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| Jiangan Jiangzhi Pill improved the lipid metabolism and inflammatory mechanism of nonalcoholic steatohepatitis mice by activating the NRF2 pathway |
| Hits 258 Download times 117 Received:June 16, 2025 |
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| DOI
10.11656/j.issn.1672-1519.2025.12.16 |
| Key Words
Jiangan Jiangzhi Pill;NRF2 pathway;nonalcoholic steatohepatitis;antioxidation;lipid metabolism;inflammatory mechanism |
| Author Name | Affiliation | E-mail | | JIAO Xue | Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China | | | LI Ping | Tianjin Second People's Hospital, Tianjin 300192, China | tjlp2023@163.com | | WANG Li | Tianjin Second People's Hospital, Tianjin 300192, China | |
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| Abstract
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| [Objective] To observe the lipid metabolism and inflammatory mechanism of Jiangan Jiangzhi Pills on nonalcoholic steatohepatitis（NASH） mice induced by methionine choline deficient（MCD）. [Methods] The mice were randomly divided into a control group，model group，positive drug group，and Jiangan Jiangzhi Pills low-dose，medium-dose，high-dose groups，with 10 mice in each group. The control group was fed a normal diet，while the other experimental groups received an MCD diet. The positive drug group was intraperitoneally injected with polyene phosphatidylcholine（150 mg/kg），and the Jiangan Jiangzhi Pill low-dose，medium-dose，and high-dose groups were orally administered the pill at doses of 100，200 and 400 mg/kg，respectively，once daily. The control and model groups were given an equal volume of saline in parallel. Body weight was measured and recorded every 7 days for a total duration of 6 weeks. Hematoxylin-eosin（HE） staining was used to observe histopathological changes in liver tissue. Serum concentrations of alanine aminotransferase（ALT） and aspartate aminotransferase（AST） were measured using biochemical assay kits. The levels of total cholesterol（TC），triglycerides（TG），superoxide dismutase（SOD），malondialdehyde（MDA），and glutathione peroxidase（GSH-Px） in liver tissue homogenates were quantified using a BCA protein assay kit. PCR was performed to detect the mRNA expression levels of nuclear factor erythroid 2-related factor 2（NRF2），heme oxygenase-1（HO-1），glutamate-cysteine ligase catalytic subunit（GCLC），and NAD（P）H quinone oxidoreductase 1（NQO1） in mouse liver tissue. Western blot analysis was conducted to measure the expression levels of NRF2 pathway-related proteins in mouse liver tissue. [Results] Compared with the normal group，the results showed that compared with the normal group，the model group had severe liver pathological damage，hepatocyte structure destruction，widening and collapse of cell septum，and a large number of inflammatory cells infiltrated，serum ALT，AST，TG，TC levels were significantly increased（P＜0.01）. The activities of antioxidant indexes SOD and GSH-Px decreased，the levels of MDA increased，and the mRNA and protein expressions of NRF2，HO-1，GCLC and NQO1 in liver tissue were significantly decreased（P＜0.01）；compared with the model group，the liver cell structure of mice in the positive drug group and the low-dose，medium-dose and high-dose groups of Jiangan Jiangzhi Pills tended to be clear，the cell interval was shortened，the inflammatory cell infiltration was reduced，the body weight increased，the liver index decreased，the serum levels of ALT，AST，TG and TC decreased significantly，the activities of SOD and GSH-Px increased，the MDA level decreased，and the expression levels of NRF2 pathway-related mRNA and protein in liver tissue were significantly up-regulated. [Conclusion] This study revealed for the first time that Jiangan Jiangzhi Pill has a multi-dimensional improvement effect on MCD-induced NASH mice，and its therapeutic effect is closely related to the function of regulating NRF2 signaling pathway and enhancing the antioxidant defense system，and enhancing the liver’s antioxidant capacity by up-regulating the expression of downstream target genes such as HO-1，GCLC，and NQO1，and improving the lipid metabolism disorder and inflammatory damage induced by MCD. Based on the experimental results，the activation of NRF2 pathway may be one of the important ways for Jiangan Jiangzhi Pills to improve NASH. |
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