Premium
Mechanisms of Vasodilatory Effects of Total Flavonoids from Euphorbia humifusa in Rat Aorta
Author(s) -
Ji Xiao Wei,
Wu Bo,
Zhou Zi Qi,
Kang Dae Gill,
Lee Ho Sub,
Cho Kyung Woo,
Jin Song Nan,
Wen Jin Fu
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.835.13
Subject(s) - chemistry , pharmacology , vasodilation , soluble guanylyl cyclase , channel blocker , nitric oxide , nitric oxide synthase , wortmannin , endothelium , glibenclamide , receptor , biochemistry , endocrinology , biology , protein kinase b , calcium , phosphorylation , organic chemistry , diabetes mellitus , guanylate cyclase
Euphorbia humifusa (EH) is, rich in flavonoids, used for treating bacillary dysentery and enteritis in many Asian countries. It is noteworthy that the beneficial actions of EH, such as inhibiting inflammation, antioxidation, enhancing immunity and lowering blood pressure, might be mainly attributed to its abundant flavonoids. However, the effects of total flavonoids of EH (TFEH) on the vascular function and its pharmacological mechanisms of action have not been studied. The aim of the present study was to evaluate the vascular effects of TFEH and its action mechanisms in rats. The vasoactive effect of TFEH and its underlying mechanisms in rat thoracic aortas were investigated using the organ bath system. TFEH induced a concentration‐dependent vasorelaxation in endothelium‐intact (+E) aortic rings, which was abolished by the removal of endothelium. The nitric oxide synthase inhibitor L‐NAME and the soluble guanylate cyclase inhibitor ODQ significantly attenuated the endothelium‐dependent vasorelaxation of TFEH. However, inhibition of cyclooxygenases with indomethacin had no effects on the TFEH‐induced vasorelaxation. Extracellular Ca 2+ depletion, inhibition of L‐type Ca 2+ channels with diltiazem and modulators of the store‐operated Ca 2+ entry (SOCE), Gd 3+ and 2‐aminoethyl diphenylborinate markedly attenuated the TFEH‐induced vasorelaxation in +E vessels. Wortmannin, an inhibitor of Akt, significantly attenuated the TFEH‐induced vasorelaxation in +E vessels. Furthermore, K + channel blockers, such as a non‐selective K Ca channels blocker tetraethylammonium and K ATP channel blocker glibenclamide, and inhibitors of muscarinic and adrenergic receptors had no significant effects on the vasorelaxation. These data demonstrate that TFEH induces vasorelaxation through activation of endothelium‐dependent two‐step signaling: first is an activation of the Akt‐ and Ca 2+ ‐eNOS‐NO signaling in the endothelial cells and then subsequent stimulation of the NO‐soluble guanylyl cyclase‐cGMP signaling in the vascular smooth muscle cells. Support or Funding Information This work was supported by research grants from the National Natural Science Foundation of China (Nos. 81270920, 31571175), the Natural Science Foundation of Shandong Province (No. ZR2015HM037), and the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (2008‐0062484).