Antioxidative and Anti-inflammatory Effects of Kojic Acid in A beta-Induced Mouse Model of Alzheimer's Disease
- Khan, Amjad; Park, Tae Ju; Ikram, Muhammad; Ahmad, Sareer; Ahmad, Riaz; Jo, Min Gi; Kim, Myeong Ok
- Issue Date
- Alzheimer' s disease; Kojic acid; Oxidative stress; Neuroinflammation; Neurodegeneration
- MOLECULAR NEUROBIOLOGY, v.58, no.10, pp.5127 - 5140
- Journal Title
- MOLECULAR NEUROBIOLOGY
- Start Page
- End Page
- 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 A beta(1-42) (5 mu L/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 (A beta) 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 A beta + kojic acid co-treated mice brains. Moreover, kojic acid decreased neuroinflammation by inhibiting Toll-like receptor 4, phosphorylated nuclear factor-kappa B, tumor necrosis factor-alpha, interleukin 1-beta (TLR-4, p-NF kappa B, TNF alpha, and IL-1 beta, 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 A beta 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.
- Files in This Item
- There are no files associated with this item.
- Appears in
- ETC > Journal Articles
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.