Effects of Pelargonium sidoides root extract on paw oedema, nitric oxide signaling, and synovial vascular changes in a rat model of adjuvant-induced arthritis

Rheumatoid arthritis (RA) is characterized by chronic synovitis with pannus formation and progressive joint destruction. Pannus growth relies on angiogenesis, and nitric oxide (NO) contributes to vascular and inflammatory signaling. Although Pelargonium sidoides (PS) has not been evaluated in experimental arthritis, prior work suggests that PS can modulate NO production in activated macrophages. Arthritis was induced with complete Freund's adjuvant (CFA) on day 0. On day 17, rats with ≥ 5% paw swelling were treated. From day 17 to day 27, rats received daily oral P. sidoides (100, 200, or 500 mg/kg), ibuprofen (100 mg/kg), or vehicle. Paw diameter was recorded during treatment. On day 27, tissues were collected for histopathology (inflammation, angiogenesis, granuloma formation, synovial hyperplasia) and blood was analysed for nitrite/nitrate (NOx) and oxidative/antioxidant markers (asymmetric dimethylarginine (ADMA), malondialdehyde (MDA), superoxide dismutase (SOD), catalase, and glutathione). All doses of P. sidoides reduced paw oedema. The 200 mg/kg dose resulted in NOx levels and synovial microvessel densities that were numerically closer to healthy control values; however, these improvements did not reach statistical significance when compared directly to the vehicle group. Other oxidative markers showed no consistent changes. Plasma glutathione decreased across PS-treated groups without accompanying increases in MDA or body-weight loss, which is compatible with increased utilization during phytochemical clearance rather than overt systemic toxicity. In conclusion, P. sidoides improved macroscopic swelling in adjuvant arthritis and, at 200 mg/kg, showed numerical shifts toward control-like values in plasma NOx and synovial microvessel density, although studies with greater statistical power are needed to confirm these exploratory tissue-level signals.