title: Anti-TNF-α and anti-arthritic effect of patuletin: A rare flavonoid from Tagetes patula.
abstract: Rheumatoid arthritis (RA) poses a serious health problem as a chronic autoimmune joint disease with significant mortality and morbidity. Proinflammatory cytokines TNF-α and IL-1β, 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-α and IL-1β. 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-κB after treatment of compound was observed by western blotting. Patuletin showed potent inhibitory effects on TNF-α 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.
authors.affiliation: Panjwani Center for Molecular Medicine and Drug Research (PCMD), International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan. Electronic address: almas79_jabeen@yahoo.com.
authors.forename: Almas
authors.initials: A
authors.lastname: Jabeen
authors.affiliation: Panjwani Center for Molecular Medicine and Drug Research (PCMD), International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan; Faculty of Medicine, University of Tabuk, P.O. Box 741, Tabuk 71491, Kingdom of Saudi Arabia. Electronic address: mmesaik@hotmail.com.
authors.forename: M Ahmed
authors.initials: MA
authors.lastname: Mesaik
authors.affiliation: H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan. Electronic address: sh01us@hotmail.com.
authors.forename: Shabana U
authors.initials: SU
authors.lastname: Simjee
authors.affiliation: H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan. Electronic address: lubnazaheer_789@hotmail.com.
authors.lastname: Lubna
authors.affiliation: H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan. Electronic address: saminabano786@hotmail.com.
authors.forename: Samina
authors.initials: S
authors.lastname: Bano
authors.affiliation: H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan. Electronic address: shaheenfaizi@hotmail.com.
authors.forename: Shaheen
authors.initials: S
authors.lastname: Faizi
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000188:drug therapy*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002867:Chromones / Q000627:therapeutic use*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D031686:Tagetes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D002867:Chromones; D053583:Interleukin-1beta; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; C079162:patuletin
keywords: Anti TNF-α; Immunosuppressive; Patuletin; Rheumatoid arthritis