Resveratrol loaded solid lipid nanoparticles attenuate mitochondrial oxidative stress in vascular dementia by activating Nrf2/HO-1 pathway.

Abstract

Vascular dementia (VaD) is the leading cause of cognitive decline resulting from vascular lesions. Recent studies have shown that mitochondrial dysfunctions and oxidative stress are involved in cognitive decline. The aim of the present study was to evaluate the beneficial effects of resveratrol-loaded solid lipid nanoparticles (R-SLNs) in permanent bilateral common carotid artery occlusion (BCCAO) induced model of VaD. R-SLNs prepared had average size of 286 nm and 91.25% drug encapsulation efficiency with sustained release. Moreover, R-SLNs had 4.5 times higher levels of resveratrol (RSV) in brain compared to when administered as free RSV. Neurobehavioral analyses revealed that R-SLNs administration successfully ameliorated cognitive decline observed in BCCAO rats. Administration of R-SLNs to BCCAO animals showed significant reduction in mitochondrial reactive oxygen species (ROS) generation, lipid peroxidation, and protein carbonyls. In addition, R-SLNs significantly improved redox ratio and Mn-superoxide dismutase (Mn-SOD) activity. R-SLNs administration resulted in significant reduction in hypoxia-inducible factor 1α (HIF-1α) levels, whereas, nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and heme oxygenase 1 (HO-1) levels were increased after R-SLNs treatment. Taken together, the results demonstrate that R-SLNs could be a novel and promising therapeutic strategy in VaD as well in other age-related neurodegenerative disorders.

• Authors: Aarti Yadav, Aditya Sunkaria, Nitin Singhal, Rajat Sandhir
• Journal: Neurochemistry international (Neurochem Int) Vol. 112 Pg. 239-254 (01 2018) ISSN: 1872-9754 [Electronic] England
• PMID: 28782592 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017 Elsevier Ltd. All rights reserved.

Chemical References

• Antioxidants
• Drug Carriers
• Liposomes
• Membrane Proteins
• NF-E2-Related Factor 2
• Nfe2l2 protein, mouse
• Reactive Oxygen Species
• Heme Oxygenase-1
• Hmox1 protein, mouse
• Resveratrol

Topics

• Animals
• Antioxidants (administration & dosage)
• Dementia, Vascular (drug therapy, metabolism)
• Drug Carriers (administration & dosage)
• Heme Oxygenase-1 (metabolism)
• Liposomes
• Male
• Membrane Proteins (agonists, metabolism)
• Mitochondria (drug effects, metabolism)
• NF-E2-Related Factor 2 (agonists, metabolism)
• Nanoparticles (administration & dosage)
• Oxidative Stress (drug effects, physiology)
• Rats
• Rats, Sprague-Dawley
• Reactive Oxygen Species (metabolism)
• Resveratrol (administration & dosage)
• Signal Transduction (drug effects, physiology)