Molecular Mechanism of Shengxiantang in Treating Myasthenia Gravis： Based on Network Pharmacology and Molecular Docking
10.13422/j.cnki.syfjx.20220411
- VernacularTitle:基于网络药理学和分子对接探讨升陷汤治疗重症肌无力的作用机制
- Author:
Yi-bin ZHANG
1
;
Bai-tong WANG
2
;
Zhi-guo LYU
2
;
Peng XU
2
;
Dong-mei ZHANG
2
;
Qiao-ying LI
2
;
Ying ZHANG
2
;
Jing LU
2
;
Li JIANG
1
;
Qi LU
3
;
Jian WANG
2
Author Information
1. College of Traditional Chinese Medicine， Changchun University of Chinese Medicine， Changchun 130117，China
2. The Affiliated Hospital to Changchun University of Chinese Medicine，Changchun 130021，China
3. The Third Affiliated Hospital of Changchun University of Chinese Medicine，Changchun 130117，China
- Publication Type:Journal Article
- Keywords:
Shengxiantang;
myasthenia gravis;
network pharmacology;
molecular docking;
animal experiment
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2022;28(6):142-150
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo predict the pharmacodynamic basis and core target of Shengxiantang in the treatment of myasthenia gravis （MG） by network pharmacology and molecular docking and to further verify the molecular mechanism through animal experiment. MethodThe active components and potential targets of Shengxiantang were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， and the disease-related targets from GeneCards and other databases. Then the common targets of the decoction and the disease were screened out， followed by the construction of protein-protein interaction （PPI） network， and Gene Ontology （GO） term enrichment and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment of the common targets based on STRING database and Cytoscape 3.8.2. Afterward， Cytoscape 3.8.2 was employed to construct the disease-active component-target network. AutoDock and PyMOL were used for molecular docking of key components and hub genes. Finally， we used the Rα97-116 peptide to induce experimental autoimmune myasthenia gravis （EAMG） in rats and then verified the core target yielded in the docking with the model rats. ResultA total of 655 disease-related targets， 118 active components of the decoction， 21 common targets of the disease and the decoction， and 3 hub genes were screened out. The common targets were mainly involved in the GO terms of regulation of active oxygen metabolism， positive regulation of protein transport， and positive regulation of protein localization， and the KEGG pathways of toll-like receptor signaling pathway， phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway， hypoxia inducible factor-1 （HIF-1） signaling pathway， and T cell receptor signaling pathway. The results of molecular docking showed that quercetin and Akt1 had the lowest and stable binding energy and interacted with each other through the amino acid residue LYS-30. Western blot demonstrated that Shengxiantang significantly inhibited the expression of p-Akt protein in the spleen of EAMG rats. ConclusionThe pharmacological mechanism of Shengxiantang in the treatment of MG may be that the main chemical components regulate the expression of the core protein Akt， and then may participate in and affect PI3K/Akt signaling pathways， laying a theoretical and experimental basis for further research.
