title: Mitigating effect of chrysin loaded solid lipid nanoparticles against Amyloid β25-35 induced oxidative stress in rat hippocampal region: An efficient formulation approach for Alzheimer's disease.
abstract: Alzheimer's disease (AD) is the most prevalent form of dementia. Amyloid-β25-35 (Aβ25-35), a well-established neurotoxicant, is reported to be involved in the etiology of AD. Chrysin (CN) with its wide range of biological activities in terms of reversing the neuronal damage once induced is limited due to its compromised bioavailability. Solid lipid nanoparticles (SLNs) on the other hand due to its improved protein stability, avoids proteolytic degradation, as well as sustained release of the incorporated molecules could be widely applied as a drug delivery vehicle. Hence, in the present investigation, we prepared CN loaded SLNs (CN-SLNs) and investigated its therapeutic role in alleviating Aβ25-35 administered neuronal damage. All the antioxidant enzymes and non-antioxidant enzyme in hippocampus were reduced significantly (P<0.01) in the Aβ25-35 injected group, whereas lipid peroxidation and acetylcholine esterase were increased significantly (P<0.01). These changes were restored significantly (P<0.01) by CN-SLNs (5mg/kg and 10mg/kg) and (P<0.05) by free CN (50mg/kg and 100mg/kg). Aβ25-35 also resulted in poor memory retention in behavioral tasks and histopathological sections of the hippocampal region showed the extent of neuronal loss which was thereby restored back on treatment with CN-SLNs and free CN. Our findings demonstrate that the therapeutic efficacy of CN could be attained at lower dose and also its oral bioavailability could be increased by encapsulating CN in SLNs. Thus the results suggest that CN-SLNs could be used as a potential therapeutic and a brain targeting strategy to combat the global burden of Alzheimer's disease.
authors.affiliation: Department of Medical Biochemistry, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai 600 113, Tamil Nadu, India.
authors.forename: Aishwarya
authors.initials: A
authors.lastname: Vedagiri
authors.affiliation: Department of Medical Biochemistry, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai 600 113, Tamil Nadu, India. Electronic address: drsumathi.bioscience@gmail.com.
authors.forename: Sumathi
authors.initials: S
authors.lastname: Thangarajan
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001205:Ascorbic Acid / Q000378:metabolism; D016503:Drug Delivery Systems; D005419:Flavonoids / Q000008:administration & dosage*; D005978:Glutathione / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D053758:Nanoparticles / Q000008:administration & dosage*; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D018384:Oxidative Stress / Q000187:drug effects*; D010446:Peptide Fragments / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D021641:Recognition, Psychology / Q000187:drug effects
chemical_list: D016229:Amyloid beta-Peptides; D000975:Antioxidants; D005419:Flavonoids; D018696:Neuroprotective Agents; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); C043561:chrysin; D000110:Acetylcholinesterase; D005978:Glutathione; D001205:Ascorbic Acid
keywords: Alzheimer's disease; Amyloid β(25–35); Chrysin; Solid lipid nanoparticles