ReferenceID 5543

Antioxidative and Anti-inflammatory Effects of Kojic Acid in Aβ-Induced Mouse Model of Alzheimer's Disease

Mol Neurobiol

Alzheimer's disease (AD) is a common cause of dementia that is clinically characterized by the loss of memory and cognitive functions. Currently, there is no specific cure for the management of AD, although natural compo

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Reference Id
5543
Evidence Id
22133
Core Evidence Id
22133
Source Reference Id
4315
Herb2 Reference Id
HBREF005112
Subject Paper Key
HBIN032235_34255249
Pubmed Id
34255249
Doi
10.1007/s12035-021-02460-4
Paper Title
Antioxidative and Anti-inflammatory Effects of Kojic Acid in Aβ-Induced Mouse Model of Alzheimer's Disease
Paper Abstract
Alzheimer's disease (AD) is a common cause of dementia that is clinically characterized by the loss of memory and cognitive functions. Currently, there is no specific cure for the management of AD, although natural compounds are showing promising therapeutic potentials because of their safety and easy availability. Herein, we evaluated the neuroprotective properties of kojic acid (KA) in an AD mouse model. Intracerebroventricular injection (i.c.v) of Abeta1-42 (5 muL/5 min/mouse) into wild-type adult mice induced AD-like pathological changes in the mouse hippocampus by increasing oxidative stress and neuroinflammation, affecting memory and cognitive functions. Interestingly, oral treatment of kojic acid (50 mg/kg/mouse for 3 weeks) reversed the AD pathology by reducing the expression of amyloid-beta (Abeta) and beta-site amyloid precursor protein cleaving enzyme1 (BACE-1). Moreover, kojic acid reduced oxidative stress by enhancing the expression of nuclear factor erythroid-related factor 2 (Nrf2) and heme oxygenase 1 (HO1). Also, kojic acid reduced the lipid peroxidation and reactive oxygen species in the Abeta + kojic acid co-treated mice brains. Moreover, kojic acid decreased neuroinflammation by inhibiting Toll-like receptor 4, phosphorylated nuclear factor-kappaB, tumor necrosis factor-alpha, interleukin 1-beta (TLR-4, p-NFkappaB, TNFalpha, and IL-1beta, respectively), and glial cells. Furthermore, kojic acid enhanced synaptic markers (SNAP-23, SYN, and PSD-95) and memory functions in AD model mice. Additionally, kojic acid treatment also decreased Abeta expression, oxidative stress, and neuroinflammation in vitro in HT-22 mouse hippocampal cells. To the best of our knowledge, this is the first study to show the neuroprotective effects of kojic acid against an AD mouse model. Our findings could serve as a favorable and alternative strategy for the discovery of novel drugs to treat AD-related neurodegenerative conditions.
Journal
Mol Neurobiol
Publish Year
2021
Experiment Subject
mouse; ht-22 mouse hippocampal cells
Experiment Type
Animal Experiment
Phenotype Related
Dementia; Alzheimer's Disease; Neurodegenerative Conditions
Paper Title Cn
Paper Title En
Antioxidative and Anti-inflammatory Effects of Kojic Acid in Aβ-Induced Mouse Model of Alzheimer's Disease
Bilingual Status
semi_complete