Explore the Mechanism of Limonin Against Hepatic Fibrosis Based on Network Pharmacology and Animal Experiments
10.13748/j.cnki.issn1007-7693.20223848
- VernacularTitle:基于网络药理学和动物实验探讨柠檬苦素抗肝纤维化的作用机制
- Author:
Yuhong XIAO
1
;
Zhenxiang AN
2
;
Fang WANG
2
;
Jinwen WANG
3
;
Xia SHAO
3
;
Ying YUAN
3
Author Information
1. The First Clinical Medical College of Guizhou University of Traditional Chinese Medicine, Guiyang 550001, China；Dazhou City, Dachuan District Hospital of Traditional Chinese Medicine, Dazhou 635000, China
2. The First Clinical Medical College of Guizhou University of Traditional Chinese Medicine, Guiyang 550001, China；The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang 550001, China
3. The First Clinical Medical College of Guizhou University of Traditional Chinese Medicine, Guiyang 550001, China
- Publication Type:Journal Article
- Keywords:
network pharmacology ；molecular docking ； limonin ； hepatic fibrosis ； angiogenesis
- From:
Chinese Journal of Modern Applied Pharmacy
2024;41(4):460-468
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE :To explore the mechanism of limonin treating in hepatic fibrosis through network pharmacology, and validate its mechanism by molecular docking and animal experiments.
METHODS
Firstly, the targets of limonin and hepatic fibrosis were screened from the SwissTargetPrediction, GeneCards and DisGeNet database, etc. Meanwhile, the common targets of limonin and hepatic fibrosis were obtained from the bioinformatics website. The protein protein interaction network of common target was constructed by using STRING database and Cytoscape software, and the CytoNCA plug-in was used to screen core targets. And then the enrichment analysis of GO and KEGG on the common target was performed by Metascape database. Thereby, the possible mechanism of limonin against hepatic fibrosis were predicted. Finally, the AutoDock Vina was used for molecular docking verification, and the prediction results of network pharmacology were verified by animal experiments.
RESULTS
The prediction results indicated that limonin might acted on 86 targets including AKT1, VEGFA and HIF1A, and participated in biological processes including hormone response, protein phosphorylation, angiogenesis, and PI3K-Akt pathway, HIF-1 pathway, VEGF pathway and other signaling pathways related to hepatic fibrosis. The results of protein protein interaction network topology analysis showed that the 11 core targets including AKT1, VEGFA, HIF1A and PIK3CA, etc. Molecular docking results showed that limonin had strong affinity and relatively stable binding conformation with the core targets. In the animal experiments, compared with the model group, hyaluronidase(HA) and laminin(LN) in rat serume in high-dose group of limonin(LH) and low-dose group of limonin(LL)(except for LN in LL group) were declined(P<0.01 or P<0.05), and the degree of inflammation and hepatic fibrosis were relieved to different degrees in liver tissue of the LH group and LL group; Western blotting and qPCR detection showed that protein and mRNA expression levels of AKT, HIF-1α and VEGF(except for VEGF in LL group) was down-regulated in the LH group and LL group(P<0.01 or P<0.05).
CONCLUSION
Limonin may acts on AKT1, VEGFA, HIF1A and other core targets to treat hepatic fibrosis angiogenesis, which may be related to the inhibition of AKT/HIF-1α/VEGF signaling pathway.
