Mangiferin protects against ‭intestinal ischemia/reperfusion-induced ‭liver injury: ‬‬Involvement of PPAR-‭γ, GSK-3β and Wnt/β-catenin pathway‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬

Eur J Pharmacol. 2017 Aug 15:809:80-86. doi: 10.1016/j.ejphar.2017.05.021. Epub 2017 May 12.

Abstract

Aim: Mangiferin (MF), a xanthonoid from Mangifera indica, possesses anti-inflammatory, immunomodulatory, and potent antioxidant effects; however, its protective effect against mesenteric ischemia/reperfusion (I/R)-induced liver injury has not been fully clarified. The study was designed to assess the possible mechanism of action of MF against mesenteric I/R model.

Main methods: Male Wister rats were treated with MF (20mg/kg, i.p) or the vehicle for 3 days before I/R, which was induced by clamping the superior mesenteric artery for 30min followed by declamping for 60min.

Key findings: The mechanistic studies revealed that MF protected the 2 organs studied, viz., liver and intestine partly via increasing the content of β-catenin and PPAR-γ along with decreasing that of GSK-3β and the phosphorylated NF-қB-p65. MF antioxidant effect was evidenced by increasing contents of total antioxidant capacity and GST, besides normalizing that of MDA. Regarding the anti-inflammatory effect, MF reduced IL-1β and IL-6, effects that were mirrored on the tissue content of MPO. Moreover, MF possessed anti-apoptotic character evidenced by elevating Bcl-2 content and reducing that of caspase-3. In the serum, intestinal I/R increased the activity of ALT, AST, and creatine kinase.

Significance: The intimated protective mechanisms of MF against mesenteric I/R are mediated, partially, by modulation of oxidative stress, inflammation, and apoptosis possibly via the involvement of Wnt/β-catenin/NF-қβ/ PPAR-γ signaling pathways.

Keywords: GSK-3β; Intestinal ischemia/reperfusion; Mangiferin; Mangiferin (PubChem CID: 5281647); PPAR-γ; Wnt/β-Catenin; malondialdehyde (PubChem CID: 10964); thiobarbituric acid (PubChem CID: 2723628).

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Biomarkers / metabolism
  • Cytoprotection / drug effects
  • Glycogen Synthase Kinase 3 beta / metabolism*
  • Interleukin-6 / metabolism
  • Intestines / blood supply*
  • Liver / drug effects
  • Liver / injuries*
  • Male
  • Neutrophil Infiltration / drug effects
  • Oxidative Stress / drug effects
  • PPAR gamma / metabolism*
  • Rats
  • Rats, Wistar
  • Reperfusion Injury / immunology
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / pathology*
  • Transcription Factor RelA / metabolism
  • Wnt Signaling Pathway / drug effects*
  • Xanthones / pharmacology*

Substances

  • Biomarkers
  • Interleukin-6
  • PPAR gamma
  • Transcription Factor RelA
  • Xanthones
  • mangiferin
  • Glycogen Synthase Kinase 3 beta