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.
Highlights
Cardiovascular diseases (CVDs) are the main cause of death in many nations
A qualitative phytochemical analysis was made and the results showed the presence of triterpenoids, glycosides, saponins, flavonoids, tannins, carbohydrates, and organic acid in the Pomegranate hydroalcoholic extract (PHE) (Table 1)
The treatment was able to prevent the progression of hypertension in ovariectomized rats (OVX)-PHE (150 ± 1.5 mmHg, P < 0.05) group when compared to the beginning of the treatment
Summary
Cardiovascular diseases (CVDs) are the main cause of death in many nations. Characteristics such as age, sex and genetic predisposition can be highlighted among the “non-modifiable” risk factors; whereas diet and lifestyle are considered “modifiable” (Leifert and Abeywardena, 2008; Mozaffarian et al, 2016).Hypertension has been recognized as a major risk factor for CVDs (Pickering, 1972). While some authors demonstrated that estrogen could modulates kinases proteins expression such as Akt (Bhuiyan et al, 2011; Turdi et al, 2015), PKG (Word and Cornwell, 1998) and PKC (Hunter and Korzick, 2005; Hunter et al, 2007), others suggest that there is no modulation by estrogen on these kinases (Teede et al, 2001; Cao et al, 2015; Leung et al, 2015) Taken together, these studies showed that the relationship between the expression of kinases and estrogen levels is very complex which becomes a limiting factor for the use of estrogen therapy in postmenopausal women. Even though some studies have shown beneficial effects of pomegranate, further research is needed
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