Journal Article

Study on the Mechanism of Improving HIV/AIDS Immune Function with Jian Aikang Concentrated Pill Based on Network Pharmacology Combined with Experimental Validation

Sang, Feng, Shao, Cancan, Xu, Liran, Wang, Haojie

2022

Overview

This study was the first to screen the active compounds of Jian Aikang Concentrated Pill (JAKCP) with network pharmacology, predict its potential targets, screen the signaling pathways, and combine with cellular experimental validation to explore the potential mechanism of JAKCP for the treatment of acquired immunodeficiency syndrome (AIDS). The main compounds and targets of Chinese herbs in JAKCP were identified by TCMSP; the targets of AIDS were collected from Genecards, Online Mendelian Inheritance in Man (OMIM), Disgenet, Therapeutic Target Database (TTD) and Drugbank; the network of \"Chinese herbs-active compounds-targets\" for JAKCP was constructed by Cytoscape, and protein-protein interaction (PPI) network was constructed using STRING to generate the intersection targets, Metascape was conducted to analyze the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), and the network of \"main active compounds-core targets-pathways\" was constructed by Cytoscape. Finally, the effect of JAKCP on the survival rate of HIV pseudovirus-infected MT-4 cells was investigated by CCK-8 assay, and the predicted targets were verified by ELISA, qPCR and Western blot. A total of 147 active compounds of JAKCP were screened covering 351 targets and 416 AIDS disease targets were obtained, besides 140 intersection targets and 321 KEGG pathways were collected. Ultimately, quercetin, kaempferol, stigmasterol, beta-sitosterol, epigallocatechin gallate were identified as the important compounds, the core targets are HSP90AA1, IL-10, IL-6, TNF, IL-1β, TP53, and IL-1ɑ, and the biological pathways and processes mainly include T cell activation, regulation of DNA-binding transcription factor activity and apoptotic signaling pathway. Experiments on the targets of \"T cell activation\" demonstrated that JAKCP promotes the survival of HIV pseudovirus-infected MT-4 cells. Also, JAKCP down-regulated mRNA and protein levels of IL-1ɑ, IL-1β, and IL-6 while up-regulated mRNA and protein levels of IL-2, IL-6ST, and IL-10 in vitro. JAKCP exerted regulatory immune functions through multi-component, multi-target and multi-pathway, thereby providing novel ideas and clues for the treatment of AIDS.

• Publisher: Dove Medical Press Limited,Taylor & Francis Ltd,Dove,Dove Medical Press
• Subject: Acquired immune deficiency syndrome / Acquired Immunodeficiency Syndrome - drug therapy / AIDS / Apoptosis / Biological activity / Catechin / Cell activation / Cholecystokinin / Connectivity / Deoxyribonucleic acid / Disease / DNA / Drug dosages / Drug resistance / Drug therapy / Drugs, Chinese Herbal - pharmacology / Drugs, Chinese Herbal - therapeutic use / Encyclopedias / Enzyme-linked immunosorbent assay / Epigallocatechin gallate / Gene regulation / Genes / Genetic transcription / Genomes / Genomics / Health aspects / Health services / Herbs / Heredity / HIV / hiv/aids / Human immunodeficiency virus / Humans / IL-1β / Immune response / Immune system / Immunity / Immunodeficiency / Interleukin 10 / Interleukin 2 / Interleukin 6 / jian aikang concentrated pill / Kaempferol / Laboratories / Life expectancy / Lymphocytes / Lymphocytes T / mechanism / Medicine, Botanic / Medicine, Herbal / Molecular Docking Simulation / Mortality / multi-pathway / network pharmacology / Network Pharmacology - methods / Original Research / p53 Protein / Pharmacology / Phytosterols / Protein-protein interactions / Proteins / Quercetin / RNA / RNA, Messenger / Signal transduction / Signaling / Survival / T cells / Therapeutic targets / Traditional Chinese medicine / Transcription activation / Tumor necrosis factor / Tumor proteins