Punica granatum, L.

Micucci, M., Bolchi, C., Budriesi, R., Cevenini, M., Maroni, L., Capozza, S., Chiarini, A., Pallavicini, M. & Angeletti, A., 2020, Antihypertensive phytocomplexes of proven efficacy and well-established use: Mode of action and individual characterization of the active constituents, Phytochemistry (112222) 170, pp. 1-19 : 9-10

2.11. Punica granatum L

Punica granatum L. currently known as Pomegranate, has been used in Uighur Medicine for the treatment of cardiovascular diseases. Chemical composition of pomegranate fruits extracts and juices include ellagitannins, such as punicalagin and ellagic acid, gallotannins, such as glucogallin and gallic acid, lactone derivatives, flavones such as luteolin, and anthocyans ( Fig. 11 ) (Abdulla et al., 2017; Aguilar-Zarate et al., 2017; Brighenti et al., 2017; Garcia-Villalba et al., 2015). On the other hand, pomegranate seed oil mainly contains fatty acids like palmitic, stearic, oleic, linoleic, punicic acid, phytosterols including campesterol, stigmasterol, β- sitosterol, Δ5-avenasterol, β- amyrin, cycloartenol, citrostadienol (Caligiani et al., 2010; Siano et al., 2016).

The administration of pomegranate juice and fruit extract to rats fed with an atherogenic diet resulted in an increased acetylcholine-induced relaxation of aorta. This effect was less evident with pomegranate seed oil. In addition, pomegranate juice and fruit extract inhibited proatherogenic effects resultant from the altered shear stress. Pomegranate fruit extract administration increased vascular expression of eNOS and NOx levels, reducing Thrombospondin 1 and Transforming Growth Factor-β1 expression, augmenting the effects of NO and improving arterial functions in obese rats (de Nigris et al., 2007). The endothelium-dependent mechanisms for the antihypertensive effect of pomegranate hydroalcoholic extract was also reported by Delgado (Delgado et al., 2016), who demonstrated that it ameliorates endothelium-dependent coronary relaxation through the inhibition of eNOS phosphorylation and reduction of oxidative stress.

The modulation of renin-angiotensin system seems to be involved in the antihypertensive effect of pomegranate juice extract in diabetic rats, as its administration, by inhibiting ACE activity, prevented angiotensin II-mediated BP increase. A reduction in the diabetes-induced oxidative stress upon juice treatment was also observed (Mohan et al., 2010). Both antioxidant- and ACE-inhibitory-effects were also observed in an aging and spontaneously hypertensive rat model (Dos Santos et al., 2016).

Interestingly, ACE activity inhibition occurred also in hypertensive patients that were administered pomegranate juice (Aviram and Dornfeld, 2001) and was also sheared by other flavonoids such as luteolin (Loizzo et al., 2007), delphinidin−3- O -glucoside, cyanidin-3- O - glucoside, pelargonidin-3- O -glucoside (Hidalgo et al., 2012).

Finally, the in vivo hypotensive effect of pomegranate juice was reported to be accompanied by improved endothelial function caused by a decrease in Vascular Cell Adhesion Molecule 1 plasma concentration (Asgary et al., 2014). These properties, along with the inhibitory effect on oxidative stress and on serum ACE activity, made pomegranate juice an interesting supplement to be used against cardiovascular diseases.

The pomegranate effects towards NO are due, at least in part, to punicalagin (Chen et al., 2008; Shao et al., 2016), ellagic acid (Berkban et al., 2015; Ou et al., 2010; Olgar et al., 2014; Jordao et al., 2017), gallic acid (de Oliveira et al., 2016), flavonoids such as luteolin (Si et al., 2014), cyanidin−3- O -glucoside (Fratantonio et al., 2017). Furthermore, ellagic acid was found to prevent isoproterenol induced oxidative stress in myocardial infarction in rats through electrocardiological, biochemical and histological studies (Kanan and Quine, 2011). On the other hand, ACE inhibition and protection against angiotensin II activity were evidenced for luteolin (Loizzo et al., 2007; Nakayama et al., 2015).

Figures

Fig. 11. Antihypertensive principles of Punica granatum L. fruits extracts and juices.