An Integrated Analysis of Network Pharmacology, Molecular Docking, and Experiment Validation to Explore the Mechanism of Danbai Granules in Treating Sequelae of Pelvic Inflammatory Disease

Abstract

PurposeTo explore the possible pharmacological mechanisms of Danbai Granules (DBG) against sequelae of pelvic inflammatory disease (SPID) by the method of network pharmacology and molecular docking combined with experimental validation. MethodsFirstly, biologically active compounds, targets of DBG, and related targets of SPID were collected from public databases. The protein- protein interaction (PPI) network, Gene GO and KEGG enrichment analysis were carried out via R language to find the potential biological processes and pathways of DBG against SPID. Subsequently, molecular docking was used to calculate the affinity between the top six targets and the top ten compounds, respectively. Finally, the above analysis results were verified by in vivo experiments. ResultsA total of 106 crossover genes were selected from 220 potential medicine genes and 952 SPID-related genes. PPI network analysis indicated that IL-6, IL-1{beta}, VEGFA, CASP3, PTGS2, JUN, etc., were core targets. GO and KEGG enrichment analysis revealed that PI3K-Akt, AGE-RAGE, IL-17, TNF, HIF-1 and Toll-like receptors signaling pathways were the main signaling pathways. Molecular docking showed that 15 pairs of target-ingredient combinations have good binding activity. The animal experiments showed that DBG administration inhibited the expression of TLR4/MyD88/NF-{kappa}B p65 signaling pathway-related proteins expression, altered the high expression of IL-6, IL-1{beta}, and low level of IL-4, IL-10, thereby relieving the pelvic inflammation of SPID. ConclusionThrough the network pharmacology and molecular docking, our findings predicted the active ingredients and potential targets of DBG in treating SPID. The experimental verification preliminarily revealed that DBG may inhibit the inflammatory response of SPID rats by regulating the TLR4/MyD88/NF-{kappa}B p65 signaling pathway. which provides a theoretical basis for the study of the pharmacodynamic material basis and mechanism of DBG against SPID at the comprehensive level.