Anti-TNF-α and anti-arthritic effect of patuletin: A rare flavonoid from Tagetes patula

Int Immunopharmacol. 2016 Jul:36:232-240. doi: 10.1016/j.intimp.2016.04.034. Epub 2016 May 10.

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.

Keywords: Anti TNF-α; Immunosuppressive; Patuletin; Rheumatoid arthritis.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / therapeutic use*
  • Arthritis, Experimental / drug therapy*
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / immunology
  • CD4-Positive T-Lymphocytes / drug effects*
  • CD4-Positive T-Lymphocytes / physiology
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Chromones / therapeutic use*
  • Cytotoxicity, Immunologic / drug effects
  • Disease Models, Animal
  • Female
  • Humans
  • Interleukin-1beta / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species / metabolism
  • Tagetes / immunology*
  • Tumor Necrosis Factor-alpha / metabolism*

Substances

  • Anti-Inflammatory Agents
  • Chromones
  • Interleukin-1beta
  • Reactive Oxygen Species
  • Tumor Necrosis Factor-alpha
  • patuletin