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Confirmation of inhibitingTLR4/MyD88/NF-κB Signalling Pathway by Duhuo Jisheng Decoction on Osteoarthritis: A Network
Linglong Liu1, Limei Xu1,2, Shengjie Wang3
1College of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, China.
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.
Insights
Duhuo Jisheng Decoction (DHJSD) effectively treats osteoarthritis (OA) by targeting the Toll-like receptor 4/MyD88/NF-κB signalling pathway. This pathway is crucial for DHJSD
Area of Science:
- Pharmacology
- Molecular Biology
- Traditional Chinese Medicine
Background:
- Osteoarthritis (OA) is a degenerative joint disease with limited treatment options.
- Duhuo Jisheng Decoction (DHJSD) is a traditional Chinese medicine used for OA.
- The precise molecular mechanisms of DHJSD in OA remain unclear.
Purpose of the Study:
- To investigate the role of the Toll-like receptor 4/MyD88/NF-κB (TLR4/MyD88/NF-κB) signalling pathway in DHJSD's OA treatment.
- To elucidate the molecular targets and pathways involved in DHJSD's therapeutic effects on OA.
Main Methods:
- Network pharmacology approach (NPA) to identify key pathways and genes.
- Experimental validation using western blot and quantitative polymerase chain reaction (qPCR).
- Investigation of microRNA (miRNA) changes (miR-146a-5p and miR-34a-5p) in cellular OA models.
Main Results:
- NPA identified the TLR4/MyD88/NF-κB pathway as critical for DHJSD's OA treatment.
- Western blot and qPCR confirmed the pathway's involvement.
- DHJSD administration restored miR-146a-5p and miR-34a-5p levels, contributing to OA therapy.
- miRNA-regulated pathways enriched the toll-like receptor and NF-κB signalling pathways.
Conclusions:
- The TLR4/MyD88/NF-κB signalling pathway is essential for the anti-inflammatory effects of DHJSD in OA.
- DHJSD's efficacy in OA treatment is mediated through this inflammatory pathway and specific miRNAs.
- This study provides a foundation for understanding DHJSD's mechanism of action in OA.
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