The clinical efficacy and mechanism of Rhodiola rosea in treating rheumatoid arthritis in high-altitude areas by regulating the HIF-1α signaling pathway.

OBJECTIVE: To evaluate the clinical efficacy of Rhodiola rosea in high-altitude rheumatoid arthritis (RA) patients and to investigate, in vitro, whether its anti-inflammatory mechanism is mediated by the HIF-1α signaling pathway. METHODS: This study adopted a retrospective analysis. Patients with RA in high-altitude areas were divided into the Rhodiola rosea treatment group (74 cases) and the conventional treatment group (86 cases). Baseline data, disease activity score (DAS28), inflammatory factors (CRP, ESR, TNF-α, and IL-6), serum HIF-1α levels, imaging data, and adverse reaction monitoring data were collected to evaluate the clinical efficacy and safety of Rhodiola rosea. Human synovial cells (HFLS-RA) were used for in vitro experiments to establish a hypoxic model. Using CCK-8, qRT-PCR, Western Blot, and gene overexpression techniques, the molecular mechanism was further explored. RESULTS: The Rhodiola rosea treatment group showed significantly better improvements in DAS28, CRP, ESR, TNF-α, and IL-6 compared to the conventional treatment group (p < 0.05). Imaging assessment showed greater reductions in synovial thickness and blood-flow signals in the knee and metacarpophalangeal joints in the Rhodiola rosea group than in the conventional treatment group. The serum HIF-1α level in the Rhodiola rosea group was significantly lower, and the incidence of adverse reactions (18.92%) was significantly lower than that of the conventional treatment group (34.88%), without any serious adverse events. The in vitro experiments showed that Rhodiola rosea injection (RRI) reduced hypoxia-induced expression of HIF-1α and its downstream factors MMP-3, VEGF, COX-2, and ICAM-1. CONCLUSION: Rhodiola rosea was associated with improved disease activity and inflammatory markers in high-altitude RA patients, with a favorable safety profile. The in vitro findings suggest that inhibition of HIF-1α signaling may be one potential mechanism, although prospective and translational validation is still required.