Integrating network pharmacology, molecular docking, and experimental verification to demonstrate that Jiawei Duhuo Parasitic Decoction treated osteoarthritis by inhibiting PTGS2 expression

Abstract

Introduction

Jiawei Duhuo Parasitic Decoction (JDPD) is a traditional Chinese medicine commonly used to treat osteoarthritis (OA). However, the specific mechanisms by which JDPD acts against OA have not been fully elucidated. This study aimed to explore the potential mechanisms through which JDPD inhibits the onset and progression of OA.

Methods

The active components and targets of JDPD were identified using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Traditional Chinese Medicine Information Database (TCMID) databases. Potential OA-related targets were obtained from GeneCards, DisGeNET, DrugBank, and OMIM databases. The overlapping targets between JDPD and OA were analyzed using a protein - protein interaction (PPI) network and MCODE subnetwork, and central gene targets were identified through topological analysis. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted using the Database for Annotation, Visualization and Integrated Discovery (DAVID) database. Subsequently, an active ingredient-target-pathway network was then constructed and validated through molecular docking. Finally, in vitro and in vivo models of OA-induced cartilage injury were established to verify the potential mechanisms by which JDPD inhibits OA-related cartilage damage.

Results

A total of 205 active components and 68 OA-related targets of JDPD were identified. Further analysis revealed eighteen key targets, primarily associated with therapeutic effects related to the expression of inflammatory factors and cell proliferation. The active ingredient-target-pathway network was constructed and validated using molecular docking. Finally, in vitro and in vivo experiments demonstrated that JDPD ameliorates OA-induced cartilage damage by inhibiting prostaglandin-endoperoxide synthase 2 (PTGS2)-mediated chondrocyte inflammation and extracellular matrix degradation.

Discussion

Our findings suggest that JDPD may treat OA through a multi-component, multi-target mechanism, with PTGS2 identified as a validated target. These results provide an experimental basis for the potential development of JDPD as a therapeutic agent for OA in the future.