PMID- 33735723
OWN - NLM
STAT- MEDLINE
DCOM- 20210518
LR  - 20210518
IS  - 1618-095X (Electronic)
IS  - 0944-7113 (Linking)
VI  - 85
DP  - 2021 May
TI  - Hydroxysafflor yellow A alleviates cerebral ischemia reperfusion injury by 
      suppressing apoptosis via mitochondrial permeability transition pore.
PG  - 153532
LID - S0944-7113(21)00074-X [pii]
LID - 10.1016/j.phymed.2021.153532 [doi]
AB  - BACKGROUND: Mitochondria are key cellular organelles that are essential for cell 
      fate decisions. Hydroxysafflor yellow A (HSYA) has displayed an impressively 
      essential role in protection of cerebral ischemia/reperfusion (I/R). However, the 
      mitochondrial effect of HSYA on Brain Microvascular Endothelial Cells (BMECs) 
      under I/R remains to be largely unclear. PURPOSE: To evaluate the protective 
      effects of HSYA-mediated mitochondrial permeability transition pore (mPTP) on 
      cerebral I/R injury and its mechanism. METHODS: Cerebral I/R injury was 
      established by the model of Middle cerebral artery occlusion (MCAO) in rats. 
      Furthermore, to further clarify the relevant mechanism of HSYA's effects on mPTP, 
      inhibition of extracellular regulated protein kinases (ERK) with U0126 and 
      transfect with Cyclophilin D (CypD) SiRNA to reversely verified whether the 
      protective effects of HSYA were exerted by regulating the Mitogen-activated 
      protein kinase kinase (MEK)/ERK/CypD pathway. RESULTS: HSYA treatment 
      significantly increased BMECs viability, decreased the generation of ROS, opening 
      of mPTP and translocation of cytochrome c after OGD/R. In addition to inhibited 
      CypD, HSYA potentiated MEK and increased phosphorylation of ERK expression in 
      BMECs, inhibited apoptosis mediated by mitochondrial. Notably, HSYA also 
      significantly ameliorated neurological deficits and decreased the infarct volume 
      in rats. CONCLUSION: HSYA reduced the CytC export from mitochondrial by inhibited 
      the open of mPTP via MEK/ERK/CypD pathway, contributing to the protection of I/R. 
      Thus, our study not only revealed novel mechanisms of HSYA for its anti-I/R 
      function, but also provided a template for the design of novel mPTP inhibitor for 
      the treatment of various mPTP-related diseases.
CI  - Copyright (c) 2021. Published by Elsevier GmbH.
FAU - Huang, Ping
AU  - Huang P
AD  - Anhui Province Key Laboratory of Chinese Medicinal Formula, Anhui University of 
      Chinese Medicine, Hefei 230012, China; Anhui Province Key Laboratory of Research 
      & Development of Chinese Medicine, Anhui University of Chinese Medicine, Hefei 
      230012, China.
FAU - Wu, Si-Peng
AU  - Wu SP
AD  - Anhui Province Key Laboratory of Chinese Medicinal Formula, Anhui University of 
      Chinese Medicine, Hefei 230012, China; State Key Laboratory of Cellular Stress 
      Biology, School of Life Sciences, Xiamen University, Xiamen 361005, China. 
      Electronic address: wsphefei@163.com.
FAU - Wang, Ning
AU  - Wang N
AD  - Anhui Province Key Laboratory of Chinese Medicinal Formula, Anhui University of 
      Chinese Medicine, Hefei 230012, China; Anhui Province Key Laboratory of Research 
      & Development of Chinese Medicine, Anhui University of Chinese Medicine, Hefei 
      230012, China. Electronic address: wnsci123@163.com.
FAU - Seto, Saiwang
AU  - Seto S
AD  - Department of Applied Biology and Chemical Technology, Hong Kong Polytechnic 
      University, Hung Hom, Kowloon, Hong Kong SAR, China.
FAU - Chang, Dennis
AU  - Chang D
AD  - National Institute of Complementary Medicine, Western Sydney University; Penrith, 
      NSW 2751, Australia.
LA  - eng
PT  - Journal Article
DEP - 20210228
PL  - Germany
TA  - Phytomedicine
JT  - Phytomedicine : international journal of phytotherapy and phytopharmacology
JID - 9438794
RN  - 0 (Mitochondrial Permeability Transition Pore)
RN  - 0 (Quinones)
RN  - 146087-19-6 (hydroxysafflor yellow A)
RN  - 5S5A2Q39HX (Chalcone)
SB  - IM
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - Brain Ischemia/drug therapy
MH  - Chalcone/*analogs & derivatives/pharmacology
MH  - Endothelial Cells/*drug effects/metabolism
MH  - MAP Kinase Signaling System
MH  - Male
MH  - Mitochondria/drug effects
MH  - *Mitochondrial Permeability Transition Pore
MH  - Phosphorylation
MH  - Quinones/*pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reperfusion Injury/*drug therapy
OTO - NOTNLM
OT  - Apoptosis, BMECs
OT  - Cerebral ischemia/reperfusion injury
OT  - HSYA
OT  - Mitochondrial permeability transition pore
EDAT- 2021/03/19 06:00
MHDA- 2021/05/19 06:00
CRDT- 2021/03/18 20:17
PHST- 2020/12/18 00:00 [received]
PHST- 2021/02/15 00:00 [revised]
PHST- 2021/02/25 00:00 [accepted]
PHST- 2021/03/19 06:00 [pubmed]
PHST- 2021/05/19 06:00 [medline]
PHST- 2021/03/18 20:17 [entrez]
AID - S0944-7113(21)00074-X [pii]
AID - 10.1016/j.phymed.2021.153532 [doi]
PST - ppublish
SO  - Phytomedicine. 2021 May;85:153532. doi: 10.1016/j.phymed.2021.153532. Epub 2021 
      Feb 28.