Icariin regulates PRMT/ADMA/DDAH pathway to improve endothelial function.
BACKGROUND
Oxidative stress may affect PRMT/ADMA/DDAH (protein arginine methyltransferases/asymmetric dimethylarginine/dimethylarginine dimethylaminohydrolase) pathway to impair endothelial dysfunction. The present study was carried out to test the effect of icariin on endothelial function and the mechanisms responsible for this.


METHODS
Eighty mice at 12 weeks of age were separated randomly into four groups (n = 20): C57BL/6J control, untreated apolipoprotein E-deficient (ApoE(-/-)), two groups of icariin-treated (10 or 30 mg/kg body wt/day, intragastrically) ApoE(-/-). Primary human umbilical vein endothelial cells (HUVECs) were randomly divided into 7 groups: control group, vehicle of icariin (10 μmol/L) group, icariin (10 μmol/L) group, lysophosphatidylcholine (LPC) (10 μg/mL) group, LPC plus icariin (1 μmol/L) group, LPC plus icariin (3 μmol/L) group, and LPC plus icariin (10 μmol/L) group.


RESULTS
In ApoE(-/-) mice and primary HUVECs, icariin treatment decreased reactive oxygen species production, PRMT I expression, ADMA level, half-maximum effective concentration of ApoE(-/-) mice aortic rings. Icariin increased DDAH II expression, DDAH activity, maximal relaxation value and endothelium-dependent vasorelaxation in aortic rings from ApoE(-/-) mice (p < 0.05 or p < 0.01).


CONCLUSIONS
The present results suggest that icariin regulates PRMT/ADMA/DDAH pathway to improve endothelial function.
College of Veterinary Medicine, Hunan Agricultural University, Changsha, China. Electronic address: xhbzhb@yahoo.com.
Hong-Bo
HB
Xiao
College of Veterinary Medicine, Hunan Agricultural University, Changsha, China.
Zi-Kui
ZK
Liu
Hunan Collaborative Innovation Center for Utilization of Botanical Functional Ingredients, Changsha, China.
Xiang-Yang
XY
Lu
The Third Hospital of Changsha, Changsha, China.
Chun-Na
CN
Deng
Department of Basic Medicine, Xiangnan University, Chenzhou, China.
Zhi-Feng
ZF
Luo
D000581:Amidohydrolases / Q000378:metabolism*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001057:Apolipoproteins E / Q000235:genetics; D001120:Arginine / Q000031:analogs & derivatives* / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D011484:Protein-Arginine N-Methyltransferases / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects
D001057:Apolipoproteins E; D005419:Flavonoids; D017382:Reactive Oxygen Species; C018524:N,N-dimethylarginine; D001120:Arginine; C546338:Prmt1 protein, mouse; D011484:Protein-Arginine N-Methyltransferases; D000581:Amidohydrolases; C059999:dimethylargininase; C056599:icariin
Asymmetric dimethylarginine; Dimethylarginine dimethylaminohydrolase; Endothelial dysfunction; Icariin; Protein arginine methyltransferases