PMID- 31592228
OWN - NLM
STAT- MEDLINE
DCOM- 20200427
LR  - 20200427
IS  - 1449-2288 (Electronic)
IS  - 1449-2288 (Linking)
VI  - 15
IP  - 10
DP  - 2019
TI  - Vascular Protection of TPE-CA on Hyperhomocysteinemia-induced Vascular 
      Endothelial Dysfunction through AA Metabolism Modulated CYPs Pathway.
PG  - 2037-2050
LID - 10.7150/ijbs.35245 [doi]
AB  - A high concentration of homocysteine (Hcy) in plasma induces vascular endothelial 
      dysfunction, and it may ultimately accelerate the development of cardiovascular 
      diseases (CVDs). Although several B vitamins have been clinically applied for 
      hyperhomocysteinemia (HHcy) treatment, the outcomes are not satisfied due to 
      their limited therapeutic mechanism. Hence, in order to improve the curative 
      effect, development of new effective therapeutic strategies should be put on the 
      agenda. Total phenolic extracts of Citrus aurantium L. (TPE-CA) is a naturally 
      obtained phenolic mixture, mainly containing flavones, flavanones and their 
      glycosyl derivatives, flavonols, polymethoxyflavones and coumarins. Previous 
      reports indicated that bioactive phenolic compounds possessed potent vascular 
      protective effects and regarded as a protective agent against CVDs. Intriguingly, 
      the exact mechanism underlying the suppressed effects of TPE-CA on HHcy could 
      assist in revealing their therapy on CVDs. Here, the multi-targeted synergistic 
      mechanism of TPE-CA on HHcy-induced vascular endothelial dysfunction was 
      uncovered in a deduced manner. TPE-CA treatment exhibited an obvious superiority 
      than that of B vitamins treatment. Network pharmacology was employed to identify 
      the interrelationships among compounds, potential targets and putative pathways. 
      Further experimental validation suggested that the treatment of TPE-CA for HHcy 
      could not only effectively reduce the Hcy level in plasma through up-regulating 
      transsulfuration pathway in Hcy metabolism, but also restore the HHcy-induced 
      vascular endothelial dysfunction by activating cytochrome P450 enzymes (CYPs) 
      epoxygenase signal cascades and inhibiting CYPs hydroxylase signal cascades in 
      arachidonic acid (AA) metabolism.
CI  - (c) The author(s).
FAU - Li, Hui
AU  - Li H
AD  - School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 
      100029, China.
FAU - Liu, Zhenli
AU  - Liu Z
AD  - Institution of Basic Theory, China Academy of Chinese Medical Sciences, Beijing 
      100700, China.
FAU - Liu, Linlin
AU  - Liu L
AD  - School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 
      100029, China.
FAU - Li, Wen
AU  - Li W
AD  - School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 
      100029, China.
FAU - Cao, Zhiwen
AU  - Cao Z
AD  - School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 
      100029, China.
FAU - Song, Zhiqian
AU  - Song Z
AD  - Institution of Basic Theory, China Academy of Chinese Medical Sciences, Beijing 
      100700, China.
FAU - Yang, Qianqian
AU  - Yang Q
AD  - School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 
      100029, China.
FAU - Lu, Aiping
AU  - Lu A
AD  - School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hongkong, 
      China.
FAU - Lu, Cheng
AU  - Lu C
AD  - Institute of Basic Research in Clinical Medicine, China Academy of Chinese 
      Medical Sciences, Beijing 100700, China.
FAU - Liu, Yuanyan
AU  - Liu Y
AD  - School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 
      100029, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190725
PL  - Australia
TA  - Int J Biol Sci
JT  - International journal of biological sciences
JID - 101235568
RN  - 0 (Plant Extracts)
RN  - 27YG812J1I (Arachidonic Acid)
RN  - 9035-51-2 (Cytochrome P-450 Enzyme System)
SB  - IM
MH  - Animals
MH  - Arachidonic Acid/*metabolism
MH  - Cardiovascular Diseases/*metabolism/*prevention & control
MH  - Citrus/*chemistry
MH  - Cytochrome P-450 Enzyme System/*metabolism
MH  - Endothelial Cells/drug effects/metabolism
MH  - Fruit/*chemistry
MH  - Hyperhomocysteinemia/*complications/*microbiology
MH  - Lipid Metabolism/drug effects
MH  - Male
MH  - Plant Extracts/*therapeutic use
MH  - Rats
MH  - Rats, Sprague-Dawley
PMC - PMC6775291
OTO - NOTNLM
OT  - Arachidonic acid metabolism
OT  - CYPs signal pathway
OT  - Hyperhomocysteinemia
OT  - Total phenolic extracts of Citrus aurantium L.
OT  - Vascular endothelial dysfunction
COIS- Competing Interests: The authors have declared that no competing interest exists.
EDAT- 2019/10/09 06:00
MHDA- 2020/04/28 06:00
PMCR- 2019/01/01
CRDT- 2019/10/09 06:00
PHST- 2019/03/26 00:00 [received]
PHST- 2019/06/05 00:00 [accepted]
PHST- 2019/10/09 06:00 [entrez]
PHST- 2019/10/09 06:00 [pubmed]
PHST- 2020/04/28 06:00 [medline]
PHST- 2019/01/01 00:00 [pmc-release]
AID - ijbsv15p2037 [pii]
AID - 10.7150/ijbs.35245 [doi]
PST - epublish
SO  - Int J Biol Sci. 2019 Jul 25;15(10):2037-2050. doi: 10.7150/ijbs.35245. 
      eCollection 2019.