiedu prescription in treating ulcerative colitis （UC） by regulating mitophagy. MethodsThe genes related to mitophagy and UC were retrieved from GeneCards， and then the common genes of mitophagy and UC were analyzed by metascape to identify the genes related to mitophagy in UC. Animal experiments were carried out to decipher the mechanism by which Huazhuo Jiedu prescription treated UC by regulating mitophagy. Sixty C57BL/6 male mice were randomized into normal， model， high-， medium-， and low-dose （50， 25， 12.5 g·kg-1， respectively） Huazhuo Jiedu prescription， and mesalazine （0.52 g·kg-1·d-1） groups， with 10 mice in each group. After successful modeling by the dextran sulfate sodium-free drinking method， the colonic mucosal damage was observed by hematoxylin-eosin staining， and the ultracellular structure of colon mucosa was observed by transmission electron microscopy. The expression levels of mitophagy-related proteins PTEN-induced putative kinase 1 （PINK1） and Parkin protein were determined by Western blot. The expression of prohibitin 2 （PHB2）， ubiquitin-specific protease 15 （USP15）， ubiquitin-specific protease 30 （USP30） in the colon tissue was detected by immunofluorescence （IF）. ResultsAll the drug intervention groups showed ameliorated pathological manifestations of the colonic mucosa and improved mitochondrial structures in UC mice. Compared with the normal group， the model group demonstrated up-regulated protein levels of PINK1 and Parkin （P<0.05）， enhanced average fluorescence intensity of PHB2 （P<0.05）， and weakened average fluorescence intensity of USP15 and USP30 （P<0.05）. Compared with the model group， the mesalazine group and the high- and medium-dose Huazhuo Jiedu prescription groups showcased down-regulated protein levels of PINK1 and Parkin （P<0.05）， decreased average fluorescence intensity of PHB2 （P<0.05）， and enhanced average fluorescence intensity of USP15 and USP30 （P<0.05）. The low-dose Huazhuo Jiedu prescription group showed down-regulated protein levels of PINK1 and Parkin （P<0.05）， weakened average fluorescence intensity of PHB2 （P<0.05）， and enhanced average fluorescence intensity of USP15 and USP30 （P<0.05）. ConclusionHuazhuo Jiedu prescription can attenuate the intestinal mucosal injury and improve the mitochondrial cell ultrastructure in UC mice by regulating the expression of PINK1-Parkin pathway and inhibiting excessive mitophagy.
