Abstract
Rheumatoid arthritis (RA) poses a serious health problem as a chronic autoimmune joint disease with significant mortality and morbidity. Proinflammatory cytokines TNF-alpha and IL-1 beta, reactive oxygen species (ROS), and activated CD4(+) T-cells play key roles in the progression of arthritis. The aim of the study is to evaluate the in vitro and in vivo immunomodulatory and anti-arthritic effect of flavonoid patuletin, isolated from Tagetes patula. ELISA was applied for quantification of TNF-alpha and IL-1 beta. Intracellular and extracellular ROS production from phagocytes was measured by the chemiluminescence technique. Proliferation of T-cells was observed using a liquid scintillation counter. Cytotoxicity was assessed by a MTT assay. The serological and histological analysis studies were performed using a rodent model of adjuvant-induced arthritis (AIA). Expression of p38 and NF-kappa B after treatment of compound was observed by western blotting. Patuletin showed potent inhibitory effects on TNF-alpha in vitro as well as inhibited the production of both cytokines in vivo. It also showed potent suppression of proliferation of T-cells and significantly inhibited the extracellular and intracellular ROS production. Patuletin revealed significant anti-inflammatory and anti-arthritic activities in the rodent model of adjuvant-induced arthritis (AIA). Histologically, it causes mild bone destruction compared to the arthritic control group, thus representing its anti arthritic potential. Based on these studies, patuletin could be considered as a potential immunosuppressive and anti-arthritic lead candidate. (C) 2016 Elsevier B.V. All rights reserved.