Login Register Cart 0
Generic placeholder image

Endocrine, Metabolic & Immune Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Genistein in the Treatment of Hypertension: A Review

Author(s): Paulina Sigowska, Michał Zimoch, Aleksandra Baska*, Jakub Kazik, Kamil Leis and Grzegorz Grześk

Volume 22, Issue 14, 2022

Published on: 04 August, 2022

Page: [1367 - 1377] Pages: 11

DOI: 10.2174/1871530322666220510125115

Price: $65

Abstract

Genistein, a natural compound belonging to the group of isoflavones has a confirmed positive effect in such diseases as hormone-dependent cancers, osteoporosis, and cardiovascular diseases, including arterial and pulmonary hypertension. The multiway hypotensive effect is based on vasodilation with simultaneous inhibition of vasoconstriction and RAA interference. It impacts both vascular smooth muscles and endothelium due to its influence on many molecular pathways and peptides; among them: protection against oxidative stress, RhoA/Rho pathway inhibition, enhancing cAMP activation, modification of cellular calcium influx, and the increase of eNOS concentrations. Despite little research on genistein effect on pulmonary hypertension, it seems that the natural compound reduces harmful hypoxia effects and, consequently, inhibits vessels remodelling. In our review, we present mechanisms of lowering blood pressure and juxtapose in vivo research on both animal and human models. On the basis of our results, it might be deduced that the abovementioned isoflavone seems to be a safe and effective hypotensive drug. Its impact on arterial and pulmonary hypertension should be further estimated, both in monotherapy, and in combination treatment.

Keywords: Genistein, hypertension, pulmonary hypertension, isoflavones, natural compounds, phytoestrogen.

« Previous Next »
Graphical Abstract

[1]
Valenzuela, P.L.; Carrera-Bastos, P.; Gálvez, B.G.; Ruiz-Hurtado, G.; Ordovas, J.M.; Ruilope, L.M.; Lucia, A. Lifestyle interventions for the prevention and treatment of hypertension. Nat. Rev. Cardiol., 2021, 18(4), 251-275.
[http://dx.doi.org/10.1038/s41569-020-00437-9] [PMID: 33037326]
[2]
Curfman, G.; Bauchner, H.; Greenland, P. Treatment and control of hypertension in 2020: The need for substantial improvement. JAMA, 2020, 324(12), 1166-1167.
[http://dx.doi.org/10.1001/jama.2020.13322] [PMID: 32902571]
[3]
Song, J.J.; Ma, Z.; Wang, J.; Chen, L.X.; Zhong, J.C. Gender differences in hypertension. J. Cardiovasc. Transl. Res., 2020, 13(1), 47-54.
[http://dx.doi.org/10.1007/s12265-019-09888-z] [PMID: 31044374]
[4]
Saiz, L.C.; Gorricho, J.; Garjón, J.; Celaya, M.C.; Erviti, J.; Leache, L. Blood pressure targets for the treatment of people with hypertension and cardiovascular disease. Cochrane Database Syst. Rev., 2020, 9, CD010315.
[PMID: 32905623]
[5]
Flack, J.M.; Adekola, B. Blood pressure and the new ACC/AHA hypertension guidelines. Trends Cardiovasc. Med., 2020, 30(3), 160-164.
[http://dx.doi.org/10.1016/j.tcm.2019.05.003] [PMID: 31521481]
[6]
Tuli, H.S.; Tuorkey, M.J.; Thakral, F.; Sak, K.; Kumar, M.; Sharma, A.K.; Sharma, U.; Jain, A.; Aggarwal, V.; Bishayee, A. Molecular mechanisms of action of genistein in cancer: Recent advances. Front. Pharmacol., 2019, 10, 1336.
[http://dx.doi.org/10.3389/fphar.2019.01336] [PMID: 31866857]
[7]
Imai-Sumida, M.; Dasgupta, P.; Kulkarni, P.; Shiina, M.; Hashimoto, Y.; Shahryari, V.; Majid, S.; Tanaka, Y.; Dahiya, R.; Yamamura, S. Genistein represses HOTAIR/chromatin remodeling pathways to suppress kidney cancer. Cell. Physiol. Biochem., 2020, 54(1), 53-70.
[http://dx.doi.org/10.33594/000000205] [PMID: 31961100]
[8]
Braxas, H.; Rafraf, M.; Hasanabad, S.K.; Jafarabadi, M.A. Genistein supplementation improves some cardiovascular risk factors in postmenopausal women with type 2 diabetes mellitus. Nutr. Food Sci., 2020, 15(1), 125-136.
[9]
Guo, T.L.; Chen, Y.; Xu, H.S.; McDonough, C.M.; Huang, G. Gut microbiome in neuroendocrine and neuroimmune interactions: The case of genistein. Toxicol. Appl. Pharmacol., 2020, 402, 115130.
[http://dx.doi.org/10.1016/j.foodres.2019.108764] [PMID: 31955737]
[10]
Hemati, N.; Asis, M.; Moradi, S.; Mollica, A.; Stefanucci, A.; Nikfar, S. Effects of genistein on blood pressure: A systematic review and meta-analysis. Food Res. Int., 2020, 128, 108764.
[11]
Guo, J.; Yang, G.; He, Y.; Xu, H.; Fan, H.; An, J.; Zhang, L.; Zhang, R.; Cao, G.; Hao, D.; Yang, H. Involvement of α7nAChR in the protective effects of genistein against β-amyloid-induced oxidative stress in neurons via a PI3K/Akt/Nrf2 pathway-related mechanism. Cell. Mol. Neurobiol., 2021, 41(2), 377-393.
[http://dx.doi.org/10.1007/s10571-020-01009-8] [PMID: 33215356]
[12]
Tang, H.; Wang, S.; Li, X.; Zou, T.; Huang, X.; Zhang, W.; Chen, Y.; Yang, C.; Pan, Q.; Liu, H.F. Prospects of and limitations to the clinical applications of genistein. Discov. Med., 2019, 27(149), 177-188.
[PMID: 31361980]
[13]
Sureda, A.; Sanches Silva, A.; Sánchez-Machado, D.I.; López-Cervantes, J.; Daglia, M.; Nabavi, S.F.; Nabavi, S.M. Hypotensive effects of genistein: From chemistry to medicine. Chem. Biol. Interact., 2017, 268, 37-46.
[http://dx.doi.org/10.1016/j.cbi.2017.02.012] [PMID: 28242380]
[14]
Silva, H. The vascular effects of isolated isoflavones-A focus on the determinants of blood pressure regulation. Biology (Basel), 2021, 10(1), 49.
[http://dx.doi.org/10.3390/biology10010049] [PMID: 33445531]
[15]
Maaliki, D.; Shaito, A.A.; Pintus, G.; El-Yazbi, A.; Eid, A.H. Flavonoids in hypertension: A brief review of the underlying mechanisms. Curr. Opin. Pharmacol., 2019, 45, 57-65.
[http://dx.doi.org/10.1016/j.coph.2019.04.014] [PMID: 31102958]
[16]
Mita, M.; Tanaka, H.; Yanagihara, H.; Nakagawa, J.; Hishinuma, S.; Sutherland, C.; Walsh, M.P.; Shoji, M. Membrane depolarization-induced RhoA/Rho-associated kinase activation and sustained contraction of rat caudal arterial smooth muscle involves genistein-sensitive tyrosine phosphorylation. J. Smooth Muscle Res., 2013, 49, 26-45.
[http://dx.doi.org/10.1540/jsmr.49.26] [PMID: 24133693]
[17]
Ng, W.W.; Keung, W.; Xu, Y.C.; Ng, K.F.; Leung, G.P.; Vanhoutte, P.M.; Choy, P.C.; Man, R.Y. Genistein potentiates protein kinase A activity in porcine coronary artery. Mol. Cell. Biochem., 2008, 311(1-2), 37-44.
[http://dx.doi.org/10.1007/s11010-007-9691-3] [PMID: 18165926]
[18]
McDaniel, N.L.; Rembold, C.M.; Richard, H.M.; Murphy, R.A. Cyclic AMP relaxes swine arterial smooth muscle predominantly by decreasing cell Ca2+ concentration. J. Physiol., 1991, 439(1), 147-160.
[http://dx.doi.org/10.1113/jphysiol.1991.sp018661] [PMID: 1654411]
[19]
Valero, M.S.; Garay, R.P.; Gros, P.; Alda, J.O. Cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel and Na-K-Cl cotransporter NKCC1 isoform mediate the vasorelaxant action of genistein in isolated rat aorta. Eur. J. Pharmacol., 2006, 544(1-3), 126-131.
[http://dx.doi.org/10.1016/j.ejphar.2006.06.048] [PMID: 16859673]
[20]
Galán-Martínez, L.; Herrera-Estrada, I.; Fleites-Vázquez, A. Direct actions of the flavonoids naringenin, quercetin and genistein on rat cardiac and vascular muscles. J. Pharm. Pharmacogn, 2018, 6(3), 158-166.
[21]
Li, H.F.; Wang, L.D.; Qu, S.Y. Phytoestrogen genistein decreases contractile response of aortic artery in vitro and arterial blood pressure in vivo. Acta Pharmacol. Sin., 2004, 25(3), 313-318.
[PMID: 15000884]
[22]
Touyz, R.M.; Alves-Lopes, R.; Rios, F.J.; Camargo, L.L.; Anagnostopoulou, A.; Arner, A.; Montezano, A.C. Vascular smooth muscle contraction in hypertension. Cardiovasc. Res., 2018, 114(4), 529-539.
[http://dx.doi.org/10.1093/cvr/cvy023] [PMID: 29394331]
[23]
Bai, B.; Lu, N.; Zhang, W.; Lin, J.; Zhao, T.; Zhou, S.; Khasanova, E.; Zhang, L. Inhibitory effects of genistein on vascular smooth muscle cell proliferation induced by Ox-LDL: Role of BKCa channels. Anal. Cell. Pathol. (Amst.), 2020, 2020, 8895449.
[http://dx.doi.org/10.1155/2020/8895449] [PMID: 33415067]
[24]
Je, H.D.; Sohn, U.D. Inhibitory effect of genistein on agonist-induced modulation of vascular contractility. Mol. Cells, 2009, 27(2), 191-198.
[http://dx.doi.org/10.1007/s10059-009-0052-9] [PMID: 19277501]
[25]
Stadnicka, A.; Kwok, W.M.; Warltier, D.C.; Bosnjak, Z.J. Protein tyrosine kinase-dependent modulation of isoflurane effects on cardiac sarcolemmal K(ATP) channel. Anesthesiology, 2002, 97(5), 1198-1208.
[http://dx.doi.org/10.1097/00000542-200211000-00025] [PMID: 12411806]
[26]
Flagg, T.P.; Enkvetchakul, D.; Koster, J.C.; Nichols, C.G. Muscle KATP channels: Recent insights to energy sensing and myoprotection. Physiol. Rev., 2010, 90(3), 799-829.
[http://dx.doi.org/10.1152/physrev.00027.2009] [PMID: 20664073]
[27]
Goto, K.; Kitazono, T. Endothelium-Dependent Hyperpolarization (EDH) in diet-induced obesity. Endocr. Metabol. Sci., 2020, 1(3-4), 100062.
[http://dx.doi.org/10.1016/j.endmts.2020.100062]
[28]
Chen, Z.; D.S., Oliveira S.; Zimnicka, A.M.; Jiang, Y.; Sharma, T.; Chen, S.; Lazarov, O.; Bonini, M.G.; Haus, J.M.; Minshall, R.D. Reciprocal regulation of eNOS and caveolin-1 functions in endothelial cells. Mol. Biol. Cell, 2018, 29(10), 1190-1202.
[http://dx.doi.org/10.1091/mbc.E17-01-0049] [PMID: 29563255]
[29]
Gao, Y.; Chen, T.; Raj, J.U. Endothelial and smooth muscle cell interactions in the pathobiology of pulmonary hypertension. Am. J. Respir. Cell Mol. Biol., 2016, 54(4), 451-460.
[http://dx.doi.org/10.1165/rcmb.2015-0323TR] [PMID: 26744837]
[30]
Grześk, G.; Nowaczyk, A. Current modulation of guanylate cyclase pathway activity-mechanism and clinical implications. Molecules, 2021, 26(11), 3418.
[http://dx.doi.org/10.3390/molecules26113418] [PMID: 34200064]
[31]
Liu, D.; Homan, L.L.; Dillon, J.S. Genistein acutely stimulates nitric oxide synthesis in vascular endothelial cells by a cyclic adenosine 5′-monophosphate-dependent mechanism. Endocrinology, 2004, 145(12), 5532-5539.
[http://dx.doi.org/10.1210/en.2004-0102] [PMID: 15319357]
[32]
Liu, D.; Si, H.; Jiang, H. Phytoestrogen genistein up‐regulates endothelial nitric oxide synthase expression via activation of cAMP‐responsive element‐binding protein in human aortic endothelial cells. 2012.
[http://dx.doi.org/10.1096/fasebj.26.1_supplement.112.2]
[33]
Vera, R.; Sánchez, M.; Galisteo, M.; Villar, I.C.; Jimenez, R.; Zarzuelo, A.; Pérez-Vizcaíno, F.; Duarte, J. Chronic administration of genistein improves endothelial dysfunction in spontaneously hypertensive rats: Involvement of eNOS, caveolin and calmodulin expression and NADPH oxidase activity. Clin. Sci. (Lond.), 2007, 112(3), 183-191.
[http://dx.doi.org/10.1042/CS20060185] [PMID: 17007611]
[34]
Mahn, K.; Borrás, C.; Knock, G.A.; Taylor, P.; Khan, I.Y.; Sugden, D.; Poston, L.; Ward, J.P.; Sharpe, R.M.; Viña, J.; Aaronson, P.I.; Mann, G.E. Dietary soy isoflavone induced increases in antioxidant and eNOS gene expression lead to improved endothelial function and reduced blood pressure in vivo. FASEB J., 2005, 19(12), 1755-1757.
[http://dx.doi.org/10.1096/fj.05-4008fje] [PMID: 16107535]
[35]
Räthel, T.R.; Leikert, J.F.; Vollmar, A.M.; Dirsch, V.M. The soy isoflavone genistein induces a late but sustained activation of the endothelial nitric oxide-synthase system in vitro. Br. J. Pharmacol., 2005, 144(3), 394-399.
[http://dx.doi.org/10.1038/sj.bjp.0706075] [PMID: 15655515]
[36]
Si, H.; Liu, D. Genistein, a soy phytoestrogen, upregulates the expression of human endothelial nitric oxide synthase and lowers blood pressure in spontaneously hypertensive rats. J. Nutr., 2008, 138(2), 297-304.
[http://dx.doi.org/10.1093/jn/138.2.297] [PMID: 18203895]
[37]
Pinna, C.; Sala, A. Sex-specific activity of hesperidin, diosmin and genistein on human umbilical vein. Biomed. Res. Clin. Pract., 2019, 4, 1-5.
[http://dx.doi.org/10.15761/BRCP.1000196]
[38]
Lin, A.H.; Leung, G.P.; Leung, S.W.; Vanhoutte, P.M.; Man, R.Y. Genistein enhances relaxation of the spontaneously hypertensive rat aorta by transactivation of epidermal growth factor receptor following binding to membrane estrogen receptors-α and activation of a G protein-coupled, endothelial nitric oxide synthase-dependent pathway. Pharmacol. Res., 2011, 63(3), 181-189.
[http://dx.doi.org/10.1016/j.phrs.2010.11.007] [PMID: 21111822]
[39]
Goto, K.; Ohtsubo, T.; Kitazono, T. Endothelium-Dependent Hyperpolarization (EDH) in hypertension: The role of endothelial ion channels. Int. J. Mol. Sci., 2018, 19(1), 315.
[http://dx.doi.org/10.3390/ijms19010315] [PMID: 29361737]
[40]
Mishra, S.K.; Abbot, S.E.; Choudhury, Z.; Cheng, M.; Khatab, N.; Maycock, N.J.; Zavery, A.; Aaronson, P.I. Endothelium-dependent relaxation of rat aorta and main pulmonary artery by the phytoestrogens genistein and daidzein. Cardiovasc. Res., 2000, 46(3), 539-546.
[http://dx.doi.org/10.1016/S0008-6363(00)00049-3] [PMID: 10912464]
[41]
Yamagata, K.; Yamori, Y. Inhibition of endothelial dysfunction by dietary flavonoids and preventive effects against cardiovascular disease. J. Cardiovasc. Pharmacol., 2020, 75(1), 1-9.
[http://dx.doi.org/10.1097/FJC.0000000000000757] [PMID: 31613843]
[42]
Squadrito, F.; Altavilla, D.; Morabito, N.; Crisafulli, A.; D’Anna, R.; Corrado, F.; Ruggeri, P.; Campo, G.M.; Calapai, G.; Caputi, A.P.; Squadrito, G. The effect of the phytoestrogen genistein on plasma nitric oxide concentrations, endothelin-1 levels and endothelium dependent vasodilation in postmenopausal women. Atherosclerosis, 2002, 163(2), 339-347.
[http://dx.doi.org/10.1016/S0021-9150(02)00013-8] [PMID: 12052481]
[43]
Rodrigo, M.C.; Martin, D.S.; Eyster, K.M. Vascular ECE-1 mRNA expression decreases in response to estrogens. Life Sci., 2003, 73(23), 2973-2983.
[http://dx.doi.org/10.1016/j.lfs.2003.05.001] [PMID: 14519446]
[44]
Hernandez-Montes, E.; Pollard, S.E.; Vauzour, D.; Jofre-Montseny, L.; Rota, C.; Rimbach, G.; Weinberg, P.D.; Spencer, J.P. Activation of glutathione peroxidase via Nrf1 mediates genistein’s protection against oxidative endothelial cell injury. Biochem. Biophys. Res. Commun., 2006, 346(3), 851-859.
[http://dx.doi.org/10.1016/j.bbrc.2006.05.197] [PMID: 16780800]
[45]
Han, S.; Wu, H.; Li, W.; Gao, P. Protective effects of genistein in homocysteine-induced endothelial cell inflammatory injury. Mol. Cell. Biochem., 2015, 403(1-2), 43-49.
[http://dx.doi.org/10.1007/s11010-015-2335-0] [PMID: 25626894]
[46]
Rajkumar, V.; Waseem, M. Hypoaldosteronism; StatPearls; 2021. Available from:https://www.ncbi.nlm.nih.gov/books/NBK555992/
[47]
Poasakate, A.; Maneesai, P.; Rattanakanokchai, S.; Bunbupha, S.; Tong-Un, T.; Pakdeechote, P. Genistein prevents nitric oxide deficiency-induced cardiac dysfunction and remodeling in rats. Antioxidants, 2021, 10(2), 237.
[http://dx.doi.org/10.3390/antiox10020237] [PMID: 33557258]
[48]
Xu, J.W.; Ikeda, K.; Yamori, Y. Genistein inhibits expressions of NADPH oxidase p22phox and angiotensin II type 1 receptor in aortic endothelial cells from stroke-prone spontaneously hypertensive rats. Hypertens. Res., 2004, 27(9), 675-683.
[http://dx.doi.org/10.1291/hypres.27.675] [PMID: 15750262]
[49]
Vera, R.; Jiménez, R.; Lodi, F.; Sánchez, M.; Galisteo, M.; Zarzuelo, A.; Pérez-Vizcaíno, F.; Duarte, J. Genistein restores caveolin-1 and AT-1 receptor expression and vascular function in large vessels of ovariectomized hypertensive rats. Menopause, 2007, 14(5), 933-940.
[http://dx.doi.org/10.1097/gme.0b013e31802d9785] [PMID: 17667142]
[50]
Ajdzanović, V.; Sosić-Jurjević, B.; Filipović, B.; Trifunović, S.; Manojlović-Stojanoski, M.; Sekulić, M.; Milosević, V. Genistein-induced histomorphometric and hormone secreting changes in the adrenal cortex in middle-aged rats. Exp. Biol. Med. (Maywood), 2009, 234(2), 148-156.
[http://dx.doi.org/10.3181/0807-RM-231] [PMID: 19064942]
[51]
Ajdžanović, V.; Miler, M.; Šošić-Jurjević, B.; Filipović, B.; Milenkovic, D.; Jakovljević, V.; Milošević, V. Soy isoflavone-caused shunting of the corticosteroidogenesis pathways in andropausal subjects: Top-down impulse for the optimal supplementation design. Med. Hypotheses, 2021, 148, 110516.
[http://dx.doi.org/10.1016/j.mehy.2021.110516] [PMID: 33548764]
[52]
Khan, M.Y.; Kumar, V. Mechanism of antihypertensive effect of Mucuna pruriens L. seed extract and its isolated compounds. J. Complement. Integr. Med., 2017, 14(4), /j/jcim.2017.14.issue-4/jcim-2017-0014/jcim-2017-0014.xml..
[http://dx.doi.org/10.1515/jcim-2017-0014] [PMID: 28640753]
[53]
Jeong, E.W.; Park, S.Y.; Yang, Y.S.; Baek, Y.J.; Yun, D.M.; Kim, H.J.; Go, G.W.; Lee, H.G. Black soybean and adzuki bean extracts lower blood pressure by modulating the renin-angiotensin system in spontaneously hypertensive rats. Foods, 2021, 10(7), 1571.
[http://dx.doi.org/10.3390/foods10071571] [PMID: 34359440]
[54]
Jankowski, M.; Wang, D.; Danalache, B.; Gangal, M.; Gutkowska, J. Cardiac oxytocin receptor blockade stimulates adverse cardiac remodeling in ovariectomized spontaneously hypertensive rats. Am. J. Physiol. Heart Circ. Physiol., 2010, 299(2), H265-H274.
[http://dx.doi.org/10.1152/ajpheart.00487.2009] [PMID: 20671291]
[55]
Sun, L.; Zhao, T.; Ju, T.; Wang, X.; Li, X.; Wang, L.; Zhang, L.; Yu, G. A combination of intravenous genistein plus Mg2+ enhances antihypertensive effects in SHR by endothelial protection and BKCa channel inhibition. Am. J. Hypertens., 2015, 28(9), 1114-1120.
[http://dx.doi.org/10.1093/ajh/hpv005] [PMID: 25714131]
[56]
Jalili, C.; Rashidi, I.; Roshankhah, S.; Jalili, F.; Salahshoor, M.R. Protective effect of genistein on the morphine-induced kidney disorders in male mice. Electron. J. Gen. Med., 2020, 17(3) Available from: https://www.ejgm.co.uk/article/protective-effect-of-genistein-on-the-morphine-induced-kidney-disorders-in-male-mice-7874
[57]
Li, J.; Xie, Z.Z.; Tang, Y.B. Genistein prevents myocardial hypertrophy in 2-kidney 1-clip renal hypertensive rats by restoring eNOS pathway. Pharmacology, 2010, 86(4), 240-248.
[http://dx.doi.org/10.1159/000320457] [PMID: 20938214]
[58]
Cho, T.M.; Peng, N.; Clark, J.T.; Novak, L.; Roysommuti, S.; Prasain, J.; Wyss, J.M. Genistein attenuates the hypertensive effects of dietary NaCl in hypertensive male rats. Endocrinology, 2007, 148(11), 5396-5402.
[http://dx.doi.org/10.1210/en.2007-0245] [PMID: 17673523]
[59]
Palanisamy, N.; Venkataraman, A.C. Beneficial effect of genistein on lowering blood pressure and kidney toxicity in fructose-fed hypertensive rats. Br. J. Nutr., 2013, 109(10), 1806-1812.
[http://dx.doi.org/10.1017/S0007114512003819] [PMID: 23116847]
[60]
Al-Nakkash, L.; Martin, J.B.; Petty, D.; Lynch, S.M.; Hamrick, C.; Lucy, D.; Robinson, J.; Peterson, A.; Rubin, L.J.; Broderick, T.L. Dietary genistein induces sex-dependent effects on murine body weight, serum profiles, and vascular function of thoracic aortae. Gend. Med., 2012, 9(5), 295-308.
[http://dx.doi.org/10.1016/j.genm.2012.07.001] [PMID: 22863843]
[61]
Mosallanezhad, Z.; Mahmoodi, M.; Ranjbar, S.; Hosseini, R.; Clark, C.C.T.; Carson-Chahhoud, K.; Norouzi, Z.; Abbasian, A.; Sohrabi, Z.; Jalali, M. Soy intake is associated with lowering blood pressure in adults: A systematic review and meta-analysis of randomized double-blind placebo-controlled trials. Complement. Ther. Med., 2021, 59, 102692.
[http://dx.doi.org/10.1016/j.ctim.2021.102692] [PMID: 33636295]
[62]
Liang, Y.L.; Teede, H.; Dalais, F.; McGrath, B.P. The effects of phytoestrogen on blood pressure and lipids in healthy volunteers. Zhonghua Xin Xue Guan Bing Za Zhi, 2006, 34(8), 726-729.
[PMID: 17081400]
[63]
Rivan, N.F.M.; Shahar, S.; Haron, H.; Ambak, R.; Othman, F. Association between intake of soy isoflavones and blood pressure among urban and rural Malaysian adults. Malays. J. Nutr., 2018, 24, 381-393.
[64]
Rivas, M.; Garay, R.P.; Escanero, J.F.; Cia, P., Jr; Cia, P.; Alda, J.O. Soy milk lowers blood pressure in men and women with mild to moderate essential hypertension. J. Nutr., 2002, 132(7), 1900-1902.
[http://dx.doi.org/10.1093/jn/132.7.1900] [PMID: 12097666]
[65]
Nasca, M.M.; Zhou, J.R.; Welty, F.K. Effect of soy nuts on adhesion molecules and markers of inflammation in hypertensive and normotensive postmenopausal women. Am. J. Cardiol., 2008, 102(1), 84-86.
[http://dx.doi.org/10.1016/j.amjcard.2008.02.100] [PMID: 18572041]
[66]
Wenner, M.M.; Taylor, H.S.; Stachenfeld, N.S. Peripheral microvascular vasodilatory response to estradiol and genistein in women with insulin resistance. Microcirculation, 2015, 22(5), 391-399.
[http://dx.doi.org/10.1111/micc.12208] [PMID: 25996650]
[67]
Wang, X.; Wang, Y.; Xu, W.; Lan, L.; Li, Y.; Wang, L. Dietary isoflavones intake is inversely associated with non-alcoholic fatty liver disease, hyperlipidaemia and hypertension. Int. J. Food Sci. Nutr., 2021, 1-11.
[PMID: 33899670]
[68]
Maleki, Z.; Jazayeri, S.; Eslami, O.; Shidfar, F.; Hosseini, A.F.; Agah, S.; Norouzi, H. Effect of soy milk consumption on glycemic status, blood pressure, fibrinogen and malondialdehyde in patients with non-alcoholic fatty liver disease: A randomized controlled trial. Complement. Ther. Med., 2019, 44, 44-50.
[http://dx.doi.org/10.1016/j.ctim.2019.02.020] [PMID: 31126574]
[69]
Amanat, S.; Eftekhari, M.H.; Fararouei, M.; Bagheri Lankarani, K.; Massoumi, S.J. Genistein supplementation improves insulin resistance and inflammatory state in non-alcoholic fatty liver patients: A randomized, controlled trial. Clin. Nutr., 2018, 37(4), 1210-1215.
[http://dx.doi.org/10.1016/j.clnu.2017.05.028] [PMID: 28647291]
[70]
Dechichi, J.G.C.; Mariano, I.M.; Giolo, J.S.; Batista, J.P.; Amaral, A.L.; Ribeiro, P.A.B.; de Oliveira, E.P.; Puga, G.M. Isoflavone supplementation does not potentiate the effect of combined exercise training on resting and ambulatory blood pressure in non-obese postmenopausal women: A randomized double-blind controlled trial-A pilot study. Nutrients, 2020, 12(11), 3495.
[http://dx.doi.org/10.3390/nu12113495] [PMID: 33203003]
[71]
Irace, C.; Marini, H.; Bitto, A.; Altavilla, D.; Polito, F.; Adamo, E.B.; Arcoraci, V.; Minutoli, L.; Di Benedetto, A.; Di Vieste, G.; de Gregorio, C.; Gnasso, A.; Corrao, S.; Licata, G.; Squadrito, F. Genistein and endothelial function in postmenopausal women with metabolic syndrome. Eur. J. Clin. Invest., 2013, 43(10), 1025-1031.
[http://dx.doi.org/10.1111/eci.12139] [PMID: 23899172]
[72]
Bitto, A.; Altavilla, D.; Di Benedetto, A.; Cucinotta, D.; Squadrito, F. Genistein aglycone a nutraceutical approach to metabolic syndrome: Results from a randomized clinical trial in postmenopausal women. Atherosclerosis, 2014, 235(2), e109.
[http://dx.doi.org/10.1016/j.atherosclerosis.2014.05.294]
[73]
Squadrito, F.; Marini, H.; Bitto, A.; Altavilla, D.; Polito, F.; Adamo, E.B.; D’Anna, R.; Arcoraci, V.; Burnett, B.P.; Minutoli, L.; Di Benedetto, A.; Di Vieste, G.; Cucinotta, D.; de Gregorio, C.; Russo, S.; Corrado, F.; Saitta, A.; Irace, C.; Corrao, S.; Licata, G. Genistein in the metabolic syndrome: Results of a randomized clinical trial. J. Clin. Endocrinol. Metab., 2013, 98(8), 3366-3374.
[http://dx.doi.org/10.1210/jc.2013-1180] [PMID: 23824420]
[74]
Bitto, A.; Arcoraci, V.; Alibrandi, A.; D’Anna, R.; Corrado, F.; Atteritano, M.; Minutoli, L.; Altavilla, D.; Squadrito, F. Visfatin correlates with hot flashes in postmenopausal women with metabolic syndrome: Effects of genistein. Endocrine, 2017, 55(3), 899-906.
[http://dx.doi.org/10.1007/s12020-016-0968-8] [PMID: 27126198]
[75]
Xia, K.; Ding, R.; Yang, Y.; Wu, B.; Zhang, Q.; Hu, D. Association between serum leptin, adiponectin, visfatin, obesity and hypertension in female. Zhonghua Nei Ke Za Zhi, 2015, 54(9), 768-772.
[PMID: 26674794]
[76]
Bhogal, S.; Mukherjee, D.; Banerjee, S.; Tan, W.; Paul, T.K. Current trends and future perspectives in the treatment of pulmonary arterial hypertension. Curr. Probl. Cardiol., 2018, 43(5), 191-216.
[http://dx.doi.org/10.1016/j.cpcardiol.2017.10.002] [PMID: 29174585]
[77]
Oliveira, A.C.; Richards, E.M.; Raizada, M.K. Pulmonary hypertension: Pathophysiology beyond the lung. Pharmacol. Res., 2020, 151, 104518.
[http://dx.doi.org/10.1016/j.phrs.2019.104518] [PMID: 31730803]
[78]
Condon, D.F.; Nickel, N.P.; Anderson, R.; Mirza, S.; de Jesus Perez, V.A. The 6th World Symposium on Pulmonary Hypertension: what’s old is new. F1000 Res., 2019, 8
[79]
Maeder, M.T.; Weber, L.; Buser, M.; Gerhard, M.; Haager, P.K.; Maisano, F.; Rickli, H. Pulmonary hypertension in aortic and mitral valve disease. Front. Cardiovasc. Med., 2018, 5, 40.
[http://dx.doi.org/10.3389/fcvm.2018.00040] [PMID: 29876357]
[80]
Zhang, M.; Wu, Y.; Wang, M.; Wang, Y.; Tausif, R.; Yang, Y. Genistein rescues hypoxia-induced pulmonary arterial hypertension through estrogen receptor and β-adrenoceptor signaling. J. Nutr. Biochem., 2018, 58, 110-118.
[http://dx.doi.org/10.1016/j.jnutbio.2018.04.016] [PMID: 29886191]
[81]
Matori, H.; Umar, S.; Nadadur, R.D.; Sharma, S.; Partow-Navid, R.; Afkhami, M.; Amjedi, M.; Eghbali, M. Genistein, a soy phytoestrogen, reverses severe pulmonary hypertension and prevents right heart failure in rats. Hypertension, 2012, 60(2), 425-430.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.112.191445] [PMID: 22753213]
[82]
Zheng, Z.; Yu, S.; Zhang, W.; Peng, Y.; Pu, M.; Kang, T.; Zeng, J.; Yu, Y.; Li, G. Genistein attenuates monocrotaline-induced pulmonary arterial hypertension in rats by activating PI3K/Akt/eNOS signaling. Histol. Histopathol., 2017, 32(1), 35-41.
[PMID: 27087006]
[83]
Suzuki, Y.J.; Ibrahim, Y.F.; Rybka, V.; Bowens, J.R.; Falade, A.S.; Shults, N.V. Strategies to treat pulmonary hypertension using programmed cell death-inducing anti-cancer drugs without damaging the heart. In: Sakuma, K.; Ed. Muscle Cell and Tissue-Novel Molecular Targets and Current Advances, IntechOpen: London, UK, 2020.

Rights & Permissions Print Cite
Article Metrics
47
3
© 2024 Bentham Science Publishers | Privacy Policy