identifier	taxonID	type	CVterm	format	language	title	description	additionalInformationURL	UsageTerms	rights	Owner	contributor	creator	bibliographicCitation
03E4D873FFF6DC56FC8DB371BEC71A3D.text	03E4D873FFF6DC56FC8DB371BEC71A3D.taxon	http://purl.org/dc/dcmitype/Text	http://rs.tdwg.org/ontology/voc/SPMInfoItems#GeneralDescription	text/html	en	Morus alba L.	<div><p>2.1. Morus alba L</p></div>	https://treatment.plazi.org/id/03E4D873FFF6DC56FC8DB371BEC71A3D	Public Domain	No known copyright restrictions apply. See Agosti, D., Egloff, W., 2009. Taxonomic information exchange and copyright: the Plazi approach. BMC Research Notes 2009, 2:53 for further explanation.		Plazi	Micucci, M.;Bolchi, C.;Budriesi, R.;Cevenini, M.;Maroni, L.;Capozza, S.;Chiarini, A.;Pallavicini, M.;Angeletti, A.	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: 1-19, DOI: 10.1016/j.phytochem.2019.112222, URL: http://dx.doi.org/10.1016/j.phytochem.2019.112222
03E4D873FFF4DC53FC8DB1B0BFD91C0F.text	03E4D873FFF4DC53FC8DB1B0BFD91C0F.taxon	http://purl.org/dc/dcmitype/Text	http://rs.tdwg.org/ontology/voc/SPMInfoItems#GeneralDescription	text/html	en	Hibiscus sabdari L.	<div><p>2.3. Hibiscus sabdari ff a L</p><p>Hibiscus sabdari ff a L. (Syn: Roselle, Rozelle, Indian sorrel, Sour tea and Karkade) has been used for several purposes in folk medicine. In India, Africa and Mexico, leaves or calyces are used to prepare infusions that are believed to exert choleretic, febrifugal, diuretic, and hypotensive effects (Da-Costa-Rocha et al., 2014).</p><p>The chemical composition of H. sabdari ff a extracts includes hibiscus acid, hibiscus acid glucosides, caffeoylquinic acids, flavonoids such as quercetin-3-rutinoside, kaempferol-3-O-rutinoside, myricetin, anthocyanins such as delphinidin-3-sambubioside and cyanidin-3-sambubioside (Fig. 3) (Da-Costa-Rocha et al., 2014; Ramirez-Rodrigues et al., 2011).</p><p>H. sabdari ff a tea has been shown to be able to lower food intake, decrease lipogenesis, increase lipolysis, stimulate fatty acids β- oxidation and attenuate inflammatory responses and oxidative stress (Herranz-Lopez et al., 2017).</p><p>H. sabdari ff a extracts decrease BP in normotensive and hypertensive animals by several mechanisms (Mojiminiyi et al., 2007; Onyenekwe et al., 1999). A methanolic extract from H. sabdari ff a calyces reduces the rat aorta rings contractions induced by KCl and phenylephrine (Ajay et al., 2007), suggesting its ability to inhibit calcium influx. The relaxant effect of the hibiscus flower extract was also observed in guinea pig aorta and ileum, where it exerts a calcium antagonistic effect (Micucci et al., 2015). In addition, it was also demonstrated that the vasorelaxation was possibly mediated by the endothelium-derived nitric oxide-cGMP-relaxant pathway and by the inhibition of calciuminflux into vascular smooth muscle cells, as it was inhibited by removal of endothelium and by the presence of atropine, L-NAME or methylene blue (Ajay et al., 2007).</p><p>Another effect responsible for the hypotensive activity is ACE inhibition, which is due, at least in part, to delphinidin-3-sambubioside and cyanidin-3-O-sambubioside (Fig. 3) (Ojeda et al., 2010).</p><p>In vivo experiments demonstrated that the oral administration of the water extract from H. sabdari ff a calyces to male albino Sprague–Dawley rats causes a diuretic effect (Alarcon-Alonso et al., 2012) probably related to quercetin. Polyphenol water extract, in fact, seems to inhibit ATPase activity (Mezesova et al., 2010) affecting the Na + /K + concentration gradient in nephron tubular segment epithelial cells. In addition, the diuretic- as well as natriuretic- and potassium sparing-effects of the extract seems to be due to H. sabdari ff a ability to downregulate aldosterone (Jimenez-Ferrer et al., 2012).</p><p>Interestingly, the hypotensive activity was observed also in humans (Nwachukwu et al., 2015). In particular, clinical studies demonstrated that the administration of H. sabdari ff a extracts to hypertensive patients reduces BP (Nwachukwu et al., 2015, 2017; Herrera-Arellano et al., 2004, 2007; McKay et al., 2010). In a double-blind placebo-controlled clinical trial, daily consumption of H. sabdari ff a L. calyx powder decreased systolic BP and serum triglycerides in metabolic syndrome patients (Asgary et al., 2016). In addition, the polyphenol content influences the course of obesity (Rodriguez-Perez et al., 2017). Moreover, Hibiscus sabdari ff a consumption was reported to improve renal function in a population study of Nigerians with mild to moderate hypertension (Nwachukwu et al., 2017).</p><p>The compounds contained in H. sabdari ff a extracts and individually studied for antihypertensive effects are caffeoylquinic acids, in particular the 5-caffeoyl regioisomer, and rutin previously mentioned as active constituents of M. alba leaves and leaf extracts. In addition, studies have been dedicated to hibiscus acid and garcinia acid, to the flavonoid myricetin and to the glucosides of the anthocyanins delphinidin and cyanidin (Fig. 3). The two acids exert vasorelaxant action likely due to the inhibition of Ca 2+ influx via voltage-dependent Ca 2+ channels (Zheoat et al., 2019). Myricetin has been proved to significantly inhibit atherogenesis (Sasaki et al., 2018) and it could prevent the development of high blood pressure induced by a diet rich in fructose (Godse et al., 2010). Lastly, ACE inhibition and decreasing of its mRNA production have been demonstrated for the two antocyanins and quercetin (Ojeda et al., 2010; Parichatikanond et al., 2012).</p></div>	https://treatment.plazi.org/id/03E4D873FFF4DC53FC8DB1B0BFD91C0F	Public Domain	No known copyright restrictions apply. See Agosti, D., Egloff, W., 2009. Taxonomic information exchange and copyright: the Plazi approach. BMC Research Notes 2009, 2:53 for further explanation.		Plazi	Micucci, M.;Bolchi, C.;Budriesi, R.;Cevenini, M.;Maroni, L.;Capozza, S.;Chiarini, A.;Pallavicini, M.;Angeletti, A.	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: 1-19, DOI: 10.1016/j.phytochem.2019.112222, URL: http://dx.doi.org/10.1016/j.phytochem.2019.112222
03E4D873FFF4DC54FFDBB0FDBC501DFA.text	03E4D873FFF4DC54FFDBB0FDBC501DFA.taxon	http://purl.org/dc/dcmitype/Text	http://rs.tdwg.org/ontology/voc/SPMInfoItems#GeneralDescription	text/html	en	Mangifera indica L.	<div><p>2.2. Mangifera indica L</p><p>Mangifera indica L. ( Anacardiaceae) fruits, commonly known as “mango”, are widely used in the tropical and subtropical regions. In folk medicine of Africa and India, stem bark- and leaves-based preparations are considered as useful tools for the treatment of several diseases, including gastrointestinal, SNC and cardiovascular pathologies, in particular hypertension (Burkill et al., 1985; Eridiweera et al., 2017; Shah et al., 2010).</p><p>Mango leaves extracts contain an essential oil, sugars, xanthones, including mangiferin, gallates, gallotannins, ellagitannins, benzophenones and flavonoids, the most important of which is quercetin-3-Osophoroside (quercetin-3-O-α- glucopyranosyl-(1 → 2)-β- glucopyranoside) (Qudsia and Arshad, 2009).</p><p>A M. indica stem bark water extract reverted both noradrenaline- and thromboxane A2 (TP) analogue U46619-induced contraction in rat mesenteric resistance arteries, suggesting the ability of the extract to act as a non-competitive antagonist of TP receptors (Beltran et al., 2004). Further mechanisms that may contribute consist in the extract ability to inhibit the expression of different inflammatory mediators such as leukotriene B4 and prostaglandin E2 production in calcium ionophore and lipopolysaccharide-stimulated macrophages, respectively (Delgado Hernandez et al., 2001). In addition, a M. indica leaves dichloromethanic fraction exerts an ACE-inhibitory activity similar to captopril either in vitro and in vivo, suggesting flavonoids as main contributors to this activity (Ronchi et al., 2015).</p><p>Mangiferin is the constituent of mango individually investigated for its antihypertensive effects (Fig. 2). It alleviates hypertension induced by hyperuricemia via increasing NO release and improving endothelial function (Yang et al., 2018) and it has been found to exert anti-hepatosteatotic effects in fructose-fed spontaneously hypertensive rats (Xing et al., 2014). However, the demonstrated inhibitory effect of mango extracts on vasoconstrictor responses would be mediated by other constituents (Beltran et al., 2004), reasonably the many flavonoids and isoflavonoids because mangiferin itself has little effect on blood pressure (Yao et al., 2017).</p></div>	https://treatment.plazi.org/id/03E4D873FFF4DC54FFDBB0FDBC501DFA	Public Domain	No known copyright restrictions apply. See Agosti, D., Egloff, W., 2009. Taxonomic information exchange and copyright: the Plazi approach. BMC Research Notes 2009, 2:53 for further explanation.		Plazi	Micucci, M.;Bolchi, C.;Budriesi, R.;Cevenini, M.;Maroni, L.;Capozza, S.;Chiarini, A.;Pallavicini, M.;Angeletti, A.	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: 1-19, DOI: 10.1016/j.phytochem.2019.112222, URL: http://dx.doi.org/10.1016/j.phytochem.2019.112222
03E4D873FFF3DC53FFDBB55FB9571D16.text	03E4D873FFF3DC53FFDBB55FB9571D16.taxon	http://purl.org/dc/dcmitype/Text	http://rs.tdwg.org/ontology/voc/SPMInfoItems#GeneralDescription	text/html	en	Eucommia ulmoides Oliv	<div><p>2.4. Eucommia ulmoides Oliv</p><p>Eucommia ulmoides Oliv. Is a medicinal plant widely used for medical purposes in China. In Traditional Chinese Medicine, in fact, it is used as a treatment for hypertension, rheumatoid arthritis, kidney deficiency pain, weak bones, bone fractures and joint diseases, as well as lower back pain (Xing et al., 2019).</p><p>The main compounds isolated from E. ulmoides are lignans, flavonoids, iridoids, phenolic acids, steroids and terpenoids. Fatty acids, polysaccharides, amino acids, microelements, vitamins were also detected (He et al., 2014).</p><p>The antihypertensive effect of E. ulmoides leaves and bark occurs by several mechanisms, including inhibition of cAMP phosphodiesterase activity, modulation of NO and renin-angiotensin system, a direct blood vessel relaxant effect and an increase in coronary flow (Kwan et al., 2004; Luo et al., 2010; Hosoo et al., 2015). In particular, the vasorelaxant effect of E. ulmoides bark water extracts is, at least in part, endothelium-dependent, as it was antagonized by L-NAME and bluemethilene (Kwan et al., 2004). The water extract of the leaves also possesses vasorelaxant, endothelium-dependent properties (Jin et al., 2008).</p><p>Singly studied constituents of E. ulmoides extracts are depicted in Fig. 4. They are the iridoids (cyclopentanpyrans) geniposidic acid and asperuloside, to which increased levels of adiponectin have been imputed (Hosoo et al., 2017) and, in the case of geniposidic acid, also enhanced secretion of atrial natriuretic peptide from cardiomyocytes (Nakamura et al., 2018). The glucosides of monoepoxylignans related to olivil and of bisepoxylignans related to pinoresinol have been proposed for inhibition of hypertensive vascular remodelling (Gu et al., 2011) and for enhancing plasma level of NO and lowering levels of angiotensin II and renin activities (Luo et al., 2010). A controlled, randomized clinical trial showed that the administration of 3 g of an E. ulmoides bark extract standardized to eight percent pinoresinol di-β- Dglucoside reduces BP, has β- adrenergic blocking activity and is well tolerated (Greenway et al., 2011).</p><p>Among the flavonoids, wogonin and its iduronic acid derivative, wogonoside, may contribute to the hypotensive effect by inhibiting both Ca 2+ influx and Ca 2+ release in isolated rat aorta (Qu et al., 2015), while oroxylin A may be relevant to the vasorelaxant effect by acting through an endothelium-dependent mechanism which involves endothelin 1 receptors (Akinyi et al., 2014) and the quercetin 3-galattoside, hyperin, may exert ACE inhibition (Nileeka Balasuriya and Vasantha Rupasinghe, 2011).</p></div>	https://treatment.plazi.org/id/03E4D873FFF3DC53FFDBB55FB9571D16	Public Domain	No known copyright restrictions apply. See Agosti, D., Egloff, W., 2009. Taxonomic information exchange and copyright: the Plazi approach. BMC Research Notes 2009, 2:53 for further explanation.		Plazi	Micucci, M.;Bolchi, C.;Budriesi, R.;Cevenini, M.;Maroni, L.;Capozza, S.;Chiarini, A.;Pallavicini, M.;Angeletti, A.	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: 1-19, DOI: 10.1016/j.phytochem.2019.112222, URL: http://dx.doi.org/10.1016/j.phytochem.2019.112222
03E4D873FFF3DC52FC8DB4A8BEBC1C18.text	03E4D873FFF3DC52FC8DB4A8BEBC1C18.taxon	http://purl.org/dc/dcmitype/Text	http://rs.tdwg.org/ontology/voc/SPMInfoItems#GeneralDescription	text/html	en	Elettaria cardamomum ((L.)) Maton	<div><p>2.5. Elettaria cardamomum (L.) Maton</p><p>Elettaria cardamomum (L.) Maton, commonly known as cardamom, is widely used in India, Pakistan, Burma and Sri Lanka as a food and also as a vegetal drug for the treatment of several diseases including, among others, diarrhoea, dyspepsia, vomiting, and cardiovascular diseases (Duke, 2001). Extracts from cardamom fruits and seeds contain a wide number of cyclic and acyclic terpenes, with content prevalence of cineol and linalool, together with phytosterols (Shaban et al., 1987; Gopalakrishnan et al., 1990; Duke, 1992; Kuyumcu Savan and Kucukbay, 2013).</p><p>A crude extract from cardamom fruits was shown to relax in a concentration-dependent fashion endothelium-intact rat aorta rings pre-contracted with phenylephrine or KCl. In addition, this extract induced a concentration-dependent suppression of the atrial contractions (Gilani et al., 2008). The petroleum spirit, chloroform and the ethyl acetate fractions seem to be the most active as regards the vasorelaxant effects. These properties were confirmed in vivo, as the intravenous injection to anaesthetized rats resulted in a drop of arterial BP (Gilani et al., 2008). Furthermore, the administration of 3 g of cardamom powder to patients with essential hypertension (primary hypertension) reduces systolic and diastolic BP, in addition to enhancing fibrinolysis and improving total antioxidant status (Verma et al., 2009).</p><p>Isolated components of cardamom extract characterized for antihypertensive activity are depicted in Fig. 5. For cineol, the major constituent, antihypertensive effect was demonstrated in rats chronically exposed to nicotine and this effect was associated with regulation of NO and oxidative stress (Moon et al., 2013). Another important constituent, linalool, was studied, free and β- cyclodextrin complexed, in both normotensive and hypertensive rats demonstrating antihypertensive effects associated to a direct action on the vascular smooth muscle leading to vasodilation, to increased vasodilator responsiveness and reduced sensitivity to the sympathetic agonist phenylephrine (Anjos et al., 2013; Camargo et al., 2018). For limonene, the blood pressure attenuation was imputed to antioxidant activity, lipid lowering and promotion of vascular remodelling (Santiago et al., 2010; Wang et al., 2018). Direct effect on the vascular smooth muscle leading to vasodilation was suggested for citronellol (Bastos et al., 2009; Ribeiro-Filho et al., 2016), while β- pinene was suggested to induce endothelium-independent vasorelaxation caused by the inhibition of the Ca 2+ influx through L-type Ca 2+ channel associated to a decrease in calcium sensitivity (Moreira et al., 2016).</p></div>	https://treatment.plazi.org/id/03E4D873FFF3DC52FC8DB4A8BEBC1C18	Public Domain	No known copyright restrictions apply. See Agosti, D., Egloff, W., 2009. Taxonomic information exchange and copyright: the Plazi approach. BMC Research Notes 2009, 2:53 for further explanation.		Plazi	Micucci, M.;Bolchi, C.;Budriesi, R.;Cevenini, M.;Maroni, L.;Capozza, S.;Chiarini, A.;Pallavicini, M.;Angeletti, A.	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: 1-19, DOI: 10.1016/j.phytochem.2019.112222, URL: http://dx.doi.org/10.1016/j.phytochem.2019.112222
03E4D873FFF2DC51FC8DB552B80A1A92.text	03E4D873FFF2DC51FC8DB552B80A1A92.taxon	http://purl.org/dc/dcmitype/Text	http://rs.tdwg.org/ontology/voc/SPMInfoItems#GeneralDescription	text/html	en	Allium sativum L.	<div><p>2.6. Allium sativum L</p><p>The use of Allium sativum L. (Garlic) is reported in several medical systems, including Egyptian, Greek and Indian traditions (Rivlin, 2001). Garlic-based preparations contain a large variety of phytochemicals including many organosulphides (alliin, allicin, S-allyl-cysteine, S-1- propenylcysteine, vinyldithianes and vinyldithiins, allixin, sulfides, such as diallyl-, methyl allyl-, and dipropyl mono-, di-, tri- and tetrasulfides), flavonoids, saponins and sapogenins, phenolic compounds, amides and proteins (Kopec et al., 2013; Lanzotti et al., 2014; Rekowska and Skupie ń, 2009). The hypotensive activity of garlic occurs, at least in part, through an endothelium-dependent mechanism, as it inhibits the hypertensive effect of N(ω)-nitro-L-arginine methyl ester (L-NAME) in normal and two kidney-one clip (2 K–1C) rats, and increases NO synthesis in in vivo and in vitro (Al-Qattan et al., 2006; Morihara et al., 2006). Fresh garlic extract exerts NO-dependent vasodilation (Ku et al., 2002) and fresh garlic homogenate inhibits angiotensin converting enzyme (ACE) and lowers BP in rats and guinea pigs (Asdaq and Inamdar, 2010). In addition, garlic and some related phytochemicals seem to modulate cellular sodium levels by inhibiting the activity of epithelial sodium channel (Krumm et al., 2012) and to augment sodium concentrations in urine in a kidney reperfusion injury model (Bagheri et al., 2011). It is also endowed of antihypertensive action in the 2 K–1C model of hypertension, which is partly mediated by the interaction between prostanoids and the Na + /H + exchanger isoforms 1 (Al-Qattan et al., 2003). Garlic extracts act also directly on vascular smooth muscle. Several garlic extracts and fractions, in fact, inhibit KCl and phenylephrine induced contractions in rats isolated aorta, suggesting calcium antagonistic and α- antagonistic properties (Ganado et al., 2004). A meta-analysis of randomized controlled trials showed that, respect to placebo, garlic is able significantly to decrease systolic and diastolic BP without any severe adverse effect (Xiong et al., 2015).</p><p>Allicin, S-allylcysteine, S-1-propenylcysteine, alliin, diallylsulfides and some dipeptides are the most studied garlic constituents (Fig. 6). Allicin exerts NO-dependent vasodilation (Ku et al., 2002), shows the ability to suppress cholesterol biosynthesis and, by decomposition, it releases hydrogen sulphide, which lowers BP by relaxation of smoothmuscle cells (Borlinghaus et al., 2014). The above-mentioned inhibition of epithelial sodium channels by garlic has been imputed to allicin (Krumm et al., 2012). Allicin counteracts cardiovascular diseases in various ways and further efforts are necessary better to understand the molecular basis of its action. S-Allylcysteine was shown to exert ACE inhibitory activity and to lower BP in rats and guinea pigs (Asdaq and Inamdar, 2010). Recently, S-1-propenylcysteine, but not S-allylcysteine, was shown significantly to decrease systolic BP of spontaneously hypertensive rats (Ushijima et al., 2018). Garlic ingredients, such as alliin, allyl disulphide and diallyl trisulfide result in significant increase of human endothelial cell NO production (Mousa and Mousa, 2007). Lastly, seven dipeptides with ACE inhibitory properties were isolated from garlic aqueous extracts and tested for ACE inhibition, finding that Phe-Tyr was the most potent one (Suetsuna, 1998).</p></div>	https://treatment.plazi.org/id/03E4D873FFF2DC51FC8DB552B80A1A92	Public Domain	No known copyright restrictions apply. See Agosti, D., Egloff, W., 2009. Taxonomic information exchange and copyright: the Plazi approach. BMC Research Notes 2009, 2:53 for further explanation.		Plazi	Micucci, M.;Bolchi, C.;Budriesi, R.;Cevenini, M.;Maroni, L.;Capozza, S.;Chiarini, A.;Pallavicini, M.;Angeletti, A.	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: 1-19, DOI: 10.1016/j.phytochem.2019.112222, URL: http://dx.doi.org/10.1016/j.phytochem.2019.112222
03E4D873FFF1DC50FC8DB233BDB21985.text	03E4D873FFF1DC50FC8DB233BDB21985.taxon	http://purl.org/dc/dcmitype/Text	http://rs.tdwg.org/ontology/voc/SPMInfoItems#GeneralDescription	text/html	en	Alpinia zerumbet (Pers.) B. L. Burtt & R. M. Sm	<div><p>2.7. Alpinia zerumbet (Pers.) B.L.Burtt &amp; R.M.Sm</p><p>Alpinia zerumbet (Pers.) B.L.Burtt &amp; R.M.Sm is a tropical plant that originates in South America and Asia, whose leaves are used in folk medicine for the treatment of hypertension and gastrointestinal ailments.</p><p>Extracts from leaves mainly contain flavonoids, such as (+)-catechin, (−)-epicatechin, rutin, quercetin, kaempferol and its glucosides, and kava pyrones, including dihydro-5,6-dehydrokawain and 5,6-dehydrokawain (Mpalantinos et al., 1998).</p><p>A. zerumbet leaves extract produces vasodilation in the mesenteric vascular bed, which was reverted by L-NAME and [1,2,3]oxadiazolo [4,4-a]quinoxalin-1-one (ODQ), suggesting the involvement of endothelium. This effect is due, at least in part, to activation of NO synthase and soluble guanylyl cyclase (GC), and to B2 bradykinin receptors antagonism (de Moura et al., 2005; Galleano et al., 2010). In vivo experiments showed also the involvement of endothelium-derived relaxing factors in the hypotensive action of A. zerumbet leaves extract (de Moura et al., 2005). Studies on the hypotensive activity of the purified flavonoids have been cited above (see M. alba). Here, two recent researches have to be mentioned which demonstrate the ACE inhibition activity of catechin (He, 2017) and the NO levels stimulation by epicatechin (Fig. 7) (Ramirez-Sanchez et al., 2018).</p><p>Essential oil, obtained by leaves, is also used. This contains a wide range of monoterpenes, of which terpinen-4-ol and 1,8-cineol are the main constituents (Fig. 7) (Lahlou et al., 2003; Pinto et al., 2009). The i. v. administration of the A. zerumbet essential oil to both Deoxycorticosterone acetate (DOCA) salt hypertensive and uninephrectomized, normotensive rats results in a decrease of BP (Lahlou et al., 2003), mainly due to terpinen-4-ol. The vasorelaxant effect occurs also by an endothelium-independent mechanism, as A. zerumbet essential oil methanolic fraction, rich in terpinen-4-ol and 1,8-cineol, inhibits calcium influx, acting on receptor-operated calcium channels and voltage-operated calcium channels (VOCC) (da Cunha et al., 2013). Recently, terpinen-4-ol has been proved to change intracellular Ca 2+ handling and to induce pacing disturbance in rat hearts (Gondim et al., 2017).</p><p>The plant has also properties of inhibiting the ox-LDL-mediated dysfunction of the vascular endothelium (Shen et al., 2012). In humans, the essential oil has effect on post-stroke muscle spasticity (Maia et al., 2016).</p></div>	https://treatment.plazi.org/id/03E4D873FFF1DC50FC8DB233BDB21985	Public Domain	No known copyright restrictions apply. See Agosti, D., Egloff, W., 2009. Taxonomic information exchange and copyright: the Plazi approach. BMC Research Notes 2009, 2:53 for further explanation.		Plazi	Micucci, M.;Bolchi, C.;Budriesi, R.;Cevenini, M.;Maroni, L.;Capozza, S.;Chiarini, A.;Pallavicini, M.;Angeletti, A.	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: 1-19, DOI: 10.1016/j.phytochem.2019.112222, URL: http://dx.doi.org/10.1016/j.phytochem.2019.112222
03E4D873FFF0DC50FFDBB0D7BC601D78.text	03E4D873FFF0DC50FFDBB0D7BC601D78.taxon	http://purl.org/dc/dcmitype/Text	http://rs.tdwg.org/ontology/voc/SPMInfoItems#GeneralDescription	text/html	en	Aniba canelilla (Kunth) Mez	<div><p>2.8. Aniba canelilla (Kunth) Mez</p><p>Aniba canelilla (Kunth) Mez (Lauraceae) [Syn. A. Elliptica A.C. SM., Cryptocarya canelilla Kunth], also known as ‘‘casca-preciosa’‘, is a plant belonging to Lauraceae family, growing in the Amazon region. In folk medicine, the bark is used to prepare decoctions that are believed to exert antispasmodic, digestive stimulating, and carminative properties. Chemical composition of A. canelilla wood and bark oil includes benzenoids and terpenoids, 1-nitro-2-phenylethane and methyleugenol being the two major components (Fig. 8) (Giongo et al., 2017; Lahlou et al., 2005).</p><p>The essential oil causes a concentration-dependent reduction of potassium-induced contraction of rat aorta with endothelium and it counters CaCl 2 -induced contractions, but not those induced by caffeine suggesting an inhibition of calcium inward current (Lahlou et al., 2005). In conscious rats pretreated with L-NAME, the hypotensive effect of the essential oil was partly, but significantly reduced supporting the essential oil ability to affect the endothelial L-arginine/nitric oxide pathway (Lahlou et al., 2005). These effects are mainly due to 1-nitro-2- phenylethane (Fig. 8), that was shown to induce vasorelaxant and hypotensive effects in vit ro and in vivo through a myogenic endothelium-independent mechanism (de Siqueira et al., 2010; Interaminense Lde et al., 2011; Interaminense Lde et al., 2013). The other main constituent, methyleugenol (Fig. 8), was also studied for its cardiovascular effects. In particular, it was found to elicit hypotension in either anaesthetized or conscious rats through an active vascular relaxation, significantly reduced by pretreatment with L- NAME or mechanical endothelium removal (Lahlou et al., 2004; Magalhaes et al., 2008).</p><p>Ethanol extract of A. canelilla is also endowed of antioxidant properties (Martins et al., 2016).</p></div>	https://treatment.plazi.org/id/03E4D873FFF0DC50FFDBB0D7BC601D78	Public Domain	No known copyright restrictions apply. See Agosti, D., Egloff, W., 2009. Taxonomic information exchange and copyright: the Plazi approach. BMC Research Notes 2009, 2:53 for further explanation.		Plazi	Micucci, M.;Bolchi, C.;Budriesi, R.;Cevenini, M.;Maroni, L.;Capozza, S.;Chiarini, A.;Pallavicini, M.;Angeletti, A.	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: 1-19, DOI: 10.1016/j.phytochem.2019.112222, URL: http://dx.doi.org/10.1016/j.phytochem.2019.112222
03E4D873FFF0DC50FFDBB44DBEBC1BBB.text	03E4D873FFF0DC50FFDBB44DBEBC1BBB.taxon	http://purl.org/dc/dcmitype/Text	http://rs.tdwg.org/ontology/voc/SPMInfoItems#GeneralDescription	text/html	en	Arbutus unedo L.	<div><p>2.9. Arbutus unedo L</p><p>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.</p><p>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).</p><p>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).</p><p>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.</p><p>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).</p></div>	https://treatment.plazi.org/id/03E4D873FFF0DC50FFDBB44DBEBC1BBB	Public Domain	No known copyright restrictions apply. See Agosti, D., Egloff, W., 2009. Taxonomic information exchange and copyright: the Plazi approach. BMC Research Notes 2009, 2:53 for further explanation.		Plazi	Micucci, M.;Bolchi, C.;Budriesi, R.;Cevenini, M.;Maroni, L.;Capozza, S.;Chiarini, A.;Pallavicini, M.;Angeletti, A.	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: 1-19, DOI: 10.1016/j.phytochem.2019.112222, URL: http://dx.doi.org/10.1016/j.phytochem.2019.112222
03E4D873FFF0DC5FFC8DB533BCCA1E15.text	03E4D873FFF0DC5FFC8DB533BCCA1E15.taxon	http://purl.org/dc/dcmitype/Text	http://rs.tdwg.org/ontology/voc/SPMInfoItems#GeneralDescription	text/html	en	Olea europaea L	<div><p>2.10. Olea europaea L</p><p>In folk medicine, this tree is mainly considered useful due to its diuretic, hypotensive, emollient, febrifuge and tonic actions and for urinary and bladder infections treatment.</p><p>Olea europaea L . leaves extract was shown to inhibit K + -induced contraction in guinea pigs ileum and aorta, suggesting a calcium antagonistic effect (Scheffler et al., 2008; Micucci et al., 2015). The vasorelaxant and antihypertensive effects of O. europaea leaves extract were confirmed also by in vivo studies (Romero et al., 2016) and clinical trials (Susalit et al., 2011). The antihypertensive effect of the extract can be also related to factors involving reversal of vascular changes contributing to L-NAME-induced hypertension (Khayyal et al., 2002).</p><p>Quite recently, the combination of O. europaea leaves and H. sabdari ff a flowers (13:2, respectively) has been proposed with the aim to obtain a mixture endowed with higher activity than the single components. In particular, it has been demonstrated that this mixture exerts a negative inotropic activity comparable to the singular phytocomplexes, and, at the same time, is endowed of additional properties such as vasorelaxant and a mild negative chronotropic-effect as well as higher in vitro cytoprotective and antioxidant activity (Micucci et al., 2015). On the basis of these results, a possible nutraceutical use of the above formulation for the management of preclinical hypertension has been suggested, especially in consideration of its antihypertensive effects along with its good toxicologic profile (Campbell et al., 2015). The combination of H. sabdari ff a flowers and O. europaea leaves (2:1 respectively) is able to normalize in vivo BP in L-NAME-mediated hypertension. In this experimental model, the combination can also improve hepatic and renal dysfunction (Abdel-Rahman et al., 2017). Olive oil may also contribute providing cardiovascular beneficial effects, preventing LDL oxidation and maintaining normal blood HDL cholesterol concentrations as it contains oleuropein and hydroxytyrosol (Clodoveo et al., 2016; Roselli et al., 2017). According to EFSA, in fact, the daily administration of hydroxytyrosol (5 mg) and its derivatives prevents LDL oxidation (Scientific opinion, EFSA Journal 2011, 9, 2033). In both leaves extract and olive oil, oleuropein and hydroxytyrosol have been demonstrated to be the main constituents responsible for the antihypertensive effects and cardiovascular benefits (Fig. 10). Hydroxytyrosol protects against the impairing effects of oxidative stress on the NO • -mediated relaxation of isolated rat aorta (Rietjens et al., 2007) and exhibits analogous antioxidant effects in vivo as demonstrated by studies on rats treated with cyclosporine, which causes oxidative stress, haemodynamic alterations and renal damages (Capasso et al., 2008). Recent reports have confirmed the beneficial antioxidant properties of hydroxytyrosol (Hu et al., 2014) and its ability to improve endothelial function and to lower systolic blood pressure in a diet-induced rat model of metabolic syndrome (Poudyal et al., 2017). Oleuropein attenuates, through ACE inhibition, the cardiac remodelling after infarction leading to excessive heart fibrosis (Mnafgui et al., 2015) and diminishes the increased ROS production in the hypothalamic paraventricular nucleus, associated to hypertension, by improving mitochondrial function (Sun et al., 2017).</p></div>	https://treatment.plazi.org/id/03E4D873FFF0DC5FFC8DB533BCCA1E15	Public Domain	No known copyright restrictions apply. See Agosti, D., Egloff, W., 2009. Taxonomic information exchange and copyright: the Plazi approach. BMC Research Notes 2009, 2:53 for further explanation.		Plazi	Micucci, M.;Bolchi, C.;Budriesi, R.;Cevenini, M.;Maroni, L.;Capozza, S.;Chiarini, A.;Pallavicini, M.;Angeletti, A.	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: 1-19, DOI: 10.1016/j.phytochem.2019.112222, URL: http://dx.doi.org/10.1016/j.phytochem.2019.112222
03E4D873FFFFDC5EFFDBB7ADBC591D8A.text	03E4D873FFFFDC5EFFDBB7ADBC591D8A.taxon	http://purl.org/dc/dcmitype/Text	http://rs.tdwg.org/ontology/voc/SPMInfoItems#GeneralDescription	text/html	en	Punica granatum L.	<div><p>2.11. Punica granatum L</p><p>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).</p><p>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.</p><p>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).</p><p>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).</p><p>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.</p><p>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).</p></div>	https://treatment.plazi.org/id/03E4D873FFFFDC5EFFDBB7ADBC591D8A	Public Domain	No known copyright restrictions apply. See Agosti, D., Egloff, W., 2009. Taxonomic information exchange and copyright: the Plazi approach. BMC Research Notes 2009, 2:53 for further explanation.		Plazi	Micucci, M.;Bolchi, C.;Budriesi, R.;Cevenini, M.;Maroni, L.;Capozza, S.;Chiarini, A.;Pallavicini, M.;Angeletti, A.	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: 1-19, DOI: 10.1016/j.phytochem.2019.112222, URL: http://dx.doi.org/10.1016/j.phytochem.2019.112222
03E4D873FFFEDC5DFFDBB4D9BC881F89.text	03E4D873FFFEDC5DFFDBB4D9BC881F89.taxon	http://purl.org/dc/dcmitype/Text	http://rs.tdwg.org/ontology/voc/SPMInfoItems#GeneralDescription	text/html	en	Salvia miltiorrhiza Bunge	<div><p>2.12. Salvia miltiorrhiza Bunge</p><p>The dried roots from Salvia miltiorrhiza Bunge (Danshen in Chinese) have been used for the treatment of cardiovascular and cerebrovascular pathologies in China and Japan. The main phytochemicals isolated from S. miltiorrhiza roots are hydrophilic phenolic acids and lipophilic diterpene quinones (Liang et al., 2017).</p><p>The administration of a water-soluble extract of S. miltiorrhiza roots to rats resulted in a decrease of mean arterial BP, which was also observed in the tissues pretreated with phenylephrine (Leung et al., 2010).</p><p>These data are in agreement with those by Zhang (Zhang et al., 2016), who observed that i.p. administration of a S. milthiorriza water roots extract and of a mixture of four constituents of the extract caused hypotension in spontaneously hypertensive rats. This was the result of several activities such as the decrease in plasma levels of angiontensin II, endothelin-1, malondialdehyde, transforming growth factor-β1, superoxide dismutase, the mRNA expression levels of collagen type I, α- smooth muscle actin, nicotinamide adenine dinucleotide phosphate oxidases (NOX), the suppression of angiotensin II-mediated effects including ROS-generation, morphological changes in the thoracic aorta tunica media and adventitia thickness. The hypotensive effect of a water extract from S. milthiorriza was confirmed in 2 K1C rats, where it mainly occurred by angiotensin converting enzyme inhibition (Kang et al., 2002).</p><p>In conclusion, the hypotensive action of S. milthiorriza is mainly due to ACE inhibition properties and thus to the decrease in plasma levels of angiotensin II and endothelin-1, to the suppression of ROS generation and vascular remodelling.</p><p>Fig. 12 shows the main danshen constituents characterized for antihypertensive and cardiovascular effects. Salvianolic acid A is one of the above cited four components (Zhang et al., 2016) and it has been singly studied, in spontaneously hypertensive rats, for its ability to inhibit endothelial dysfunctions (Teng et al., 2016) and, in particular, to prevent cardiac remodelling through matrix metalloproteinase-9 (MMP-9) inhibition (Jiang et al., 2013; Zhang et al., 2014). For salvianolic acid B, another of the above four components (Zhang et al., 2016), ACE inhibition (Kang et al., 2003) and endothelial function restoring associated with angiotensin receptor AT 1 inhibition have been proposed (Ling et al., 2017). Salvianolic acid A and B exert also antiatherosclerotic effects (Ba et al., 2014; Chen et al., 2011; Joe et al., 2012; Lin et al., 2007; Liu and Liu, 2002), while salvianolic acid B has been proved to inhibit platelets-mediated inflammation in vascular endothelial cells (Xu et al., 2015) and its magnesium salt, tanshinoate B, to decrease blood pressure also after treatment with phenylephrine (Leung et al., 2010) and to protect endothelium from hyperglycemiainduced dysfunction (Kim et al., 2010). Salvianic acid (danshensu), the third constituent (Zhang et al., 2016), seems to exert effects on several pharmacological targets in hypertension (Tang et al., 2011) and, in particular, it prevents pulmonary hypertension in rats inhibiting the proliferation of pulmonary artery smooth muscle (Zhang et al., 2018). For protocatechuic aldehyde, the last constituent of the four (Zhang et al., 2016), different mechanisms of action have been proposed in preventing atherosclerosis pathogenesis (Moon et al., 2012; Tong et al., 2016; Xing et al., 2012; Zhou et al., 2005).</p><p>The complex mechanisms underlying the antiatherosclerosis activity and protecting effects against cardiac hypertrophy of tanshinone IIA have been recently investigated evidencing the involvement of different signalling pathways (Wang et al., 2017; Zhao et al., 2016; Zhu et al., 2017; Pang et al., 2014; Feng et al., 2017; Wu et al., 2017). Therapeutic potential in ameliorating atherosclerosis through vasodilatatory, anti-coagulant, anti-thrombotic, anti-inflammatory, anti-oxidant, and immunomodulatory activities (Fang et al., 2018) strongly supports the option of using tanshinones from S. milthiorriza, in particular tanshinone IIA and cryptotanshinone, as a strategy to counteract atherosclerosis-related cardiovascular and metabolic diseases.</p><p>Interestingly, since hypertension is a common complication of type 2 diabetes mellitus, dihydrotanshinone I has been proposed as a substance with both anti-hypertensive activity, due to mineralocorticoid receptor antagonism, and antihyperglycemic effects (Liu et al., 2010). Diabetes-induced vascular dysfunction are attenuated by rosmarinic acid, which acts as a vasoactive substance and a cardioprotector through its antioxidant property (Karthik et al., 2011; Sotnikova et al., 2013; Javidanpour et al., 2017) .</p></div>	https://treatment.plazi.org/id/03E4D873FFFEDC5DFFDBB4D9BC881F89	Public Domain	No known copyright restrictions apply. See Agosti, D., Egloff, W., 2009. Taxonomic information exchange and copyright: the Plazi approach. BMC Research Notes 2009, 2:53 for further explanation.		Plazi	Micucci, M.;Bolchi, C.;Budriesi, R.;Cevenini, M.;Maroni, L.;Capozza, S.;Chiarini, A.;Pallavicini, M.;Angeletti, A.	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: 1-19, DOI: 10.1016/j.phytochem.2019.112222, URL: http://dx.doi.org/10.1016/j.phytochem.2019.112222
03E4D873FFFDDC5CFC8DB462BF631C4E.text	03E4D873FFFDDC5CFC8DB462BF631C4E.taxon	http://purl.org/dc/dcmitype/Text	http://rs.tdwg.org/ontology/voc/SPMInfoItems#GeneralDescription	text/html	en	Zingiber Roscoe	<div><p>2.13. Zingiber o ffi cinale Roscoe</p><p>Zingiber o ffi cinale Roscoe rhizome is widely used in Ayurvedic medicine, as a treatment for gastrointestinal and cardiovascular ailments. The rhizome contains phenolic compounds and non-volatile pungent active principles including gingerols, paradols, shogaols and gingerones (Semwal et al., 2015).</p><p>A water extract from Z. o ffi cinale was shown to inhibit ACE activity in a concentration-dependent manner (Akinyemi et al., 2014). This effect occurs also in vivo, in rats fed with a high cholesterol diet (Akinyemi et al., 2014). The same extract reduces mean arterial BP in L-NAME induced hypertensive rats. Butanol and ethyl acetate fractions seem to be more active than the water fraction (Manosroi et al., 2013). Efficacy of ginger supplementation on BP in clinical trials has been recently reviewed (Hasani et al., 2019).</p><p>In vitro experiments on guinea pig isolated tissues showed that the decoction of ginger possesses weak negative inotropic and chronotropic intrinsic activities, along with a significant intrinsic relaxant activity on smooth muscle with a greater potency on ileum than on aorta. The study on the main pure components supports the relationship between 6- and 8-gingerol and 6-shogaol and these effects. These results are in agreement with the activity of calcium channel modulators, which influence more strongly the not vascular muscles than vascular one (Leoni et al., 2017). Previous researches had evidenced, for 6-, 8- and 10- gingerol and, to a minor extent, also for 6-shogaol (Fig. 13), a vasodilator effect through a combination of NO releasing and calcium antagonist mechanism (Ghayur et al., 2005). More recently, 6-gingerol has been shown to attenuate the increased level of blood glucose and to improve cardiac hemodynamics in diabetic rats (El-Bassossy et al., 2016) and it has been identified as a novel angiotensin II type 1 receptor antagonist (Liu et al., 2013). Inhibition of TGF-β- stimulated biglycan synthesis by 6-gingerol suggests the potential role of ginger in the prevention of atherosclerosis (Kamato et al., 2013) .</p></div>	https://treatment.plazi.org/id/03E4D873FFFDDC5CFC8DB462BF631C4E	Public Domain	No known copyright restrictions apply. See Agosti, D., Egloff, W., 2009. Taxonomic information exchange and copyright: the Plazi approach. BMC Research Notes 2009, 2:53 for further explanation.		Plazi	Micucci, M.;Bolchi, C.;Budriesi, R.;Cevenini, M.;Maroni, L.;Capozza, S.;Chiarini, A.;Pallavicini, M.;Angeletti, A.	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: 1-19, DOI: 10.1016/j.phytochem.2019.112222, URL: http://dx.doi.org/10.1016/j.phytochem.2019.112222
