PMID- 26607471
OWN - NLM
STAT- MEDLINE
DCOM- 20160921
LR  - 20151215
IS  - 1879-0712 (Electronic)
IS  - 0014-2999 (Linking)
VI  - 769
DP  - 2015 Dec 15
TI  - Hydroxysafflor yellow A exerts neuroprotective effects in cerebral ischemia 
      reperfusion-injured mice by suppressing the innate immune TLR4-inducing pathway.
PG  - 324-32
LID - S0014-2999(15)30371-X [pii]
LID - 10.1016/j.ejphar.2015.11.036 [doi]
AB  - The innate immune response, which is tightly regulated by Toll-like receptor 4 
      (TLR4) pathway, has been shown to play a critical role in brain damage following 
      cerebral ischemia-reperfusion injury. Hydroxysafflor yellow A (HSYA) is the 
      active component extracted from the Flos Carthami and has been reported to 
      decrease neurological deficit scores following ischemia-reperfusion injury. 
      However, the precise mechanism by which it exerts these neuroprotective effects 
      remains poorly understood. In this study, we demonstrated that the administration 
      of HSYA could significantly down-regulate TLR4 expression in middle cerebral 
      artery occlusion (MCAO) mice. Following the down-regulation of TLR4 by HSYA 
      treatment, cerebral infarction and inflammatory neuronal damage was alleviated. 
      The number of apoptotic neurons in the HSYA-treated group was significantly 
      decreased along with the decrease in TLR4 expression in MCAO mice. Activation of 
      the NF-kappaB and MAPK signaling pathways was observed at 1h following ischemia and 
      at 24h post-reperfusion. HSYA could significantly inhibit NF-kappaB p-p65, ERE1/2, 
      JNK and p38 phosphorylation, which coincided with the suppressed secretion of 
      inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta 
      (IL-1beta) and nitric oxide (NO). Moreover, brain-derived neurotrophic factor (BDNF) 
      was up-regulated following 1h of ischemia and continued to increase initially 
      during reperfusion but was down-regulated at later stages. Following treatment 
      with HSYA, BDNF was up-regulated relative to control MCAO mice at 1h 
      post-ischemia and at 12 and 24h post-reperfusion. Our data suggest that HSYA 
      exerts neurotrophic and anti-inflammatory functions against ischemic stroke by 
      inhibiting TLR4 pathway-mediated signaling responses.
CI  - Copyright (c) 2015 Elsevier B.V. All rights reserved.
FAU - Lv, Yanni
AU  - Lv Y
AD  - The First Affiliated Hospital of Nanchang University, Nanchang 330006, China.
FAU - Qian, Yisong
AU  - Qian Y
AD  - Institute of Translational Medicine of Nanchang University, Nanchang 330001, 
      China.
FAU - Fu, Longsheng
AU  - Fu L
AD  - The First Affiliated Hospital of Nanchang University, Nanchang 330006, China.
FAU - Chen, Xuanying
AU  - Chen X
AD  - The First Affiliated Hospital of Nanchang University, Nanchang 330006, China.
FAU - Zhong, Haili
AU  - Zhong H
AD  - The First Affiliated Hospital of Nanchang University, Nanchang 330006, China.
FAU - Wei, Xiaohua
AU  - Wei X
AD  - The First Affiliated Hospital of Nanchang University, Nanchang 330006, China. 
      Electronic address: 305260242@qq.com.
LA  - eng
PT  - Journal Article
DEP - 20151125
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (NF-kappa B)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Quinones)
RN  - 0 (Tlr4 protein, mouse)
RN  - 0 (Toll-Like Receptor 4)
RN  - 146087-19-6 (hydroxysafflor yellow A)
RN  - 5S5A2Q39HX (Chalcone)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Chalcone/*analogs & derivatives/pharmacology/therapeutic use
MH  - Immunity, Innate/*drug effects
MH  - Infarction, Middle Cerebral Artery/*complications
MH  - Mice
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - NF-kappa B/metabolism
MH  - Neuroprotective Agents/pharmacology/therapeutic use
MH  - Quinones/*pharmacology/therapeutic use
MH  - Reperfusion Injury/*complications/*drug therapy/metabolism/pathology
MH  - Signal Transduction/*drug effects/immunology
MH  - Toll-Like Receptor 4/*metabolism
MH  - Up-Regulation/drug effects
OTO - NOTNLM
OT  - Anti-inflammatory
OT  - Cerebral ischemia reperfusion
OT  - Hydroxysafflor yellow A
OT  - Neuroprotective effects
OT  - Neurotrophy
OT  - TLR4
EDAT- 2015/11/27 06:00
MHDA- 2016/09/23 06:00
CRDT- 2015/11/27 06:00
PHST- 2015/03/24 00:00 [received]
PHST- 2015/11/14 00:00 [revised]
PHST- 2015/11/18 00:00 [accepted]
PHST- 2015/11/27 06:00 [entrez]
PHST- 2015/11/27 06:00 [pubmed]
PHST- 2016/09/23 06:00 [medline]
AID - S0014-2999(15)30371-X [pii]
AID - 10.1016/j.ejphar.2015.11.036 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2015 Dec 15;769:324-32. doi: 10.1016/j.ejphar.2015.11.036. Epub 
      2015 Nov 25.