Abstract
This study was conducted to identify whether the TLR4/MyD88/NF-κB signalling pathway plays a vital role in osteoarthritis (OA) treatment with Duhuo Jisheng Decoction (DHJSD) on the basis of a network pharmacology approach (NPA)-integrated experiment. Two experiments were conducted as follow: NPA for DHJSD using six OA-related gene series and the key pathway was screened out using NPA. NPA identified a vital role for the TLR4/MyD88/NF-κB signalling pathway in OA treatment with DHJSD, the conventional western blot analysis and qPCR confirmed it. Furthermore, changes of miR-146a-5p and miR-34a-5p in the cellular models were recovered by DHJSD administration, which synergistically contributed to OA therapy. The toll-like receptor signalling pathway and the NF-κB signalling pathway were meaningfully enriched by the miRNA-regulated gene pathways. This study identified and confirmed the TLR4/MyD88/NF-κB signalling pathway is an essential inflammatory signalling pathway in the DHJSD underlying OA treatment. The results provide a basis for further evaluation of the regulatory mechanism of the drug’s efficacy in treating OA.
Highlights
Osteoarthritis (OA) is a progressive, degenerative disease characterised by inflammation-driven cartilage degradation in the elderly (Kwon et al, 2018; Funck-Brentano et al, 2019; Peat and Thomas, 2021)
For series 1, the network consisted of 175 nodes (131 compounds for Duhuo Jisheng Decoction (DHJSD) and 44 compound targets) and 358 edges (Figure 2A)
The KEGG and Gene Ontology (GO) enrichment analyses identified several inflammatory signalling pathways highly associated with DHJSD, and the results of Venn analysis between the target gene and PPI network topology analysis action point supported that the NF-κB signalling pathway and the toll-like signalling
Summary
Osteoarthritis (OA) is a progressive, degenerative disease characterised by inflammation-driven cartilage degradation in the elderly (Kwon et al, 2018; Funck-Brentano et al, 2019; Peat and Thomas, 2021). Pharmacological treatments for OA are aimed at alleviating the clinical symptoms rather than treating the underlying causes. It is in desperate need of more effective and. Studies have shown that DHJSD could alleviate OA by suppressing inflammation and chondrocyte apoptosis (Liu et al, 2018; Liu et al, 2020). Our previous studies shown that DHJSD inhibits chondrocyte apoptosis by affect the mitochondrial-dependent apoptotic pathway (Liu et al, 2014) and suppresses the endoplasmic reticulum stressmediated apoptosis (Lin et al, 2015). The specific pharmacological mechanisms of DHJSD and their interaction with OArelated targets and pathways is not yet elucidated and require further investigation
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