Pentahydroxy flavonoid isolated from Madhuca indica ameliorated adjuvant-induced arthritis: Possible role of TNF-α, IL’s, NF-kβ, Ikβα, COX-2, P2X7

Abstract

Background Rheumatoid arthritis (RA) is a chronic autoimmune disorder associated with progressive joint disability. Madhuca indica J. F. Gmel (family Sapotaceae) is an Indian medicinal plant reported to have an array of pharmacological properties. Objective To evaluate the anti-arthritic activity of isolated phytoconstituent from methanolic extract of Madhuca indica Leaves (MI-ALC) and its possible mechanism of action in FCA induced experimental arthritis. Materials and methods Polyarthritis was induced in female Wistar rats by intradermal administration of FCA (0.1 ml) into the tail. Polyarthritis was allowed to develop for the next 32 days. Then rats were treated with isolated phytoconstituent from MI-ALC (5, 10, and 20 mg/kg, p.o.) Results HPTLC, FTIR, and LC-MS spectral analysis of phytoconstituent isolated from MI-ALC confirmed the structure as 3,5,7,3′,4′- Pentahydroxy flavone (i.e., QTN). Treatment with QTN (10 and 20 mg/kg) showed significant inhibition (p < 0.05) in FCA-induced increased paw volume, joint diameter, paw withdrawal threshold, and latency. The elevated synovial oxido-nitrosative stress and protein levels of TNF-α, IL-1β, and IL-6 were significantly reduced (p < 0.05)by QTN. Western blot analysis revealed QNT significantly ameliorated (p < 0.05) up-regulated NF-kβ, Ikβα, COX-2, and P2X7 protein expressions. Conclusion QTN ameliorates FCA-induced hyperalgesia via inhibition of elevated oxido-nitrosative stress, inflammatory mediators (NF-kβ, Ikβα, COX-2, and P2X7), and pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) in experimental rats.