PMID- 31586637
OWN - NLM
STAT- MEDLINE
DCOM- 20200325
LR  - 20200325
IS  - 1879-0712 (Electronic)
IS  - 0014-2999 (Linking)
VI  - 864
DP  - 2019 Dec 1
TI  - Protective effects of oxymatrine on homocysteine-induced endothelial injury: 
      Involvement of mitochondria-dependent apoptosis and Akt-eNOS-NO signaling 
      pathways.
PG  - 172717
LID - S0014-2999(19)30669-7 [pii]
LID - 10.1016/j.ejphar.2019.172717 [doi]
AB  - Homocysteine (Hcy) is an independent risk factor in the development of 
      cardiovascular diseases (CVD). Hyperhomocysteinemia (HHcy), induces the injury of 
      vascular endothelial cells via oxidative stress. Oxymatrine (OMT), one of the 
      main components of Sophora flavescens, has displayed anti-inflammatory, 
      anti-oxidant and anti-apoptotic activity. However, the effect of OMT on the 
      Hcy-induced endothelial injury is not clearly defined yet. The aim of this study 
      was to determine the protective effect of OMT on the Hcy-induced endothelial 
      injury and its mechanisms involved. Human umbilical vein endothelial cells 
      (HUVECs) were cultured in vitro. Methyl thiazolyl tetrazolium assay (MTT), 
      fluorescence staining, flow cytometry and western blotting were used in this 
      study. OMT prevented the Hcy-induced toxicity and apoptosis in HUVECs. Moreover, 
      OMT suppressed Hcy-induced increases in reactive oxygen species, lactate 
      dehydrogenase, malondialdehyde levels and increased superoxide dismutase levels. 
      OMT reversed the Hcy-induced decrease in the protein expression of nuclear factor 
      erythroid-2-related factor 2 (Nrf2). In addition, OMT reversed the Hcy-induced 
      apoptosis related biochemical changes such as decreased mitochondrial membrane 
      potential and Bcl-2/Bax protein ratio, and increased protein expression of 
      caspase-9 and caspase-3. Furthermore, OMT elevated the phosphorylation levels of 
      Akt and eNOS, and the formation of nitric oxide (NO) in injured cells. These 
      results suggest that OMT prevents Hcy-induced endothelial injury by regulating 
      mitochondrial-dependent apoptosis and Akt-eNOS-NO signaling pathways 
      concomitantly with accentuation of Nrf2 expression.
CI  - Copyright (c) 2019 Elsevier B.V. All rights reserved.
FAU - Wu, Bo
AU  - Wu B
AD  - School of Pharmacy, Shandong First Medical University & Shandong Academy of 
      Medical Sciences, Taian, Shandong, 271016, China.
FAU - Yue, Hua
AU  - Yue H
AD  - School of Pharmacy, Shandong First Medical University & Shandong Academy of 
      Medical Sciences, Taian, Shandong, 271016, China.
FAU - Zhou, Guang Hai
AU  - Zhou GH
AD  - Institute of Cardiovascular Endocrinology, Key Laboratory of Atherosclerosis in 
      Universities of Shandong, Shandong First Medical University & Shandong Academy of 
      Medical Sciences, Taian, Shandong, 271000, China.
FAU - Zhu, Yuan Yuan
AU  - Zhu YY
AD  - School of Pharmacy, Shandong First Medical University & Shandong Academy of 
      Medical Sciences, Taian, Shandong, 271016, China.
FAU - Wu, Tian Hua
AU  - Wu TH
AD  - School of Pharmacy, Shandong First Medical University & Shandong Academy of 
      Medical Sciences, Taian, Shandong, 271016, China.
FAU - Wen, Jin Fu
AU  - Wen JF
AD  - Institute of Cardiovascular Endocrinology, Key Laboratory of Atherosclerosis in 
      Universities of Shandong, Shandong First Medical University & Shandong Academy of 
      Medical Sciences, Taian, Shandong, 271000, China. Electronic address: 
      jfwen0603@aliyun.com.
FAU - Cho, Kyung Woo
AU  - Cho KW
AD  - Institute of Cardiovascular Endocrinology, Key Laboratory of Atherosclerosis in 
      Universities of Shandong, Shandong First Medical University & Shandong Academy of 
      Medical Sciences, Taian, Shandong, 271000, China.
FAU - Jin, Song Nan
AU  - Jin SN
AD  - School of Pharmacy, Shandong First Medical University & Shandong Academy of 
      Medical Sciences, Taian, Shandong, 271016, China. Electronic address: 
      snjin0504@aliyun.com.
LA  - eng
PT  - Journal Article
DEP - 20191003
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Alkaloids)
RN  - 0 (Quinolizines)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 85U4C366QS (oxymatrine)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Alkaloids/*pharmacology
MH  - Apoptosis/*drug effects
MH  - Cytoprotection/drug effects
MH  - Homocysteine/*adverse effects
MH  - Human Umbilical Vein Endothelial Cells/cytology/*drug effects/metabolism
MH  - Humans
MH  - Mitochondria/drug effects/metabolism
MH  - Nitric Oxide/*metabolism
MH  - Nitric Oxide Synthase Type III/*metabolism
MH  - Oxidative Stress/drug effects
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Quinolizines/*pharmacology
MH  - Signal Transduction/drug effects
OTO - NOTNLM
OT  - Endothelial cells
OT  - Homocysteine
OT  - Mitochondrial membrane potential
OT  - Nitric oxide
OT  - Nrf2
OT  - Oxymatrine
EDAT- 2019/10/07 06:00
MHDA- 2020/03/26 06:00
CRDT- 2019/10/07 06:00
PHST- 2019/04/30 00:00 [received]
PHST- 2019/09/26 00:00 [revised]
PHST- 2019/10/02 00:00 [accepted]
PHST- 2019/10/07 06:00 [pubmed]
PHST- 2020/03/26 06:00 [medline]
PHST- 2019/10/07 06:00 [entrez]
AID - S0014-2999(19)30669-7 [pii]
AID - 10.1016/j.ejphar.2019.172717 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2019 Dec 1;864:172717. doi: 10.1016/j.ejphar.2019.172717. Epub 
      2019 Oct 3.