The Effects of Sumac on Saturated Fat-induced Inflammation in Human Vascular Smooth Muscle Cells and Isolated Mesenteric Arteries from Rats

Cardiovascular disease (CVD) is characterized by impaired vasodilation and the development of atherosclerosis.78 A diet high in saturated fat, such as palmitate, contributes to this by promoting inflammation and oxidative stress in human vascular smooth muscle cells (VSMC). 11,12,84,88 The inflammation cascade that occurs increases pro-inflammatory cytokines, like tumor necrosis factor alpha (TNF-alpha) and increases proinflammatory enzymes like cyclooxygenase 2 (COX-2) contributing to inflammation, oxidative stress, blood pressure shifts, and atherosclerosis.11,12,69,84 Palmitate has been found to upregulate TNF-alpha,85 and COX-2. 11,12, 84

In various studies, sumac, a Mediterranean spice and known antioxidant,39,7,66,67 has been shown to have antioxidant properties through its ability to inhibit reactive oxygen species (ROS) such as superoxide.39,7,66,67 Sumac has also been found to reduce TNF-alpha.100 Results from a study of hypertensive human subjects fed a sumac supplement showed a decrease in blood pressure.59

In the current study, COX-2 levels were determined to evaluate the level of inflammation in response to palmitate when primary aortic human vascular smooth muscle cells (HAoVSM) were treated with sumac. The treatments included: vehicle (bovine serum albumin), 100 µM palmitate, and 10, 20, 40, 60, and 80 µg/mL sumac. Sumac did not alter COX-2 protein levels between vehicle and sumac groups. Additional studies were designed to examine whether 80 µg/mL sumac could reverse impaired vasodilation caused by 10 weeks of high fat intake, consisting of 60% of total calories from fat, in Sprague-Dawley rats. Mesenteric arteries were isolated and exposed to sumac. High fat diet (HFD) arteries had impaired vasodilation compared to arteries from chow-fed fats. HFD arteries exposed to sumac had similar endothelium-dependent vasodilation responses as those not exposed to sumac, however, there were trends for improved vasodilation. I suggest that sumac likely exhibits antioxidant capabilities that prevent superoxide from decreasing the bioavailability of nitric oxide in the vasculature, thus promoting endothelium-dependent vasodilation and preventing the creation of more harmful reactive oxygen species. Isolated arteries from chow fed rats developed irreversible vasodilation when exposed to sumac and were therefore not responsive to pre-constriction with phenylephrine (PE) likely related to nitrates and gallic acid naturally present in sumac whereby inhibiting PE.