Geranium wallichianum D. Don Ex Sweet Ameliorates Rheumatoid Arthritis by Curtailing the Expression of COX-II and Inflammatory Cytokines as Well as by Alleviating the Oxidative Stress

Geranium wallichianum D. Don ex sweet traditionally been used as home remedy for backaches, joint pain, colic, and rheumatism. The objective of this study was to investigate the therapeutic benefits of plant in an adjuvant-induced arthritis paradigm. Immune-mediated rheumatoid arthritis was developed by injecting complete Freund's adjuvant (CFA) into the hind paws of rats and the aqueous methanolic crude extract was administered. The animals were physically monitored for changes in paw edema size and arthritic score. Hematological parameters and systemic inflammatory indicators evaluated. Genetic expressions of tumor necrosis factor (TNF-alpha), interleukins (IL-1 beta, IL-6), necrosis factor (NF-kappa B), and cyclooxygenase (COX-II) enzyme were studied using real-time qPCR. PGE2 levels in blood were quantified through Enzyme Linked Immunosorbent Assay (ELISA). On the 14th day, Immunoglobulin E (IGE) exhibited a substantial decline in paw edema and arthritic score. At the doses of 500 mg/Kg (P <=.05) and 1000 mg/Kg (P <=.001), IGE significantly reduced TNF-alpha, interleukins, and COX-II mRNA expression. IGE significantly lowered the MDA levels at the doses of 500 and 1000 mg/Kg (13.18 +/-.70 and 9.04 +/-.26 mu M/L respectively) as compared to arthritic control (30.82 +/- 1.12 mu M/L) group. IGE significantly improved the antioxidant enzyme activities of CAT and SOD(P <=.001) in treated animals. TNF-alpha, interleukins, and COXII mRNA expression were also significantly reduced at the doses of 300 (P <=.05), 500 (P <=.01) and 1000mg/Kg (P <=.001) which were expressed as fold changes. This study shows that Geranium wallichianum D. Don ex sweet has a strong potential to alleviate immunemediated arthritis by lowering oxidative stress and downregulating the proinflammatory cytokines signaling mechanisms.