Ethanolic Garcinia mangostana extract and α-mangostin improve dextran sulfate sodium-induced ulcerative colitis via the suppression of inflammatory and oxidative responses in ICR mice

J Ethnopharmacol. 2021 Jan 30:265:113384. doi: 10.1016/j.jep.2020.113384. Epub 2020 Sep 11.

Abstract

Ethnopharmacological relevance: Ulcerative colitis (UC) is an inflammatory disorder of the colon. Garcinia mangostana Linn. (GM) has been traditionally used for its anti-inflammatory and antioxidant activities.

Aim of the study: The effects of GM and its bioactive constituent α-mangostin on dextran sulfate sodium (DSS)-induced UC in mice were investigated.

Materials and methods: Adult ICR mice (n = 63) were pretreated with ethanolic GM extract at 40, 200, and 1000 mg/kg/day (GM40, GM200, and GM1000), α-mangostin at 30 mg/kg/day, or sulfasalazine at 100 mg/kg/day (SA) for 7 consecutive days. On days 4-7, UC was induced in the mice by the oral administration of DSS (40 kDa, 6 g/kg/day), while control mice received distilled water. The UC disease activity index (DAI) and histological changes were recorded. The activities of myeloperoxidase, catalase, and superoxide dismutase, and the levels of reactive oxygen species (ROS), nitric oxide (NO), and malondialdehyde (MDA) were determined. The mRNA expression of inflammatory related genes including proinflammatory cytokine Tnf-α, Toll-like receptor (Tlr-2), adhesion molecules (Icam-1 and Vcam-1), and monocyte chemoattractant protein (Mcp-1) were evaluated.

Results: Treatment with GM or α-mangostin decreased the UC DAI and protected against colon shortening and spleen and kidney enlargement. GM and α-mangostin prevented histological damage, reduced mast cell infiltration in the colon, and decreased myeloperoxidase activity. GM and α-mangostin increased catalase and superoxide dismutase activity and decreased ROS, NO, and MDA production. GM downregulated mRNA expression of Tnf-α, Tlr-2, Icam-1, Vcam-1, and Mcp-1.

Conclusions: GM and α-mangostin attenuated the severity of DSS-induced UC via anti-inflammatory and antioxidant effects. Therefore, GM is a promising candidate for development into a novel therapeutic agent for UC.

Keywords: Bowel disease; DSS; Inflammation; Mangosteen; Myeloperoxidase.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / isolation & purification
  • Anti-Inflammatory Agents / pharmacology*
  • Antioxidants / administration & dosage
  • Antioxidants / isolation & purification
  • Antioxidants / pharmacology
  • Colitis, Ulcerative / drug therapy*
  • Colitis, Ulcerative / pathology
  • Dextran Sulfate
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Ethanol / chemistry
  • Garcinia mangostana / chemistry*
  • Male
  • Mice
  • Mice, Inbred ICR
  • Nitric Oxide / metabolism
  • Oxidative Stress / drug effects
  • Plant Extracts / pharmacology*
  • Xanthones / administration & dosage
  • Xanthones / isolation & purification
  • Xanthones / pharmacology

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Plant Extracts
  • Xanthones
  • Nitric Oxide
  • Ethanol
  • Dextran Sulfate
  • mangostin