Anti-Inflammatory Effects of Vicatia thibetica De Boiss. in Rheumatoid Arthritis and Associated Multi-Pathway Modulation In Vivo.

Vicatia thibetica de Boiss. (VTDB) is not only used as an important Tibetan medicine but is also consumed as a common wild vegetable. Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by persistent synovial inflammation and progressive destruction of cartilage and bone. VTDB is recorded in the Four Medical Classics for treating "Huang-Shui," a condition resembling RA. To preliminarily investigate its potential therapeutic basis, VTDB and its polarity-based fractions were evaluated for their effects against RA. The chemical constituents of VTDB-TE were profiled using UHPLC-Q-Orbitrap MS/MS, and network pharmacology analysis predicted possible involvement of the PI3K/Akt and JAK2/STAT3 signaling pathways. Among the tested fractions, VTDB-nBuOH exhibited the most pronounced pharmacological activity in the collagen-induced arthritis (CIA) rat model. VTDB-nBuOH treatment was associated with reduced paw swelling, lower serum levels of rheumatoid factor (RF) and C-reactive protein (CRP), and improved synovial histopathology. The treatment was also associated with reduced levels of pro-inflammatory cytokines and alterations in the levels of proteins associated with PI3K/Akt, JAK2/STAT3, and the downstream IKK/IκB/NF-κB axis. Additionally, VTDB-nBuOH treatment was associated with a shift in macrophage polarization markers toward an anti-inflammatory M2-like phenotype, suggesting a possible restoration of the M1/M2 balance within the joint microenvironment. 16S rRNA sequencing revealed VTDB-nBuOH treatment-associated changes in gut microbial composition, including enrichment of certain beneficial genera and reduction of some pathogenic taxa. Proteomic analysis also pointed to the PI3K/Akt pathway as a potential node of interest. Collectively, these correlative findings suggest that VTDB-nBuOH may alleviate synovial inflammation and cartilage and bone damage through multi-pathway modulation, though further mechanistic studies are needed to establish causality. VTDB-nBuOH shows preliminary promise for further investigation as a potential candidate for RA treatment.