PMID- 29793313
OWN - NLM
STAT- MEDLINE
DCOM- 20181005
LR  - 20181005
IS  - 1950-6007 (Electronic)
IS  - 0753-3322 (Linking)
VI  - 97
DP  - 2018 Jan
TI  - Therapeutic effects of scoparone on pilocarpine (Pilo)-induced seizures in mice.
PG  - 1501-1513
LID - S0753-3322(17)32981-5 [pii]
LID - 10.1016/j.biopha.2017.09.127 [doi]
AB  - Epilepsy is a common and devastating neurological disorder. Inflammatory 
      processes and apoptosis in brain tissue have been reported in human epilepsy. 
      Scoparone (6,7-dimethoxycoumarin) is an important chemical substance, which has 
      multiple beneficial activities, including antitumor, anti-inflammatory and 
      anti-coagulant properties. In our present study, we attempted to investigate if 
      scoparone could attenuate seizures-induced blood brain barrier breakdown, 
      inflammation and apoptosis. Pilocarpine (Pilo) and methylscopolamine were used to 
      establish acute seizure animal model. Scoparone suppressed the leakage of blood 
      brain barrier, inflammation and apoptosis. In hippocampus and cortex, the 
      expression of inflammation-associated molecules, such as chemokine (CXC motif) 
      ligand 1 (CXCL-1), interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), IL-6, 
      hypoxia-inducible factor 1alpha (HIF-1alpha), and monocyte chemoattractant protein-1 
      (MCP-1), were reduced by scoparone through inactivating toll-like receptor 
      4/nuclear factor-kappa B (TLR4/NF-kappaB) pathway. Scoparone reduced apoptotic levels 
      in hippocampus by TUNEL analysis, along with decreased Caspase-3 and PARP 
      cleavage. In addition, phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) 
      pathway in Pilo-induced acute seizures was also inactivated by scoparone. In 
      vitro, we confirmed that scoparone inhibited LPS-caused astrocytes activation as 
      proved by the reduced glial fibrillary acidic protein (GFAP) levels, inflammation 
      and apoptosis, which were at least partly dependent on AKT suppression. The 
      results above indicated that scoparone could relieve pilocarpine (Pilo)-induced 
      seizures against neural cell inflammation and apoptosis.
CI  - Copyright (c) 2017. Published by Elsevier Masson SAS.
FAU - Xia, Jie
AU  - Xia J
AD  - Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, Hubei 
      430060, PR China.
FAU - Li, Cheng-Yan
AU  - Li CY
AD  - Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, Hubei 
      430060, PR China. Electronic address: lichengyanwhu@foxmail.com.
FAU - Wang, Hui
AU  - Wang H
AD  - Department of Anesthesiology, Renhe Hospital of China Three Gorges University, 
      Yichang, Hubei 443002, PR China.
FAU - Zhang, Qi-Mei
AU  - Zhang QM
AD  - Institute of Neurology, China Three Gorges University, Yichang, Hubei 443002, PR 
      China.
FAU - Han, Zhong-Mou
AU  - Han ZM
AD  - Institute of Neurology, China Three Gorges University, Yichang, Hubei 443002, PR 
      China.
LA  - eng
PT  - Journal Article
DEP - 20171120
PL  - France
TA  - Biomed Pharmacother
JT  - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
JID - 8213295
RN  - 0 (Coumarins)
RN  - 0 (Cytokines)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B)
RN  - 0 (Toll-Like Receptor 4)
RN  - 01MI4Q9DI3 (Pilocarpine)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - H5841PDT4Y (scoparone)
SB  - IM
MH  - Acute Disease
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Astrocytes/drug effects/metabolism/pathology
MH  - Blood-Brain Barrier/drug effects/pathology
MH  - Coumarins/pharmacology/*therapeutic use
MH  - Cytokines/metabolism
MH  - Enzyme Activation/drug effects
MH  - Inflammation/pathology
MH  - Inflammation Mediators/metabolism
MH  - Lipopolysaccharides
MH  - Male
MH  - Mice, Inbred C57BL
MH  - NF-kappa B/metabolism
MH  - Neurons/drug effects/metabolism/pathology
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Pilocarpine
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Rats, Sprague-Dawley
MH  - Seizures/*chemically induced/*drug therapy/enzymology/pathology
MH  - Toll-Like Receptor 4/metabolism
OTO - NOTNLM
OT  - Apoptosis
OT  - Epilepsy
OT  - Inflammation
OT  - PI3K/AKT
OT  - Scoparone
EDAT- 2018/05/26 06:00
MHDA- 2018/10/06 06:00
CRDT- 2018/05/26 06:00
PHST- 2017/06/21 00:00 [received]
PHST- 2017/09/24 00:00 [revised]
PHST- 2017/09/24 00:00 [accepted]
PHST- 2018/05/26 06:00 [entrez]
PHST- 2018/05/26 06:00 [pubmed]
PHST- 2018/10/06 06:00 [medline]
AID - S0753-3322(17)32981-5 [pii]
AID - 10.1016/j.biopha.2017.09.127 [doi]
PST - ppublish
SO  - Biomed Pharmacother. 2018 Jan;97:1501-1513. doi: 10.1016/j.biopha.2017.09.127. 
      Epub 2017 Nov 20.