PMID- 30134790
OWN - NLM
STAT- MEDLINE
DCOM- 20190118
LR  - 20231213
IS  - 1528-3658 (Electronic)
IS  - 1076-1551 (Print)
IS  - 1076-1551 (Linking)
VI  - 24
IP  - 1
DP  - 2018 Mar 19
TI  - Stachydrine protects eNOS uncoupling and ameliorates endothelial dysfunction 
      induced by homocysteine.
PG  - 10
LID - 10.1186/s10020-018-0010-0 [doi]
LID - 10
AB  - BACKGROUND: Hyperhomocysteinemia (HHcy) is an independent risk factor for 
      cardiovascular diseases (CVDs). Stachydrine (STA) is an active component in 
      Chinese motherwort Leonurus heterophyllus sweet, which has been widely used for 
      gynecological and cardiovascular disorders. This study is aimed to examine the 
      effects of STA on homocysteine (Hcy)-induced endothelial dysfunction. METHODS: 
      The effects of STA on vascular relaxation in rat thoracic aortas (TA), mesenteric 
      arteries (MA) and renal arteries (RA) were measured by using Multi Myograph 
      System. The levels of nitric oxide (NO), tetrahydrobiopterin (BH4) and guanosine 
      3', 5' cyclic monophosphate (cGMP) were determined. Endothelial nitric oxide 
      synthase (eNOS) dimers and monomers were assayed by using Western blotting. GTP 
      cyclohydrolase 1 (GTPCH1) and dihydrofolate reductase (DHFR) expressions were 
      measured by using quantitative reverse transcriptase-PCR (qRT-PCR) and Western 
      blotting. RESULTS: STA effectively blocked Hcy-induced impairment of 
      endothelium-dependent vasorelaxation in rat TA, MA and RA. STA-elicited arterial 
      relaxations were reduced by NOS inhibitor NG-nitro-L-arginine methyl ester 
      (L-NAME) or the NO-sensitive guanylyl cyclase inhibitor 1H- [1, 2, 4] 
      Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), but not by inducible iNOS inhibitor 
      1400 W nor the nonselective COX inhibitor indomethacin. Hcy caused eNOS 
      uncoupling and decreases in NO, cGMP and BH4, which were attenuated by STA. 
      Moreover, STA prevented decreases of GTPCH1 and DHFR levels in Hcy-treated BAECs. 
      CONCLUSION: We demonstrated that STA effectively reversed the Hcy-induced 
      endothelial dysfunction and prevented eNOS uncoupling by increasing the 
      expression of GTPCH1 and DHFR. These results revealed a novel mechanism by which 
      STA exerts its beneficial vascular effects.
FAU - Xie, Xinya
AU  - Xie X
AD  - Cardiovascular Research Center, School of Basic Medical Sciences, Xi'an Jiaotong 
      University, Xi'an, 710061, China.
FAU - Zhang, Zihui
AU  - Zhang Z
AD  - Cardiovascular Research Center, School of Basic Medical Sciences, Xi'an Jiaotong 
      University, Xi'an, 710061, China.
FAU - Wang, Xinfeng
AU  - Wang X
AD  - Cardiovascular Research Center, School of Basic Medical Sciences, Xi'an Jiaotong 
      University, Xi'an, 710061, China.
FAU - Luo, Zhenyu
AU  - Luo Z
AD  - Cardiovascular Research Center, School of Basic Medical Sciences, Xi'an Jiaotong 
      University, Xi'an, 710061, China.
FAU - Lai, Baochang
AU  - Lai B
AD  - Cardiovascular Research Center, School of Basic Medical Sciences, Xi'an Jiaotong 
      University, Xi'an, 710061, China.
FAU - Xiao, Lei
AU  - Xiao L
AD  - Cardiovascular Research Center, School of Basic Medical Sciences, Xi'an Jiaotong 
      University, Xi'an, 710061, China. xiaolei0122@xjtu.edu.cn.
FAU - Wang, Nanping
AU  - Wang N
AD  - The Advanced Institute for Medical Sciences, Dalian Medical University, Dalian, 
      116044, China. nanpingwang2003@yahoo.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180319
PL  - England
TA  - Mol Med
JT  - Molecular medicine (Cambridge, Mass.)
JID - 9501023
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 0 (Biopterins)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 9DLQ4CIU6V (Proline)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
RN  - EGX657432I (sapropterin)
RN  - H2D2X058MU (Cyclic GMP)
RN  - S1L688345C (stachydrine)
SB  - IM
MH  - Animals
MH  - Aorta, Thoracic/drug effects/physiology
MH  - Biopterins/analogs & derivatives/metabolism
MH  - Cattle
MH  - Cell Line
MH  - Cyclic GMP/metabolism
MH  - Endothelial Cells/drug effects/physiology
MH  - Endothelium, Vascular/*drug effects/physiology
MH  - Homocysteine
MH  - Male
MH  - Mesenteric Arteries/drug effects/physiology
MH  - Nitric Oxide/metabolism
MH  - Nitric Oxide Synthase Type III/*physiology
MH  - Proline/*analogs & derivatives/pharmacology
MH  - Rats, Sprague-Dawley
MH  - Renal Artery/drug effects/physiology
MH  - Vasodilation/drug effects
PMC - PMC6016886
OTO - NOTNLM
OT  - DHFR
OT  - GTPCH1
OT  - Stachydrine
OT  - Vasorelaxation
OT  - eNOS uncoupling
COIS- ETHICS APPROVAL: The protocols for the animal experiments were approved by the 
      institutional review board of Xi'an Jiaotong University and performed in 
      accordance with the institutional and national guidelines for the care and use of 
      animals (No. XJTULAC 2015-646). CONSENT FOR PUBLICATION: Not applicable. 
      COMPETING INTERESTS: The authors declare that they have no competing interests as 
      defined by Molecular Medicine or other interests that might be perceived to 
      influence the results and discussion reported in this paper. PUBLISHER'S NOTE: 
      Springer Nature remains neutral with regard to jurisdictional claims in published 
      maps and institutional affiliations.
EDAT- 2018/08/24 06:00
MHDA- 2019/01/19 06:00
PMCR- 2018/03/19
CRDT- 2018/08/24 06:00
PHST- 2018/02/21 00:00 [received]
PHST- 2018/03/02 00:00 [accepted]
PHST- 2018/08/24 06:00 [entrez]
PHST- 2018/08/24 06:00 [pubmed]
PHST- 2019/01/19 06:00 [medline]
PHST- 2018/03/19 00:00 [pmc-release]
AID - 10.1186/s10020-018-0010-0 [pii]
AID - 10 [pii]
AID - 10.1186/s10020-018-0010-0 [doi]
PST - epublish
SO  - Mol Med. 2018 Mar 19;24(1):10. doi: 10.1186/s10020-018-0010-0.