Polystichum braunii extracts inhibit Complete Freund's adjuvant-induced arthritis via upregulation of I-κB, IL-4, and IL-10, downregulation of COX-2, PGE2, IL-1β, IL-6, NF-κB, and TNF-α, and subsiding oxidative stress.

Polystichum braunii (Spenn.) Fée is a traditional remedy for rheumatoid arthritis, a chronic inflammatory disorder of polygenetic origin. The current project was intended to demonstrate the role of inflammatory and oxidative stress biomarkers in the anti-arthritic activity of the P. braunii extracts. Methanolic and aqueous extracts of the plant roots were prepared by triple maceration. The phytochemical evaluation of the plant extracts was carried out by high-performance liquid chromatography (HPLC). The plant extracts at 150, 300, and 600 mg/kg/day and piroxicam (10 mg/kg/day) were orally administered to Wistar rats for 21 days that were previously immunized with Complete Freund's adjuvant (150 µl on right hind paw) except normal and arthritic control rats. Both plant extracts mitigated the paw oedema, restored the immune organ and body weights, and ameliorated the level of blood parameters such as haemoglobin, red blood cells, platelets, white blood cells, alkaline phosphatase (ALP), C-reactive proteins, and rheumatoid factor. The evaluation of gene expression using quantitative-real-time polymerase chain reaction (qRT-PCR) revealed the substantial downregulation of tumor necrosis factor (TNF)-α, Interleukin (IL)-6, IL-1β, cyclo-oxygenase (COX)-2, nuclear factor (NF)-κB, and upregulation of IL-4, IL-10 and I-κB in polyarthritic rats treated with the plant extracts. Methanolic plant extract exhibited the maximum effect on upregulation of IL-4 (79 ± 3%), IL-10 (62.66 ± 4.93%), and I-κB (73.66 ± 3.05%) at 600 mg/kg/day. Treatment with the plant extracts also reduced the level of prostaglandin E2 and TNF-α in the serum of arthritic rats' dose dependently. It was also found that the plant extracts and piroxicam increased (p < 0.05) the activities of superoxide dismutase and catalase in the liver tissue while reduced the level of malondialdehyde in arthritic rats. Histological examination of ankle joints revealed that the plant extracts decreased the pannus formation, inflammation, and synovial hyperplasia in arthritic animals. HPLC analysis depicted that the plant extracts had contained kaempferol, quercetin, gallic acid, and other phenolic acids. It can be elucidated from the results that the extracts of P. braunii roots exhibited anti-arthritic activity in Wistar rats through modulation of inflammatory cytokines and boosting the antioxidant defense mechanism.