Mechanism of tanshinone ⅡA in ameliorating acetaminophen-induced liver injury based on network pharmacology and molecular docking techniques
10.12206/j.issn.2097-2024.202412022
- VernacularTitle:基于网络药理学和分子对接技术探讨丹参酮ⅡA改善对乙酰氨基酚致肝损伤的作用机制
- Author:
Tingyan ZHANG
1
;
Tingting LI
2
;
Xiaofeng YUAN
3
;
Chuan ZHANG
2
;
Kai HAO
3
;
Jun BIAN
1
Author Information
1. Jiangxi University of Chinese Medicine, Nanchang 330004, China.
2. School of Medicine, Shanghai University, Shanghai 200444, China.
3. The 71st Group Army Hospital of PLA, Xuzhou 221004, China.
- Publication Type:Originalarticles
- Keywords:
Tanshinone ⅡA;
acute liver injury;
network pharmacology;
mechanism of action;
molecular docking
- From:
Journal of Pharmaceutical Practice and Service
2026;44(8):417-425
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the potential protective mechanism of tanshinone ⅡA against acetaminophen （APAP）-induced acute liver injury. Methods Thirty mice were randomly divided into the normal group, model group, low-dose tanshinone ⅡA group （5 mg/kg）, medium-dose tanshinone ⅡA group （10 mg/kg） and high-dose tanshinone ⅡA group （20 mg/kg）. All groups were intragastrically administered once daily for 7 consecutive days. On the 7th day, except for the normal group, mice in the remaining groups were intraperitoneally injected with 400 mg/kg APAP to establish the acute lung injury （ALI） model. The protective effect of tanshinone ⅡA was evaluated based on the liver weight ratio, the levels of aspartate aminotransferase （AST） and alanine aminotransferase （ALT）, and HE staining. Targets of tanshinone ⅡA were predicted by the Traditional Chinese Medicine Systems Pharmacology （TCMSP）, and a shared target protein-protein interaction （PPI） network was constructed by Search Tool for the Retrieval of Interacting Genes/Proteins （STRING） 11.5 in combination with disease targets from GeneCards. The Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis was performed by Database for Annotation, Visualization and Integrated Discovery （DAVID）, and the component-target-pathway network was constructed. The molecular docking between tanshinone ⅡA and the core targets was performed by AutoDock and visualised. Results Compared with the normal group, the liver weight ratio and serum aminotransferase level of mice with acute liver injury were significantly elevated （P<0.05）, and the pathological injury of liver tissue was obvious. After tanshinone ⅡA treatment, the above index were significantly reduced （P<0.05）, and the pathological injury was significantly improved. Further network pharmacological analysis was carried out and found that KEGG pathway enrichment analysis focused on IL-17 signaling pathway and tumor necrosis factor （TNF） signaling pathway, etc. In addition, the PPI core network showed that the key targets of tanshinone ⅡA to ameliorate acute liver injury mainly included TP53, AKT1, SRC, TNF and JUN. The molecular docking results showed that tanshinone ⅡA had high binding scores with the targets of MMP9, NFKB1, TNF, EP300 and SMAD3; and was able to bind to the targets of TP53, AKT1, SRC and JUN. Conclusion Tanshinone ⅡA may play a protective role against acute liver injury by regulating genes such as AKT1, JUN and TNF, and participating in signaling pathways such as TNF and IL-17.
