Pomegranate Extract Enhances Endothelium-Dependent Coronary Relaxation in Isolated Perfused Hearts from Spontaneously Hypertensive Ovariectomized Rats

Abstract

Decline in estrogen levels promotes endothelial dysfunction and, consequently, the most prevalent cardiovascular diseases in menopausal women. The use of natural therapies such as pomegranate can change these results. Pomegranate [Punica granatum L. (Punicaceae)] is widely used as a phytotherapeutic agent worldwide, including in Brazil. We hypothesized that treatment with pomegranate hydroalcoholic extract (PHE) would improve coronary vascular reactivity and cardiovascular parameters. At the beginning of treatment, spontaneously hypertensive female rats were divided into Sham and ovariectomized (OVX) groups, which received pomegranate extract (PHE) (250 mg/kg) or filtered water (V) for 30 days by gavage. Systolic blood pressure was measured by tail plethysmography. After euthanasia, the heart was removed and coronary vascular reactivity was assessed by Langendorff retrograde perfusion technique. A dose-response curve for bradykinin was performed, followed by L-NAME inhibition. The protein expression of p-eNOS Ser1177, p-eNOS Thr495, total eNOS, p-AKT Ser473, total AKT, SOD-2, and catalase was quantified by Western blotting. The detection of coronary superoxide was performed using the protocol of dihydroethidium (DHE) staining Plasma nitrite measurement was analyzed by Griess method. Systolic blood pressure increased in both Sham-V and OVX-V groups, whereas it was reduced after treatment in Sham-PHE and OVX-PHE groups. The baseline coronary perfusion pressure was reduced in the Sham-PHE group. The relaxation was significantly higher in the treated group, and L-NAME attenuated the relaxation in all groups. The treatment has not changed p-eNOS (Ser1177), total eNOS, p-AKT (Ser473) and total AKT in any groups. However, in Sham and OVX group the treatment reduced the p-eNOS (Thr495) and SOD-2. The ovariectomy promoted an increasing in the superoxide anion levels and the treatment was able to prevent this elevation and reducing oxidative stress. Moreover, the treatment prevented the decreasing in plasmatic nitrite. We observed a reduction in total cholesterol and LDL in the Sham-PHE group. The treatment with PHE enhances the endothelium-dependent coronary relaxation and improves cardiovascular parameters, which suggests a therapeutic role of PHE.

Pomegranate prevents binge alcohol-induced gut leakiness and hepatic inflammation by suppressing oxidative and nitrative stress

“…Pomegranate (POM, Punica granatum ) is one of the edible fruits and mainly grown in middle east, India, southern Asia and Mediterranean Europe, as well as in warm climate areas of the world including Americas [20] . It is a rich source of polyphenolic compounds like anthocyanidins (delphinidin, cyanidin and pelargonidin) and hydrolysable tannins (such as punicalagin, pedunculagin, punicalin, gallagic, ellagic acid esters of glucose) [21] against a variety of diseases including cancer [22] , cardiovascular disorders [23] , diabetes [24] , Alzheimer's disease [25] , aging [26] , and AIDS [27] . Recently, it was shown to prevent development of non-alcoholic fatty liver disease in rats [28] and ethanol-induced toxicity in HepG2 human hepatoma cells [29] .…”

Vasculoprotective Effects of Pomegranate (Punica granatum L.)

“…Administration of hydroalcoholic peel or leaf extracts of pomegranate for 28 days decreased blood glucose levels in a Wister rat model of diabetes induced by streptozotocin (Salwe et al, 2015 ). Hydroalcoholic peel extracts of pomegranate were also tested in spontaneously hypertensive ovariectomized female rats (an animal model for menopause characterized by an increase in the superoxide anion levels; Delgado et al, 2016 ). Such treatment diminished elevation of superoxide anion levels and lessened oxidative stress in this animal model (Delgado et al, 2016 ).…”

“…Hydroalcoholic peel extracts of pomegranate were also tested in spontaneously hypertensive ovariectomized female rats (an animal model for menopause characterized by an increase in the superoxide anion levels; Delgado et al, 2016 ). Such treatment diminished elevation of superoxide anion levels and lessened oxidative stress in this animal model (Delgado et al, 2016 ). Treatment of spontaneously hypertensive rats of different ages for 30 days with pomegranate peel extracts, significantly reduced systolic blood pressure, ACE activity, oxidative stress as well as vascular remodeling (Dos Santos et al, 2016 ).…”

Antimicrobial Potential and Cytotoxicity of Silver Nanoparticles Phytosynthesized by Pomegranate Peel Extract

“…Furthermore, it is possible that some compounds in the extracts may have a synergistic effect with the silver nanoparticles [ 48 ], making them less toxic to human cells. Furthermore, extracts of Punica granatum have exhibited antioxidant [ 49 ] and anti-inflammatory [ 50 ] activity, and may have contributed to reducing the cytotoxicity of green- in comparison with chemical-silver nanoparticles.…”