PMID- 34481870
OWN - NLM
STAT- MEDLINE
DCOM- 20220316
LR  - 20220316
IS  - 1872-9711 (Electronic)
IS  - 0161-813X (Linking)
VI  - 87
DP  - 2021 Dec
TI  - Genkwanin suppresses MPP(+)-induced cytotoxicity by inhibiting TLR4/MyD88/NLRP3 
      inflammasome pathway in a cellular model of Parkinson's disease.
PG  - 62-69
LID - S0161-813X(21)00103-0 [pii]
LID - 10.1016/j.neuro.2021.08.018 [doi]
AB  - Parkinson's disease (PD) is a complicated multifactorial neurodegenerative 
      disorder. Oxidative stress, neuroinflammatory response, and activation of 
      apoptosis have been proposed to be tightly involved in the pathogenesis of PD. 
      Genkwanin is a typical bioactive non-glycosylated flavonoid with 
      anti-inflammatory and anti-oxidant activities. However, the effect of genkwanin 
      on PD remains unclear. Cell viability, lactate dehydrogenase (LDH) release, 
      caspase-3/7 activity, and apoptosis was evaluated by MTT, LDH release assay, 
      caspase-3/7 activity assay, and TUNEL assay, respectively. The secretion of 
      prostaglandin E(2) (PGE(2)), tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, 
      and IL-6 were measured by respective commercial ELISA kits. The mRNA expression 
      of TNF-alpha, IL-1beta, and IL-6 was detected by qRT-PCR. The protein levels of 
      cycloxygenase-2 (COX-2), toll-like receptor 4 (TLR4), myeloid differentiation 
      factor 88 (MyD88), and NOD-like receptor (NLR) protein: 3 (NLRP3) were determined 
      by western blot analysis. Genkwanin at concentrations less than 40 muM had no 
      impact on cell viability and LDH release. Genkwanin suppressed MPP(+)-induced 
      neuroinflammation in SH-SY5Y cells. MPP(+) treatment inhibited cell viability, 
      increased LDH release, apoptosis, and ROS generation, and reduced superoxide 
      dismutase (SOD) activity in SH-SY5Y cells, which were abolished by genkwanin 
      treatment. Genkwanin suppressed MPP(+)-induced activation of TLR4/MyD88/NLRP3 
      inflammasome pathway in SH-SY5Y cells. TLR4 overexpression weakened the 
      anti-inflammatory and anti-neurotoxicity of genkwanin in SH-SY5Y cells. In 
      conclusion, genkwanin attenuated neuroinflammation and neurotoxicity by 
      inhibiting TLR4/MyD88/NLRP3 inflammasome pathway in MPP(+)-induced cellular model 
      of PD.
CI  - Copyright (c) 2021. Published by Elsevier B.V.
FAU - Li, Qiang
AU  - Li Q
AD  - Department of Neurology and Neurosurgery & Clinical College of 
      Neurorehabilitation of Tianjin Medical University, Tianjin, 300350, China; 
      Department of Neurology, Affiliated Hospital of Hebei University, Baoding, 
      071030, China.
FAU - Zhang, Peilan
AU  - Zhang P
AD  - Department of Neurology, Tianjin Huanhu Hospital, Tianjin, 300350, China. 
      Electronic address: peilzhang1@163.com.
FAU - Cai, Yun
AU  - Cai Y
AD  - Department of Neurology, Affiliated Hospital of Hebei University, Baoding, 
      071030, China.
LA  - eng
PT  - Journal Article
DEP - 20210902
PL  - Netherlands
TA  - Neurotoxicology
JT  - Neurotoxicology
JID - 7905589
RN  - 0 (Flavones)
RN  - 0 (Inflammasomes)
RN  - 0 (MYD88 protein, human)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (NLRP3 protein, human)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (TLR4 protein, human)
RN  - 0 (Toll-Like Receptor 4)
RN  - 5K3I5D6B2B (genkwanin)
RN  - R865A5OY8J (1-Methyl-4-phenylpyridinium)
SB  - IM
MH  - 1-Methyl-4-phenylpyridinium/*toxicity
MH  - Apoptosis/drug effects
MH  - Blotting, Western
MH  - Cell Line
MH  - Flavones/*pharmacology
MH  - Humans
MH  - Inflammasomes/*drug effects
MH  - Myeloid Differentiation Factor 88/*metabolism
MH  - NLR Family, Pyrin Domain-Containing 3 Protein/*metabolism
MH  - Neuroinflammatory Diseases/chemically induced/drug therapy
MH  - Neuroprotective Agents/*pharmacology
MH  - Oxidative Stress/drug effects
MH  - Parkinson Disease/*drug therapy
MH  - Real-Time Polymerase Chain Reaction
MH  - Signal Transduction/*drug effects
MH  - Toll-Like Receptor 4/*metabolism
OTO - NOTNLM
OT  - Genkwanin
OT  - MPP(+)
OT  - Neuroinflammation
OT  - Neurotoxicity
OT  - Parkinson's disease
OT  - TLR4/MyD88/NLRP3 inflammasome pathway
EDAT- 2021/09/06 06:00
MHDA- 2022/03/17 06:00
CRDT- 2021/09/05 20:36
PHST- 2021/06/21 00:00 [received]
PHST- 2021/08/09 00:00 [revised]
PHST- 2021/08/31 00:00 [accepted]
PHST- 2021/09/06 06:00 [pubmed]
PHST- 2022/03/17 06:00 [medline]
PHST- 2021/09/05 20:36 [entrez]
AID - S0161-813X(21)00103-0 [pii]
AID - 10.1016/j.neuro.2021.08.018 [doi]
PST - ppublish
SO  - Neurotoxicology. 2021 Dec;87:62-69. doi: 10.1016/j.neuro.2021.08.018. Epub 2021 
      Sep 2.