The mechanism of Gejie Zhilao Pill in treating tuberculosis based on network pharmacology and molecular docking verification.

INTRODUCTION

Gejie Zhilao Pill (GJZLP), a traditional Chinese medicine formula is known for its unique therapeutic effects in treating pulmonary tuberculosis. The aim of this study is to further investigate its underlying mechanisms by utilizing network pharmacology and molecular docking techniques.

METHODS

Using TCMSP database the components, potential targets of GJZLP were identified. Animal-derived components were supplemented through the TCMID and BATMAN-TCM databases. Tuberculosis-related targets were collected from the TTD, OMIM, and GeneCards databases. The intersection target was imported into the String database to build the PPI network. The Metascape platform was employed to carry out Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Heatmaps were generated through an online platform (https://www.bioinformatics.com.cn). Molecular docking was conducted between the core targets and core compounds to explore their binding strengths and patterns at the molecular level.

RESULTS

61 active ingredients and 118 therapeutic targets were identified. Quercetin, Luteolin, epigallocatechin gallate, and beta-sitosterol showed relatively high degrees in the network. IL6, TNF, JUN, TP53, IL1B, STAT3, AKT1, RELA, IFNG, and MAPK3 are important core targets. GO and KEGG revealed that the effects of GJZLP on tuberculosis mainly involve reactions to bacterial molecules, lipopolysaccharides, and cytokine stimulation. Key signaling pathways include TNF, IL-17, Toll-like receptor and C-type lectin receptor signaling. Molecular docking analysis demonstrated a robust binding affinity between the core compounds and the core proteins. Stigmasterol exhibited the lowest binding energy with AKT1, indicating the most stable binding interaction.

DISCUSSION

This study has delved into the efficacious components and molecular mechanisms of GJZLP in treating tuberculosis, thereby highlighting its potential as a promising therapeutic candidate for the treatment of tuberculosis.