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

• Published in: European journal of pharmacology 2017-08, Vol.809, p.80-86
• Main Authors: El-Sayyad, Shorouk M., Soubh, Ayman A., Awad, Azza S., El-Abhar, Hanan S.
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis - drug effects; Biomarkers - metabolism; Cytoprotection - drug effects; Glycogen Synthase Kinase 3 beta - metabolism; GSK-3β; Interleukin-6 - metabolism; Intestinal ischemia/reperfusion; Intestines - blood supply; Liver - drug effects; Liver - injuries; Male; Mangiferin; Neutrophil Infiltration - drug effects; Oxidative Stress - drug effects; PPAR gamma - metabolism; PPAR-γ; Rats; Rats, Wistar; Reperfusion Injury - immunology; Reperfusion Injury - metabolism; Reperfusion Injury - pathology; Transcription Factor RelA - metabolism; Wnt Signaling Pathway - drug effects; Wnt/β-Catenin; Xanthones - pharmacology
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2017.05.021

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. 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. 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. 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.