Omics-based pharmacological evaluation reveals Yuanhu Zhitong oral liquid ameliorates arthritis by regulating PKC/ERK/NF-κB signaling pathway.

Ethnopharmacological Relevance: Successful use of herbal medicine in the treatment of rheumatoid arthritis (RA) creates opportunities for alternative therapies. Yuanhu Zhitong oral liquid (YZOL) is an herbal preparation known for its potent analgesic and anti-inflammatory properties in traditional use. However, the pharmacological mechanism of YZOL for treating RA remains unclear.

Aim Of The Study: The aim of this study was to evaluate the efficacy of YZOL in the treatment of RA and to explore its potential mechanisms through omics analysis.

Materials And Methods: Type II collagen was used to induce an arthritis rat model. The effects of YZOL on paw swelling, inflammatory cytokines, oxidative stress, and histopathological changes were systematically investigated. A pathway-driven transcriptomic analysis was performed to identify key signaling pathways associated with YZOL therapy. The key alterations were validated by qRT-PCR, Western blot, and immunohistochemistry assays.

Results: YZOL significantly attenuated arthritis progression, reduced paw swelling rate, and lowered arthritis score in CIA rats. YZOL also inhibited systemic inflammation and associated oxidative stress during RA. Transcriptomic analysis identified 341 genes with significantly altered expression following YZOL treatment. These genes were enriched in inflammation-related pathways, particularly in the NF-κB and MAPK signaling pathways. In addition, we discovered that YZOL can alleviate inflammation in the local synovial tissue. The effect of YZOL was confirmed by the suppression of PKC/ERK/NF-κB p65 signaling at systemic and local levels.

Conclusions: This study provides novel evidence that YZOL treatment ameliorates RA by suppressing the PKC/ERK/NF-κB pathway, suggesting its potential as an alternative therapy for RA.