# Multi-targeted inhibition of NF-κB signaling underlies the anti-osteoarthritic effects of BGJXF and its key component dehydrocorydaline

## TL;DR

This study shows that BGJXF, a traditional Chinese medicine, treats knee osteoarthritis by targeting multiple pathways, especially the NF-κB signaling pathway.

## Contribution

The study reveals BGJXF's multi-target mechanism via NF-κB inhibition and identifies dehydrocorydaline as a key active component.

## Key findings

- BGJXF contains 91 chemical constituents and targets 62 genes related to KOA.
- Dehydrocorydaline suppresses NF-κB p65 and TNF-α in chondrocytes.
- BGJXF reduces inflammation and cartilage damage in a rat model of KOA.

## Abstract

Knee osteoarthritis (KOA) poses a significant global health challenge due to its high prevalence and the limited availability of effective treatment options. This study aims to elucidate the multi-target therapeutic mechanisms of bu gan jian xi fang (BGJXF), a traditional Chinese medicine (TCM) formula, in the treatment of KOA.

The study employed integrated liquid chromatography-mass spectrometry (LC–MS) analysis to identify the chemical constituents of BGJXF. Network pharmacology was subsequently utilized to predict potential therapeutic targets shared by BGJXF and KOA. Enrichment analysis was conducted to identify key pathways, while molecular docking was used to assess the binding affinities of principal components to core targets. These mechanisms were further validated through in vitro experiments, measuring NF-κB p65 and TNF-α levels in LPS-stimulated human chondrocytes treated with dehydrocorydaline. Additionally, in vivo validation was performed using a papain-induced KOA rat model to evaluate serum cytokines (IL-1β, IL-6), histopathological cartilage damage and inflammation, and the tissue microenvironment via immunofluorescence following BGJXF treatment.

LC–MS analysis identified 91 chemical constituents in BGJXF. Network pharmacology predicted 62 shared therapeutic targets, which were significantly enriched in the AGE-RAGE and HIF-1 signaling pathways. Molecular docking identified dehydrocorydaline as a key component with strong binding affinities to IL-6, BCL2, MMP9, and CCND1. In vitro, dehydrocorydaline effectively suppressed LPS-induced overexpression of NF-κB p65 and TNF-α in chondrocytes. In vivo, BGJXF treatment significantly reduced serum IL-1β and IL-6 levels, mitigated cartilage structural damage and inflammatory cell infiltration as shown by histopathological analysis, and modulated tissue heterogeneity in the KOA rat model.

Collectively, these findings indicate that BGJXF, driven by dehydrocorydaline, exerts chondroprotective and anti-inflammatory effects primarily through inhibition of the NF-κB pathway via a multi-target mechanism. The overall therapeutic efficacy of BGJXF may be mediated by its modulation of the dual-pathology axis of “glycometabolic stress-hypoxic injury,” which is formed by the AGE-RAGE and HIF-1 signaling pathways. This study lays a pharmacological foundation for the application of BGJXF as a multi-target therapeutic strategy for the management of KOA.