A Self-Microemulsifying Formulation of Oxyresveratrol Prevents Amyloid Beta Protein-Induced Neurodegeneration in Mice

The polyphenol compound, oxyresveratrol (OXY) possesses potent antioxidant and neuroprotective properties of potential utility in the treatment of Alzheimer ' s disease. However, the low oral bioavailability limits its neuroprotective effect and clinical application. The neuroprotective effect of orally administered OXY-loaded self-microemulsifying drug delivery system (OXY-SMEDDS) was compared with free OXY in vivo. Mice were orally administered either free OXY or OXYSMEDDS once daily at a dose of 90, 180, or 360 mg/kg for 14 d. Mice received a single intracerebroventricular injection of the neurotoxic amyloid beta (A beta) 25-35 peptide at day 8 during oral treatment. The OXY-SMEDDS formulation resulted in four-times reduction of the free OXY dose required for prevention of neurotoxicity effects due to A beta 25-35 peptide as demonstrated by a significant decline in behavior impairments, lipid oxidation levels, and neuronal cell loss in all hippocampal subfields (p < 0.0001). These results indicate the potential of OXY-SMEDDS by oral delivery to improve the efficacy of this compound in the treatment of Alzheimer's disease.