Abstract
Oroxylin A, a flavonoid, is naturally produced in many medicinal plants. Our previous study identified it as a phytoestrogen. Based on this, the present study investigated its vasoconstriction reducing effects and whether the action was mediated by the estrogen receptor (ER) signal pathway. Long-term in vitro treatment with oroxylin A reduced Ach-induced vasorelaxation and NE-mediated or KCl-mediated contractile responses in rat aortic rings. These effects were interfered by an ER inhibitor ICI 182,780. Rat cardiac microvascular endothelial cells (CMECs) and aortic vascular smooth muscle cells (VSMCs) were used to study the possible underlying mechanisms. Oroxylin A activated the ER signal pathway. In CMECs, it increased NO production and eNOS protein expression. In VSMCs, it promoted NO production and iNOS protein expression. These effects were also inhibited by ICI 182,780. Besides, oroxylin A stimulated ERα and ERβ protein expression in CMECs and VSMCs. All these findings suggest that the ER signal pathway takes part in the vasoconstriction reducing effects of oroxylin A.
Highlights
It has been known for many years that exogenous estrogen exerts protective effects on the vasculature in premenopausal women receiving estrogen replacement therapy [1]. ese protections have been found to be associated with its direct effects on blood vessels in part at least [2]
Fetal bovine serum (FBS) and Dulbecco’s modified Eagle’s medium (DMEM) were purchased from GIBCO (Grand Island, USA); 17β-estradiol (E2) was purchased from National Institute for the Control of Pharmaceutical and Biological Products (Beijing, China); NGnitro-L-arginine methylester (L-NAME), estrogen receptor (ER) antagonist ICI 182,780, norepinephrine (NE), and acetyl chloride (Ach) were purchased from Shanghai Aladdin Biochemical Technology Limited liability company (Shanghai, China); anti-eNOS antibody and anti-iNOS antibody were purchased from MDL (Beijing, China); anti-ERα antibody and anti-ERβ antibody were purchased from Abcam (Cambridge, UK); oroxylin A was purchased from Tianjin Wanxiang Hengyuan Biochemical Technology Limited liability company (Tianjin, China); DMSO was purchased from Macklin (Shanghai, China)
Oroxylin A treatment (0.5, 5, 20 μM) for 12 h increased cardiac microvascular endothelial cells (CMECs) NO production and eNOS protein expression, which were prevented by ICI 182,780 (0.1 μM, n 3, Figure 2(a) and Figure 2(b))
Summary
It has been known for many years that exogenous estrogen exerts protective effects on the vasculature in premenopausal women receiving estrogen replacement therapy [1]. ese protections have been found to be associated with its direct effects on blood vessels in part at least [2]. It has been known for many years that exogenous estrogen exerts protective effects on the vasculature in premenopausal women receiving estrogen replacement therapy [1]. Ese protections have been found to be associated with its direct effects on blood vessels in part at least [2]. Erefore, it is important to search for a safe and effective selective regulator of ER for the estrogen replacement therapy to make up for the shortage of estrogen. Study has found that it had anticancer and cardiovascular protective activity. Wei et al reported that oroxylin A could inhibit breast cancer cells glycolysis-dependent proliferation [5]. Lu et al reported that oroxylin A could suppress cell adhesion, invasion, and migration in MDA-MB-231 human breast cancer cells [6]. Oroxylin A lowered the coronary perfusion pressure in the isolated rat heart and exhibited anti-inflammatory effect in RAW 264.7 cells [8, 9]
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