Thesis (Ph.D.) - Cairo University - Faculty of Pharmacy - Department of Pharmacology and Toxicology

Aim:Mangiferin (MF), a xanthonoid from Mangiferaindica, possesses anti-inflammatory, immunomodulatory, and potent antioxidant effects; however, its protective effect against multiple organ dysfunction syndrome has not been fully clarified. The study was designed to assess the possible mechanism of action of MF20 and its nano-formulation (NMF10) against mesenteric I/R model. MainMethods:Male Wister rats were randomly allocated into 6 groups (n= 6); in the first group, rats received saline and the SMA was manipulated only to serve as the sham-operated group. In the 5 other groups rats were subjected to I/R, which was induced by clamping the superior mesenteric artery for 30 minutes followed by declamping for 60 minutes. Group 2 was donated as the untreated I/R control and animals received saline only, while in groups 3 and 4, animals were pre-treated with MF (20 mg/kg, i.p) or NMF (10mg/kg, i.p), for 3 days before I/R, while rats in groups 5 and 6 received the two blockers; viz.,methyllycaconitine (MLA) and atropine (Sigma-Aldrich Chemical Company, MO, USA) 30 min before NMF10for 3 days. MF20 was dissolved in the vehicle (2% DMSO in saline), while NMF10 were sonicated well before administration. Atropine and methyllycaconitine (MLA) were diluted with 0.9% saline prior to the experiment. Key findings: The mechanistic studies revealed that MF20 protected the 3 organs studied, viz., liver, kidney and intestine partly via increasing the content of Ý-catenin and PPAR-Þ along with decreasing that of GSK-3Ý and the phosphorylated NF-{u049B}B-p65. MF20 and NMF10 antioxidant effect was evidenced by increasing contents of total antioxidant capacity and GST, besides normalizing that of MDA and increasing m-RNA levels of NRF-2 and HO-1

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