RESUMO
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.
RESUMO
Shengxiantang， one of the classical traditional Chinese medicine （TCM） prescriptions， was developed by ZHANG Xi-chun， a well-known doctor in the Republic of China， to treat the syndrome of pectoral Qi sinking. Due to the unique herbal composition， this prescription has yielded remarkable outcomes， and it is still widely used for dealing with diseases of various systems. This paper reviewed the clinical research concerning Shengxiantang in order to provide reference for its clinical application. Following the retrieval of related articles published in the past ten years from China National Knowledge Infrastructure （CNKI）， Wanfang Data Knowledge Service Platform， Chongqing Weipu Database for Chinese Technical Periodicals （VIP）， and Chinese Biomedical Literature Service System （SinoMed） with the Chinese key words of “Shengxiantang （升陷汤）”， “sinking of pectoral Qi （大气下陷）”， “replenishing Qi and raising the sinking （益气升陷）”， and“pectoral Qi theory （大气理论）”， this paper collated the clinical application experience of Shengxiantang. To be specific， the corresponding etiology and pathogenesis， interpretations of Shengxiantang， as well as its indications， application experience and precautions were summarized to provide a basis for its further research and application. Based on the collected more than 50 representative articles， it was found that Shengxiantang has been extensively utilized for treating complex and critical diseases of various systems， especially the circulatory and respiratory diseases and organ prolapse. The research on the clinical application of Shengxiantang has deepened， exhibiting a promising development trend， which will provide new ideas for its clinical application.