Subscribe to RSS
DOI: 10.1055/s-0034-1396310
Managing Hypertension by Polyphenols
Publication History
received 29 July 2014
revised 15 January 2015
accepted 15 January 2015
Publication Date:
25 February 2015 (online)
![](https://www.thieme-connect.de/media/plantamedica/201508/lookinside/thumbnails/10-1055-s-0034-1396310_pmy0869-1.jpg)
Abstract
Some polyphenols, obtained from plants of broad use, induce a favorable endothelial response in hypertension and beneficial effects in the management of other metabolic cardiovascular risks. Previous studies in our laboratories using the calyces of Hibiscus sabdariffa as a source of polyphenols show that significant effects on hypertension are noticeable in humans only when provided in high amounts. Available data are suggestive in animal models and ex vivo experiments, but data in humans are difficult to acquire. Additionally, and despite the low bioavailability of polyphenols, intervention studies provide evidence for the protective effects of secondary plant metabolites. Assumptions on public health benefits are limited by the lack of scientific knowledge, robust data derived from large randomized clinical trials, and an accurate assessment of the bioactive components provided by common foodstuff. Because it is likely that clinical effects are the result of multiple interactions among different polyphenols rather than the isolated action of unique compounds, to provide polyphenol-rich botanical extracts as dietary supplements is a suggestive option. Unfortunately, the lack of patent perspectives for the pharmaceutical industries and the high cost of production and release for alimentary industries will hamper the performance of the necessary clinical trials. Here we briefly discuss whether and how such limitations may complicate the extensive use of plant-derived products in the management of hypertension and which steps are the necessary to deal with the predictable complexity in a possible clinical practice.
Key words
Hibiscus sabdariffa - Malvaceae - botanical extracts - cardiovascular risk - hypertension - oxidation - metabolism - polyphenols-
References
- 1 James PA, Oparil S, Carter BL, Cushman WC, Dennison-Himmelfarb C, Handler J, Lackland DT, LeFevre ML, MacKenzie TD, Ogedegbe O, Smith jr. SC, Svetkey LP, Taler SJ, Townsend RR, Wright jr. JT, Narva AS, Ortiz E. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA 2014; 311: 507-520
- 2 Rodriguez CJ, Swett K, Agarwal SK, Folsom AR, Fox ER, Loehr LR, Ni H, Rosamond WD, Chang PP. Systolic blood pressure levels among adults with hypertension and incident cardiovascular events: the atherosclerosis risk in communities study. JAMA Intern Med 2014; 174: 1252-1261
- 3 Ferré N, Feliu A, García-Heredia A, Marsillach J, París N, Zaragoza-Jordana M, Mackness B, Mackness M, Escribano J, Closa-Monasterolo R, Joven J, Camps J. Impaired paraoxonase-1 status in obese children. Relationships with insulin resistance and metabolic syndrome. Clin Biochem 2013; 46: 1830-1836
- 4 Calhoun DA, Jones D, Textor S, Goff DC, Murphy TP, Toto RD, White A, Cushman WC, White W, Sica D, Ferdinand K, Giles TD, Falkner B, Carey RM. Resistant hypertension: diagnosis, evaluation, and treatment. A scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research. Hypertension 2008; 51: 1403-1419
- 5 Black HR, Elliott WJ, Neaton JD, Grandits G, Grambsch P, Grimm jr. RH, Hansson L, Lacouciere Y, Muller J, Sleight P, Weber MA, White WB, Williams G, Wittes J, Zanchetti A, Fakouhi TD, Anders RJ. Baseline characteristics and early blood pressure control in the CONVINCE trial. Hypertension 2001; 37: 12-18
- 6 Burt VL, Cutler JA, Higgins M, Horan MJ, Labarthe D, Whelton P, Brown C, Roccella EJ. Trends in the prevalence, awareness, treatment, and control of hypertension in the adult US population. Data from the health examination surveys, 1960–1991. Hypertension 1995; 26: 60-69
- 7 Phillips LS, Branch WT, Cook CB, Doyle JP, El-Kebbi IM, Gallina DL, Miller CD, Ziemer DC, Barnes CS. Clinical inertia. Ann Intern Med 2001; 135: 825-834
- 8 Iʼve heard the hibiscus tea is helpful for high blood pressure. Is that true?. Mayo Clin Health Lett 2014; 32: 8
- 9 Joven J, March I, Espinel E, Fernández-Arroyo S, Rodríguez-Gallego E, Aragonès G, Beltrán-Debón R, Alonso-Villaverde C, Rios L, Martin-Paredero V, Menendez JA, Micol V, Segura-Carretero A, Camps J. Hibiscus sabdariffa extract lowers blood pressure and improves endothelial function. Mol Nutr Food Res 2014; 58: 1374-1378
- 10 Ali BH, Al Wabel N, Blunden G. Phytochemical, pharmacological, and toxicological aspects of Hibiscus sabdariffa L.: a review. Phytother Res 2005; 19: 369-375
- 11 Tseng TH, Kao ES, Chu CY, Chou FP, Lin Wu HW, Wang CJ. Protective effects of dried flower extracts of Hibiscus sabdariffa L. against oxidative stress in rat primary hepatocytes. Food Chem Toxicol 1997; 35: 1159-1164
- 12 Aguwa CN, Ndu OO, Nwanma CC, Udeogaranya PO, Akwara NO. Verification of the folkloric diuretic claim of Hibiscus sabdariffa L. petal extract. Nigerian J Pharm Res 2004; 3: 1-8
- 13 Alarcon-Aguilar FJ, Zamilpa A, Perez-Garcia MD, Almanza-Perez JC, Romero-Nuñez E, Campos-Sepulveda EA, Vazquez-Carrillo LI, Roman-Ramos R. Effect of Hibiscus sabdariffa on obesity in MSG mice. J Ethnopharmacol 2007; 114: 66-71
- 14 Cáceres A, Girón LM, Martínez AM. Diuretic activity of plants used for the treatment of urinary ailments in Guatemala. J Ethnopharmacol 1987; 19: 233-245
- 15 Onyenekwe PC, Ajani EO, Ameh DA, Gamaniel KS. Antihypertensive effect of roselle (Hibiscus sabdariffa) calyx infusion in spontaneously hypertensive rats and a comparison of its toxicity with that in Wistar rats. Cell Biochem Funct 1999; 17: 199-206
- 16 Ribeiro Rde A, de Barros F, de Melo MM, Muniz C, Chieia S, Wanderley M das G, Gomes C, Trolin G. Acute diuretic effects in conscious rats produced by some medicinal plants used in the state of São Paulo, Brasil. J Ethnopharmacol 1988; 24: 19-29
- 17 Herrera-Arellano A, Miranda-Sánchez J, Avila-Castro P, Herrera-Alvarez S, Jiménez-Ferrer JE, Zamilpa A, Román-Ramos R, Ponce-Monter H, Tortoriello J. Clinical effects produced by a standardized herbal medicinal product of Hibiscus sabdariffa on patients with hypertension. A randomized, double-blind, lisinopril-controlled clinical trial. Planta Med 2007; 73: 6-12
- 18 Kirdpon S, Nakorn SN, Kirdpon W. Changes in urinary chemical composition in healthy volunteers after consuming roselle (Hibiscus sabdariffa Linn.) juice. J Med Assoc Thai 1994; 77: 314-321
- 19 Prasongwatana V, Woottisin S, Sriboonlue P, Kukongviriyapan V. Uricosuric effect of Roselle (Hibiscus sabdariffa) in normal and renal-stone former subjects. J Ethnopharmacol 2008; 117: 491-495
- 20 Wahabi HA, Alansary LA, Al-Sabban AH, Glasziuo P. The effectiveness of Hibiscus sabdariffa in the treatment of hypertension: a systematic review. Phytomedicine 2010; 17: 83-86
- 21 Ngamjarus C, Pattanittum P, Somboonporn C. Roselle for hypertension in adults. Cochrane Database Syst Rev 2010; CD007894
- 22 Mancia G, Omboni S, Parati G, Ravogli A, Villani A, Zanchetti A. Lack of placebo effect on ambulatory blood pressure. Am J Hypertens 1995; 8: 311-315
- 23 Nissen N, Manderson L. Researching alternative and complementary therapies: mapping the field. Med Anthropol 2013; 32: 1-7
- 24 Fønnebø V, Grimsgaard S, Walach H, Ritenbaugh C, Norheim AJ, MacPherson H, Lewith G, Launsø L, Koithan M, Falkenberg T, Boon H, Aickin M. Researching complementary and alternative treatments–the gatekeepers are not at home. BMC Med Res Methodol 2007; 7: 7
- 25 Hopkins AL, Lamm MG, Funk JL, Ritenbaugh C. Hibiscus sabdariffa L. in the treatment of hypertension and hyperlipidemia: a comprehensive review of animal and human studies. Fitoterapia 2013; 85: 84-94
- 26 Mohagheghi A, Maghsoud S, Khashayar P, Ghazi-Khansari M. The effect of Hibiscus sabdariffa on lipid profile, creatinine, and serum electrolytes: a randomized clinical trial. ISRN Gastroenterol 2011; 2011: 976019 DOI: 10.5402/2011/976019.
- 27 McKay DL, Chen CYO, Saltzman E, Blumberg JB. Hibiscus sabdariffa L. tea (tisane) lowers blood pressure in prehypertensive and mildly hypertensive adults. J Nutr 2010; 140: 298-303
- 28 Gurrola-Diaz CM, Garcia-Lopez PM, Sanchez-Enriquez S, Troyo-Sanroman R, Andrade-Gonzalez I, Gomez-Leyva JF. Effects of Hibiscus sabdariffa extract powder and preventive treatment (diet) on the lipid profiles of patients with metabolic syndrome (MeSy). Phytomedicine 2010; 17: 500-505
- 29 Ali BH, Wabel NA, Blunden G. Phytochemical, pharmacological and toxicological aspects of Hibiscus sabdariffa L.: a review. Phytother Res 2005; 19: 369-375
- 30 Haji Faraji M, Haji Tarkhani AH. The effect of sour tea (Hibiscus sabdariffa) on essential hypertension. J Ethnopharmacol 1999; 65: 231-236
- 31 Mozaffari-Khosravi H, Jalali-Khanabadi BA, Afkhami-Ardekani M, Fatehi F, Noori-Shadkam M. The effects of sour tea (Hibiscus sabdariffa) on hypertension in patients with type II diabetes. J Hum Hypertens 2009; 23: 48-54
- 32 Holmes JS, Shevrin M, Goldman B, Share D. Translating research into practice: are physicians following evidence-based guidelines in the treatment of hypertension?. Med Care Res Rev 2004; 61: 453-473
- 33 Cranney M, Warren E, Walley T. Hypertension in the elderly: attitudes of British patients and general practitioners. J Hum Hypertens 1998; 12: 539-545
- 34 Sever P, Beevers G, Bulpitt CJ. Management guidelines in essential hypertension: report of the second working party of the British Hypertension Society. BMJ 1993; 306: 983-987
- 35 Cranney M, Warren E, Barton W, Gardner K, Walley T. Why do GPs not implement evidence-based guidelines? A descriptive study. Fam Pract 2001; 18: 359-363
- 36 Cheng TO. All teas are not created equal: the Chinese green tea and cardiovascular health. Int J Cardiol 2006; 108: 301-308
- 37 Steen RG, Dager SR. Evaluating the evidence for evidence-based medicine: are randomized clinical trials less flawed than other forms of peer-reviewed medical research?. FASEB J 2013; 27: 3430-3436
- 38 Taubert D, Roesen R, Schömig E. Effect of cocoa and tea intake on blood pressure: a meta-analysis. Arch Intern Med 2007; 167: 626-634
- 39 Ras RT, Zock PL, Draijer R. Tea consumption enhances endothelial-dependent vasodilation; a meta-analysis. PLoS One 2011; 6: e16974
- 40 Onakpoya I, Spencer E, Heneghan C, Thompson M. The effect of green tea on blood pressure and lipid profile: a systematic review and meta-analysis of randomized clinical trials. Nutr Metab Cardiovasc Dis 2014; 24: 823-836
- 41 Ried K, Sullivan TR, Fakler P, Frank OR, Stocks NP. Effect of cocoa on blood pressure. Cochrane Database Syst Rev 2012; (8) CD008893
- 42 European Food Safety Authority (EFSA) Panel on Dietetic Products, Nutrition and Allergies. Scientific opinion on the substantiation of a health claim related to cocoa flavanols and maintenance of normal endothelium-dependent vasodilation pursuant to Article 13(5) of Regulation (EC) No. 1924/20061. EFSA J 2012; 10: 2809
- 43 Cádiz-Gurrea ML, Lozano-Sanchez J, Contreras-Gámez M, Legeai-Mallet L, Fernández-Arroyo S, Segura-Carretero A. Isolation, comprehensive characterization and antioxidant activities of Theobroma cacao extract. J Funct Foods 2014; 10: 485-498
- 44 Gu Y, Lambert JD. Modulation of metabolic syndrome-related inflammation by cocoa. Mol Nutr Food Res 2013; 57: 948-961
- 45 Kim J, Kim J, Shim J, Lee CY, Lee KW, Lee HJ. Cocoa phytochemicals: recent advances in molecular mechanisms on health. Crit Rev Food Sci Nutr 2014; 54: 1458-1472
- 46 Fernández-Arroyo S, Herranz-López M, Beltrán-Debón R, Borrás-Linares I, Barrajón-Catalán E, Joven J, Fernández-Gutiérrez A, Segura-Carretero A, Micol V. Bioavailability study of a polyphenol-enriched extract from Hibiscus sabdariffa in rats and associated antioxidant status. Mol Nutr Food Res 2012; 56: 1590-1595
- 47 Joven J, Espinel E, Rull A, Aragonès G, Rodríguez-Gallego E, Camps J, Micol V, Herranz-López M, Menéndez JA, Borrás I, Segura-Carretero A, Alonso-Villaverde C, Beltrán-Debón R. Plant-derived polyphenols regulate expression of miRNA paralogs miR-103/107 and miR-122 and prevent diet-induced fatty liver disease in hyperlipidemic mice. Biochim Biophys Acta 2012; 1820: 894-899
- 48 Herranz-López M, Fernández-Arroyo S, Pérez-Sanchez A, Barrajón-Catalán E, Beltrán-Debón R, Menéndez JA, Alonso-Villaverde C, Segura-Carretero A, Joven J, Micol V. Synergism of plant-derived polyphenols in adipogenesis: perspectives and implications. Phytomedicine 2012; 19: 253-261
- 49 Beltrán-Debón R, Alonso-Villaverde C, Aragonès G, Rodríguez-Medina I, Rull A, Micol V, Segura-Carretero A, Fernández-Gutiérrez A, Camps J, Joven J. The aqueous extract of Hibiscus sabdariffa calices modulates the production of monocyte chemoattractant protein-1 in humans. Phytomedicine 2010; 17: 186-191
- 50 Rodríguez-Medina IC, Beltrán-Debón R, Molina VM, Alonso-Villaverde C, Joven J, Menéndez JA, Segura-Carretero A, Fernández-Gutiérrez A. Direct characterization of aqueous extract of Hibiscus sabdariffa using HPLC with diode array detection coupled to ESI and ion trap MS. J Sep Sci 2009; 32: 3441-3448
- 51 Segura-Carretero A, Puertas-Mejía MA, Cortacero-Ramírez S, Beltrán R, Alonso-Villaverde C, Joven J, Dinelli G, Fernández-Gutiérrez A. Selective extraction, separation, and identification of anthocyanins from Hibiscus sabdariffa L. using solid phase extraction-capillary electrophoresis-mass spectrometry (time-of-flight/ion trap). Electrophoresis 2008; 29: 2852-2861
- 52 Masana L, Camprubi M, Sarda P, Sola R, Joven J, Turner PR. The Mediterranean-type diet: is there a need for further modification?. Am J Clin Nutr 1991; 53: 886-889
- 53 Rull A, Geeraert B, Aragonès G, Beltrán-Debón R, Rodríguez-Gallego E, García-Heredia A, Pedro-Botet J, Joven J, Holvoet P, Camps J. Rosiglitazone and fenofibrate exacerbate liver steatosis in a mouse model of obesity and hyperlipidemia. A transcriptomic and metabolomic study. J Proteome Res 2014; 13: 1731-1743
- 54 Ji HF, Li XJ, Zhang HY. Natural products and drug discovery. Can thousands of years of ancient medical knowledge lead us to new and powerful drug combinations in the fight against cancer and dementia?. EMBO Rep 2009; 10: 194-200
- 55 Nijveldt RJ, van Nood E, van Hoorn DEC, Boelens PG, van Norren K, van Leeuwen PAM. Flavonoids: a review of probable mechanisms of action and potential applications. Am J Clin Nutr 2001; 74: 418-425
- 56 Jiménez-Ferrer E, Alarcón-Alonso J, Aguilar-Rojas A, Zamilpa A, Jiménez-Ferrer I C, Tortoriello J, Herrera-Ruiz M. Diuretic effect of compounds from Hibiscus sabdariffa by modulation of the aldosterone activity. Planta Med 2012; 78: 1893-1898
- 57 Ames BN, Shigenaga MK, Hagen TM. Oxidants, antioxidants, and the degenerative diseases of aging. Proc Natl Acad Sci U S A 1993; 90: 7915-7922
- 58 Camps J, Rodríguez-Gallego E, García-Heredia A, Triguero I, Riera-Borrull M, Hernández-Aguilera A, Luciano-Mateo F, Fernández-Arroyo S, Joven J. Paraoxonases and chemokine (C-C motif) ligand-2 in noncommunicable diseases. Adv Clin Chem 2014; 63: 247-308
- 59 Rull A, Camps J, Alonso-Villaverde C, Joven J. Insulin resistance, inflammation, and obesity: role of monocyte chemoattractant protein-1 (or CCL2) in the regulation of metabolism. Mediators Inflamm 2010; 2010: 326580
- 60 Hollman PC, Cassidy A, Comte B, Heinonen M, Richelle M, Richling E, Serafini M, Scalbert A, Sies H, Vidry S. The biological relevance of direct antioxidant effects of polyphenols for cardiovascular health in humans is not established. J Nutr 2011; 141: 989S-1009S
- 61 Qian G, Xue K, Tang L, Wang F, Song X, Chyu MC, Pence BC, Shen CL, Wang JS. Mitigation of oxidative damage by green tea polyphenols and Tai Chi exercise in postmenopausal women with osteopenia. PLoS One 2012; 7: e48090
- 62 Joven J, Micol V, Segura-Carretero A, Alonso-Villaverde C, Menéndez JA. Polyphenols and the modulation of gene expression pathways: can we eat our way out of the danger of chronic disease?. Crit Rev Food Sci Nutr 2014; 54: 985-1001
- 63 Rull A, Rodríguez F, Aragonès G, Marsillach J, Beltrán R, Alonso-Villaverde C, Camps J, Joven J. Hepatic monocyte chemoattractant protein-1 is upregulated by dietary cholesterol and contributes to liver steatosis. Cytokine 2009; 48: 273-279
- 64 Tous M, Ferré N, Rull A, Marsillach J, Coll B, Alonso-Villaverde C, Camps J, Joven J. Dietary cholesterol and differential monocyte chemoattractant protein-1 gene expression in aorta and liver of apo E-deficient mice. Biochem Biophys Res Commun 2006; 340: 1078-1084
- 65 Marsillach J, Camps J, Ferré N, Beltran R, Rull A, Mackness B, Mackness M, Joven J. Paraoxonase-1 is related to inflammation, fibrosis and PPAR delta in experimental liver disease. BMC Gastroenterol 2009; 9: 3
- 66 Duluc L, Jacques C, Soleti R, Iacobazzi F, Simard G, Andriantsitohaina R. Modulation of mitochondrial capacity and angiogenesis by red wine polyphenols via estrogen receptor, NADPH oxidase and nitric oxide synthase pathways. Int J Biochem Cell Biol 2013; 45: 783-791
- 67 Ojeda D, Jiménez-Ferrer E, Zamilpa A, Herrera-Arellano A, Tortoriello J, Alvarez L. Inhibition of angiotensin converting enzyme (ACE) activity by the anthocyanins delphinidin- and cyanidin-3-O-sambubiosides from Hibiscus sabdariffa . J Ethnopharmacol 2010; 127: 7-10
- 68 Kalupahana NS, Moustaid-Moussa N. The renin-angiotensin system: a link between obesity, inflammation and insulin resistance. Obes Rev 2012; 13: 136-149
- 69 Vaidya A, Williams JS. The relationship between vitamin D and the renin-angiotensin system in the pathophysiology of hypertension, kidney disease, and diabetes. Metabolism 2012; 61: 450-458
- 70 Hu FB. Plant-based foods and prevention of cardiovascular disease: an overview. Am J Clin Nutr 2003; 78 (Suppl. 03) S544-S551
- 71 Manach C, Hubert J, Llorach R, Scalbert A. The complex links between dietary phytochemicals and human health deciphered by metabolomics. Mol Nutr Food Res 2009; 53: 1303-1315
- 72 Gottlieb A, Altman RB. Integrating systems biology sources illuminates drug action. Clin Pharmacol Ther 2014; 95: 663-669
- 73 Joven J, Rull A, Rodriguez-Gallego E, Camps J, Riera-Borrull M, Hernández-Aguilera A, Martin-Paredero V, Segura-Carretero A, Micol V, Alonso-Villaverde C, Menéndez JA. Multifunctional targets of dietary polyphenols in disease: a case for the chemokine network and energy metabolism. Food Chem Toxicol 2013; 51: 267-279