Equisetum diffusum whole plant methanol extract attenuates rheumatoid arthritis by modulating the expression of key inflammatory biomarkers in rat models

Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with subsequent damage to the bone joints with a global incidence rate of 0.5-1%. To combat with RA various commercially available anti-inflammatory drugs like non-steroidal anti-inflammatory drugs (NSAIDs) are commonly practiced; however, their long-term exposure often results in eliciting gastrointestinal and renal toxicity. Given this, the scientific communities are searching for an alternative therapeutic option that seems less injurious and equally efficacious. Equisetum diffusum D. Don, from the Equisetaceae family, is a native pteridophyte species of the sub-Himalayan region of India and has been reported to have a diverse array of pharmacological properties. The decoction and macerated whole plant extract has been used by various tribal communities (like Tagin, Galo, Adi, Kukis, Meiteis, Mulam) throughout the tropical and sub-tropical Asian countries for the treatment of arthritis, bone fractures, back pain, and abrasives. The present research is focused on determining the anti-arthritic potential of E. diffusum whole plant methanol extract (EDME) in adjuvant-induced arthritic rats. Oral administration with 250 and 500 mg/kg b.w. doses of EDME significantly restored paw-edema, arthritic scoring, and normal body weight. EDME treatment also normalized the haematological, biochemical, radiological, and histological status when compared to the arthritic control rats. The methanol extract significantly (p < 0.05) attenuated arthritis progression by downregulating the gene expression of pro-inflammatory mediators, like COX-2, TNF-α, IL-6, and upregulating the expression of anti-inflammatory mediators PPAR-γ, Iκβ in the blood, in a dose-dependent manner. Significantly, EDME also reduced the serum concentration of COX-2, TNF-α, and IL-6 compared to arthritic control rats (p < 0.05). The treatment with EDME also normalized the oxidative stress level in liver by restoring the GSH level, CAT and SOD activities and reducing the elevated MDA level. HPTLC and LC-MS/MS analyses of EDME confirmed the presence of potent polyphenols (chlorogenic acid, 4-hydroxycinnamic acid) and flavonoids (kaempferol), thereby suggesting the anti-arthritic property of the plant. All our findings established the anti-arthritic potential of E. diffusum extract in chronic arthritis model on a strong ground.