Therapeutic potential of Hibiscus sabdariffa: A review of the scientific evidence;Potencial terapéutico del Hibiscus sabdariffa: Una revisión de las evidencias científicas

Endocrinologia y Nutricion

Volumn 61, Issue 5, 2014, Pages 274-295

  Guardiola, Soledad ^a   Mach, Núria ^a,b  

^a UNIVERSITAT OBERTA DE CATALUNYA   (Spain)

^b Institut National de la Recherche Agronomique   (France)

Author keywords

Atherosclerosis; Hibiscus sabdariffa; Hypertension; Lipid profile; Oxidative stress; Polyphenols

Indexed keywords

ANTHOCYANIN; HIBISCUS SABDARIFFA EXTRACT; MICRORNA; PHENOL DERIVATIVE; POLYPHENOL; PLANT EXTRACT;

ADIPOGENESIS; ATHEROSCLEROSIS; BLOOD PRESSURE; CELL CULTURE; CLINICAL RESEARCH; GENE EXPRESSION; HIBISCUS SABDARIFFA; HYPERTENSION; NONHUMAN; OXIDATION; OXIDATIVE STRESS; SHORT SURVEY; THERAPY EFFECT; ANIMAL; DRUG EFFECTS; HIBISCUS; HUMAN; LIPID METABOLISM; PHYTOTHERAPY;

ANIMALS; ATHEROSCLEROSIS; HIBISCUS; HUMANS; HYPERTENSION; LIPID METABOLISM; OXIDATIVE STRESS; PHYTOTHERAPY; PLANT EXTRACTS;

EID: 84899656138     PISSN: 15750922     EISSN: 15792021     Source Type: Journal    
DOI: 10.1016/j.endonu.2013.10.012     Document Type: Short Survey

References (105)

1. Elejalde Guerra J.I. Oxidative stress, diseases and antioxidant treatment. An Med Interna 2001, 18:326-335.
2. Céspedes T., Sánchez D. Algunos aspectos sobre el estrés oxidativo, el estado antioxidante y la terapia de suplementación. Rev Cub Cardiol 2000, 14:55-60.
3. Droge W. Free radicals in the physiological control of cell function. Physiol Rev 2002, 82:47-95.
4. Lobo V., Patil A., Phatak A., Chandra N. Free radicals, antioxidants and functional foods: Impact on human health. Pharmacogn Rev 2010, 4:118-126.
5. Wille E., Scholze J., Alegria E., Ferri C., Langham S., Stevens W., et al. Modelling the costs of care of hypertension in patients with metabolic syndrome and its consequences, in Germany, Spain and Italy. Eur J Health Econ 2011, 12:205-218.
6. Barrios V., Escobar C., Echarri R. What has been done? What to do for better results of hypertension in Spain?. Med Clin (Barc) 2010, 135:40-41.
7. Banegas J., Villar F., Graciani A., Rodríguez-Artalejo F. Epidemiología de las enfermedades cardiovasculares en España. Rev Esp Cardiol 2006, 6:3-12.
8. Janosi A. Epidemiology and prevention of cardiovascular diseases. Orv Hetil 2005, 146:683-688.
9. Jorgensen T., Willaing I., Thomsen T.F. Cardiovascular diseases. From epidemiology to prevention. Ugeskr Laeger 2005, 167:1170-1173.
10. Guilbert J.J. The world health report 2002-reducing risks, promoting healthy life. Educ Health (Abingdon) 2003, 16:230.
11. Brundtland G.H. From the World Health Organization. Reducing risks to health, promoting healthy life. JAMA 2002, 288:1974.
12. Pérez I., Villar I., Mata L., Pérez F., Maiquez A., Casasnovas J.A., et al. Control de la colesterolemia en España, 2000. Un instrumento para la prevención cardiovascular. Rev Esp Cardiol 2000, 53:815-837.
13. Touyz R.M. Reactive oxygen species in vascular biology: Role in arterial hypertension. Expert Rev Cardiovasc Ther 2003, 1:91-106.
14. Saez G.T., Tormos C., Giner V., Chaves J., Lozado J., Iradi A., et al. Factors related to the impact of antihypertensive treatment in antioxidant activities and oxidative stress by-products in human hypertension. Am J Hypertens 2004, 17:809-816.
15. Paravicini T.M., Touyz R.M. NADPH oxidases, reactive oxygen species, and hypertension clinical implications and therapeutic possibilities. Diabetes Care 2008, 31:S170-S180.
16. Rodriguez-Iturbe B., Zhan C.D., Quiroz Y., Sindhu R.K., Vaziri N.D. Antioxidant-rich diet relieves hypertension and reduces renal immune infiltration in spontaneously hypertensive rats. Hypertension 2003, 41:341-346.
17. Pham-Huy L.A., He H., Pham-Huy C. Free radicals, antioxidants in disease and health. Int J Biomed Sci 2008, 4:89-96.
18. Ward N.C., Hodgson J.M., Puddey I.B., Mori T.A., Beilin L.J., Croft K.D. Oxidative stress in human hypertension: Association with antihypertensive treatment, gender, nutrition, and lifestyle. Free Radic Biol Med 2004, 36:226-232.
19. Zicha J., Kunes J., Devynck M.A. Abnormalities of membrane function and lipid metabolism in hypertension -A review. Am J Hyperten 1999, 12:315-331.
20. Gonzalez V.L.M., de Artinano M.A.A. Abnormalities in calcium metabolism in arterial hypertension. Med Clin 1998, 111:701-709.
21. Maqueda I.G., Rabadan I.R., Romero E.A., Bouza J.P., Lama I.G. Hypertension and carbohydrate metabolism abnormalities. Rev Esp Cardiol 1998, 51:3-14.
22. Sowers J.R., Lester M. Hypertension, hormones, and aging. J Laboratory Clin Med 2000, 135:379-386.
23. Williams S.M. Endophenotypes, heritability, and underlying complexity in hypertension. Am J Hypertens 2010, 23:819.
24. Johansen C.T., Wang J., Lanktree M.B., Cao H., McIntyre A.D., Ban M.R., et al. Excess of rare variants in genes identified by genome-wide association study of hypertriglyceridemia. Nat Genet 2010, 42:684-687.
25. Silverstein R.L. Type 2 scavenger receptor CD36 in platelet activation: The role of hyperlipemia and oxidative stress. Clin Lipidol 2009, 4:767.
26. Pajukanta P., Lilja H.E., Sinsheimer J.S., Cantor R.M., Lusis A.J., Gentile M., et al. Familial combined hyperlipidemia is associated with upstream transcription factor 1 (USF1). Nature Gent 2004, 36:371-376.
27. Plaisier C.L., Horvath S., Huertas-Vazquez A., Cruz-Bautista I., Herrera M.F., Tusie-Luna T., et al. A systems genetics approach implicates USF1, FADS3, and other causal candidate genes for familial combined hyperlipidemia. PLoS Genet 2009, 5:e1000642.
28. Lahoz C., Mostaza J.M. La aterosclerosis como enfermedad sistémica. Rev Esp Cardiol 2007, 60:184-195.
29. Stocker R., Keaney J.F. Role of oxidative modifications in atherosclerosis. Physiol Rev 2004, 84:1381-1478.
30. Glass C.K., Witztum J.L. Atherosclerosis. The road ahead. Cell 2001, 104:503-516.
31. Llacuna L., Mach N. Role of antioxidants in the prevention of cancer. Rev Esp Nutr Hum Diet 2012, 16:16-24.
32. Clarkson P.M., Thompson H.S. Antioxidants: What role do they play in physical activity and health?. Am J Clin Nutr 2000, 72:637S-646S.
33. Schroeter H., Heiss C., Balzer J., Kleinbongard P., Keen C.L., Hollengerg N.K., et al. (-)-Epicatechin mediates beneficial effects of flavanol-rich cocoa on vascular function in humans. Proc Natl Acad Sci U S A 2006, 103:1024-1029.
34. Perez-Vizcaino F., Duarte J., Jimenez R., Santos-Buelga C., Osuna A. Antihypertensive effects of the flavonoid quercetin. Pharmacol Rep 2009, 61:67-75.
35. Bravo L. Polyphenols: Chemistry, dietary sources, metabolism, and nutritional significance. Nutr Rev 1998, 56:317-333.
36. Williamson G., Manach C. Bioavailability and bioefficacy of polyphenols in humans. II. Review of 93 intervention studies. Am J Clin Nutr 2005, 81:243S-255S.
37. Barbosa K.B.F., Brassan J., Zulet Ma Martínez J.A. Influencia de la dieta sobre marcadores plasmáticos de estrés oxidativo en humanos. Anal Sist Sanitario Nav 2008, 32:259-280.
38. Landete J.M. Updated knowledge about polyphenols: Functions, bioavailability, metabolism, and health. Crit Rev Food Sci Nutr 2012, 52:936-948.
39. Manach C., Scalbert A., Morand C., Remesy C., Jimenez L. Polyphenols: Food sources and bioavailability. Am J Clin Nutr 2004, 79:727-747.
40. Scalbert A., Williamson G. Dietary intake and bioavailability of polyphenols. J Nutr 2000, 130:2073S-2085S.
41. Scheepens A., Tan K., Paxton J.W. Improving the oral bioavailability of beneficial polyphenols through designed synergies. Genes Nutr 2010, 5:75-87.
42. Scholz S., Williamson G. Interactions affecting the bioavailability of dietary polyphenols in vivo. Int J Vitam Nutr Res 2007, 77:224-235.
43. Quinones M., Miguel M., Aleixandre A. The polyphenols, naturally occurring compounds with beneficial effects on cardiovascular disease. Nutr Hosp 2012, 27:76-89.
44. Pal S., Ho N., Santos C., Dubois P., Mamo J., Croft K., et al. Red wine polyphenolics increase LDL receptor expression and activity and suppress the secretion of ApoB100 from human HepG2 cells. J Nutr 2003, 133:700-706.
45. Zern T.L., Wood R.J., Greene C., West K.L., Liu Y., Aggarwal D., et al. Grape polyphenols exert a cardioprotective effect in pre- and postmenopausal women by lowering plasma lipids and reducing oxidative stress. J Nutr 2005, 135:1911-1917.
46. Actis-Goretta L., Ottaviani J.I., Fraga C.G. Inhibition of angiotensin converting enzyme activity by flavanol-rich foods. J Agric Food Chem 2006, 54:229-234.
47. Rice-Evans C.A., Miller N.J. Antioxidant activities of flavonoids as bioactive components of food. Biochem Soc Trans 1996, 24:790-795.
48. Castaner O., Covas M.I., Khymenets O., Nyyssonen K., Konstantinidou V., Zunft H.F., et al. Protection of LDL from oxidation by olive oil polyphenols is associated with a downregulation of CD40-ligand expression and its downstream products in vivo in humans. Am J Clin Nutr 2012, 95:1238-1244.
49. Castaner O., Fito M., Lopez-Sabater M.C., Poulsen H.E., Nyyssönen K., Schröder H., et al. The effect of olive oil polyphenols on antibodies against oxidized LDL. A randomized clinical trial. Clin Nutr 2011, 30:490-493.
50. Yang M.Y., Huang C.N., Chan K.C., Yang Y.S., Peng C.H., Wang C.J. Mulberry leaf polyphenols possess antiatherogenesis effect via inhibiting LDL oxidation and foam cell formation. J Agric Food Chem 2011, 59:1985-1995.
51. Ruiz-Roso B., Quintela J.C., de la Fuente E., Haya J., Pérez-Olleros L. Insoluble carob fiber rich in polyphenols lowers total and LDL cholesterol in hypercholesterolemic sujects. Plant Foods Hum Nutr 2010, 65:50-56.
52. Syam A.F. The role of tea polyphenols in LDL oxidation. Acta Med Indones 2007, 39:65.
53. Wahyudi S., Sargowo D. Green tea polyphenols inhibit oxidized LDL-induced NF-KB activation in human umbilical vein endothelial cells. Acta Med Indones 2007, 39:66-70.
54. Brito P., Almeida L.M., Dinis T.C. The interaction of resveratrol with ferrylmyoglobin and peroxynitrite; protection against LDL oxidation. Free Radic Res 2002, 36:621-631.
55. Vanden Berghe W. Epigenetic impact of dietary polyphenols in cancer chemoprevention: Lifelong remodeling of our epigenomes. Pharmacol Res 2012, 65:565-576.
56. Kato K., Long N.K., Makita H., Toida M., Yamashita T., Hatakeyama D., et al. Effects of green tea polyphenol on methylation status of RECK gene and cancer cell invasion in oral squamous cell carcinoma cells. Br J Cancer 2008, 99:647-654.
57. Fang M.Z., Wang Y., Ai N., Hou Z., Sun Y., Lu H., et al. Tea polyphenol (-)-epigallocatechin-3-gallate inhibits DNA methyltransferase and reactivates methylation-silenced genes in cancer cell lines. Cancer Res 2003, 63:7563-7570.
58. Ruiz P.A., Braune A., Holzlwimmer G., Quintanilla-Fend Haller D. Quercetin inhibits TNF-induced NF-kappaB transcription factor recruitment to proinflammatory gene promoters in murine intestinal epithelial cells. J Nutr 2007, 137:1208-1215.
59. Blade C., Baselga-Escudero L., Salvado M.J., Arola-Arnal A. miRNAs, polyphenols, and chronic disease. Mol Nutr Food Res 2013, 57:58-70.
60. Joven J., Espinel E., Rull A., Aragones G., Rodriguez-Gallego E., Camps J., et al. 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.
61. Crozier A., Jaganath I.B., Clifford M.N. Dietary phenolics: Chemistry, bioavailability and effects on health. Nat Prod Rep 2009, 26:1001-1043.
62. Sayago-Ayerdi S.G., Arranz S., Serrano J., Goni I. Dietary fiber content and associated antioxidant compounds in Roselle flower (Hibiscus sabdariffa L.) beverage. J Agric Food Chem 2007, 55:7886-7890.
63. Peng C.H., Chyau C.C., Chan K.C., Wang C.J., Huang C.N. Hibiscus sabdariffa polyphenolic extract inhibits hyperglycemia, hyperlipidemia, and glycation-oxidative stress while improving insulin resistance. J Agric Food Chem 2011, 59:9901-9909.
64. Gurrola-Diaz C.M., Garcia-Lopez P.M., Sanchez-Enriquez S., Troyo-Sanroman R., Andrade-Gonzalez I., Gomez-Leyva J.F. Effects of Hibiscus sabdariffa extract powder and preventive treatment (diet) on the lipid profiles of patients with metabolic syndrome (MeSy). Phytomed 2010, 17:500-505.
65. McKay D.L., Chen C.Y., Saltzman E., Blumberg J.B. Hibiscus sabdariffa L. tea (tisane) lowers blood pressure in prehypertensive and mildly hypertensive adults. J Nutr 2010, 140:298-303.
66. Herrera-Arellano A., Flores-Romero S., Chavez-Soto M.A., Chavez-Soto M.A., Tortoriello J. Effectiveness and tolerability of a standardized extract from Hibiscus sabdariffa in patients with mild to moderate hypertension: A controlled and randomized clinical trial. Phytomedicine 2004, 11:375-382.
67. Herrera-Arellano A., Miranda-Sanchez J., Avila-Castro P., Herrera-Alvarez S., Jimenez-Ferrer J.E., Zamilpa A., et al. 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.
68. Olatunji L.A., Adebayo J.O., Oguntoye O.B., Olatunde N.O., Olatunji V.A., Soladoye A.O. Effects of aqueous extracts of petals of red and green Hibiscus sabdariffa on plasma lipid and hematological variables in rats. Pharm Biol 2005, 43:471-474.
69. Farombi E.O., Ige O.O. Hypolipidemic and antioxidant effects of ethanolic extract from dried calyx of Hibiscus sabdariffa in alloxan-induced diabetic rats. Fundam Clin Pharmacol 2007, 21:601-609.
70. Odigie I.P., Ettarh R.R., Adigun S.A. Chronic administration of aqueous extract of Hibiscus sabdariffa attenuates hypertension and reverses cardiac hypertrophy in 2K-1 C hypertensive rats. J Ethnopharmacol 2003, 86:181-185.
71. Mohagheghi A., Maghsoud S., Khashayar P., Ghazi-Khansari. The effect of hibiscus sabdariffa on lipid profile, creatinine, and serum electrolytes: a randomized clinical trial. ISRN Gastroenterol 2011, 2011:976019.
72. Mozaffari-Khosravi H., Jalali-Khanabadi B.A., 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.
73. Kuriyan R., Kumar D.R.R.R., Kurpad A.V. An evaluation of the hypolipidemic effect of an extract of Hibiscus Sabdariffa leaves in hyperlipidemic Indians: a double blind, placebo controlled trial. BMC Complement Altern Med 2010, 10:27.
74. Dickel M.L., Rates S.M.K., Ritter M.R. Plants popularly used for loosing weight purposes in Porto Alegre, South Brazil. J Ethnopharmacol 2007, 109:60-71.
75. Hanlidou E., Karousou R., Kleftoyanni V., Kokkini S. The herbal market of Thessaloniki (N Greece) and its relation to the ethnobotanical tradition. J Ethnopharmacol 2004, 91:281-299.
76. AbouZid S.F., Mohamed A.A. Survey on medicinal plants and spices used in Beni-Sueif, Upper Egypt. J Ethnobiol Ethnomed 2011, 2011.
77. Hopkins A.L., Lamm M.G., Funk J.L., 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.
78. Wahabi H.A., Alansary L.A., Al-Sabban A.H., Glasziuo P. The effectiveness of Hibiscus sabdariffa in the treatment of hypertension: A systematic review. Phytomedicine 2010, 17:83-86.
79. Chen C.C., Hsu J.D., Wang S.F., Chiang H.C., Yang M.Y., Kao E.S., et al. Hibiscus sabdariffa extract inhibits the development of atherosclerosis in cholesterol-fed rabbits. J Agric Food Chem 2003, 51:5472-5477.
80. Ali B.H., Al Wabel N., Blunden G. Phytochemical, pharmacological and toxicological aspects of Hibiscus sabdariffa L.: A review. Phytother Res 2005, 19:369-375.
81. Christian K.R., Jackson J.C. Changes in total phenolic and monomeric anthocyanin composition and antioxidant activity of three varieties of sorrel (Hibiscus sabdariffa) during maturity. J Food Compos Anal 2009, 22:663-667.
82. Ochani P.C., D'Mello P. Antioxidant and antihyperlipidemic activity of Hibiscus sabdariffa Linn. leaves and calyces extracts in rats. Ind J Experim Biol 2009, 47:276-282.
83. Tseng T.H., Kao E.S., Chu C.Y., Chou F.P., Lin W., Wang C.J. Protective effects of dried flower extracts of Hibiscus sabdariffa L. against oxidative stress in rat primary hepatocytes. Food Chem Toxicol 1997, 35:1159-1164.
84. Tseng T.H., Wang C.J., Kao E.S., Chu H.Y. Hibiscus protocatechuic acid protects against oxidative damage induced by tert-butylhydroperoxide in rat primary hepatocytes. Chem Biol Interact 1996, 101:137-148.
85. Chang Y.C., Huang K.X., Huang A.C., Chu H.Y. Hibiscus anthocyanins-rich extract inhibited LDL oxidation and oxLDL-mediated macrophages apoptosis. Food Chem Toxicol 2006, 44:1015-1023.
86. Kao E.S., Tseng T.H., Lee H.J., Chan K.C., Wang C.J. Anthocyanin extracted from Hibiscus attenuate oxidized LDL-mediated foam cell formation involving regulation of CD36 gene. Chem Biol Interact 2009, 179:212-218.
87. Kim J.K., So H., Youn M.J., Kim H.J., Park C., Kim S.J., et al. Hibiscus sabdariffa L. water extract inhibits the adipocyte differentiation through the PI3-K and MAPK pathway. J Ethnopharmacol 2007, 114:260-267.
88. Tseng T.H., Kao T.W., Chu C.Y., Chou F.P., Lin W.L., Wang C.J. Induction of apoptosis by hibiscus protocatechuic acid in human leukemia cells via reduction of retinoblastoma (RB) phosphorylation and Bcl-2 expression. Biochem Pharmacol 2000, 60:307-315.
89. Ali B.H., Mousa H.M., El-Mougy S. The effect of a water extract and anthocyanins of hibiscus sabdariffa L on paracetamol-induced hepatoxicity in rats. Phytother Res 2003, 17:56-59.
90. Liu L.C., Wang C.J., Lee C.C., Su S.C., Chen H.L., Hsu J.D., et al. Aqueous extract of Hibiscus sabdariffa L. decelerates acetaminophen-induced acute liver damage by reducing cell death and oxidative stress in mouse experimental models. J Sci Food Agric 2010, 90:329-337.
91. Liu C.L., Wang J.M., Chu C.Y., Cheng M.T., Tseng T.H. In vivo protective effect of protocatechuic acid on tert-butyl hydroperoxide-induced rat hepatotoxicity. Food Chem Toxicol 2002, 40:635-641.
92. Lee W.C., Wang C.J., Chen Y.H., Hsu J.D., Cheng S.Y., Chen H.C., et al. Polyphenol extracts from Hibiscus sabdariffa Linnaeus attenuate nephropathy in experimental type 1 diabetes. J Agric Food Chem 2009, 57:2206-2210.
93. Wang S.C., Lee S.F., Wang C.J., Lee C.H., Lee W.C., Lee H.J. Aqueous extract from Hibiscus sabdariffa Linnaeus ameliorate diabetic nephropathy via regulating oxidative status and Akt/Bad/14-3-3γ in an experimental animal model. Evid Based Complement Alternat Med 2011, 2011:938126.
94. Carvajal-Zarrabal O., Waliszewski S.M., Barradas-Dermitz D.M.A., Orta-Flores Z., Hayward-Jones P.M., Nolasco-Hipolito C., et al. The consumption of Hibiscus sabdariffa dried calyx ethanolic extract reduced lipid profile in rats. Plant Food Hum Nutr 2005, 60:153-159.
95. Alarcon-Aguilar F.J., Zamilpa A., Perez-Garcia M.D., Almanza-Perez J.C., Romero-Nunez E., Campos-Sepulveda E.A., et al. Effect of Hibiscus sabdariffa on obesity in MSG mice. J Ethnopharmacol 2007, 114:66-71.
96. Ajiboye T.O., Salawu N.A., Yakubu M.T., Oladiji A.T., Akanji M.A., Okogun J.I. Antioxidant and drug detoxification potentials of Hibiscus sabdariffa anthocyanin extract. Drug Chem Toxicol 2011, 34:109-115.
97. Hirunpanich V., Utaipat A., Morales N.P., Bunyapraphatsara N., Sato H., Herunsale A., et al. Hypocholesterolemic and antioxidant effects of aqueous extracts from the dried calyx of Hibiscus sabdariffa L. in hypercholesterolemic rats. J Ethnopharmacol 2006, 103:252-260.
98. Frank T., Netzel G., Kammerer D.R., Carle R., Kler A., Riesl E., et al. Consumption of Hibiscus sabdariffa L. aqueous extract and its impact on systemic antioxidant potential in healthy subjects. J Sci Food Agric 2012, 92:2207-2218.
99. Tsuda T. Regulation of adipocyte function by anthocyanins; possibility of preventing the metabolic syndrome. J Agric Food Chem 2008, 56:642-646.
100. Ajay M., Chai H.J., Mustafa A.M., Gilani A.H., Mustafa M.R. Mechanisms of the anti-hypertensive effect of Hibiscus sabdariffa L. calyces. J Ethnopharmacol 2007, 109:388-393.
101. Ndu O.O., Nworu C.S., Ehiemere C.O., Ndukwe N.C., Ochiogu I.S. Herb-drug Interaction between the extract of Hibiscus sabdariffa L. and hydrochlorothiazide in experimental animals. J Med Food 2011, 14:640-644.
102. Akindahunsi A.A., Olaleye M.T. Toxicological investigation of aqueous-methanolic extract of the calyces of Hibiscus sabdariffa L. J Ethnopharmacol 2003, 89:161-164.
103. Fakeye T.O., Pal A., Bawankule D.U., Yadav N.P., Khanuja S.P. Toxic effects of oral administration of extracts of dried calyx of Hibiscus sabdariffa Linn. (Malvaceae). Phytother Res 2009, 23:412-416.
104. Fakeye T. Toxicity and immunomodulatory activity of fractions of Hibiscus sabdariffa Linn (family Malvaceae) in animal models. Afr J Tradit Complement Altern Med 2008, 5:394-398.
105. Alarcon-Alonso J, Zamilpa A, Aguilar FA, Herrera-Ruiz M, Tortoriello J, Jimenez-Ferrer E. Pharmacological characterization of the diuretic effect of Hibiscus sabdariffa Linn (Malvaceae) extract. J Ethnopharmacol. 2012;139:751-6.