Exploring the pharmacological mechanism of Duhuo Jisheng Decoction in treating intervertebral disc degeneration based on network pharmacology

Abstract

Background: The purpose of this study was to examine the mechanism of Duhuo Jisheng Decoction (DHJSD) in the treatment of intervertebral disc degeneration (IVDD). Methods: The active compounds of DHJSD and their corresponding targets were obtained from the TCMSP database. “Intervertebral disc degeneration” was used as a search term in the DisGeNET, GeneCards, Comparative Toxicogenomics Database, and MalaCards database to obtain disease-related targets. Following the discovery of overlapping DHJSD and IVDD targets, enrichment analyses for Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, Reactome, and WikiPathways were performed. Cytoscape 3.9.1 was used to build the “DHJSD-Active Ingredients-Target Genes-IVDD” network and protein-protein interaction network, and CytoHubba was used to screen the pivotal genes. Molecular docking confirmed the binding activity of hub genes and key components. Results: The bioinformatic analysis of DHJSD in the treatment of IVDD revealed 209 potential therapeutic gene targets, including 36 important gene targets and 10 of these crucial gene targets. Enrichment analysis of 36 key therapeutic targets showed that the biological processes involved in the Gene Ontology analysis of DHJSD in treating IVDD were mainly cytokine-mediated signaling pathway, inflammatory response, negative regulation of apoptotic process, and vascular endothelial growth factor production. The Kyoto Encyclopedia of Genes and Genomes signaling pathway is mainly involved in TNF signaling pathway, Th17 cell differentiation, IL-17 signaling pathway, and HIF-1 signaling pathway. The Recactome signaling pathway is mainly involved in cytokine signaling in immune system, cellular responses to stress, immune system, cytokines, and inflammatory response. HIF1A and PPARG regulation of glycolysis are mostly involved in the WikiPathways signaling system. The findings demonstrated that to cure IVDD, DHJSD affects the pathogenic processes of inflammation, extracellular matrix, cellular senescence, autophagy, apoptosis, focal death, and proliferation through the aforementioned targets and signaling pathways. The results of molecular docking demonstrated that the protein can be effectively bound by the DHJSD active component. Further evidence was provided for the molecular mechanism through which DHJSD works to treat IVDD. Conclusion: This study uncovers the multi-component, multi-target, and multi-pathway characteristics of DHJSD for the treatment of IVDD, offering fresh perspectives to further investigate the mechanism of DHJSD for the treatment of IVDD.

Duhuo Jisheng Decoction regulates intracellular zinc homeostasis by enhancing autophagy via PTEN/Akt/mTOR pathway to improve knee cartilage degeneration

“…As a complementary therapy, DHJSD is widely for the management of bone and joint diseases in China; however, its exact mechanism has not been completely elucidated. Existing studies have confirmed that DHJSD regulates inflammatory factors, reduces apoptosis and pyroptosis of nucleus pulposus cells, and inhibits extracellular matrix degradation [9][10][11][12], indicating the multiple mechanisms of action of DHJSD in osteoarthritis (OA).…”

Astragaloside IV relieves IL-1β-induced human nucleus pulposus cells degeneration through modulating PI3K/Akt signaling pathway

“…[19] Many recent studies have partially established the usefulness of Chinese medicine in treating IDD, with the primary mechanisms including reduction of oxidative stress, regulation of inflammatory response, and decrease of myeloid cell death, among others. [20,21] AS IV is a natural saponin purified from the traditional Chinese medicine Astragalus membranaceus , which has anti-inflammatory, antioxidant, anti-apoptosis and anti-cancer pharmacological activities. [22] Previous studies have shown that AS IV inhibits IL-1β-induced chondrocyte inflammatory mediators, apoptosis and ECM degradation, and alleviates the progression of osteoarthritis.…”