Possible modulation of neuroinflammation by stabilized rice bran extract through targeting PPAR gamma-NFmB signaling pathway / Yasmine Abdelaziz Abdelhamid Ali ; Supervised Mohammed Farrag Elyamany , Osama Ahmed Badary , Ola Ahmed Heikal

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

PPAR-Þ anti-inflammatory functions have received significant attention since its agonists have been shown to exert a wide range of protective effects in many experimental models of neurologic diseases. Rice bran is very rich in polyunsaturated fatty acids, which are reported to act as PPAR-Þ partial agonists. Herein, the anti-inflammatory effect of rice bran extract (RBE) through PPAR-Þ activation was evaluated in LPS-induced neuroinflammatory mouse model in comparison to pioglitazone (PG) using 80 Swiss albino mice. RBE (100 mg/kg) and PG (30 mg/kg) were given orally for 21 days and LPS (0.25 mg/kg) was injected intraperitoneally for the last 7 days. TNF-Ü and COX-2 brain contents were evaluated by real-time PCR and immunohistochemical analysis. In addition, NFmB binding to its response element was evaluated alongside with the effect of treatments on ImB gene expression. Furthermore, PPAR-Þ sumoylation was also studied. Finally, histopathological examination was performed for different brain areas. RBE administration was found to protect against the LPS-induced inflammatory effects by decreasing the inflammatory mediator expression in mice brains. It also decreased PPAR-Þ sumoylation without significant effect on ImB expression or NFmB binding to its response element. The majority of the effects were attenuated in presence of PPAR-Þ antagonist (GW9662). Such findings highlight the agonistic effect of RBE component(s) on PPAR-Þ and support the hypothesis of involvement of PPAR-Þ activation in its neuroprotective effect

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