Jian'gan Xiaozhi Decoction Regulates PINK1/Parkin Pathway Mediated Mitochondrial Autophagy to Treat Non-alcoholic Fatty Liver Disease
10.16466/j.issn1005-5509.2024.08.002
- VernacularTitle:健肝消脂方调控PINK1/Parkin通路介导的线粒体自噬治疗非酒精性脂肪肝
- Author:
Jiabao LIAO
1
,
2
;
Yun SONG
;
Si WANG
Author Information
1. 嘉兴市中医医院 浙江,嘉兴 314000
2. 云南中医药大学
- Keywords:
Jiangan Xiaozhi Decoction;
non-alcoholic fatty liver disease;
PINK1/Parkin signaling pathway;
mitochondrial autophagy;
oxidative stress;
inflammation
- From:
Journal of Zhejiang Chinese Medical University
2024;48(8):905-914
- CountryChina
- Language:Chinese
-
Abstract:
[Objective]To investigate the therapeutic effect of Jian'gan Xiaozhi Decoction(JGXZ)on non-alcoholic fatty liver disease(NAFLD)model mice and explore its mechanism from the perspective of mitochondrial autophagy mediated by the PTEN induced putative kinase 1(PINK1)/E3 uniquitin-protein ligase(Parkin)signaling pathway.[Methods]Sixty C57BL/6J mice were randomly and equally divided into 6 groups:control,model(NAFLD),polyene phosphatidyl choline(PPC)group 180 mg/kg intragastric administration,and JGXZ low,medium and high dose groups(8,16,32 g/kg)intragastric administration.Except for control group,the other 5 groups were given a high fat diet.The treatment lasted for 8 weeks,and the body weight of the mice was recorded weekly.After 8 weeks,blood samples were collected,the levels of serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)were measured,liver tissue was weighted and fixed,and histological changes in liver tissue were observed by hematoxylin-eosin(HE)and oil red O staining.The levels of total cholesterol(TC),triglyceride(TG),interleukin-1 β(IL-1 β),IL-6,tumor necrosis factor-α(TNF-α),malondialdehyde(MDA)and activities of glutathione peroxidase(GSH-Px),superoxide dismutase(SOD)in liver tissue were measured to evaluate the effects of JGXZ on inflammation and oxidative stress in NAFLD mice.Western blot was used to detect the protein expression levels of voltage-dependent anion channel 1(VDAC1),translocase of outer mitochondrial membrane 20(TOM20),cytochrome c oxidase subunit Ⅳ(COX Ⅳ),phosphatase and PINK1,Parkin,Beclin1,microtubule-associated protein light chain 3(LC3),and P62 to evaluate the effects of JGXZ on mitochondrial autophagy in NAFLD mice.[Result]Compared with model group,JGXZ intervention significantly improved the body weight of NAFLD model mice,reduced liver index,alleviated liver tissue lesions in NAFLD model mice,reduced TC,TG,ALT,AST levels,decreased IL-1[3,IL-6,TNF-α and MDA levels,increased GSH-Px and SOD activity,down-regulated VDAC1,TOM20,COXⅣ and P62 protein expression,and up-regulated PINK1,Parkin,Beclin1,LC3 protein expression.[Conclusion]JGXZ can alleviate liver injury in NAFLD mice by promoting the PINK 1/Parkin signaling pathway mediated activation of mitochondrial autophagy.
