Icariin regulates PRMT/ADMA/DDAH pathway to improve endothelial function

Abstract

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.

Keywords: Asymmetric dimethylarginine; Dimethylarginine dimethylaminohydrolase; Endothelial dysfunction; Icariin; Protein arginine methyltransferases.