Crataegus oxyacantha (hawthorn) and Hibiscus sabdariffa (sour tea) have a long history of use in traditional botanical medicine in many parts of the world for their multiple health effects, but especially in relation to cardiovascular disorders. In the last 15–20 years, modern research has expanded and clarified those uses. Hawthorn research has focused on congestive heart failure, and sour tea research has focused on hypertension and dyslipidemia, with several clinical trials emerging in the last 3–4 years. This article highlights key research on these two plants and their uses in congestive heart failure, hypertension, and dyslipidemia in particular.
Cardiovascular disease is the most common cause of office visits, hospitalizations and death in the United States. More than 650,000 people die each year of heart disease.1 Heart disease is the leading cause of death for both men and women. Half of the deaths due to heart disease are in women.1 Coronary heart disease is the most common type of heart disease, causing approximately half a million deaths per year.2 Every year about 785,000 Americans have a first heart attack. Another 470,000 who have already had one or more heart attacks have another attack.3 In 2010, heart disease cost the United States $316.4 billion.3
With this daunting state of our national health, practitioners of all philosophies and training must advance their skills in assessing risk factors, diagnostic work-ups, prevention strategies, and therapeutic interventions. While the list of lifestyle and natural therapies pertinent to cardiovascular issues is long with standouts such as smoking cessation, weight management, stress reduction, Mediterranean diet, fish oils, nicotinic acid, coenzyme Q10, and so many more, 2 botanicals with a rich historical tradition—as well as modern research—are worth a studious look to understand how and when to best use them, as well as their limitations.
Hawthorn (Crataegus species)
Hundreds of crataegus species exist; most are thorny shrubs and small trees whose berries, flowers, and leaves have been used in traditional herbal medicine througout Europe and the United States for generations. Hawthorne is widely used in Europe as a cardiotinic and for congestive heart failure.
The principle active components in hawthorn leaves, berries, and blossoms are flavonoids. One of these flavonoids, proanthocyanidin, has especially important cardiovascular effects.
Research has been conducted on various hawthorn preparations, with the majority using a proprietary preparation from the leaf and flowers (L1 132; WS 1442). Other preparations include leaf and flower combinations with and without the berries, aqueous extracts, methanolic extracts (L1 132; Faros), ethanolic extracts (Esbericard, Crataegutt), dried blossoms, and a flavonoid extract (Crataemon).
The exact mechanisms of action for hawthorn and cardiovascular disease is uncertain, but it is thought that the primary activity is its ability to increase coronary arterial blood flow, perhaps due to dilation of the coronary arteries. The inotropic effects may be due to inhibition of myocardial sodium/potassium ATPase. Hawthorn also appears to slightly increase the strength of the cardiac muscle contractions and decrease blood pressure, resulting in increased exercise tolerance and protection against congestive heart failure. Hawthorn has also been shown to exhibit antioxidant activity in a number of studies, which is likely due to its flavonoid and procyanidin constituents.4,5,6
Numerous randomized, placebo-controlled clinical trials report hawthorn’s ability to improve exercise capacity, alleviate symptoms of cardiac insufficiency, and treat mild to moderate congestive heart failure (CHF), the area of the most research.
The largest, recent, and well-known study, The Survival and Prognosis: Investigation of Crataegus Extract WS 1442 in Congestive Heart Failure (SPICE) trial, was designed to assess the safety of a standardized hawthorn extract, WS 1442, and its effects on morbidity and mortality in patients with New York Heart Association (NYHA) class II and III CHF; hawthorn was used in addition to optimal standard care.7 The randomized, multicenter, double-blind, placebo-controlled study enrolled 2,681 patients and was performed at 156 centers in 13 European countries. Patients with NYHA class II and III CHF and reduced left ventricular function ≤35%) were randomized to either the study medication (450 mg WS 1442 twice daily) or placebo in addition to conventional treatment for 24 months.
WS 1442 had no impact on the primary endpoint (composite endpoint of cardiac mortality, nonfatal myocardial infarction, and hospitalization due to progression of heart failure), with a rate of 27.9% in the treatment group vs 28.9% in the placebo group. In addition, after 24 months there was no difference in the rates of cardiac mortality or sudden cardiac death between the 2 groups. However, in a subgroup analysis of patients with a left ventricular ejection fraction (LVEF) ≥25%, sudden cardiac death was significantly lower in the WS 1442 group. These particular findings highlight the potential anti-arrhythmic and/or anti-ischemic mechanisms of hawthorn extract. Although add-on treatment with WS 1442 did not show a significant difference in cardiac death, non-fatal myocardial infarction, or hospitalization due to significant heart failure, it did reduce sudden cardiac death, which is more prominent in patients with LVEF between 25% and 35% (the upper limit for inclusion in the study). The SPICE trial was more rigorous in its primary endpoints related to heart failure when compared to the other studies below, which looked more at symptoms of dyspnea, fatigue, and cardiac performance. The SPICE trial demonstrates to clinicians that perhaps we cannot reduce the sudden death and myocardial infarctions associated with CHF unless the patient has a less compromised left ventricular function. While its effect on morbidity and mortality is not conclusive, strong evidence suggests symptoms and quality of life related to CHF may be improved with the use of hawthorn extracts.
A meta-analysis of studies using hawthorn for chronic cardiac failure provided evidence of its efficacy in chronic heart failure.8 This systematic review of controlled trials revealed that hawthorn extract was significantly more beneficial than placebo for maximal workload. Symptoms of dyspnea and fatigue also decreased significantly with hawthorn compared with placebo.
In 1996, a systematic review was done of 7 controlled trials that met the NYHA class I or II heart failure criteria.9 These studies demonstrated clinical improvement with hawthorn extract with decreases in symptoms and objective evidence of efficacy most often proven by exercise ergometry.
Additional randomized studies have also been positive. In a 1974 study, 10 mg hawthorn berry and 30 mg hawthorn leaf was added to a nitrate.10 In 25% of the patients with severe coronary sclerosis and congestive heart failure, the combination of drug treatment and hawthorn was superior to drug treatment alone. A 1984 trial using 360–1,600 mg/day of hawthorn extract demonstrated improvement in overall cardiac performance in the treatment group (77%) vs placebo (49%).11 With further analysis, only those patients with NYHA class II CHF showed significant improvement. No improvement was seen with NYHA class III CHF.
Another randomized placebo-controlled multicenter trial involved 143 adults with NYHA class II heart failure.12 Participants were given 30 drops 3 times per day of hawthorn extract tincture of fresh berries or placebo for 8 weeks. After 8 weeks, a significant increase in exercise tolerance and a non-significant improvement in blood pressure and heart rate was seen in the hawthorn group compared with placebo, but no differences were seen in cardiac symptoms. In an uncontrolled trial, 1 tablet of a 450 mg hawthorn extract (WS 1442) was given for 24 weeks to 1,011 patients with NYHA class II CHF.13 Edema of the ankle completely resolved in 83% of patients and nocturia in 50%. The primary measured outcome was a change in exercise tolerance as determined by bicycle exercise testing. Patients assessed their cardiac symptoms at rest and at higher levels of exercise by using a categorical rating scale. Ejection fractions improved, and two-thirds of the patients felt subjectively better after the hawthorn extract.
Direct comparison trials using hawthorn vs conventional medications are limited but one compared hawthorn to captopril in the treatment of CHF.14 One hundred thirty-two patients with NYHA class II CHF received either 900 mg/day in 3 doses or 37.5 mg/day of captopril. Cardiac performance significantly increased, and symptoms decreased in both groups with no statistically significant difference. Another direct comparison study compared a homeopathic preparation of hawthorn vs an ACE inhibitor plus diuretic.15 This non-randomized cohort study included 212 adults with NYHA class II heart failure. After 8 weeks, there was no statically significant difference between the groups in 15 measurable variables, and only a greater reduction in blood pressure in the standard therapy group.
Studies on hypertension are limited. A 2006 study of 79 diabetic hypertensive patients who received 1,200 mg hawthorn vs placebo for 16 weeks found modest reductions in diastolic measures in the active treatment group.16 A significant mean diastolic blood pressure reduction was seen (85.6 mmHg at baseline to 83 mmHg after 16 weeks), and the placebo group was an average of 84.5 mmHg at baseline and 85 mmHg post treatment. There was no group difference in systolic blood pressure reduction from baseline for either hawthorn or placebo. Two randomized, controlled trials found decreases in blood pressure measures. Ninety-two men and women with mild hypertension achieved a significant decrease in both systolic and diastolic blood pressure after 3 months with C. curvisepala.17 The second study showed a significant difference between the 1,200 mg of hawthorne extract and placebo group in diastolic blood pressure over a period of 16 weeks. There were no differences in systolic blood pressure.18
Individuals suffering from angina may also benefit from hawthorn. In one small study, 100 mg 3 times daily of crataegus extract or placebo was given for 4 weeks.19 Angina decreased in 91% of patients in the hawthorn group vs only 37% in the placebo group; 45% of the patients in the hawthorn group completely stopped their nitroglycerine, compared with 25% in the placebo group.
Hawthorn preparations are modestly effective in reducing blood pressure,20 preventing and treating atherosclerosis, lowering cholesterol, and preventing the oxidation of low-density lipoprotein (LDL).21 Hawthorn preparations may improve the blood supply to the heart by dilating the coronary arteries, increase the force of contraction of the heart muscle, and regulate cardiac rhythm.18
Side effects of hawthorn are minimal with doses in the range of 180–900 mg of extracts from leaf with flower, leaf with flower and fruit, and fruit preparations. Some rare adverse effects that have been reported include gastrointestinal disorders, palpitations, headache, and dizziness. Drug interactions with hawthorn are worth paying attention to with some reports that it can potentiate the effects of cardiac glycosides;22 potentiate barbiturate-induced sleeping times;23 and increase the coronary artery-dilating effect induced by theophylline, epinephrine, adenosine, papaverine, and caffeine. 24
Clinical Dosing for Practitioners
It is difficult to translate the various extracts used in all of these studies into commonly available products of tinctures, solid extracts, dried powdered herb capsules, and encapsulated standardized extracts. For CHF, the Natural Standard Herb and Supplement Reference25 offers the following dosing recommendations for 18 years and older:
- Products containing standardized extract WS 1442 (18.5% oligomeric procyanidins): 60 mg tid or 80 mg bid
- Products containing standardized extract LI 132 (2.2% flavonoids): 100 mg tid, 200 mg bid, and up to 300 mg tid
- Dosage range: Recommended doses in the review literature are 160–900 mg hawthorne extract per day in 2 or 3 divided doses (equal to 3.5 to 19.8 mg flavonoids or 30 to 168.8 mg oligomeric procyanidins). Some sources recommend 240–480 mg/day for extracts standardized to 18.75% oligomeric procyanidins.
Sour tea (Hibiscus sabdariffa)
Hibiscus sabdariffa, or sour tea, is a genus of the Malvaceae family. In Iran, it is typically known as sour tea; in English-speaking countries is it called red sorrel. Originally from Angola, it is now cultivated throughout tropical regions, especially from Sudan, Egypt, Thailand, Mexico, and China.
The calyces of H. sabdariffa are prolific in many modern commercial blends of cold and hot drinks due to it’s pleasing taste. Approximately 15–30% of the plant is made up of plant acids, including citric, malic, and tartaric acids, as well as and allo-hydroxycitric acid lactone (ie, hibiscus acid), which is specific to this plant. Other chemical constituents include alkaloids, L-ascorbic acid, anthocyanin, beta carotene, beta sitosterol, citric acid, polysaccharides (arabins and arabinogalactans), quercetin, and gossypetin, as well as small amounts of galactose, arabinose, glucose, xylose, mannose, and rhamnose. Historically, folk medicine has employed H. sabdariffa for the treatment of high blood pressure, liver diseases, and fevers. In large amounts, hibiscus tea acts as a mild laxative. In African folk medicine it has been used for its spasmolytic, antibacterial, cholagogic, diuretic, and anthelmintic properties.
Historically, folk medicine has employed H. sabdariffa for the treatment of high blood pressure, liver diseases, and fevers.
Scientific interest in Hibiscus has grown in the last several years with a small burst of published research studies, especially in the area of dyslipidemia and hypertension. More than 20 years ago, water extracts of hibiscus flowers were reported to have a relaxation effect on the uterus and to lower the blood pressure.26 Studies in both animal27,28,29,30 and human models have demonstrated that extracts and infusions affect atherosclerosis mechanisms, blood sugar, lipids, and blood pressure.31,32
In 2007, a clinical trial showed that Hibiscus reduced cholesterol by 8.3% to 14.4% after just 1 month.33 A total of 42 subjects whose total cholesterol ranged from 175 to 327 mg/dL were randomized to 3 groups for the study, conducted in Taiwan. The 500 mg hibiscus extract in the capsules was obtained by macerating 150 g of hibiscus flowers in 6 L of hot water for 2 hours and then drying and filtering the extract. Group 1 received 1 capsule of extract 3 times daily (1,500 mg/day), group 2 received 2 capsules 3 times daily (3,000 mg/day), and group 3 received 3 capsules 3 times daily (4,500 mg/day).
Overall, subjects in group 2 responded best. Groups 1 and 2, but not group 3, experienced a significant reduction in serum cholesterol levels at week 4, compared with baseline levels. In addition, group 2 experienced a significant reduction in serum cholesterol levels at week 2, compared with baseline levels. At week 2, there was a 42.9% responder rate in groups 1 and 3 and a 64.3% responder rate in group 2. By week 4, group 2 had a cholesterol reduction response in 71.4% of the subjects. In group 1, 50% were responders, and 42.9% subjects in group 3 were responders at week 4. It appeared that 1,000 mg taken 3 times daily was the optimum dose for achieving cholesterol-reduction effects. The responders in group 3, receiving the highest dose (4,500 mg/day), had the smallest response to the hibiscus extract with an average of 8.3% reduction at week 4. Group 1 received a 14.4% reduction at week 4. Although this study is small and of short duration, it showed a clear effect in reducing serum cholesterol.
In a 2009 study, 53 diabetics, mostly women, were given either hibiscus tea from Saudi Arabia or black tea (1 cup bid for 1 month).34 In the group consuming hibiscus tea, mean HDL cholesterol increased significantly (48.2 mg/dL to 56.1 mg/dL) whereas apolipoprotein A1 and lipoprotein (a) were not significant. There was also a significant decrease in the mean of total cholesterol (236.2 mg/dL to 218.6 mg/dL), LDL cholesterol (137.5 mg/dL to 128.5 mg/dL), triglycerides (246.1 mg/dL to 209.2 mg/dL) and Apo-B100 (80 to 77.3) versus baseline values in the hibiscus group. Only HDLc showed a significant change from baseline in the black tea group (46.2 mg/dL to 52.01 mg/dL). This suggests that something as simple as hibiscus tea in a diabetic, may be a welcomed intervention. Achieving a 7.6% decrease in total cholesterol, an 8.0% decrease in LDLc, a 14.9% decrease in triglycerides, a 3.4% decrease in Apo-B100, a 4.2% increase in Apo-A1 and a 16.7% increase in HDLc is no small accomplishment from merely 2 cups of tea per day.
Hibiscus extract was also studied in 222 patients—some with and some without metabolic syndrome (MS).35 A total daily dose of 100 mg H. sabdariffa extract powder (HSEP) was given for 1 month to men and women, 150 without MS and 72 with MS. Participants were randomly assigned to a preventive diet, HSEP treatment or diet combined with HSEP treatment. The MS patients receiving HSEP had significantly reduced glucose, total cholesterol and LDLc and increased HDLc. A triglyceride lowering effect was seen in all groups but was only significant in the control group that was treated with diet. The triglyceride/HDL-c ratio was also significantly reduced with HSEP in the control and MS groups, indicating an improvement in insulin resistance. It has been hypothesized that the anthocyanins regulate adipocyte function, which has important implications for both preventing and treating metabolic syndrome.
A double-blind, placebo-controlled, randomized trial in 69 subjects with elevated LDL and no history of coronary heart disease did not appear to show a blood lipid-lowering effect from hibiscus extract.36 The treatment group received 1,000 mg/day hibiscus extract for 90 days in addition to dietary and physical activity. Body weight, serum LDL, cholesterol and triglyceride levels decreased in both the extract and placebo groups, with no significant differences between the 2. It is likely that the positive effects were due to dietary and exercise activity. One wonders why the results of this study showed no effects while the 3 previous studies described above, showed positive results. One possibility is the doses and product used in all 4 studies were different. One used a tea; another used dried, powdered flowers; another used a standardized extract powder of the sepals of the flowers; and this one used an ethyl alcohol/water extract of the leaves, dried and then powdered. It is reasonable to consider that these different preparations would yield different results. More-consistent product selection and dosages used in larger randomized trials may clarify the best intervention to use.
Hypertension may also improve with the use of hibiscus. The blood pressure lowering effects of sour tea (ST) =Hibiscus sabdariffa was compared with black tea (BT) in type II diabetics with mild high blood pressure.37
Patients were randomly assigned to drink one cup of hibiscus or black tea 2 times per day for 1 month. The average systolic blood pressure (SBP) in the hibiscus group decreased from 134.4 ± 11.8 mmHg at the start of the study to 112.7 ± 5.7 mmHg after 1 month. The average SBP changed from 118.6 ± 14.9 to 127.3 ± 8.7 mmHg in the black tea group during the same time period. There were no statistically significant effects on the mean diastolic blood pressure in either group. This drop in systolic blood pressure is clinically relevant, decreasing systolic blood pressure in pre-hypertensive ranges to normal systolic blood pressure. We do not know if systolic blood pressure would be lowered by 1 cup of hibiscus tea in those with stage I or stage II hypertension.
A randomized, controlled, double-blind clinical comparison study was conducted on H. sabdariffa extract vs lisinopril (control) on patients with stage I or II hypertension.38 A dried, powdered hibiscus extract was delivered in 250 mg of water, containing a total of 250 mg anthocyanins for 4 weeks, and the control group received 10 mg/day of lisinopril. Results showed that the Hibiscus extract decreased blood pressure from 146/98 mmHg to 130/86 mmHg (P<0.05) Blood pressure reductions were lower than with lisinopril. Based on the study data, the authors concluded that the hibiscus extract did have a significant antihypertensive action through at least 2 mechanisms of action: diuretic effects (likely as an aldosterone antagonist) and ACE inhibitory effects. The study authors also noted that the diuretic activity did not alter plasma potassium levels and did not have mineralocorticoid effects.
A Cochrane review of Hibiscus effects on blood pressure published in 2010 resulted in 5 articles.39 The reviewers included randomized controlled trials (RCTs) of 3–12 weeks in duration that compared hibiscus to either placebo or no intervention at all. All 5 of these studies found significant reductions in systolic blood pressure. Although they could not draw reliable conclusions about the benefit of hibiscus for controlling or lowering blood pressure in hypertensive patients, in the articles that met the inclusion criteria, beneficial effects were found in the treatment of hypertension with hibiscus. However, the reviewers noted that well-designed, placebo-controlled RCTs are needed.
The safety profile of hibiscus is excellent. With no proven adverse reactions, hibiscus has a Generally Recognized as Safe (GRAS) status.
Clinical Dosing for Practitioners
Again, it is difficult to clarify dosing recommendations when different products are used in different studies. The following doses were used in each of the positive studies:
- For dyslipidemia: 1,000 mg dried herb tid, 1 cup of tea bid, or 100 mg of standardized extract bid
- For hypertension: 1 cup of tea bid or dried powdered hibiscus extract (250 mg anthocyanins) per day
These 2 plants, hawthorne and hibiscus, have a long ethnobotanical use as cardiac tonics. More recently we have amassed considerable data with encouraging results. This has been in the area of congestive heart failure for hawthorn, but its use in hypertension and angina should not be discounted. Studies of hibiscus have been more in the areas of hypertension and dyslipidemia. Practitioners should be encouraged about the modern research in these areas, although more robust high-quality RCTs would be welcomed and a worthy addition in our ability to help lessen the impact of cardiovascular disease. For the ever-growing number of patients who refuse statins, hawthorne and hibiscus can be important tools—especially in the context of comprehensive lifestyle changes and other nutraceutical/botanical interventions to reduce life-threatening or debilitating cardiovascular disease.
1. Heron MP, Hoyert DL, Murphy SL, Xu JQ, Kochanek KD, Tejada-Vera B. National Vital Statistics Reports. 2009;57(14). Hyattsville, MD: National Center for Health Statistics.
2. Heron MP. National Vital Statistics Reports. 2007;56(5). Hyattsville, MD: National Center for Health Statistics.
3. Lloyd-Jones D, Adams RJ, Brown TM, et al. Heart Disease and Stroke Statistics—2010 Update. A Report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2010;121:e1-e170.
4. Bahourun T, Gressier B, Trotin F, et al. Oxygen species scavenging activity of phenolic extracts from hawthorn fresh plant organs and pharmaceutical preparations. Arzneim Forsch Drug Res. 1996;11:1086-1089.
5. Bahourun T, Trotin F, Pommery J, et al. Antioxidant activities of Crataegus monogyna extracts. Planta Med. 1994;60:323-328.
6. Brehm M, Schiller E, Zeller W. Comparable antitumor activity of coxorubicin plus two radical scavenging plant extract preparations (Ginkgo biloba, Crataegus oxyacantha) and of doxorubicin alone. Contrib Oncol. 1995;48:48-52.
7. Holubarsch C, Colucci W, Meinertz T, et al. The efficacy and safety of Crataegus extract WS 1442 in patients with heart failure: The SPICE trial. Eur J Heart Failure. 2008;10:1255-1263.
8. Pittler M, Schmidt K, Ernst E. Hawthorn extract for treating chronic heart failure: meta-analysis of randomized trials. Am J Med. 2003; 114(8):665-674.
9. Weihmayr T, Ernst E. Therapeutic effectiveness of Crataegus. Fortschr Med. 1996;114(1-2):27-29.
10. Beier A, Konigstein R, Samec V. Clinical experiences with a crataegus-pentaerythrityl-tetranitrate combination drug in heart diseases due to coronary sclerosis in old age. Wien Med Wochenschr. 1974;124(24):378-381.
11. Iwamoto M, Sato T, Ishizaki T. The clinical effect of Crataegus in heart disease of ischemic or hypertensive oricin. A multicenter double-blind study. Planta Med. 1981;42(1):1-16.
12. Degenring F, Suter A, Weber M, et al. A randomised double blind placebo controlled clinical trial of a standardized extract of fresh Crataegus berries (Crataegisan) in the treatment of patients with congestive heart failureNYHA II. Phytomedicine. 2003;10(5):363-369.
13. Tauchert M, Gildor A, Lipinski J. High-dose Crataegus extract WS 1442 in the treatment of NYHA stage II heart failure. Herz. 1999;24 (6): 465-474.
14. Tauchert M, Ploch M, Hubner W. Effectiveness of hawthorn extract LI 132 compared with the ACE inhibitor captopril: multicenter double-blind study with 132 NYHA Stage II. Munch Med Wochenschr. 1994; 136 (suppl 1): S27-S33.
15. Schroder D, Weiser M, Klein P. Efficacy of a homeopathic Crataegus preparation compared with usual therapy for mild (NYHA II) cardiac insufficiency: results of an observational cohort study. Eur J Heart Fail. 2003;5(3): 319-326.
16. Walker A, Marakis G, Simpson E, et al. Hypotensive effects of hawthorn for patients with diabetes taking prescription drugs: a randomised controlled trial. Br J Gen Pract. 2006 Jun;56(527):437-443.
17. Asgary S, Naderi G, Sadeghi M, et al. Antihypertensive effect of Iranian Crataegus curvisepala Lind.: a randomized, double-blind study. Drugs Exp Clin Res. 2004;30(5-6):221-225.
18. Walker A, Marakis G, Morris A, Robinson P. Promising hypotensive effect of hawthorn extract: a randomized double-blind pilot study of mild, essential hypertension. Phytother Res. 2002 Feb;16(1):48-54.
19. WEng W, Zhang W, Liu F, et al. Therapeutic effect of Crataegus pinnatifida on 46 cases of angina pectoris—a double blind study. J Tradit Chin Med. 1984;4(4):293-294.
20. Petkov V. Plants with hypotensive, antiatheromatous and coronary dilating action. Am J Chin Med. 1979;7:197-236.
21. Wegrowski J, Robert A, Moczar M. The effect of procyanidolic oligomers on the composition of normal and hypercholesterolemic rabbit aortas. Biochem Pharm. 1984;33:3491-3497.
22. Trunzler V, Schuler E. Vergleichende Studien uber Wirkungen eines Crataegus-Extraktes, ven Digitoxin, Dikgoxin and y-Strophanthin am isolierten Warmbluterherzen. Arzneim Forsch Drug Res. 1962;12:198.
23. Della Loggia R, Tubara A, Zilli C, Redaelli C. Depressive effect of Crataegus oxyacantha L on central nervous system in mice. Pharm. 1983;51:319-324.
24. Hahn F, Klinkhammer F, Oberdorf A. Darstellung und pharmakologische Untersuchungen eins neuen therapeutischen Wirkstoffes aus Crataegus oxyacantha. Arzneim Forsch Drug Res. 1960;10:825-826.
25. Ulbright C, Basch E. Natural Standard Herb and Supplement Reference. Elsevier Mosby. (St. Louis, 2005)
26. Franz M, Franz G. Hibiscus sabdariffa. Phytotherapy. 1988;9(2):63.
27. Adegunloye B, Omoniyi J, Owolabi O, et al. Mechanisms of the blood pressure lowering effect of the calyx extract of Hibiscus sabdariffa in rats. Afr J Med Med Sci. 1996;25:235-238.
28. Ali M, Salih W, Mohamed A, Homeida A. Investigation of the antispasmodic potential of Hibiscus sabdariffa calyces. J Ethnopharmacol. 1991;31:249-257.
29. Odigie I, Ettarh R, Adigun S. Chronic administration of aqueous extract of Hibiscus sabdariffa attenuates hypertension and reverses cardiac hypertrophy in 2K-1C hypertensive rats. J Ethnopharmacol. 2003;86:181-185.
30. Onyenekwe P, Ajani E, Ameh D, Gamaniel K. Antihypertensive effect of roselle calyx infusion in spontaneously hypertensive rats and a comparison of its toxicity with that in Wistar rats. Cell Biochem Funct. 1999;17:199-206.
31. Chen C, Chou F, Ho W, et al. Inhibitory effects of Hibiscus sabdariffa L extact on low-density lipoprotein oxidation and anti-hyperlipidemia in fructose-fed and cholesterol-fed rats. J Sci Food Agr. 2004;84:1989-1996.
32. Herra-Arellano A, Flores-Romero S, Chavez-Soto M, 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.
33. Lin T, Lin H, Chen C, et al. Hibiscus sabdariffa extract reduces serum cholesterol in men and women. Nutr Res. 2007;27:140-145.
34. Mozaffari-Khosravi H, Jalali-Khanabadi B, Afkhami-Ardehani M, Fatehi F. Effects of sour tea (Hibiscus sabdariffa) on lipid profile and lipoproteins in patients with Type II diabetes. J Altern and Comp Med. 2009;15(8):899-903.
35. Gurrola-Diaz C, Garcia-Lopez P, Sanchez-Enriquez S, et al. 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.
36. Kuriyan R, Kumar D, Rajendran R, Kurpad A. An evaluation of the hypolipidemic effect of an extract of Hibiscus sabdariffa leaves in hyperlipdemic Indians: a double blind, placebo controlled trial. BMC Compl and Alt Med. 2010;10:27.
37. Mozaffari-Khosravi H, Jalali-Khanabadi B, Afkhami-Ardekani M, et al. The effects of sour tea (Hibiscus sabdariffa) on hypertension in patients with type II diabetes. J Human Hypertension. 2009;23:48-54.
38. Herrera-Arellano A, Miranda-Sanchez J, Avila-Castro P, 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.
39. Ngamjarus c, Pattanittum P, Somboonporn C. Roselle for hypertension in adults. Cochrane Database Syst Rev. 2010;Jan 20(1):CD007894.