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Effect of Linggui Zhugan Decoction in regulating PINK1/Parkin pathway to improve mitophagy in the NASH mice
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DOI   10.11656/j.issn.1672-1519.2026.02.14
Key Words   Linggui Zhugan Decoction;non-alcoholic steatohepatitis;mitochondrial autophagy;oxidative stress;PINK1/Parkin pathway
Author NameAffiliationE-mail
WU Rui Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine, Cangzhou 061000, China  
SI Yuchen Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine, Cangzhou 061000, China  
WANG Rui Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine, Cangzhou 061000, China  
LI Yuling Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine, Cangzhou 061000, China  
XU Kai Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine, Cangzhou 061000, China  
FAN Lirong Botou Hospital of Traditional Chinese Medicine, Botou 062150, China  
TIAN Tian Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine, Cangzhou 061000, China  
LYU Shuquan Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine, Cangzhou 061000, China
SU Xiuhai National Famous Traditional Chinese Medicine Experts Inheritance Studio, Cangzhou 061000, China 
 
GUO Xuan Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine, Cangzhou 061000, China  
ZHANG Hui Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine, Cangzhou 061000, China zhanghui5428@163.com 
Abstract
    [Objective]To investigate the therapeutic effect of Linggui Zhugan Decoction (LGZG) on non-alcoholic steatohepatitis (NASH) model mice and its impact on the PINK1/Parkin signaling pathway.[Methods]A NASH mouse model was established using a methionine- and choline-deficient (MCD) diet, followed by intragastric administration of different doses of LGZG. The therapeutic effect of LGZG on NASH model mice was assessed by measuring body weight, liver index, serum ALT, AST, TG, and TC levels, as well as by performing hematoxylin-eosin (HE) staining and Oil Red O staining on frozen liver tissues. The liver's antioxidant capacity was evaluated by detecting levels of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), and reactive oxygen species (ROS). To explore the effect of LGZG on mitophagy, the protein levels of mitochondrial markers (TOM20, COXⅣ, VDAC1) and key proteins of the PINK1/Parkin pathway (PINK1, Parkin, LC3-Ⅱ, P62, Beclin1) were measured.[Results]LGZG significantly increased the body weight of NASH model mice; reduced the liver index; decreased serum ALT and AST activities; lowered TC and TG levels; and ameliorated pathological changes in the liver tissue of NASH model mice. These results indicate that LGZG has a therapeutic effect on NASH model mice. LGZG increased SOD and GSH-Px levels while decreasing MDA and ROS levels, suggesting enhanced hepatic antioxidant capacity. Furthermore, LGZG increased the protein levels of PINK1, Parkin, LC3-Ⅱ, and Beclin1, while decreasing the protein levels of TOM20, COXⅣ, VDAC1, and P62. This demonstrates that LGZG improved PINK1/Parkin-mediated mitophagy in NASH mice.[Conclusion]LGZG exhibits a therapeutic effect on NASH model mice and enhances hepatic antioxidant capacity. The underlying mechanism may be associated with the regulation of the PINK1/Parkin signaling pathway to improve mitophagy.

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