Neuroprotective effects of curcumin loaded solid lipid nanoparticles on homocysteine induced oxidative stress in vascular dementia

Abstract

Vascular dementia (VaD), a diverse group of brain disorders with cognitive decline is attributable to cerebrovascular pathologies. Recent studies have shown that mitochondrial dysfunctions and oxidative stress are involved in cognitive decline. Several studies consider that oxidative stress is the main pathogenic factor in VaD. However, curcumin is having a therapeutic potential in oxidative stress and is limited due to its compromised bioavailability (BA). The current study aims to evaluate the neuroprotective effects of curcumin loaded solid lipid nanoparticles (Cur-SLNP) on homocysteine (HCY) induced oxidative stress in vascular dementia (VaD) by behavioural, biochemical, neurochemical, and histopathological alterations in different regions of the brain. Male sprague dawley rats were divided in to six groups. Group I was normal control and group II received HCY at 400 µg/kg/day, i.v for 14 days. Group III and IV received (Cur – 25 mg/kg, p.o + HCY- 400 µg/kg/day, i.v) and (Cur – 50 mg/kg, p.o + HCY- 400 µg/kg/day, i.v) . Group V and VI received Cur-SLNP at the dose (Cur – SLNP – 10 mg/kg, p.o + HCY - 400 µg/kg/day, i.v) and (Cur – SLNP – 25 mg/kg, p.o + HCY - 400 µg/kg/day, i.v) for 14 days. Subsequently, rats were tested for behavioral assessments on 0th, 7th, and 14th days and then sacrificed for biochemical, neurochemical, and histopathological assays in different regions of the brain. In the present study, the treatment with Cur-SLNP at high dose (Cur – SLNP – 25 mg/kg, p.o + HCY - 400 µg/kg/day, i.v) successfully ameliorated the oxidative stress in VaD by the estimations of biochemical, neurochemical and histological alterations. Thus, Cur-SLNP at high dose can be considered as a potential therapeutic strategy for the treatment of oxidative stress in vascular dementia induced by homocysteine in different regions of the brain. To the best of our knowledge, based on the results, this is the first study to reveal the neuroprotective effects of Cur-SLNP on HCY induced oxidative stress in vascular dementia.