Antihypertensive phytocomplexes of proven efficacy and well-established use: Mode of action and individual characterization of the active constituents Author Micucci, M. ∗ & Department of Pharmacy and Biotechnology, Alma Mater Studiorum University of Bologna, Via Belmeloro, 6, 40126, Italy Author Bolchi, C. Author Budriesi, R. Author Cevenini, M. Author Maroni, L. Author Capozza, S. Author Chiarini, A. Author Pallavicini, M. Author Angeletti, A. text Phytochemistry 2020 112222 2020-02-29 170 1 19 http://dx.doi.org/10.1016/j.phytochem.2019.112222 journal article 264564 10.1016/j.phytochem.2019.112222 4a860314-bd9c-4c55-9f10-852e402b1aef 1873-3700 8292998 2.9. Arbutus unedo L Arbutus unedo L. belongs to Ericaceae species and, in folk medicine, it has been used for many diseases, including gastrointestinal and urological pathologies, hypertension and cardiac diseases. Ziyyat (Ziyyat et al., 2002) evaluated the effects of a decoction obtained from A. unedo roots, showing that it induced an endothelium-dependent relaxation of aorta. In A. unedo roots water extracts, (+)-catechin and (−)-catechin gallate were found. Phenolic compounds, benzoic acid, caffeic acid and gallic acid were also detected (Miguel et al., 2014). The Authors who studied the pharmacological properties of the plant focused on the investigation concerning the vasorelaxant effects of the decoction and the related mechanisms of action. The results showed that the water extract causes relaxation of rats isolated norepinephrine-precontracted aorta. This effect was endothelium-dependent and it was inhibited by L-NAME pretreatment or by ODQ. In addition, this effect was not related to endothelium muscarinic receptors activation as it was unaffected by atropine. The vasorelaxant effects may be due to the presence of polyphenolic compounds, including tannins and flavonoids, and the mechanism of action might involve the stimulation of endothelial nitric-oxide synthase (Ziyyat et al., 2002). The antihypertensive effect of A. unedo roots decoction ( 250 mg /kg/ day) and leaves infusion was assessed in vivo , using rats affected by hypertension induced by L-NAME (Afkir et al., 2008). The administration of the mentioned extracts and L-NAME prevented the increase in systolic BP, improved the vascular reactivity and baroreflex sensitivity, showing that chronic treatment with these extracts not only affects BP, but also exerts a protective activity towards cardiovascular and renal systems in NO-deficient hypertension. Also antiaggregant activity (El Haouari et al., 2007), as well as antidiabetic properties (Ziyyat et al., 1997), may contribute in providing cardiovascular protection. Principal constituents of infusions and decoctions of leaves and roots examined for their antihypertensive activity are the phenolic compounds catechin, already mentioned, catechin 3-O-gallate, epicatechin 3-O-gallate, gallic acid and arbutin ( Fig. 9 ) (Oliveira et al., 2011; Morgado et al., 2018). Catechin and epicatechin 3-O-gallates were proved to exert moderate inhibitory action on ACE (Liu et al., 2003), while gallic acid has been recently investigated for its antihypertensive activity in SHRs ascribed to its ability of attenuating oxidative stress (Jin et al., 2017a,b). Lastly, arbutin was tested in a rat model of heart and mesenteric ischemia-reperfusion finding that it has antioxidant properties and reduces ROS production in mesenteric vessels (Broskova et al., 2013).