PMID- 34255249
OWN - NLM
STAT- MEDLINE
DCOM- 20220203
LR  - 20220203
IS  - 1559-1182 (Electronic)
IS  - 0893-7648 (Linking)
VI  - 58
IP  - 10
DP  - 2021 Oct
TI  - Antioxidative and Anti-inflammatory Effects of Kojic Acid in Abeta-Induced Mouse 
      Model of Alzheimer's Disease.
PG  - 5127-5140
LID - 10.1007/s12035-021-02460-4 [doi]
AB  - 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 Abeta(1-42) (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.
CI  - (c) 2021. The Author(s), under exclusive licence to Springer Science+Business 
      Media, LLC, part of Springer Nature.
FAU - Khan, Amjad
AU  - Khan A
AD  - Division of Applied Life Science (BK 21 Four), College of Natural Sciences, 
      Gyeongsang National University, Jinju, 52828, Republic of Korea.
FAU - Park, Tae Ju
AU  - Park TJ
AD  - Haemato-Oncology/Systems Medicine Group, Paul O'Gorman Leukaemia Research Centre, 
      Institute of Cancer Sciences, MVLS, University of Glasgow, Glasgow, UK.
FAU - Ikram, Muhammad
AU  - Ikram M
AD  - Division of Applied Life Science (BK 21 Four), College of Natural Sciences, 
      Gyeongsang National University, Jinju, 52828, Republic of Korea.
FAU - Ahmad, Sareer
AU  - Ahmad S
AD  - Division of Applied Life Science (BK 21 Four), College of Natural Sciences, 
      Gyeongsang National University, Jinju, 52828, Republic of Korea.
FAU - Ahmad, Riaz
AU  - Ahmad R
AD  - Division of Applied Life Science (BK 21 Four), College of Natural Sciences, 
      Gyeongsang National University, Jinju, 52828, Republic of Korea.
FAU - Jo, Min Gi
AU  - Jo MG
AD  - Division of Applied Life Science (BK 21 Four), College of Natural Sciences, 
      Gyeongsang National University, Jinju, 52828, Republic of Korea.
FAU - Kim, Myeong Ok
AU  - Kim MO
AUID- ORCID: 0000-0003-2492-5369
AD  - Division of Applied Life Science (BK 21 Four), College of Natural Sciences, 
      Gyeongsang National University, Jinju, 52828, Republic of Korea. mokim@gnu.ac.kr.
LA  - eng
PT  - Journal Article
DEP - 20210713
PL  - United States
TA  - Mol Neurobiol
JT  - Molecular neurobiology
JID - 8900963
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Antioxidants)
RN  - 0 (Peptide Fragments)
RN  - 0 (Pyrones)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (amyloid beta-protein (1-42))
RN  - 6K23F1TT52 (kojic acid)
SB  - IM
MH  - Alzheimer Disease/*chemically induced/*drug therapy/metabolism
MH  - Amyloid beta-Peptides/administration & dosage/*toxicity
MH  - Animals
MH  - Anti-Inflammatory Agents/*administration & dosage
MH  - Antioxidants/*administration & dosage
MH  - Cell Line
MH  - Injections, Intraventricular
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Peptide Fragments/administration & dosage/*toxicity
MH  - Pyrones/*administration & dosage
MH  - Reactive Oxygen Species/antagonists & inhibitors/metabolism
MH  - Treatment Outcome
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - Kojic acid
OT  - Neurodegeneration
OT  - Neuroinflammation
OT  - Oxidative stress
EDAT- 2021/07/14 06:00
MHDA- 2022/02/04 06:00
CRDT- 2021/07/13 12:28
PHST- 2020/11/25 00:00 [received]
PHST- 2021/06/10 00:00 [accepted]
PHST- 2021/07/14 06:00 [pubmed]
PHST- 2022/02/04 06:00 [medline]
PHST- 2021/07/13 12:28 [entrez]
AID - 10.1007/s12035-021-02460-4 [pii]
AID - 10.1007/s12035-021-02460-4 [doi]
PST - ppublish
SO  - Mol Neurobiol. 2021 Oct;58(10):5127-5140. doi: 10.1007/s12035-021-02460-4. Epub 
      2021 Jul 13.