Frontiers in Pharmacology (Jan 2022)

Confirmation of inhibitingTLR4/MyD88/NF-κB Signalling Pathway by Duhuo Jisheng Decoction on Osteoarthritis: A Network Pharmacology Approach-Integrated Experimental Study

  • Linglong Liu,
  • Limei Xu,
  • Limei Xu,
  • Shengjie Wang,
  • Lili Wang,
  • Lili Wang,
  • Xiaoning Wang,
  • Xiaoning Wang,
  • Huifeng Xu,
  • Huifeng Xu,
  • Xihai Li,
  • Xihai Li,
  • Hongzhi Ye,
  • Hongzhi Ye

DOI
https://doi.org/10.3389/fphar.2021.784822
Journal volume & issue
Vol. 12

Abstract

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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.

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