PMID- 37394643
OWN - NLM
STAT- MEDLINE
DCOM- 20231020
LR  - 20231020
IS  - 1347-5215 (Electronic)
IS  - 0918-6158 (Linking)
VI  - 46
IP  - 7
DP  - 2023
TI  - 3',4'-Dihydroxyflavonol Attenuates Lipopolysaccharide-Induced Neuroinflammatory 
      Responses of Microglial Cells by Suppressing AKT-mTOR and NF-kappaB Pathways.
PG  - 914-920
LID - 10.1248/bpb.b23-00033 [doi]
AB  - Microglia-related neuroinflammation contributes to the pathogenesis of a variety 
      of neurodegenerative disorders such as Alzheimer's disease. The synthetic 
      flavonoid, 3',4'-dihydroxyflavonol (3,3',4'-trihydroxyflavone), has been shown to 
      protect brain or myocardial ischemia reperfusion-induced cell death and prevent 
      the aggregation of amyloid-beta protein, a process that causes progressive 
      neurodegeneration in Alzheimer's disease. Here, we explored the 
      anti-neuroinflammatory ability of 3',4'-dihydroxyflavonol in lipopolysaccharide 
      (LPS)-activated MG6 microglial cells. 3',4'-Dihydroxyflavonol attenuated 
      LPS-induced tumor necrosis factor-alpha and nitric oxide secretion in MG6 cells. 
      LPS-induced phosphorylation of mammalian target of rapamycin (mTOR), nuclear 
      factor-kappaB (NF-kappaB), and protein kinase B (AKT) (which are all associated with the 
      neuroinflammatory response in microglia) were attenuated by 
      3',4'-dihydroxyflavonol treatment. Treatment with the mTOR inhibitor, rapamycin, 
      NF-kappaB inhibitor, caffeic acid phenethyl ester, or AKT inhibitor, LY294002, also 
      attenuated LPS-induced tumor necrosis factor-alpha and nitric oxide secretion in MG6 
      cells. LY294002 treatment attenuated LPS-induced phosphorylation of mTOR and 
      NF-kappaB in MG6 cells. Hence, our study suggests that 3',4'-dihydroxyflavonol can 
      attenuate the neuroinflammatory response of microglial cells by suppressing the 
      AKT-mTOR and NF-kappaB pathways.
FAU - Akaishi, Tatsuhiro
AU  - Akaishi T
AD  - Laboratory of Pharmacology, Faculty of Pharmacy and Research Institute of 
      Pharmaceutical Sciences, Musashino University.
FAU - Yamamoto, Shohei
AU  - Yamamoto S
AD  - Laboratory of Pharmacology, Faculty of Pharmacy and Research Institute of 
      Pharmaceutical Sciences, Musashino University.
FAU - Abe, Kazuho
AU  - Abe K
AD  - Laboratory of Pharmacology, Faculty of Pharmacy and Research Institute of 
      Pharmaceutical Sciences, Musashino University.
LA  - eng
PT  - Journal Article
PL  - Japan
TA  - Biol Pharm Bull
JT  - Biological & pharmaceutical bulletin
JID - 9311984
RN  - R1I1R1C88V (3',4'-dihydroxyflavonol)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - *Alzheimer Disease/metabolism
MH  - Inflammation/chemically induced/drug therapy/metabolism
MH  - Lipopolysaccharides
MH  - Microglia/metabolism
MH  - *NF-kappa B/metabolism
MH  - Nitric Oxide/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - Animals
MH  - Mice
OTO - NOTNLM
OT  - 3',4'-dihydroxyflavonol
OT  - mammalian target of rapamycin
OT  - microglia
OT  - nuclear factor-kappaB
OT  - protein kinase B
EDAT- 2023/07/03 00:41
MHDA- 2023/07/04 06:42
CRDT- 2023/07/02 23:39
PHST- 2023/07/04 06:42 [medline]
PHST- 2023/07/03 00:41 [pubmed]
PHST- 2023/07/02 23:39 [entrez]
AID - 10.1248/bpb.b23-00033 [doi]
PST - ppublish
SO  - Biol Pharm Bull. 2023;46(7):914-920. doi: 10.1248/bpb.b23-00033.