Exploring the Mechanism and Experimental Verification of Alhagi Sparsifolia Shap.in Treating Sepsis Based on Network Pharmacology
- VernacularTitle:基于网络药理学探究骆驼刺治疗脓毒症的作用机制及实验验证
- Author:
Zhizhen ZOU
1
;
Xiling DENG
;
Yunlai WANG
;
Jie ZHANG
;
Jiangtao DONG
;
Xiaoling LIU
;
Su LIANG
;
Ju WANG
;
Hui ZHANG
;
Jiangdong WU
;
Le ZHANG
;
Fang WU
;
Wanjiang ZHANG
Author Information
- Keywords: Alhagi sparsifolia Shap.; Sepsis; Network pharmacology; Molecular docking; Molecular dynamics; Mechanism
- From: World Science and Technology-Modernization of Traditional Chinese Medicine 2023;25(9):3024-3036
- CountryChina
- Language:Chinese
- Abstract: Objective Network pharmacology and molecular docking and molecular dynamics techniques were used to investigate the mechanism of action of Alhagi sparsifolia Shap.in the treatment of sepsis and to perform animal experimental verification.Methods First,we screened the effective ingredients and their action targets of Alhagi sparsifolia Shap.,meanwhile,screened relevant action targets for the treatment of sepsis,constructed a protein interaction(PPI)network,and performed topology analysis to draw a TCM disease target network diagram.Second,Kyoto Encyclopedia of genes and genomes enrichment analysis was performed for core targets in the network diagram,along with gene ontology functional enrichment analysis.This was followed by molecular docking and molecular dynamics simulation experiment validation of the core targets.Finally,mice were used for the verification of animal experiments.Results Thirty active components of Alhagi sparsifolia Shap.were screened out,and the top 5 ranked by degree value were quercetin,(-)-epigallocatechin,(-)-Epigallocatechin Gallate,genistein,kaempferol and epigallocatechin with 196 action targets;2144 disease-related targets for sepsis,105 targets for Alhagi sparsifolia Shap.-sepsis intersection,and the core targets were TNF,IL-6,AKT1,VEGFA,CASP3,IL-1β Et al.PI3K-Akt,TNF,HIF-1,AGE-RAGE,IL-17 and other signaling pathways are involved to mediate inflammatory responses,apoptosis and other biological processes to exert therapeutic effects on sepsis.Molecular docking results showed that camelina flavanoids bound equally well to each key target,among which the conformations with the lowest binding energy were(-)-Epigallocatechin Gallate-IL-6 and quercetin-IL-6.Molecular dynamics simulations were performed on the two pairs of complexes,and the results indicated that the stable binding could be achieved through a combination of electrostatic,van der Waals potential,and hydrogen bonding interactions.Animal experiments confirmed that Alhagi sparsifolia Shap.could inhibit the activation of PI3K/Akt signaling pathway,decrease the protein expression of Caspase-3,VEGF and reduced peripheral blood inflammatory factors secretion of TNF-α、IL-1βand IL-6,alleviating inflammatory injury in tissues and organs.Conclusion The therapeutic effect of Alhagi sparsifolia Shap.on sepsis is achieved through multi biological processes,multi targets,and multi pathways.It provides a certain theoretical basis for the clinical application of camel spines as well as sepsis treatment.
