Saussurea involucrata oral liquid alleviates joint inflammation in CIA rats by modulating macrophage polarization and glucose metabolism.

Abstract

OBJECTIVE: To evaluate the therapeutic effects of Saussurea involucrata Oral Liquid (SIOL) in a collagen-induced arthritis (CIA) rat model. METHODS: This study was conducted from April 2023 to June 2024. Sixty male SPF SD rats were randomly divided into six groups: control, model, tripterygium glycosides tablet (TGT) group, and low, medium, and high doses of SIOL. CIA was induced by subcutaneous injection of bovine type II collagen (CII) and incomplete Freund’s adjuvant (IFA). Treatment groups received corresponding doses of SIOL or TGT. Therapeutic efficacy was assessed through body weight, arthritis index (AI), ankle diameter, and toe volume. Joint tissue pathology, serum and synovial inflammatory factors, macrophage polarization, and plasma metabolites were analyzed using H&E staining, ELISA, flow cytometry, Western blotting, and LC–MS. RESULTS: SIOL significantly reduced AI, ankle diameter, toe volume, and pathological scores compared to the model group. SIOL also decreased serum and synovial proinflammatory factors TNF-α, IL-6, and IL-1β while increasing anti-inflammatory IL-10 and IL-4. Medium and high doses of SIOL notably lowered M1 macrophage markers CD86 and iNOS, while elevating M2 markers CD163 and Arg-1. No significant differences were observed between the medium/high SIOL and TGT groups regarding therapeutic effects. Additionally, SIOL (high dose) markedly reduced glucose metabolism-related plasma metabolites, particularly key metabolites in the TCA cycle. A significant correlation was found between macrophage polarization, inflammatory markers, and metabolite levels. CONCLUSION: SIOL alleviates joint inflammation in CIA rats, which is associated with modulation of macrophage polarization and alterations in glucose metabolism.