Abstract
Rhus coriaria L. (sumac) is widely used in traditional remedies and cuisine of countries of the Mediterranean as well as Central and South-West Asia. Administration of sumac to experimental models and patients with diverse pathological conditions generates multi-faceted propitious effects, including the quality as a vasodilator. Together, the effects are concertedly channeled toward cardiovasobolic protection. However, there is paucity of data on the mechanism of action for sumac’s vasodilatory effect, an attribute which is considered to be advantageous for unhealthy circulatory system. Accordingly, we sought to determine the mechanisms by which sumac elicits its vasorelaxatory effects. We deciphered the signaling networks by application of a range of pharmacological inhibitors, biochemical assays and including the quantification of cyclic nucleotide monophosphates. Herein, we provide evidence that an ethanolic extract of sumac fruit, dose-dependently, relaxes rat isolated aorta. The mechanistic effect is achieved via stimulation of multiple transducers namely PI3-K/Akt, eNOS, NO, guanylyl cyclase, cGMP, and PKG. Interestingly, the arachidonic acid pathway (cyclooxygenases), adenylyl cyclase/cAMP and ATP-dependent potassium channels appear to partake in this sumac-orchestrated attenuation of vascular tone. Clearly, our data support the favorable potential cardio-vasculoprotective action of sumac.
Highlights
Macro-arterial related dysfunction is the principal contributor to cardiovascular and cerebrovascular diseases (CVDs), such as atherosclerosis and aneurysms
We wished to determine the role of endothelium in the rings treated with sumac alone (RCE)-induced relaxation of aortic rings in order to gain a better mechanistic understanding that underpins this effect
The RCE-induced maximal arterio-relaxant response (Emax) was dramatically decreased with endothelial denudation, and no alteration in pED50 values was observed (Figure 1B). pED50 values were 4.34 ± 0.05 g/ml with 95% confidence interval of 4.45–4.24 g/ml for the endothelium-intact rings versus 4.09 ± 0.05 g/ml and a 95% confidence interval: 4.19–4.00 g/ml for the denuded ones (p < 0.01)
Summary
Macro-arterial related dysfunction is the principal contributor to cardiovascular and cerebrovascular diseases (CVDs), such as atherosclerosis (myocardial infarction, stroke, peripheral arterial disease, and renal artery stenosis) and aneurysms. Rhus coriaria and Vasorelaxation been determined for these highly complex, dynamic arteriopathological events (Hopkins, 2013; Davis et al, 2015; Bennett et al, 2016; Libby et al, 2016; Writing Group et al, 2016) Despite this immense biomedical knowledge explaining the vascular pathophysiology, together with the significant number of therapeutic armaments prescribed to patients (polypharmacy/combinatory medication), there is, an increasing acceptance in clinical practice that CVDs are suboptimally managed in a significant percentage of patients (August, 2004; Frishman et al, 2009; Wang and Xiong, 2012; Writing Group et al, 2016). The aforementioned (lack of response to current medication by patients) alludes to an urgent requirement for novel combinatory therapeutic approaches directed toward multiple patho-targets of CVDs (Bennett et al, 2016; Libby et al, 2016; Writing Group et al, 2016)
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