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Secondary Metabolites of Plants as Modulators of Endothelium Functions

. 2021 Mar 03 ; 22 (5) : . [epub] 20210303

Language English Country Switzerland Media electronic

Document type Journal Article, Review

Grant support
MUNI/A/1307/2019; MUNI/A/1246/2020 Lékařská fakulta, Masarykova univerzita

According to the World Health Organization, cardiovascular diseases are the main cause of death worldwide. They may be caused by various factors or combinations of factors. Frequently, endothelial dysfunction is involved in either development of the disorder or results from it. On the other hand, the endothelium may be disordered for other reasons, e.g., due to infection, such as COVID-19. The understanding of the role and significance of the endothelium in the body has changed significantly over time-from a simple physical barrier to a complex system encompassing local and systemic regulation of numerous processes in the body. Endothelium disorders may arise from impairment of one or more signaling pathways affecting dilator or constrictor activity, including nitric oxide-cyclic guanosine monophosphate activation, prostacyclin-cyclic adenosine monophosphate activation, phosphodiesterase inhibition, and potassium channel activation or intracellular calcium level inhibition. In this review, plants are summarized as sources of biologically active substances affecting the endothelium. This paper compares individual substances and mechanisms that are known to affect the endothelium, and which subsequently may cause the development of cardiovascular disorders.

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Sumpio B.E., Riley J.T., Dardik A. Cells in focus: Endothelial cell. Int. J. Biochem. Cell Biol. 2002;34:1508–1512. doi: 10.1016/S1357-2725(02)00075-4. PubMed DOI

Roberts D.M., Kearney J.B., Johnson J.H., Rosenberg M.P., Kumar R., Bautch V.L. The vascular endothelial growth factor (VEGF) receptor Flt-1 (VEGFR-1) modulates Flk-1 (VEGFR-2) signaling during blood vessel formation. Am. J. Pathol. 2004;164:1531–1535. doi: 10.1016/S0002-9440(10)63711-X. PubMed DOI PMC

Patan S. Vasculogenesis and angiogenesis. Cancer Treat. Res. 2004;117:3–32. doi: 10.1007/978-1-4419-8871-3_1. PubMed DOI

Kajdaniuk D., Marek B., Borgiel-Marek H., Kos-Kudła B. Vascular endothelial growth factor (VEGF)—Part 1: In physiology and pathophysiology. Endokrynol. Pol. 2011;62:444–455. PubMed

Fels J., Jeggle P., Liashkovich I., Peters W., Oberleithner H. Nanomechanics of vascular endothelium. Cell Tissue Res. 2014;355:727–737. doi: 10.1007/s00441-014-1853-5. PubMed DOI PMC

Galley H.F., Webster N.R. Physiology of the endothelium. Br. J. Anaesth. 2004;93:105–113. doi: 10.1093/bja/aeh163. PubMed DOI

Shimokawa H., Godo S. Nitric oxide and endothelium-dependent hyperpolarization mediated by hydrogen peroxide in health and disease. Basic Clin. Pharmacol. Toxicol. 2020;127:92–101. doi: 10.1111/bcpt.13377. PubMed DOI

Laroia S.T., Ganti A.K., Laroia A.T., Tendulkar K.K. Endothelium and the lipid metabolism: The current understanding. Int J. Cardiol. 2003;88:1–9. doi: 10.1016/S0167-5273(02)00366-2. PubMed DOI

Ballermann B.J., Dardik A., Eng E., Liu A. Shear stress and the endothelium. Kidney Int. Suppl. 1998;67:S100–S108. doi: 10.1046/j.1523-1755.1998.06720.x. PubMed DOI

Landmesser U., Drexler H. Effect of angiotensin II type 1 receptor antagonism on endothelial function: Role of bradykinin and nitric oxide. J. Hypertens. Suppl. 2006;24:S39–S43. doi: 10.1097/01.hjh.0000220405.38622.23. PubMed DOI

Watanabe T., Barker T.A., Berk B.C. Angiotensin II and the endothelium: Diverse signals and effects. Hypertension. 2005;45:163–169. doi: 10.1161/01.HYP.0000153321.13792.b9. PubMed DOI

Parsaee H., McEwan J.R., MacDermot J. Bradykinin-induced release of PGI2 from aortic endothelial cell lines: Responses mediated selectively by Ca2+ ions or a staurosporine-sensitive kinase. Br. J. Pharmacol. 1993;110:411–415. doi: 10.1111/j.1476-5381.1993.tb13825.x. PubMed DOI PMC

Kumar K.V., Das U.N. Are free radicals involved in the pathobiology of human essential hypertension? Free Radic. Res. Commun. 1993;19:59–66. doi: 10.3109/10715769309056499. PubMed DOI

Barbosa-Filho J.M., Martins V.K.M., Rabelo L.A., Moura M.D., Silva M.S., Cunha E.V.L., Souza M.F.V., Almeida R.N., Medeiros I.A. Natural products inhibitors of the angiotensin converting enzyme (ACE)s: A review between 1980–2000. Rev. Bras. Farmacogn. 2006;16:421–446. doi: 10.1590/S0102-695X2006000300021. DOI

Fyhrquist F., Metsärinne K., Tikkanen I. Role of angiotensin II in blood pressure regulation and in the pathophysiology of cardiovascular disorders. J. Hum. Hypertens. 1995;9(Suppl. 5):S19–S24. PubMed

Ferrario C.M. Role of angiotensin II in cardiovascular disease therapeutic implications of more than a century of research. J. Renin. Angiotensin. Aldosterone Syst. 2006;7:3–14. doi: 10.3317/jraas.2006.003. PubMed DOI

Stoll M., Steckelings U.M., Paul M., Bottari S.P., Metzger R., Unger T. The angiotensin AT2-receptor mediates inhibition of cell proliferation in coronary endothelial cells. J. Clin. Invest. 1995;95:651–657. doi: 10.1172/JCI117710. PubMed DOI PMC

Wong M.K.S. Bradykinin. In: Takei Y., Ando H., Tsutsui K., editors. Handbook of Hormones: Comparative Endocrinology for Basic and Clinical Research. Academic Press Ltd-Elsevier Science Ltd.; London, UK: 2016. p. 274. DOI

Tomiyama H., Kushiro T., Abeta H., Ishii T., Takahashi A., Furukawa L., Asagami T., Hino T., Saito F., Otsuka Y. Kinins contribute to the improvement of insulin sensitivity during treatment with angiotensin converting enzyme inhibitor. Hypertension. 1994;23:450–455. doi: 10.1161/01.HYP.23.4.450. PubMed DOI

Greaney J.L., Kutz J.L., Shank S.W., Jandu S., Santhanam L., Alexander L.M. Impaired Hydrogen Sulfide-Mediated Vasodilation Contributes to Microvascular Endothelial Dysfunction in Hypertensive Adults. Hypertension. 2017;69:902–909. doi: 10.1161/HYPERTENSIONAHA.116.08964. PubMed DOI PMC

Vallance P., Hingorani A. Endothelial nitric oxide in humans in health and disease. Int. J. Exp. Pathol. 1999;80:291–303. doi: 10.1046/j.1365-2613.1999.00137.x. PubMed DOI PMC

Ghalayini I.F. Nitric oxide-cyclic GMP pathway with some emphasis on cavernosal contractility. Int. J. Impot. Res. 2004;16:459–469. doi: 10.1038/sj.ijir.3901256. PubMed DOI

Ahmad A., Khan R.M., Alkharfy K.M. Effects of selected bioactive natural products on the vascular endothelium. J. Cardiovasc. Pharmacol. 2013;62:111–121. doi: 10.1097/FJC.0b013e3182927e47. PubMed DOI

Ozkor M.A., Quyyumi A.A. Endothelium-derived hyperpolarizing factor and vascular function. Cardiol. Res. Pract. 2011;2011:156146. doi: 10.4061/2011/156146. PubMed DOI PMC

Yang P.M., Huang Y.T., Zhang Y.Q., Hsieh C.W., Wung B.S. Carbon monoxide releasing molecule induces endothelial nitric oxide synthase activation through a calcium and phosphatidylinositol 3-kinase/Akt mechanism. Vascul. Pharmacol. 2016;87:209–218. doi: 10.1016/j.vph.2016.09.010. PubMed DOI

Jankovic G., Marinko M., Milojevic P., Stojanovic I., Nenezic D., Kanjuh V., Yang Q., He G.W., Novakovic A. Mechanisms of endothelium-dependent vasorelaxation induced by procyanidin B2 in venous bypass graft. J. Pharmacol. Sci. 2020;142:101–108. doi: 10.1016/j.jphs.2019.11.006. PubMed DOI

Li H., Xia N., Brausch I., Yao Y., Förstermann U. Flavonoids from artichoke (Cynara scolymus L.) up-regulate endothelial-type nitric-oxide synthase gene expression in human endothelial cells. J. Pharmacol. Exp. Ther. 2004;310:926–932. doi: 10.1124/jpet.104.066639. PubMed DOI

Yu J., Eto M., Akishita M., Kaneko A., Ouchi Y., Okabe T. Signaling pathway of nitric oxide production induced by ginsenoside Rb1 in human aortic endothelial cells: A possible involvement of androgen receptor. Biochem Biophys Res. Commun. 2007;353:764–769. doi: 10.1016/j.bbrc.2006.12.119. PubMed DOI

Fisher N.D., Hughes M., Gerhard-Herman M., Hollenberg N.K. Flavanol-rich cocoa induces nitric-oxide-dependent vasodilation in healthy humans. J. Hypertens. 2003;21:2281–2286. doi: 10.1097/00004872-200312000-00016. PubMed DOI

Moncada S., Vane J.R. Interrelationships between prostacyclin and thromboxane A2. Ciba Found. Symp. 1980;78:165–183. doi: 10.1002/9780470720615.ch9. PubMed DOI

Majed B.H., Khalil R.A. Molecular mechanisms regulating the vascular prostacyclin pathways and their adaptation during pregnancy and in the newborn. Pharmacol. Rev. 2012;64:540–582. doi: 10.1124/pr.111.004770. PubMed DOI PMC

Sandoo A., van Zanten J.J., Metsios G.S., Carroll D., Kitas G.D. The endothelium and its role in regulating vascular tone. Open Cardiovasc. Med. J. 2010;4:302–312. doi: 10.2174/1874192401004010302. PubMed DOI PMC

Luna-Vázquez F.J., Ibarra-Alvarado C., Rojas-Molina A., Rojas-Molina I., Zavala-Sánchez M.A. Vasodilator compounds derived from plants and their mechanisms of action. Molecules. 2013;18:5814–5857. doi: 10.3390/molecules18055814. PubMed DOI PMC

Raimundo J.M., Trindade A.P., Velozo L.S., Kaplan M.A., Sudo R.T., Zapata-Sudo G. The lignan eudesmin extracted from Piper truncatum induced vascular relaxation via activation of endothelial histamine H1 receptors. Eur. J. Pharmacol. 2009;606:150–154. doi: 10.1016/j.ejphar.2009.01.038. PubMed DOI

Raimundo J.M., de Almeida R.R., Velozo L.S., Kaplan M.A., Gattass C.R., Zapata-Sudo G. In-vitro vasodilatory activity of the hexanic extract of leaves and stems from Piper truncatum Vell. in rats. J. Pharm. Pharmacol. 2004;56:1457–1462. doi: 10.1211/0022357044779. PubMed DOI

Chau Y., Li F.S., Levsh O., Weng J.K. Exploration of icariin analog structure space reveals key features driving potent inhibition of human phosphodiesterase-5. PLoS ONE. 2019;14:e0222803. doi: 10.1371/journal.pone.0222803. PubMed DOI PMC

Lan T.H., Chen X.L., Wu Y.S., Qiu H.L., Li J.Z., Ruan X.M., Xu D.P., Lin D.Q. 3,7-Bis(2-hydroxyethyl)icaritin, a potent inhibitor of phosphodiesterase-5, prevents monocrotaline-induced pulmonary arterial hypertension via NO/cGMP activation in rats. Eur. J. Pharmacol. 2018;829:102–111. doi: 10.1016/j.ejphar.2018.04.011. PubMed DOI

Garland C.J., Hiley C.R., Dora K.A. EDHF: Spreading the influence of the endothelium. Br. J. Pharmacol. 2011;164:839–852. doi: 10.1111/j.1476-5381.2010.01148.x. PubMed DOI PMC

Knox M., Vinet R., Fuentes L., Morales B., Martínez J.L. A Review of Endothelium-Dependent and -Independent Vasodilation Induced by Phytochemicals in Isolated Rat Aorta. Animals. 2019;9:623. doi: 10.3390/ani9090623. PubMed DOI PMC

Lumsden N.G., Khambata R.S., Hobbs A.J. C-type natriuretic peptide (CNP): Cardiovascular roles and potential as a therapeutic target. Curr. Pharm. Des. 2010;16:4080–4088. doi: 10.2174/138161210794519237. PubMed DOI PMC

Mustafa A.K., Sikka G., Gazi S.K., Steppan J., Jung S.M., Bhunia A.K., Barodka V.M., Gazi F.K., Barrow R.K., Wang R., et al. Hydrogen sulfide as endothelium-derived hyperpolarizing factor sulfhydrates potassium channels. Circ. Res. 2011;109:1259–1268. doi: 10.1161/CIRCRESAHA.111.240242. PubMed DOI PMC

Bhatia M. Hydrogen sulfide as a vasodilator. IUBMB Life. 2005;57:603–606. doi: 10.1080/15216540500217875. PubMed DOI

Mombouli J.V., Bissiriou I., Agboton V., Vanhoutte P.M. Endothelium-derived hyperpolarizing factor: A key mediator of the vasodilator action of bradykinin. Immunopharmacology. 1996;33:46–50. doi: 10.1016/0162-3109(96)00083-5. PubMed DOI

Van Hinsbergh V.W. Endothelium—Role in regulation of coagulation and inflammation. Semin. Immunopathol. 2012;34:93–106. doi: 10.1007/s00281-011-0285-5. PubMed DOI PMC

Goldberg I.J., Bornfeldt K.E. Lipids and the endothelium: Bidirectional interactions. Curr. Atheroscler. Rep. 2013;15:365. doi: 10.1007/s11883-013-0365-1. PubMed DOI PMC

García X., Cartas-Heredia L., Lorenzana-Jímenez M., Gijón E. Vasoconstrictor effect of Cissus sicyoides on guinea-pig aortic rings. Gen. Pharmacol. 1997;29:457–462. doi: 10.1016/S0306-3623(96)00478-8. PubMed DOI

Bull H.A., Pittilo R.M., Blow D.J., Blow C.M., Rowles P.M., Woolf N., Machin S.J. The effects of nicotine on PGI2 production by rat aortic endothelium. Thromb. Haemost. 1985;54:472–474. doi: 10.1055/s-0038-1657876. PubMed DOI

Oakes J.M., Xu J., Morris T.M., Fried N.D., Pearson C.S., Lobell T.D., Gilpin N.W., Lazartigues E., Gardner J.D., Yue X. Effects of Chronic Nicotine Inhalation on Systemic and Pulmonary Blood Pressure and Right Ventricular Remodeling in Mice. Hypertension. 2020;75:1305–1314. doi: 10.1161/HYPERTENSIONAHA.119.14608. PubMed DOI PMC

Wölfle U., Hoffmann J., Haarhaus B., Rao Mittapalli V., Schempp C.M. Anti-inflammatory and vasoconstrictive properties of Potentilla erecta—A traditional medicinal plant from the northern hemisphere. J. Ethnopharmacol. 2017;204:86–94. doi: 10.1016/j.jep.2017.03.058. PubMed DOI

Hayat-Malik M.N., Bashir S., Khan I.U., Karim S., Mushtaq M.N., Khan H.U., Rashid M., Naz H., Samreen S. Cardiotonic and vasoconstriction effects of aqueous methanolic extract of Paspalidium flavidum L. Pak. J. Pharm. Sci. 2015;28:437–441. PubMed

Gilani A.U.H., Shaheen F. Vasoconstrictor and cardiotonic actions of Haloxylon-recurvum extract. Phytother. Res. 1994;8:115–117. doi: 10.1002/ptr.2650080215. DOI

Wahab A., Ahmed E., Nawaz S.A., Sharif A., Ul Haq R., Malik A., Choudhary M.I., Raza M. A pharmacological and toxicological evaluation of Haloxylon recurvum. Nat. Prod. Res. 2008;22:1317–1326. doi: 10.1080/14786410701824882. PubMed DOI

Chen H. Role of thromboxane A. Prostaglandins Other Lipid Med. 2018;134:32–37. doi: 10.1016/j.prostaglandins.2017.11.004. PubMed DOI

Rucker D., Dhamoon A.S. StatPearls. StatPearls Publishing; Treasure Island, FL, USA: 2020. Physiology, Thromboxane A2. PubMed

Grann M., Comerma-Steffensen S., Arcanjo D.D., Simonsen U. Mechanisms Involved in Thromboxane A. Basic Clin. Pharmacol. Toxicol. 2016;119(Suppl. 3):86–95. doi: 10.1111/bcpt.12544. PubMed DOI

Caughey G.E., Cleland L.G., Penglis P.S., Gamble J.R., James M.J. Roles of cyclooxygenase (COX)-1 and COX-2 in prostanoid production by human endothelial cells: Selective up-regulation of prostacyclin synthesis by COX-2. J. Immunol. 2001;167:2831–2838. doi: 10.4049/jimmunol.167.5.2831. PubMed DOI

Davenport A.P., Hyndman K.A., Dhaun N., Southan C., Kohan D.E., Pollock J.S., Pollock D.M., Webb D.J., Maguire J.J. Endothelin. Pharmacol. Rev. 2016;68:357–418. doi: 10.1124/pr.115.011833. PubMed DOI PMC

Drawnel F.M., Archer C.R., Roderick H.L. The role of the paracrine/autocrine mediator endothelin-1 in regulation of cardiac contractility and growth. Br. J. Pharmacol. 2013;168:296–317. doi: 10.1111/j.1476-5381.2012.02195.x. PubMed DOI PMC

Barton M., Yanagisawa M. Endothelin: 30 Years From Discovery to Therapy. Hypertension. 2019;74:1232–1265. doi: 10.1161/HYPERTENSIONAHA.119.12105. PubMed DOI

Stow L.R., Jacobs M.E., Wingo C.S., Cain B.D. Endothelin-1 gene regulation. FASEB J. 2011;25:16–28. doi: 10.1096/fj.10-161612. PubMed DOI PMC

Unic A., Derek L., Hodak N., Marijancevic D., Ceprnja M., Serdar T., Krhac M., Romic Z. Endothelins—Clinical perspectives. Biochem. Med. 2011;21:231–242. doi: 10.11613/BM.2011.032. PubMed DOI

Camussi G., Tetta C., Baglioni C. The role of platelet-activating factor in inflammation. Clin. Immunol. Immunopathol. 1990;57:331–338. doi: 10.1016/0090-1229(90)90108-3. PubMed DOI

Majewski M. Allium sativum: Facts and myths regarding human health. Rocz. Panstw. Zakl. Hig. 2014;65:1–8. PubMed

Ashraf R., Khan R.A., Ashraf I., Qureshi A.A. Effects of Allium sativum (garlic) on systolic and diastolic blood pressure in patients with essential hypertension. Pak. J. Pharm. Sci. 2013;26:859–863. PubMed

El-Saber Batiha G., Magdy Beshbishy A., G Wasef L., Elewa Y.H.A., A Al-Sagan A., Abd El-Hack M.E., Taha A.E., M Abd-Elhakim Y., Prasad Devkota H. Chemical Constituents and Pharmacological Activities of Garlic (Allium sativum L.) Nutrients. 2020;12:872. doi: 10.3390/nu12030872. PubMed DOI PMC

Pedraza-Chaverrí J., Tapia E., Medina-Campos O.N., de los Angeles Granados M., Franco M. Garlic prevents hypertension induced by chronic inhibition of nitric oxide synthesis. Life Sci. 1998;62:PL71–PL77. doi: 10.1016/S0024-3205(97)01155-7. PubMed DOI

Victorio C.P., Kuster R.M., de Moura R.S., Lage C.L.S. Vasodilator activity of extracts of field Alpinia purpurata (Vieill) K. Schum and A. zerumbet (Pers.) Burtt et Smith cultured in vitro. Braz. J. Pharm. Sci. 2009;45:507–514. doi: 10.1590/S1984-82502009000300017. DOI

De Moura R.S., Emiliano A.F., de Carvalho L.C., Souza M.A., Guedes D.C., Tano T., Resende A.C. Antihypertensive and endothelium-dependent vasodilator effects of Alpinia zerumbet, a medicinal plant. J. Cardiovasc. Pharmacol. 2005;46:288–294. doi: 10.1097/01.fjc.0000175239.26326.47. PubMed DOI

Afkir S., Nguelefack T.B., Aziz M., Zoheir J., Cuisinaud G., Bnouham M., Mekhfi H., Legssyer A., Lahlou S., Ziyyat A. Arbutus unedo prevents cardiovascular and morphological alterations in L-NAME-induced hypertensive rats Part I: Cardiovascular and renal hemodynamic effects of Arbutus unedo in L-NAME-induced hypertensive rats. J. Ethnopharmacol. 2008;116:288–295. doi: 10.1016/j.jep.2007.11.029. PubMed DOI

Xie Y.W., Ming D.S., Xu H.X., Dong H., But P.P. Vasorelaxing effects of Caesalpinia sappan involvement of endogenous nitric oxide. Life Sci. 2000;67:1913–1918. doi: 10.1016/S0024-3205(00)00772-4. PubMed DOI

Hu C.M., Kang J.J., Lee C.C., Li C.H., Liao J.W., Cheng Y.W. Induction of vasorelaxation through activation of nitric oxide synthase in endothelial cells by brazilin. Eur. J. Pharmacol. 2003;468:37–45. doi: 10.1016/S0014-2999(03)01639-X. PubMed DOI

Cherkaoui-Tangi K., Lachkar M., Wibo M., Morel N., Gilani A.H., Lyoussi B. Pharmacological studies on hypotensive, diuretic and vasodilator activities of chrysin glucoside from Calycotome villosa in rats. Phytother. Res. 2008;22:356–361. doi: 10.1002/ptr.2322. PubMed DOI

Villar I.C., Vera R., Galisteo M., O‘Valle F., Romero M., Zarzuelo A., Duarte J. Endothelial nitric oxide production stimulated by the bioflavonoid chrysin in rat isolated aorta. Planta Med. 2005;71:829–834. doi: 10.1055/s-2005-871296. PubMed DOI

Duarte J., Jiménez R., Villar I.C., Pérez-Vizcaíno F., Jiménez J., Tamargo J. Vasorelaxant effects of the bioflavonoid chrysin in isolated rat aorta. Planta Med. 2001;67:567–569. doi: 10.1055/s-2001-16492. PubMed DOI

Assreuy A.M., Fontenele S.R., Pires A.e.F., Fernandes D.C., Rodrigues N.V., Bezerra E.H., Moura T.R., do Nascimento K.S., Cavada B.S. Vasodilator effects of Diocleinae lectins from the Canavalia genus. Naunyn Schmiedebergs Arch. Pharmacol. 2009;380:509–521. doi: 10.1007/s00210-009-0465-1. PubMed DOI

Barroso-Neto I.L., Simões R.C., Rocha B.A., Bezerra M.J., Pereira-Junior F.N., Silva Osterne V.J., Nascimento K.S., Nagano C.S., Delatorre P., Pereira M.G., et al. Vasorelaxant activity of Canavalia grandiflora seed lectin: A structural analysis. Arch. Biochem. Biophys. 2014;543:31–39. doi: 10.1016/j.abb.2013.12.006. PubMed DOI

Zhang Y., Cao Y., Duan H., Wang H., He L. Imperatorin prevents cardiac hypertrophy and the transition to heart failure via NO-dependent mechanisms in mice. Fitoterapia. 2012;83:60–66. doi: 10.1016/j.fitote.2011.09.011. PubMed DOI

Bertin R., Chen Z., Martínez-Vázquez M., García-Argaéz A., Froldi G. Vasodilation and radical-scavenging activity of imperatorin and selected coumarinic and flavonoid compounds from genus Casimiroa. Phytomedicine. 2014;21:586–594. doi: 10.1016/j.phymed.2013.10.030. PubMed DOI

Vinet R., Cortes M., Alvarez R., Guzman L., Flores E. Centaurium cachanlahuen (Mol.) Robinson, a Chilean native plant with a vasodilatory effect. Bol. Latinoam. Caribe Plantas Med. Aromat. 2012;11:61–65.

Belmokhtar M., Bouanani N.E., Ziyyat A., Mekhfi H., Bnouham M., Aziz M., Matéo P., Fischmeister R., Legssyer A. Antihypertensive and endothelium-dependent vasodilator effects of aqueous extract of Cistus ladaniferus. Biochem. Biophys. Res. Commun. 2009;389:145–149. doi: 10.1016/j.bbrc.2009.08.113. PubMed DOI

Kosala K., Ismail S., Fikriah I., Magdaleni A.R. In vitro Exploration of Vasodilation Activity of the Methanol Extract of the Coptosapelta flavescens Korth stem. J. Islam. Med. Res. 2017;1:10–14.

Generalić Mekinić I., Blažević I., Mudnić I., Burčul F., Grga M., Skroza D., Jerčić I., Ljubenkov I., Boban M., Miloš M., et al. Sea fennel (Crithmum maritimum L.): Phytochemical profile, antioxidative, cholinesterase inhibitory and vasodilatory activity. J. Food Sci Technol. 2016;53:3104–3112. doi: 10.1007/s13197-016-2283-z. PubMed DOI PMC

Guerrero M.F., Puebla P., Carrón R., Martín M.L., Arteaga L., Román L.S. Assessment of the antihypertensive and vasodilator effects of ethanolic extracts of some Colombian medicinal plants. J. Ethnopharmacol. 2002;80:37–42. doi: 10.1016/S0378-8741(01)00420-2. PubMed DOI

Paez M.T., Rodriguez D.C., Lopez D.F., Castaneda J.A., Buitrago D.M., Cuca L.E., Guerrero M.F. Croton schiedeanus Schltd prevents experimental hypertension in rats induced by nitric oxide deficit. Braz. J. Pharm. Sci. 2013;49:865–871. doi: 10.1590/S1984-82502013000400027. DOI

Guerrero M.F., Puebla P., Carrón R., Martín M.L., San Román L. Quercetin 3,7-dimethyl ether: A vasorelaxant flavonoid isolated from Croton schiedeanus Schlecht. J. Pharm. Pharmacol. 2002;54:1373–1378. doi: 10.1211/002235702760345455. PubMed DOI

Mendes L.J., Capettini L.S., Lôbo L.T., da Silva G.A., Arruda M.S., Lemos V.S., Côrtes S.F. Endothelial nitric oxide-dependent vasorelaxant effect of isotirumalin, a dihydroflavonol from Derris urucu, on the rat aorta. Biol. Pharm. Bull. 2011;34:1499–1500. doi: 10.1248/bpb.34.1499. PubMed DOI

Lobo L.T., da Silva G.A., Ferreira M., da Silva M.N., Santos A.S., Arruda A.C., Guilhon G., Santos L.S., Borges R.D., Arruda M.S.P. Dihydroflavonols from the leaves of Derris urucu (Leguminosae): Structural Elucidation and DPPH Radical-Scavenging Activity. J. Braz. Chem. Soc. 2009;20:1082–1088. doi: 10.1590/S0103-50532009000600013. DOI

Rocha A.P., Carvalho L.C., Sousa M.A., Madeira S.V., Sousa P.J., Tano T., Schini-Kerth V.B., Resende A.C., Soares de Moura R. Endothelium-dependent vasodilator effect of Euterpe oleracea Mart. (Açaí) extracts in mesenteric vascular bed of the rat. Vascul. Pharmacol. 2007;46:97–104. doi: 10.1016/j.vph.2006.08.411. PubMed DOI

Xie Y.W., Xu H.X., Dong H., Fiscus R.R., But P.P. Role of nitric oxide in the vasorelaxant and hypotensive effects of extracts and purified tannins from Geum japonicum. J. Ethnopharmacol. 2007;109:128–133. doi: 10.1016/j.jep.2006.07.015. PubMed DOI

Chen X., Salwinski S., Lee T.J.F. Extracts of Ginkgo biloba and ginsenosides exert cerebral vasorelaxation via a nitric oxide pathway. Clin. Exp. Pharm. Physiol. 1997;24:958–959. doi: 10.1111/j.1440-1681.1997.tb02727.x. PubMed DOI

Nishida S., Satoh H. Mechanisms for the vasodilations induced by Ginkgo biloba extract and its main constituent, bilobalide, in rat aorta. Life Sci. 2003;72:2659–2667. doi: 10.1016/S0024-3205(03)00177-2. PubMed DOI

Hakkou Z., Maciuk A., Leblais V., Bouanani N.E., Mekhfi H., Bnouham M., Aziz M., Ziyyat A., Rauf A., Hadda T.B., et al. Antihypertensive and vasodilator effects of methanolic extract of Inula viscosa: Biological evaluation and POM analysis of cynarin, chlorogenic acid as potential hypertensive. Biomed. Pharmacother. 2017;93:62–69. doi: 10.1016/j.biopha.2017.06.015. PubMed DOI

Del Valle-Mondragón L., Tenorio-López F.A., Zarco-Olvera G., Pastelín-Hernández G. Vulgarenol, a sesquiterpene isolated from Magnolia grandiflora, induces nitric oxide synthases II and III overexpression in guinea pig hearts. Z. Naturforsch. C J. Biosci. 2007;62:725–730. doi: 10.1515/znc-2007-9-1016. PubMed DOI

Zamblé A., Martin-Nizard F., Sahpaz S., Reynaert M.L., Staels B., Bordet R., Duriez P., Gressier B., Bailleul F. Effects of Microdesmis keayana alkaloids on vascular parameters of erectile dysfunction. Phytother. Res. 2009;23:892–895. doi: 10.1002/ptr.2717. PubMed DOI

Interaminense L.F., Leal-Cardoso J.H., Magalhães P.J., Duarte G.P., Lahlou S. Enhanced hypotensive effects of the essential oil of Ocimum gratissimum leaves and its main constituent, eugenol, in DOCA-salt hypertensive conscious rats. Planta Med. 2005;71:376–378. doi: 10.1055/s-2005-864109. PubMed DOI

Pires A.F., Madeira S.V., Soares P.M., Montenegro C.M., Souza E.P., Resende A.C., Soares de Moura R., Assreuy A.M., Criddle D.N. The role of endothelium in the vasorelaxant effects of the essential oil of Ocimum gratissimum in aorta and mesenteric vascular bed of rats. Can. J. Physiol. Pharmacol. 2012;90:1380–1385. doi: 10.1139/y2012-095. PubMed DOI

Yoo M.Y., Lee B.H., Choi Y.H., Lee J.W., Seo J.H., Oh K.S., Koo H.N., Seo H.W., Yon G.H., Kwon D.Y., et al. Vasorelaxant effect of the rootbark extract of Paeonia moutan on isolated rat thoracic aorta. Planta Med. 2006;72:1338–1341. doi: 10.1055/s-2006-951678. PubMed DOI

Kim Y.M., Namkoong S., Yun Y.G., Hong H.D., Lee Y.C., Ha K.S., Lee H., Kwon H.J., Kwon Y.G. Water extract of Korean red ginseng stimulates angiogenesis by activating the PI3K/Akt-dependent ERK1/2 and eNOS pathways in human umbilical vein endothelial cells. Biol. Pharm. Bull. 2007;30:1674–1679. doi: 10.1248/bpb.30.1674. PubMed DOI

Leung K.W., Cheng Y.K., Mak N.K., Chan K.K., Fan T.P., Wong R.N. Signaling pathway of ginsenoside-Rg1 leading to nitric oxide production in endothelial cells. FEBS Lett. 2006;580:3211–3216. doi: 10.1016/j.febslet.2006.04.080. PubMed DOI

Xia N., Bollinger L., Steinkamp-Fenske K., Förstermann U., Li H. Prunella vulgaris L. Upregulates eNOS expression in human endothelial cells. Am. J. Chin. Med. 2010;38:599–611. doi: 10.1142/S0192415X10008081. PubMed DOI

Gu X., Li Y., Mu J., Zhang Y. Chemical constituents of Prunella vulgaris. J. Environ. Sci. 2013;25(Suppl. 1):S161–S163. doi: 10.1016/S1001-0742(14)60648-3. PubMed DOI

Sham T.T., Yuen A.C., Ng Y.F., Chan C.O., Mok D.K., Chan S.W. A review of the phytochemistry and pharmacological activities of raphani semen. Evid. Based Complement. Alternat. Med. 2013;2013:636194. doi: 10.1155/2013/636194. PubMed DOI PMC

Chung D.H., Kim S.H., Myung N., Cho K.J., Chang M.J. The antihypertensive effect of ethyl acetate extract of radish leaves in spontaneously hypertensive rats. Nutr. Res. Pract. 2012;6:308–314. doi: 10.4162/nrp.2012.6.4.308. PubMed DOI PMC

Moon M.K., Kang D.G., Lee J.K., Kim J.S., Lee H.S. Vasodilatory and anti-inflammatory effects of the aqueous extract of rhubarb via a NO-cGMP pathway. Life Sci. 2006;78:1550–1557. doi: 10.1016/j.lfs.2005.07.028. PubMed DOI

Oh K.S., Ryu S.Y., Kim Y.S., Lee B.H. Large conductance Ca2+-activated K+ (BKCa) channels are involved in the vascular relaxations elicited by piceatannol isolated from Rheum undulatum rhizome. Planta Med. 2007;73:1441–1446. doi: 10.1055/s-2007-990246. PubMed DOI

Yoo M.Y., Oh K.S., Lee J.W., Seo H.W., Yon G.H., Kwon D.Y., Kim Y.S., Ryu S.Y., Lee B.H. Vasorelaxant effect of stilbenes from rhizome extract of rhubarb (Rheum undulatum) on the contractility of rat aorta. Phytother. Res. 2007;21:186–189. doi: 10.1002/ptr.2042. PubMed DOI

Oh K.S., Choi Y.H., Ryu S.Y., Oh B.K., Seo H.W., Yon G.H., Kim Y.S., Lee B.H. Cardiovascular effects of lignans isolated from Saururus chinensis. Planta Med. 2008;74:233–238. doi: 10.1055/s-2008-1034310. PubMed DOI

Kang D.G., Yin M.H., Oh H., Lee D.H., Lee H.S. Vasorelaxation by amentoflavone isolated from Selaginella tamariscina. Planta Med. 2004;70:718–722. doi: 10.1055/s-2004-827201. PubMed DOI

Yu S., Yan H., Zhang L., Shan M., Chen P., Ding A., Li S.F. A Review on the Phytochemistry, Pharmacology, and Pharmacokinetics of Amentoflavone, a Naturally-Occurring Biflavonoid. Molecules. 2017;22:299. doi: 10.3390/molecules22020299. PubMed DOI PMC

Vinet R., Alvarez R., Knox M., Guzman L., Martinez J.L., Flores E. Vasodilatory properties of Solanum crispum Ruiz & Pav. a South American native plant. Bol. Latinoam. Caribe Plantas Med. Aromat. 2016;15:94–98.

Zaima K., Koga I., Iwasawa N., Hosoya T., Hirasawa Y., Kaneda T., Ismail I.S., Lajis N.H., Morita H. Vasorelaxant activity of indole alkaloids from Tabernaemontana dichotoma. J. Nat. Med. 2013;67:9–16. doi: 10.1007/s11418-012-0638-y. PubMed DOI

Rodrigues A.M., Guimarães D.O., Konno T.U., Tinoco L.W., Barth T., Aguiar F.A., Lopes N.P., Leal I.C., Raimundo J.M., Muzitano M.F. Phytochemical Study of Tapirira guianensis Leaves Guided by Vasodilatory and Antioxidant Activities. Molecules. 2017;22:304. doi: 10.3390/molecules22020304. PubMed DOI PMC

Schroeter H., Heiss C., Balzer J., Kleinbongard P., Keen C.L., Hollenberg N.K., Sies H., Kwik-Uribe C., Schmitz H.H., Kelm M. (-)-Epicatechin mediates beneficial effects of flavanol-rich cocoa on vascular function in humans. Proc. Natl. Acad. Sci. USA. 2006;103:1024–1029. doi: 10.1073/pnas.0510168103. PubMed DOI PMC

Grassi D., Necozione S., Lippi C., Croce G., Valeri L., Pasqualetti P., Desideri G., Blumberg J.B., Ferri C. Cocoa reduces blood pressure and insulin resistance and improves endothelium-dependent vasodilation in hypertensives. Hypertension. 2005;46:398–405. doi: 10.1161/01.HYP.0000174990.46027.70. PubMed DOI

Faridi Z., Njike V.Y., Dutta S., Ali A., Katz D.L. Acute dark chocolate and cocoa ingestion and endothelial function: A randomized controlled crossover trial. Am. J. Clin. Nutr. 2008;88:58–63. doi: 10.1093/ajcn/88.1.58. PubMed DOI

Karim M., McCormick K., Kappagoda C.T. Effects of cocoa extracts on endothelium-dependent relaxation. J. Nutr. 2000;130:2105S–2108S. doi: 10.1093/jn/130.8.2105S. PubMed DOI

Seya K., Furukawa K., Taniguchi S., Kodzuka G., Oshima Y., Niwa M., Motomura S. Endothelium-dependent vasodilatory effect of vitisin C, a novel plant oligostilbene from Vitis plants (Vitaceae), in rabbit aorta. Clin. Sci. 2003;105:73–79. doi: 10.1042/CS20020288. PubMed DOI

Soares De Moura R., Costa Viana F.S., Souza M.A., Kovary K., Guedes D.C., Oliveira E.P., Rubenich L.M., Carvalho L.C., Oliveira R.M., Tano T., et al. Antihypertensive, vasodilator and antioxidant effects of a vinifera grape skin extract. J. Pharm. Pharmacol. 2002;54:1515–1520. doi: 10.1211/002235702153. PubMed DOI

Leifert W.R., Abeywardena M.Y. Cardioprotective actions of grape polyphenols. Nutr. Res. 2008;28:729–737. doi: 10.1016/j.nutres.2008.08.007. PubMed DOI

Ito J., Niwa M. Absolute structures of new hydroxystilbenoids, vitisin C and viniferal, from Vitis vinifera ‘Kyohou’. Tetrahedron. 1996;52:9991–9998. doi: 10.1016/0040-4020(96)00543-1. DOI

Da Costa G.F., Ognibene D.T., da Costa C.A., Teixeira M.T., Cordeiro V.D.S.C., de Bem G.F., Moura A.S., Resende A.C., de Moura R.S.L. Grape Skin Extract Prevents Development of Hypertension and Altered Lipid Profile in Spontaneously Hypertensive Rats: Role of Oxidative Stress. Prev. Nutr. Food Sci. 2020;25:25–31. doi: 10.3746/pnf.2020.25.1.25. PubMed DOI PMC

Andriambeloson E., Stoclet J.C., Andriantsitohaina R. Mechanism of endothelial nitric oxide-dependent vasorelaxation induced by wine polyphenols in rat thoracic aorta. J. Cardiovasc. Pharmacol. 1999;33:248–254. doi: 10.1097/00005344-199902000-00011. PubMed DOI

Steinkamp-Fenske K., Bollinger L., Xu H., Yao Y., Horke S., Förstermann U., Li H. Reciprocal regulation of endothelial nitric-oxide synthase and NADPH oxidase by betulinic acid in human endothelial cells. J. Pharmacol. Exp. Ther. 2007;322:836–842. doi: 10.1124/jpet.107.123356. PubMed DOI

Othman R., Ibrahim H., Mohd M.A., Awang K., Gilani A.U., Mustafa M.R. Vasorelaxant effects of ethyl cinnamate isolated from Kaempferia galanga on smooth muscles of the rat aorta. Planta Med. 2002;68:655–657. doi: 10.1055/s-2002-32900. PubMed DOI

De Oliveira A.P., Furtado F.F., da Silva M.S., Tavares J.F., Mafra R.A., Araújo D.A., Cruz J.S., de Medeiros I.A. Calcium channel blockade as a target for the cardiovascular effects induced by the 8 (17), 12E, 14-labdatrien-18-oic acid (labdane-302) Vascul. Pharmacol. 2006;44:338–344. doi: 10.1016/j.vph.2006.01.009. PubMed DOI

Ribeiro L.A.A., Tavares J.F., Andrade N.C.d., Silva M.S.d., Silva B.A.d. The (8)17,12E,14-labdatrien-18-oic acid (labdane302), labdane-type diterpene isolated from Xylopia langsdorffiana St. Hil. & Tul. (Annonaceae) relaxes the guinea-pig trachea Ácido (8)17,12E,14-labdatrieno-18-óico (labdano302), diterpeno tipo labdano isolado de Xylopia langsdorffiana St. Hil. & Tul. (Annonaceae) relaxa a traquéia isolada de cobaia. Rev. Bras. Farmacogn. 2007;17:197–203. doi: 10.1590/s0102-695x2007000200011. DOI

Rivedal E., Sanner T. Caffeine and other phosphodiesterase inhibitors are potent inhibitors of the promotional effect of TPA on morphological transformation of hamster embryo cells. Cancer Lett. 1985;28:9–17. doi: 10.1016/0304-3835(85)90086-2. PubMed DOI

Boswell-Smith V., Spina D., Page C.P. Phosphodiesterase inhibitors. Br. J. Pharmacol. 2006;147(Suppl. 1):S252–S257. doi: 10.1038/sj.bjp.0706495. PubMed DOI PMC

Patay É., Bencsik T., Papp N. Phytochemical overview and medicinal importance of Coffea species from the past until now. Asian Pac. J. Trop Med. 2016;9:1127–1135. doi: 10.1016/j.apjtm.2016.11.008. PubMed DOI

Shindel A.W., Xin Z.C., Lin G., Fandel T.M., Huang Y.C., Banie L., Breyer B.N., Garcia M.M., Lin C.S., Lue T.F. Erectogenic and neurotrophic effects of icariin, a purified extract of horny goat weed (Epimedium spp.) in vitro and in vivo. J. Sex. Med. 2010;7:1518–1528. doi: 10.1111/j.1743-6109.2009.01699.x. PubMed DOI PMC

Xu H.B., Huang Z.Q. Icariin enhances endothelial nitric-oxide synthase expression on human endothelial cells in vitro. Vascul. Pharmacol. 2007;47:18–24. doi: 10.1016/j.vph.2007.03.002. PubMed DOI

Xu H.B., Huang Z.Q. Vasorelaxant effects of icariin on isolated canine coronary artery. J. Cardiovasc. Pharmacol. 2007;49:207–213. doi: 10.1097/FJC.0b013e3180325abe. PubMed DOI

Takır S., Sezgi B., Süzgeç-Selçuk S., Eroğlu-Özkan E., Beukelman K.J., Mat A., Uydeş-Doğan B.S. Endothelium-dependent vasorelaxant effect of Alchemilla vulgaris methanol extract: A comparison with the aqueous extract in rat aorta. Nat. Prod. Res. 2014;28:2182–2185. doi: 10.1080/14786419.2014.926352. PubMed DOI

Takır S., Altun I.H., Sezgi B., Süzgeç-Selçuk S., Mat A., Uydeş-Doǧan B.S. Vasorelaxant and blood pressure lowering effects of alchemilla vulgaris: A comparative study of methanol and aqueous extracts. Pharmacogn. Mag. 2015;11:163–169. doi: 10.4103/0973-1296.149733. PubMed DOI PMC

Duarte J., Pérez-Vizcaíno F., Torres A.I., Zarzuelo A., Jiménez J., Tamargo J. Vasodilator effects of visnagin in isolated rat vascular smooth muscle. Eur. J. Pharmacol. 1995;286:115–122. doi: 10.1016/0014-2999(95)00418-K. PubMed DOI

Lima T.C., de Jesus Souza R., da Silva F.A., Biavatti M.W. The genus Calea L.: A review on traditional uses, phytochemistry, and biological activities. Phytother. Res. 2018;32:769–795. doi: 10.1002/ptr.6010. PubMed DOI

Somoza B., de Rojas V.R.S., Ortega T., Villar A.M. Vasodilator effects of the extract of the leaves of Cistus populifolius on rat thoracic aorta. Phytother. Res. 1996;10:304–308. doi: 10.1002/(SICI)1099-1573(199606)10:4<304::AID-PTR848>3.0.CO;2-B. DOI

Jiang H., Xia Q., Wang X., Song J., Bruce I.C. Luteolin induces vasorelaxion in rat thoracic aorta via calcium and potassium channels. Pharmazie. 2005;60:444–447. PubMed

Janbaz K.H., Qayyum A., Saqib F., Imran I., Zia-Ul-Haq M., de Feo V. Bronchodilator, vasodilator and spasmolytic activities of Cymbopogon martinii. J. Physiol. Pharmacol. 2014;65:859–866. PubMed

Adaramoye O.A., Medeiros I.A. Endothelium-independent vasodilation induced by kolaviron, a biflavonoid complex from Garcinia kola seeds, in rat superior mesenteric arteries. J. Smooth Muscle Res. 2009;45:39–53. doi: 10.1540/jsmr.45.39. PubMed DOI

Chericoni S., Testai L., Calderone V., Flamini G., Nieri P., Morelli I., Martinotti E. The xanthones gentiacaulein and gentiakochianin are responsible for the vasodilator action of the roots of Gentiana kochiana. Planta Med. 2003;69:770–772. doi: 10.1055/s-2003-42784. PubMed DOI

Wang Y., Shi J.G., Wang M.Z., Che C.T., Yeung J.H. Vasodilatory actions of xanthones isolated from a Tibetan herb, Halenia elliptica. Phytomedicine. 2009;16:1144–1150. doi: 10.1016/j.phymed.2009.03.015. PubMed DOI

Zheoat A.M., Gray A.I., Igoli J.O., Ferro V.A., Drummond R.M. Hibiscus acid from Hibiscus sabdariffa (Malvaceae) has a vasorelaxant effect on the rat aorta. Fitoterapia. 2019;134:5–13. doi: 10.1016/j.fitote.2019.01.012. PubMed DOI

Campos M.G., Oropeza M.V., Villanueva T., Aguilar M.I., Delgado G., Ponce H.A. Xanthorrhizol induces endothelium-independent relaxation of rat thoracic aorta. Life Sci. 2000;67:327–333. doi: 10.1016/S0024-3205(00)00619-6. PubMed DOI

Kim B., Lee K., Chinannai K.S., Ham I., Bu Y., Kim H., Choi H.Y. Endothelium-Independent Vasorelaxant Effect of Ligusticum jeholense Root and Rhizoma on Rat Thoracic Aorta. Molecules. 2015;20:10721–10733. doi: 10.3390/molecules200610721. PubMed DOI PMC

El Bardai S., Morel N., Wibo M., Fabre N., Llabres G., Lyoussi B., Quetin-Leclercq J. The vasorelaxant activity of marrubenol and marrubiin from Marrubium vulgare. Planta Med. 2003;69:75–77. doi: 10.1055/s-2003-37042. PubMed DOI

El-Bardai S., Wibo M., Hamaide M.C., Lyoussi B., Quetin-Leclercq J., Morel N. Characterisation of marrubenol, a diterpene extracted from Marrubium vulgare, as an L-type calcium channel blocker. Br. J. Pharmacol. 2003;140:1211–1216. doi: 10.1038/sj.bjp.0705561. PubMed DOI PMC

Rendón-Vallejo P., Hernández-Abreu O., Vergara-Galicia J., Millán-Pacheco C., Mejía A., Ibarra-Barajas M., Estrada-Soto S. Ex vivo study of the vasorelaxant activity induced by phenanthrene derivatives isolated from Maxillaria densa. J. Nat. Prod. 2012;75:2241–2245. doi: 10.1021/np300508v. PubMed DOI

Gilani A.H., Mandukhail S.U., Iqbal J., Yasinzai M., Aziz N., Khan A. Antispasmodic and vasodilator activities of Morinda citrifolia root extract are mediated through blockade of voltage dependent calcium channels. BMC Complement. Altern. Med. 2010;10:2. doi: 10.1186/1472-6882-10-2. PubMed DOI PMC

Sanni D.M., Fatoki T.H., Kolawole A.O., Akinmoladun A.C. Xeronine structure and function: Computational comparative mastery of its mystery. In Silico Pharmacol. 2017;5:8. doi: 10.1007/s40203-017-0028-y. PubMed DOI PMC

Liew S.Y., Mukhtar M.R., Hadi A.H., Awang K., Mustafa M.R., Zaima K., Morita H., Litaudon M. Naucline, a new indole alkaloid from the bark of Nauclea officinalis. Molecules. 2012;17:4028–4036. doi: 10.3390/molecules17044028. PubMed DOI PMC

Ishizuka M., Koga I., Zaima K., Kaneda T., Hirasawa Y., Hadi A.H., Morita H. Vasorelaxant effects on rat aortic artery by two types of indole alkaloids, naucline and cadamine. J. Nat. Med. 2013;67:399–403. doi: 10.1007/s11418-012-0689-0. PubMed DOI

Berrougui H., Herrera-Gonzalez M.D., Marhuenda E., Ettaib A., Hmamouchi M. Relaxant activity of methanolic extract from seeds of Peganum harmala on isolated rat aorta. Therapie. 2002;57:236–241. PubMed

Shi C.C., Liao J.F., Chen C.F. Comparative study on the vasorelaxant effects of three harmala alkaloids in vitro. Jpn. J. Pharmacol. 2001;85:299–305. doi: 10.1254/jjp.85.299. PubMed DOI

Berrougui H., Martín-Cordero C., Khalil A., Hmamouchi M., Ettaib A., Marhuenda E., Herrera M.D. Vasorelaxant effects of harmine and harmaline extracted from Peganum harmala L. seeds in isolated rat aorta. Pharmacol. Res. 2006;54:150–157. doi: 10.1016/j.phrs.2006.04.001. PubMed DOI

Lin L.L., Huang F., Chen S.B., Yang D.J., Chen S.L., Yang J.S., Xiao P.G. Xanthones from the roots of Polygala caudata and their antioxidation and vasodilatation activities in vitro. Planta Med. 2005;71:372–375. doi: 10.1055/s-2005-864108. PubMed DOI

Fang L.H., Mu Y.M., Lin L.L., Xiao P.G., Du G.H. Vasorelaxant effect of euxanthone in the rat thoracic aorta. Vascul. Pharmacol. 2006;45:96–101. doi: 10.1016/j.vph.2006.03.011. PubMed DOI

Lee K., Ham I., Yang G., Lee M., Bu Y., Kim H., Choi H.Y. Vasorelaxant effect of Prunus yedoensis bark. BMC Complement. Altern. Med. 2013;13:31. doi: 10.1186/1472-6882-13-31. PubMed DOI PMC

Kim B., Jo C., Choi H.Y., Lee K. Prunetin Relaxed Isolated Rat Aortic Rings by Blocking Calcium Channels. Molecules. 2018;23:2372. doi: 10.3390/molecules23092372. PubMed DOI PMC

Ghayur M.N., Gilani A.H. Studies on cardio-suppressant, vasodilator and tracheal relaxant effects of Sarcococca saligna. Arch. Pharm. Res. 2006;29:990–997. doi: 10.1007/BF02969283. PubMed DOI

Sargazi Zadeh G., Panahi N. Endothelium-independent vasorelaxant activity of Trachyspermum ammi essential oil on rat aorta. Clin. Exp. Hypertens. 2017;39:133–138. doi: 10.1080/10641963.2016.1235178. PubMed DOI

Zhang W.B., Chen C.X., Sim S.M., Kwan C.Y. In vitro vasodilator mechanisms of the indole alkaloids rhynchophylline and isorhynchophylline, isolated from the hook of Uncaria rhynchophylla (Miquel) Naunyn Schmiedebergs Arch. Pharmacol. 2004;369:232–238. doi: 10.1007/s00210-003-0854-9. PubMed DOI

Horie S., Yano S., Aimi N., Sakai S., Watanabe K. Effects of hirsutine, an antihypertensive indole alkaloid from Uncaria rhynchophylla, on intracellular calcium in rat thoracic aorta. Life Sci. 1992;50:491–498. doi: 10.1016/0024-3205(92)90388-6. PubMed DOI

Hernández-Abreu O., Castillo-España P., León-Rivera I., Ibarra-Barajas M., Villalobos-Molina R., González-Christen J., Vergara-Galicia J., Estrada-Soto S. Antihypertensive and vasorelaxant effects of tilianin isolated from Agastache mexicana are mediated by NO/cGMP pathway and potassium channel opening. Biochem. Pharmacol. 2009;78:54–61. doi: 10.1016/j.bcp.2009.03.016. PubMed DOI

Flores-Flores A., Hernández-Abreu O., Rios M.Y., León-Rivera I., Aguilar-Guadarrama B., Castillo-España P., Perea-Arango I., Estrada-Soto S. Vasorelaxant mode of action of dichloromethane-soluble extract from Agastache mexicana and its main bioactive compounds. Pharm. Biol. 2016;54:2807–2813. doi: 10.1080/13880209.2016.1184690. PubMed DOI

Wang Z.T., Lau C.W., Chan F.L., Yao X., Chen Z.Y., He Z.D., Huang Y. Vasorelaxant effects of cardamonin and alpinetin from Alpinia henryi K. Schum. J. Cardiovasc. Pharmacol. 2001;37:596–606. doi: 10.1097/00005344-200105000-00011. PubMed DOI

Fusi F., Cavalli M., Mulholland D., Crouch N., Coombes P., Dawson G., Bova S., Sgaragli G., Saponara S. Cardamonin is a bifunctional vasodilator that inhibits Ca(v)1.2 current and stimulates K(Ca)1.1 current in rat tail artery myocytes. J. Pharmacol. Exp. Ther. 2010;332:531–540. doi: 10.1124/jpet.109.161265. PubMed DOI

Channa S., Dar A., Ahmed S. Evaluation of Alstonia scholaris leaves for broncho-vasodilatory activity. J. Ethnopharmacol. 2005;97:469–476. doi: 10.1016/j.jep.2004.12.009. PubMed DOI

Bello I., Usman N.S., Mahmud R., Asmawi M.Z. Mechanisms underlying the antihypertensive effect of Alstonia scholaris. J. Ethnopharmacol. 2015;175:422–431. doi: 10.1016/j.jep.2015.09.031. PubMed DOI

Arai H., Zaima K., Mitsuta E., Tamamoto H., Saito A., Hirasawa Y., Rahman A., Kusumawati I., Zaini N.C., Morita H. Alstiphyllanines I-O, ajmaline type alkaloids from Alstonia macrophylla showing vasorelaxant activity. Bioorg. Med. Chem. 2012;20:3454–3459. doi: 10.1016/j.bmc.2012.04.013. PubMed DOI

Ozolua R.I., Adejayan A., Aigbe O.P., Uwaya D.O., Argawal A. Some characteristic relaxant effects of aqueous leaf extract of Andrographis paniculata and andrographolide on guinea pig tracheal rings. Niger. J. Physiol. Sci. 2011;26:119–124. PubMed

Zhang C.Y., Tan B.K. Hypotensive activity of aqueous extract of Andrographis paniculata in rats. Clin. Exp. Pharmacol. Physiol. 1996;23:675–678. doi: 10.1111/j.1440-1681.1996.tb01756.x. PubMed DOI

Zhang C.Y., Tan B.K. Vasorelaxation of rat thoracic aorta caused by 14-deoxyandrographolide. Clin. Exp. Pharmacol. Physiol. 1998;25:424–429. doi: 10.1111/j.1440-1681.1998.tb02226.x. PubMed DOI

Awang K., Abdullah N.H., Hadi A.H., Fong Y.S. Cardiovascular activity of labdane diterpenes from Andrographis paniculata in isolated rat hearts. J. Biomed. Biotechnol. 2012;2012:876458. doi: 10.1155/2012/876458. PubMed DOI PMC

Lee K., Shin M.S., Ham I., Choi H.Y. Investigation of the mechanisms of Angelica dahurica root extract-induced vasorelaxation in isolated rat aortic rings. BMC Complement. Altern. Med. 2015;15:395. doi: 10.1186/s12906-015-0889-8. PubMed DOI PMC

Deng G.G., Wei W., Yang X.W., Zhang Y.B., Xu W., Gong N.B., Lü Y., Wang F.F. New coumarins from the roots of Angelica dahurica var. formosana cv. Chuanbaizhi and their inhibition on NO production in LPS-activated RAW264.7 cells. Fitoterapia. 2015;101:194–200. doi: 10.1016/j.fitote.2015.01.016. PubMed DOI

He J.Y., Zhang W., He L.C., Cao Y.X. Imperatorin induces vasodilatation possibly via inhibiting voltage dependent calcium channel and receptor-mediated Ca2+ influx and release. Eur. J. Pharmacol. 2007;573:170–175. doi: 10.1016/j.ejphar.2007.06.043. PubMed DOI

Nie H., Meng L.Z., Zhou J.Y., Fan X.F., Luo- Y., Zhang G.W. Imperatorin is responsible for the vasodilatation activity of Angelica Dahurica var. Formosana regulated by nitric oxide in an endothelium-dependent manner. Chin. J. Integr. Med. 2009;15:442–447. doi: 10.1007/s11655-009-0442-z. PubMed DOI

Rhyu M.R., Kim J.H., Kim E.Y. Radix angelica elicits both nitric oxide-dependent and calcium influx-mediated relaxation in rat aorta. J. Cardiovasc. Pharmacol. 2005;46:99–104. doi: 10.1097/01.fjc.0000164092.88821.49. PubMed DOI

Matsuura M., Kimura Y., Nakata K., Baba K., Okuda H. Artery relaxation by chalcones isolated from the roots of Angelica keiskei. Planta Med. 2001;67:230–235. doi: 10.1055/s-2001-12011. PubMed DOI

Zhang Y.H., Park Y.S., Kim T.J., Fang L.H., Ahn H.Y., Hong J.T., Kim Y., Lee C.K., Yun Y.P. Endothelium-dependent vasorelaxant and antiproliferative effects of apigenin. Gen. Pharmacol. 2000;35:341–347. doi: 10.1016/S0306-3623(02)00113-1. PubMed DOI

Ko F.N., Huang T.F., Teng C.M. Vasodilatory action mechanisms of apigenin isolated from Apium graveolens in rat thoracic aorta. Biochim. Biophys. Acta. 1991;1115:69–74. doi: 10.1016/0304-4165(91)90013-7. PubMed DOI

Ma X., He D., Ru X., Chen Y., Cai Y., Bruce I.C., Xia Q., Yao X., Jin J. Apigenin, a plant-derived flavone, activates transient receptor potential vanilloid 4 cation channel. Br. J. Pharmacol. 2012;166:349–358. doi: 10.1111/j.1476-5381.2011.01767.x. PubMed DOI PMC

Dar A., Channa S. Calcium antagonistic activity of Bacopa monniera on vascular and intestinal smooth muscles of rabbit and guinea-pig. J. Ethnopharmacol. 1999;66:167–174. doi: 10.1016/S0378-8741(98)00240-2. PubMed DOI

Channa S., Dar A., Yaqoob M., Anjum S., Sultani Z. Broncho-vasodilatory activity of fractions and pure constituents isolated from Bacopa monniera. J. Ethnopharmacol. 2003;86:27–35. doi: 10.1016/S0378-8741(03)00013-8. PubMed DOI

Kamkaew N., Paracha T.U., Ingkaninan K., Waranuch N., Chootip K. Vasodilatory Effects and Mechanisms of Action of. Molecules. 2019;24:2243. doi: 10.3390/molecules24122243. PubMed DOI PMC

Kamkaew N., Scholfield C.N., Ingkaninan K., Maneesai P., Parkington H.C., Tare M., Chootip K. Bacopa monnieri and its constituents is hypotensive in anaesthetized rats and vasodilator in various artery types. J. Ethnopharmacol. 2011;137:790–795. doi: 10.1016/j.jep.2011.06.045. PubMed DOI

Ko W.H., Yao X.Q., Lau C.W., Law W.I., Chen Z.Y., Kwok W., Ho K., Huang Y. Vasorelaxant and antiproliferative effects of berberine. Eur. J. Pharmacol. 2000;399:187–196. doi: 10.1016/S0014-2999(00)00339-3. PubMed DOI

Neag M.A., Mocan A., Echeverría J., Pop R.M., Bocsan C.I., Crişan G., Buzoianu A.D. Berberine: Botanical Occurrence, Traditional Uses, Extraction Methods, and Relevance in Cardiovascular, Metabolic, Hepatic, and Renal Disorders. Front. Pharmacol. 2018;9:557. doi: 10.3389/fphar.2018.00557. PubMed DOI PMC

Moore R.J., Jackson K.G., Minihane A.M. Green tea (Camellia sinensis) catechins and vascular function. Br. J. Nutr. 2009;102:1790–1802. doi: 10.1017/S0007114509991218. PubMed DOI

Ghayur M.N., Khan H., Gilani A.H. Antispasmodic, bronchodilator and vasodilator activities of (+)-catechin, a naturally occurring flavonoid. Arch. Pharm. Res. 2007;30:970–975. doi: 10.1007/BF02993965. PubMed DOI

Aggio A., Grassi D., Onori E., D’Alessandro A., Masedu F., Valenti M., Ferri C. Endothelium/nitric oxide mechanism mediates vasorelaxation and counteracts vasoconstriction induced by low concentration of flavanols. Eur. J. Nutr. 2013;52:263–272. doi: 10.1007/s00394-012-0320-x. PubMed DOI

Alvarez E., Campos-Toimil M., Justiniano-Basaran H., Lugnier C., Orallo F. Study of the mechanisms involved in the vasorelaxation induced by (-)-epigallocatechin-3-gallate in rat aorta. Br. J. Pharmacol. 2006;147:269–280. doi: 10.1038/sj.bjp.0706507. PubMed DOI PMC

Romano M.R., Lograno M.D. Epigallocatechin-3-gallate relaxes the isolated bovine ophthalmic artery: Involvement of phosphoinositide 3-kinase-Akt-nitric oxide/cGMP signalling pathway. Eur. J. Pharmacol. 2009;608:48–53. doi: 10.1016/j.ejphar.2009.02.034. PubMed DOI

Assaidi A., Dib I., Tits M., Angenot L., Bellahcen S., Bouanani N., Legssyer A., Aziz M., Mekhfi H., Bnouham M., et al. Chenopodium ambrosioides induces an endothelium-dependent relaxation of rat isolated aorta. J. Integr. Med. 2019;17:115–124. doi: 10.1016/j.joim.2019.01.006. PubMed DOI

Jiang H.D., Cai J., Xu J.H., Zhou X.M., Xia Q. Endothelium-dependent and direct relaxation induced by ethyl acetate extract from Flos Chrysanthemi in rat thoracic aorta. J. Ethnopharmacol. 2005;101:221–226. doi: 10.1016/j.jep.2005.04.018. PubMed DOI

Affuso F., Mercurio V., Fazio V., Fazio S. Cardiovascular and metabolic effects of Berberine. World J. Cardiol. 2010;2:71–77. doi: 10.4330/wjc.v2.i4.71. PubMed DOI PMC

Wang Y., Huang Y., Lam K.S., Li Y., Wong W.T., Ye H., Lau C.W., Vanhoutte P.M., Xu A. Berberine prevents hyperglycemia-induced endothelial injury and enhances vasodilatation via adenosine monophosphate-activated protein kinase and endothelial nitric oxide synthase. Cardiovasc. Res. 2009;82:484–492. doi: 10.1093/cvr/cvp078. PubMed DOI

Gong L.L., Fang L.H., Qin H.L., Lv Y., Du G.H. Analysis of the mechanisms underlying the vasorelaxant action of coptisine in rat aortic rings. Am. J. Chin. Med. 2012;40:309–320. doi: 10.1142/S0192415X12500243. PubMed DOI

Tan H.L., Chan K.G., Pusparajah P., Duangjai A., Saokaew S., Mehmood Khan T., Lee L.H., Goh B.H. Rhizoma Coptidis: A Potential Cardiovascular Protective Agent. Front. Pharmacol. 2016;7:362. doi: 10.3389/fphar.2016.00362. PubMed DOI PMC

Qiao M.M., Liu F., Liu Y., Guo L., Zhou Q.M., Peng C., Xiong L. Curcumane C and (±)-curcumane D, an unusual seco-cadinane sesquiterpenoid and a pair of unusual nor-bisabolane enantiomers with significant vasorelaxant activity from Curcuma longa. Bioorg. Chem. 2019;92:103275. doi: 10.1016/j.bioorg.2019.103275. PubMed DOI

Yu S.M., Cheng Z.J., Kuo S.C. Endothelium-dependent relaxation of rat aorta by butein, a novel cyclic AMP-specific phosphodiesterase inhibitor. Eur. J. Pharmacol. 1995;280:69–77. doi: 10.1016/0014-2999(95)00190-V. PubMed DOI

Yu S.M., Kuo S.C. Vasorelaxant effect of isoliquiritigenin, a novel soluble guanylate cyclase activator, in rat aorta. Br. J. Pharmacol. 1995;114:1587–1594. doi: 10.1111/j.1476-5381.1995.tb14943.x. PubMed DOI PMC

Ma F.Y., Luo M., Zhao C.J., Li C.Y., Wang W., Gu C.B., Wei Z.F., Zu Y.G., Fu Y.J. Simple and efficient preparation of biochanin A and genistein from Dalbergia odorifera T. Chen leaves using macroporous resin followed by flash chromatography. Sep. Purif. Technol. 2013;120:310–318. doi: 10.1016/j.seppur.2013.09.035. DOI

Kumar T., Sharma M., Rana A., Lingaraju M.C., Parida S., Kumar D., Singh T.U. Biochanin-A elicits relaxation in coronary artery of goat through different mechanisms. Res. Vet. Sci. 2020;131:206–214. doi: 10.1016/j.rvsc.2020.05.003. PubMed DOI

Wang H.P., Mei R.H., Li X.Y., Zhao M.H., Lu Y., Xia Q., Bruce I. Endothelium-independent Vasorelaxant Effect of the Phyto-oestrogen Biochanin A on Rat Thoracic Aorta; Proceedings of the 2005 IEEE Engineering in Medicine and Biology 27th Annual Conference; Shanghai, China. 17–18 January 2006; pp. 2244–2247. PubMed DOI

Choi S., Jung W.S., Cho N.S., Ryu K.H., Jun J.Y., Shin B.C., Chung J.H., Yeum C.H. Mechanisms of phytoestrogen biochanin A-induced vasorelaxation in renovascular hypertensive rats. Kidney Res. Clin. Pract. 2014;33:181–186. doi: 10.1016/j.krcp.2014.08.003. PubMed DOI PMC

Migkos T., Pourová J., Vopršalová M., Auger C., Schini-Kerth V., Mladěnka P. Biochanin A, the Most Potent of 16 Isoflavones, Induces Relaxation of the Coronary Artery Through the Calcium Channel and cGMP-dependent Pathway. Planta Med. 2020;86:708–716. doi: 10.1055/a-1158-9422. PubMed DOI

Sá R.e.C., Almeida R.N., Bhattacharyya J. Pharmaceutical properties and toxicology of Dioclea grandiflora. Pharm. Biol. 2013;51:659–667. doi: 10.3109/13880209.2012.755208. PubMed DOI

Trigueiro F., Cortes S.F., Almeida R.N., Lemos V.S. Endothelium-independent vasorelaxant effect of dioclein, a new flavonoid isolated from Dioclea grandiflora, in the rat aorta. J. Pharm. Pharmacol. 2000;52:1431–1434. doi: 10.1211/0022357001777441. PubMed DOI

Côrtes S.F., Rezende B.A., Corriu C., Medeiros I.A., Teixeira M.M., Lopes M.J., Lemos V.S. Pharmacological evidence for the activation of potassium channels as the mechanism involved in the hypotensive and vasorelaxant effect of dioclein in rat small resistance arteries. Br. J. Pharmacol. 2001;133:849–858. doi: 10.1038/sj.bjp.0704147. PubMed DOI PMC

Gonçalves R.L., Lugnier C., Keravis T., Lopes M.J., Fantini F.A., Schmitt M., Cortes S.F., Lemos V.S. The flavonoid dioclein is a selective inhibitor of cyclic nucleotide phosphodiesterase type 1 (PDE1) and a cGMP-dependent protein kinase (PKG) vasorelaxant in human vascular tissue. Eur. J. Pharmacol. 2009;620:78–83. doi: 10.1016/j.ejphar.2009.08.008. PubMed DOI

Lemos V.S., Côrtes S.F., dos Santos M.H., Ellena J., Moreira M.E., Doriguetto A.C. Structure and vasorelaxant activity of floranol, a flavonoid isolated from the roots of Dioclea grandiflora. Chem. Biodivers. 2006;3:635–645. doi: 10.1002/cbdv.200690066. PubMed DOI

Marques A.M., Provance D.W., Kaplan M.A.C., Figueiredo M.R. Echinodorus grandiflorus: Ethnobotanical, phytochemical and pharmacological overview of a medicinal plant used in Brazil. Food Chem. Toxicol. 2017;109:1032–1047. doi: 10.1016/j.fct.2017.03.026. PubMed DOI

Tibiriçá E., Almeida A., Caillleaux S., Pimenta D., Kaplan M.A., Lessa M.A., Figueiredo M.R. Pharmacological mechanisms involved in the vasodilator effects of extracts from Echinodorus grandiflorus. J. Ethnopharmacol. 2007;111:50–55. doi: 10.1016/j.jep.2006.10.030. PubMed DOI

Prando T.B., Barboza L.N., Araújo V.e.O., Gasparotto F.M., de Souza L.M., Lourenço E.L., Gasparotto Junior A. Involvement of bradykinin B2 and muscarinic receptors in the prolonged diuretic and antihypertensive properties of Echinodorus grandiflorus (Cham. & Schltdl.) Micheli. Phytomedicine. 2016;23:1249–1258. doi: 10.1016/j.phymed.2015.10.020. PubMed DOI

Peng H., Xing Y., Gao L., Zhang L., Zhang G. Simultaneous separation of apigenin, luteolin and rosmarinic acid from the aerial parts of the copper-tolerant plant Elsholtzia splendens. Environ. Sci. Pollut. Res. Int. 2014;21:8124–8132. doi: 10.1007/s11356-014-2747-5. PubMed DOI

Wang H.P., Lu J.F., Zhang G.L., Li X.Y., Peng H.Y., Lu Y., Zhao L., Ye Z.G., Bruce I.C., Xia Q., et al. Endothelium-dependent and -independent vasorelaxant actions and mechanisms induced by total flavonoids of Elsholtzia splendens in rat aortas. Environ. Toxicol. Pharmacol. 2014;38:453–459. doi: 10.1016/j.etap.2014.07.019. PubMed DOI

Ferreira H.C., Serra C.P., Endringer D.C., Lemos V.S., Braga F.C., Cortes S.F. Endothelium-dependent vasodilation induced by Hancornia speciosa in rat superior mesenteric artery. Phytomedicine. 2007;14:473–478. doi: 10.1016/j.phymed.2006.11.008. PubMed DOI

Chan S.S., Choi A.O., Jones R.L., Lin G. Mechanisms underlying the vasorelaxing effects of butylidenephthalide, an active constituent of Ligusticum chuanxiong, in rat isolated aorta. Eur. J. Pharmacol. 2006;537:111–117. doi: 10.1016/j.ejphar.2006.03.015. PubMed DOI

Cao Y.X., Zhang W., He J.Y., He L.C., Xu C.B. Ligustilide induces vasodilatation via inhibiting voltage dependent calcium channel and receptor-mediated Ca2+ influx and release. Vascul. Pharmacol. 2006;45:171–176. doi: 10.1016/j.vph.2006.05.004. PubMed DOI

Chan S.S., Cheng T.Y., Lin G. Relaxation effects of ligustilide and senkyunolide A, two main constituents of Ligusticum chuanxiong, in rat isolated aorta. J. Ethnopharmacol. 2007;111:677–680. doi: 10.1016/j.jep.2006.12.018. PubMed DOI

Kim E.Y., Kim J.H., Rhyu M.R. Endothelium-independent vasorelaxation by Ligusticum wallichii in isolated rat aorta: Comparison of a butanolic fraction and tetramethylpyrazine, the main active component of Ligusticum wallichii. Biol. Pharm. Bull. 2010;33:1360–1363. doi: 10.1248/bpb.33.1360. PubMed DOI

Guedes D.N., Silva D.F., Barbosa-Filho J.M., de Medeiros I.A. Endothelium-dependent hypotensive and vasorelaxant effects of the essential oil from aerial parts of Mentha x villosa in rats. Phytomedicine. 2004;11:490–497. doi: 10.1016/j.phymed.2004.04.002. PubMed DOI

Guedes D.N., Silva D.F., Barbosa-Filho J.M., Medeiros I.A. Muscarinic agonist properties involved in the hypotensive and vasorelaxant responses of rotundifolone in rats. Planta Med. 2002;68:700–704. doi: 10.1055/s-2002-33795. PubMed DOI

Guedes D.N., Silva D.F., Barbosa-Filho J.M., Medeiros I.A. Calcium antagonism and the vasorelaxation of the rat aorta induced by rotundifolone. Braz. J. Med. Biol. Res. 2004;37:1881–1887. doi: 10.1590/S0100-879X2004001200014. PubMed DOI

Silva D.F., Araújo I.G., Albuquerque J.G., Porto D.L., Dias K.L., Cavalcante K.V., Veras R.C., Nunes X.P., Barbosa-Filho J.M., Araújo D.A., et al. Rotundifolone-induced relaxation is mediated by BK(Ca) channel activation and Ca(v) channel inactivation. Basic Clin. Pharmacol. Toxicol. 2011;109:465–475. doi: 10.1111/j.1742-7843.2011.00749.x. PubMed DOI

Dongmo A., Kamanyi M.A., Tan P.V., Bopelet M., Vierling W., Wagner H. Vasodilating properties of the stem bark extract of Mitragyna ciliata in rats and guinea pigs. Phytother. Res. 2004;18:36–39. doi: 10.1002/ptr.1350. PubMed DOI

Zaima K., Takeyama Y., Koga I., Saito A., Tamamoto H., Azziz S.S., Mukhtar M.R., Awang K., Hadi A.H., Morita H. Vasorelaxant effect of isoquinoline derivatives from two species of Popowia perakensis and Phaeanthus crassipetalus on rat aortic artery. J. Nat. Med. 2012;66:421–427. doi: 10.1007/s11418-011-0600-4. PubMed DOI

Senejoux F., Girard-Thernier C., Berthelot A., Bévalot F., Demougeot C. New insights into the mechanisms of the vasorelaxant effects of apocynin in rat thoracic aorta. Fundam. Clin. Pharmacol. 2013;27:262–270. doi: 10.1111/j.1472-8206.2011.01025.x. PubMed DOI

Perassa L.A., Graton M.E., Potje S.R., Troiano J.A., Lima M.S., Vale G.T., Pereira A.A., Nakamune A.C., Sumida D.H., Tirapelli C.R., et al. Apocynin reduces blood pressure and restores the proper function of vascular endothelium in SHR. Vascul. Pharmacol. 2016;87:38–48. doi: 10.1016/j.vph.2016.06.005. PubMed DOI

Luna-Vázquez F.J., Ibarra-Alvarado C., Rojas-Molina A., Romo-Mancillas A., López-Vallejo F.H., Solís-Gutiérrez M., Rojas-Molina J.I., Rivero-Cruz F. Role of Nitric Oxide and Hydrogen Sulfide in the Vasodilator Effect of Ursolic Acid and Uvaol from Black Cherry Prunus serotina Fruits. Molecules. 2016;21:78. doi: 10.3390/molecules21010078. PubMed DOI PMC

Park J.Y., Shin H.K., Lee Y.J., Choi Y.W., Bae S.S., Kim C.D. The mechanism of vasorelaxation induced by Schisandra chinensis extract in rat thoracic aorta. J. Ethnopharmacol. 2009;121:69–73. doi: 10.1016/j.jep.2008.09.031. PubMed DOI

Park J.Y., Shin H.K., Choi Y.W., Lee Y.J., Bae S.S., Han J., Kim C.D. Gomisin A induces Ca2+-dependent activation of eNOS in human coronary artery endothelial cells. J. Ethnopharmacol. 2009;125:291–296. doi: 10.1016/j.jep.2009.06.028. PubMed DOI

Park J.Y., Lee S.J., Yun M.R., Seo K.W., Bae S.S., Park J.W., Lee Y.J., Shin W.J., Choi Y.W., Kim C.D. Gomisin A from Schisandra chinensis induces endothelium-dependent and direct relaxation in rat thoracic aorta. Planta Med. 2007;73:1537–1542. doi: 10.1055/s-2007-993757. PubMed DOI

Ding L., Jia C., Zhang Y., Wang W., Zhu W., Chen Y., Zhang T. Baicalin relaxes vascular smooth muscle and lowers blood pressure in spontaneously hypertensive rats. Biomed. Pharmacother. 2019;111:325–330. doi: 10.1016/j.biopha.2018.12.086. PubMed DOI

Lin Y.L., Dai Z.K., Lin R.J., Chu K.S., Chen I.J., Wu J.R., Wu B.N. Baicalin, a flavonoid from Scutellaria baicalensis Georgi, activates large-conductance Ca2+-activated K+ channels via cyclic nucleotide-dependent protein kinases in mesenteric artery. Phytomedicine. 2010;17:760–770. doi: 10.1016/j.phymed.2010.01.003. PubMed DOI

Paredes A., Palacios J., Quispe C., Nwokocha C.R., Morales G., Kuzmicic J., Cifuentes F. Hydroalcoholic extract and pure compounds from Senecio nutans Sch. Bip (Compositae) induce vasodilation in rat aorta through endothelium-dependent and independent mechanisms. J. Ethnopharmacol. 2016;192:99–107. doi: 10.1016/j.jep.2016.07.008. PubMed DOI

Auger C., Chabert P., Lugnier C., Mushtaq M.N., Schini-Kerth V.B. Mechanisms underlying vasorelaxation induced in the porcine coronary arteries by Thymus linearis, Benth. J. Ethnopharmacol. 2018;225:211–219. doi: 10.1016/j.jep.2018.07.010. PubMed DOI

Getiye Y., Tolessa T., Engidawork E. Antihypertensive activity of 80% methanol seed extract of Calpurnia aurea (Ait.) Benth. subsp. aurea (Fabaceae) is mediated through calcium antagonism induced vasodilation. J. Ethnopharmacol. 2016;189:99–106. doi: 10.1016/j.jep.2016.04.056. PubMed DOI

Khan M., Gilani A.H. Studies on Blood Pressure Lowering, Vasodilator and Cardiac Suppressant Activities of Vitex negundo: Involvement of K+ Channel Activation and Ca++ Channel Blockade. Int. J. Pharmacol. 2015;11:137–142. doi: 10.3923/ijp.2015.137.142. DOI

Dongmo A.B., Ndom J.C., Massoma L.D., Dzikouk D.G., Fomani M., Bissoue N., Kamanyi A., Vierling W. Vasodilating effect of the root bark extract of Ficus saussureana on guinea pig aorta. Pharmaceutical. Biol. 2003;41:371–374.

Kim B., Kim K.W., Lee S., Jo C., Lee K., Ham I., Choi H.Y. Endothelium-dependent vasorelaxant effect of Prunus persica branch on isolated rat thoracic aorta. Nutrients. 2019;11:1816. doi: 10.3390/nu11081816. PubMed DOI PMC

Ramón Sánchez de Rojas V., Somoza B., Ortega T., Villar A.M., Tejerina T. Vasodilatory effect in rat aorta of eriodictyol obtained from Satureja obovata. Planta Med. 1999;65:234–238. doi: 10.1055/s-1999-13986. PubMed DOI

Derojas V.R.S., Ortega T., Villar A. Pharmacological activity of the extracts of 2 Satureja obovata varieties on isolated smooth-muscle preparations. Phytother. Res. 1994;8:212–217. doi: 10.1002/ptr.2650080405. DOI

Ch‘ng Y.S., Loh Y.C., Tan C.S., Ahmad M., Asmawi M.Z., Wan Omar W.M., Yam M.F. Vasorelaxant properties of Vernonia amygdalina ethanol extract and its possible mechanism. Pharm. Biol. 2017;55:2083–2094. doi: 10.1080/13880209.2017.1357735. PubMed DOI PMC

Gkaliagkousi E., Gavriilaki E., Triantafyllou A., Douma S. Clinical Significance of Endothelial Dysfunction in Essential Hypertension. Curr. Hypertens. Rep. 2015;17:85. doi: 10.1007/s11906-015-0596-3. PubMed DOI

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