Prediction and experimental verification of network target of celastrol in alleviating hepatic inflammatory injuries
10.3760/cma.j.cn115398-20230516-00204
- VernacularTitle:雷公藤红素减轻肝脏炎性损伤网络靶标预测及实验验证
- Author:
Jiaqi XIN
1
;
Lve SUN
;
Yongsheng ZHAO
;
Mengxi JIANG
;
Hui ZHAO
Author Information
1. 首都医科大学中医药学院，北京 100069
- Keywords:
Celastrol;
Inflammation;
Reperfusion injury;
Network pharmacology;
Mice
- From:
International Journal of Traditional Chinese Medicine
2024;46(5):614-621
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the action targets and mechanism of celastrol in alleviating liver inflammatory injuries using network pharmacology; To verify the key targets through liver ischemia-reperfusion injury inducing inflammation mouse model.Methods:The targets of celastrol were integrated by searching SymMap, BATMAN-TCM, TCMSP, HIT 2.0, LigTMap, SEA, SwissTarget, Super-PRED, STITCH databases. The molecular targets of hepatic inflammatory injuries were investigated by GeneCards and DisGeNET databases. The intersection of drug targets and disease targets was obtained by Venn diagram to obtain the possible targets of celastrol in alleviating hepatic inflammatory diseases. Cytoscape 3.9.1 software was used to analyze the key targets of protein interaction (PPI) networks based on STRING database, and enrichment analysis was conducted through DAVID database. Based on the key targets, the ceRNA network was mapped by retrieving the starBase database. Molecular docking was used to evaluated the binding of celastrol with the key target proteins. The mice were divided into sham-operation solvent group, sham- operation medication group, model group, and Tripterygium wilfordii extract low- (0.1 mg/kg), medium- (0.3 mg/kg), and high- (1 mg/kg) dosage groups according to body weight, with 3-4 mice in each group. After 7 days of corresponding drug intervention, except for the sham-operation solvent group and sham-operation medication group, other groups were prepared with ischemia-reperfusion induced liver inflammation mouse models. The serum transaminase levels in mice were detected; the pathological morphology of mouse liver tissue was observed using HE staining; the expressions of IL-6 and TNF-α were detected in liver tissue using immunohistochemistry staining.Results:The key targets of celastrol in alleviating liver inflammation were inflammatory cytokines such as IL6 and TNF. The analysis of functional enrichment results showed that the key signaling pathways of Tripterygium wilfordii extract in reducing liver inflammatory injury included inflammatory response, cell apoptosis and proliferation, HIF1, and other pathways. Triptolide pretreatment could reduce serum aminotransferase level ( P<0.01) and liver inflammatory factors expression such as IL-6 and TNF-α ( P<0.05, P<0.01) after hepatic ischemia-reperfusion. Conclusion:Celastrol can alleviate hepatic ischemia-reperfusion injury, and its mechanism is closely related to the reduction of inflammatory factors such as IL-6 and TNF-α and the alleviation of hepatic inflammatory injury.
