Hibiscus sabdariffa / Hibiscus

Hibiscus

Scientific Name(s): Hibiscus sabdariffa L. Family: Malvaceae (mallows)

Common Name(s): Hibiscus , Jamaica sorrel , karkade (Egyptian hibiscus tea), karkadi , red sorrel , red tea , rosa de Jamaica , rosella , roselle , soborodo , sour tea , Zobo drink

Uses of Hibiscus

The leaves and calyces have been used as food and the flowers steeped for tea. Hibiscus has been used in folk medicine as a diuretic and mild laxative, as well as in treating cancer and cardiac and nerve diseases. Although information is limited, the potential for hibiscus use in treating hypertension and cancer, as well as for its lipid-lowering and renal effects, are being investigated.

Hibiscus Dosing

In trials investigating the hypotensive effect of hibiscus, daily dosages of dry calyx 10 g (approximately anthocyanin 9.6 mg) as an infusion in water, and total anthocyanin 250 mg per dose have been used for 4 weeks.

Contraindications

Contraindications have not been identified.

Pregnancy/Lactation

Documented adverse reactions. Avoid use.

Hibiscus Interactions

Studies in healthy volunteers have shown altered chloroquine, acetaminophen, and diclofenac pharmacokinetics. The clinical effects of these interactions have not been evaluated.

Hibiscus Adverse Reactions

Preparations used in clinical trials were well tolerated.

Toxicology

Data are limited.

Botany

H. sabdariffa is native to Central and West Africa, but grows throughout many tropical areas. This annual herb grows to 1.5 m or higher and produces elegant red flowers. The flowers (calyx and bract portions) are collected when slightly immature. The major producing countries are Jamaica and Mexico. 1 , 2 , 3 A related species, Hibiscus rosa-sinensis (rose of Sharon), is widely cultivated for ornamental planting.

History

Hibiscus has a long history of use in Africa and neighboring tropical countries for many conditions, including hypertension, liver diseases, cancer, constipation, and fever. The fleshy red calyx is used in the preparation of jams, jellies, drinks, and cold and warm teas. The plant is also widely used in Egypt, Iran, and Thailand, as well as in Western countries. Hibiscus flowers often are found as components of herbal tea mixtures 2 , 3 , 4 , 5 , 6 ; it is a major component of the popular herbal blend Red Zinger .

Chemistry

A large variety of compounds have been isolated from the hibiscus plant. 2 As expected from their vivid color, hibiscus flowers contain various polyphenols, including anthocyanins, proanthocyanidins, flavonols, and other pigments. 2, 7 , 8 , 9 Oxalic, malic, citric, stearic, and tartaric acids have been identified and are, along with 15% to 28% of hibiscic or hibiscus acid (lactone of hydroxycitric acid), most likely contribute to the tartness of the herb and its teas. Roselle seed oil contains more than 25 volatile compounds, mainly unsaturated hydrocarbons, aldehydes, and alcohols. 2 , 5 The oil is rich in gamma tocopherol. 10 The saturated fatty acids (palmitic and stearic) and unsaturated fatty acids (oleic and linoleic) contents have been described. 2 , 5 The seeds and flowers contain high amounts of protein and crude oil, ash, and carbohydrate. High amounts of arginine, aspartic acid, and glutamic acid were found in the protein isolated from the seed. 5 , 9

Hibiscus Uses and Pharmacology

Cancer

Numerous in vitro experiments have evaluated the effects of hibiscus flower or anthocyanin extracts against various cancer cell lines. Proposed mechanisms of action focus on antioxidant activity and the ability to induce apoptosis. 2, 11 , 12 , 13 , 14 , 15 , 16 , 17

Animal data

Studies in rats have evaluated effects against liver, oral, colon, bladder, and stomach cancers. 2

Clinical data

Clinical trials evaluating the use of hibiscus as a chemopreventive or therapeutic agent are lacking. In vitro experiments have shown apoptotic activity against human leukemia (HL-60), 2 , 12 , 13 , 14 gastric, 15 and cervical 17 cell lines.

Cholesterol

In vitro experiments attribute lipid-lowering action to inhibition of low-density lipoprotein (LDL) oxidation. 2 , 18 , 19 , 20 , 21 , 22 , 23 , 24

Animal data

Studies in hyperlipidemic mice, rats, and rabbits have evaluated the effects of dried calyx extracts on the lipid profile. Although not consistently, the experiments largely demonstrate decreases in serum cholesterol, triglycerides, and LDL, with no effect on high-density lipoprotein (HDL). 2 , 18 , 19 , 20 , 21 , 22 , 23 , 24

Additional effects observed in these experiments include a hypoglycemic effect 24 and antiatherosclerotic (histological) action. 23

Clinical data

Clinical trials evaluating the hypolipidemic effect of hibiscus are lacking.

Hypertension

Animal data

Experiments in animals have shown aqueous and methanol extracts of the plant calyces have hypertensive actions. 2 , 25 , 26 , 27 Suggested mechanisms of action include inhibition of angiotensin I converting enzyme, 2 partial cholinergic and/or histaminic mechanisms, 2 vasodilation, 26 and natriuric effects. 27

Clinical data

A number of small clinical trials evaluated the effect of aqueous calyx extracts on blood pressure. 2 Methods of randomization and blinding are not clearly described in the studies. In addition, differences in baseline parameters among study groups and lack of intention-to-treat analyses limit confidence in the findings. 6 , 28 , 29

A dose-dependent decrease in systolic and diastolic blood pressure has been demonstrated for aqueous preparations of the hibiscus calyx comparable in effect to that of captopril and lisinopril. A natriuric effect was also observed in these studies. 28 , 29 In an earlier trial, patients with essential, but untreated, hypertension demonstrated a decrease in blood pressure with sour tea therapy. Their hypertensive state returned on cessation of therapy. 6

Renal system

Animal data

Studies in rats suggest a uricosuric effect of the calyx extract. 2

Clinical data

Conflicting clinical data exist regarding the effect of hibiscus extracts on the excretion of uric acid. 2 , 30 , 31 The study parameters vary with respect to dose, preparation used, and study population, making conclusions difficult. Increased urinary sodium excretion has been demonstrated in trials evaluating hypotensive effects of hibiscus extracts. 2 , 28 , 29

Other effects

Aqueous hibiscus extracts have shown inhibitory effects on the contractility of various muscle tissues, including uterine. 2 , 32 In other experiments, extracts have demonstrated a mild cathartic activity in rats 4 in the absence of increased peristalsis, as well as stimulatory effects in frogs' abdominal/rectal tissues. 2

Roselle tea extract exhibited high inhibition against porcine pancreatic alpha-amylase. Proposed uses for this inhibition include decreased glucose absorption and inhibition of HIV replication. 33

Protective effects of the plant extracts on induced testicular and hepatic toxicity have been demonstrated in animals and are attributed to antioxidant action. 34 , 35 , 36

Dosage

In trials investigating the hypotensive effect of hibiscus, daily dosages of dry calyx 10 g (equivalent to anthocyanin 9.6 mg) as an infusion in water 28 and total anthocyanin 250 mg per dose 29 have been used for 4 weeks. The kinetics and urinary excretion of the anthocyanin glycosides have been studied in healthy volunteers. An estimated half-life of 2.6 hours and a maximum excretion at 1.5 to 2 hours was noted. 37

Pregnancy/Lactation

Documented adverse reactions. Avoid use. 2 , 32 , 38

Interactions

Studies in healthy volunteers have shown altered chloroquine, 39 acetaminophen, 2 and diclofenac 40 pharmacokinetics with concomitant consumption of hibiscus preparations. The clinical effects of these interactions have not been evaluated.

Adverse Reactions

Research reveals little to no information regarding adverse reactions with the use of hibiscus. 2 , 28

Toxicology

Data are limited. The median lethal dose of the calyx extract in rats is estimated to be higher than 5 g/kg. 2

An experiment in rats using dosages of up to 5 g/kg daily over 12 weeks found a reduction in epididymal sperm count, evidence of histological damage, and disintegration of sperm cells. 2 Conversely, a study evaluating the effects of hibiscus 1 g/kg/day on cisplatin-induced reproductive toxicity found a protective effect as measured by sperm motility. The effect was attributed to an antioxidant effect. 41

Bibliography

1. Hibiscus sabdariffa L. USDA, NRCS. 2009. The PLANTS Database ( http://plants.usda.gov , January 2009). National Plant Data Center, Baton Rouge, LA 70874-4490 USA.

2. Ali BH, Al Wabel N, Blunden G. Phytochemical, pharmacological and toxicological aspects of Hibiscus sabdariffa L.: a review. Phytother Res . 2005;19(5):369-375.

3. Leung AY. Encyclopedia of Common Natural Ingredients Used in Food, Drugs, and Cosmetics . New York, NY: J Wiley; 1980.

4. Haruna AK. Cathartic activity of soborodo : the aqueous extract of calyx of Hibiscus sabdariffa L. Phytother Res . 1997;11:307-308.

5. Abu-Tarboush HM, Ahmed SA, Al Kahtani HA. Some nutritional and functional properties of karkade ( Hibiscus sabdariffa ) seed products. Cereal Chem . 1997;74(3):352-355.

6. Haji Faraji M, Haji Tarkhani AH. The effect of sour tea ( Hibiscus sabdariffa ) on essential hypertension. J Ethnopharmacol . 1999;65(3):231-236.

7. Du CT, Francis FJ. Anthocyanins of roselle ( Hibiscus sabdariffa ). J Food Sci . 1973;38:810-812.

8. Wilkinson M, Sweeney JG, Lacobucci GA. High performance liquid chromatography of anthocyanins. J Chromatogr . 1977;132:349-351.

9. Sayago-Ayerdi SG, 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(19):7886-7890.

10. Mohamed R, Fernandez J, Pineda M, Aguilar M. Roselle ( Hibiscus sabdariffa ) seed oil is a rich source of gamma-tocopherol. J Food Sci . 2007;72(3):S207-S211.

11. Tseng TH, Hsu JD, Lo MH, et al. Inhibitory effect of Hibiscus protocatechuic acid on tumor promotion in mouse skin. Cancer Lett . 1998;126(2):199-207.

12. Tseng TH, Kao TW, Chu CY, Chou FP, Lin WL, Wang CJ. 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(3):307-315.

13. Chang YC, Huang HP, Hsu JD, Yang SF, Wang CJ. Hibiscus anthocyanins rich extract-induced apoptotic cell death in human promyelocytic leukemia cells. Toxicol Appl Pharmacol . 2005;205(3):201-212.

14. Hou DX, Tong X, Terahara N, Luo D, Fujii M. Delphinidin 3-sambubioside, a Hibiscus anthocyanin, induces apoptosis in human leukemia cells through reactive oxygen species-mediated mitochondrial pathway. Arch Biochem Biophys . 2005;440(1):101-109.

15. Lin HH, Chen JH, Kuo WH, Wang CJ. Chemopreventive properties of Hibiscus sabdariffa L. on human gastric carcinoma cells through apoptosis induction and JNK/p38 MAPK signaling activation. Chem Biol Interact . 2007;165(1):59-75.

16. Lo CW, Huang HP, Lin HM, Chien CT, Wang CJ. Effect of Hibiscus anthocyanins-rich extract induces apoptosis of proliferating smooth muscle cell via activation of P38 MAPK and p53 pathway. Mol Nutr Food Res . 2007;51(12):1452-1460.

17. Olvera-García V, Castaño-Tostado E, Rezendiz-Lopez RI, et al. Hibiscus sabdariffa L. extracts inhibit the mutagenicity in microsuspension assay and the proliferation of HeLa cells. J Food Sci . 2008;73(5):75-81.

18. Hirunpanich V, Utaipat A, Morales NP, et al. Antioxidant effects of aqueous extracts from dried calyx of Hibiscus sabdariffa Linn. (Roselle) in vitro using rat low-density lipoprotein (LDL). Biol Pharm Bull . 2005;28(3):481-484.

19. Hirunpanich V, Utaipat A, Morales NP, et al. Hypocholesterolemic and antioxidant effects of aqueous extracts from the dried calyx of Hibiscus sabdariffa L. in hypercholesterolemic rats. J Ethnopharmacol . 2006;103(2):252-260.

20. Chang YC, Huang KX, Huang AC, Ho YC, Wang CJ. Hibiscus anthocyanins-rich extract inhibited LDL oxidation and oxLDL-mediated macrophages apoptosis. Food Chem Toxicol . 2006;44(7):1015-1023.

21. Carvajal-Zarrabal O, Waliszewski SM, Barradas-Dermitz DM, et al. The consumption of Hibiscus sabdariffa dried calyx ethanolic extract reduced lipid profile in rats. Plant Foods Hum Nutr . 2005;60(4):153-159.

22. Alarcon-Aguilar FJ, Zamilpa A, Perez-Garcia MD, et al. Effect of Hibiscus sabdariffa on obesity in MSG mice. J Ethnopharmacol . 2007;114(1):66-71.

23. Chen CC, Hsu JD, Wang SF, et al. Hibiscus sabdariffa extract inhibits the development of atherosclerosis in cholesterol-fed rabbits. J Agric Food Chem . 2003;51(18):5472-5477.

24. Farombi EO, Ige OO. Hypolipidemic and antioxidant effects of ethanolic extract from dried calyx of Hibiscus sabdariffa in alloxan-induced diabetic rats. Fundam Clin Pharmacol . 2007;21(6):601-609.

25. Odigie IP, Ettarh RR, Adigun SA. Chronic administration of aqueous extract of Hibiscus sabdariffa attenuates hypertension and reverses cardiac hypertrophy in 2K-1C hypertensive rats. J Ethnopharmacol . 2003;86(2-3):181-185.

26. Ajay M, Chai HJ, Mustafa AM, Gilani AH, Mustafa MR. Mechanisms of the anti-hypertensive effect of Hibiscus sabdariffa L. calyces. J Ethnopharmacol . 2007;109(3):388-393.

27. Mojiminiyi FB, Dikko M, Muhammad BY, et al. Antihypertensive effect of an aqueous extract of the calyx of Hibiscus sabdariffa . Fitoterapia . 2007;78(4):292-297.

28. Herrera-Arellano A, Flores-Romero S, Chavez-Soto MA, 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(5):375-382.

29. Herrera-Arellano A, Miranda-Sánchez 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(1):6-12.

30. 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(6):314-321.

31. 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(3):491-495.

32. Fouda AM, Daba MH, Dahab GM. Inhibitory effects of aqueous extract of Hibiscus sabdariffa on contractility of the rat bladder and uterus. Can J Physiol Pharmacol . 2007;85(10):1020-1031.

33. Hansawasdi C, Kawabata J, Kasai T. α-Amylase inhibitors from roselle ( Hibiscus sabdariffa Linn.) tea. Biosci Biotechnol Biochem . 2000;64(5):1041-1043.

34. Wang CJ, Wang JM, Lin WL, Chu CY, Chou FP, Tseng TH. Protective effect of Hibiscus anthocyanins against tert -butyl hydroperoxide-induced hepatic toxicity in rats. Food Chem Toxicol . 2000;38(5):411-416.

35. Amin A, Hamza AA. Effects of Roselle and Ginger on cisplatin-induced reproductive toxicity in rats. Asian J Androl . 2006;8(5):607-612.

36. Liu JY, Chen CC, Wang WH, Hsu JD, Yang MY, Wang CJ. The protective effects of Hibiscus sabdariffa extract on CCl4-induced liver fibrosis in rats. Food Chem Toxicol . 2006;44(3):336-343.

37. Frank T, Janssen M, Netzel M, et al. Pharmacokinetics of anthocyanidin-3-glycosides following consumption of Hibiscus sabdariffa L. extract. J Clin Pharmacol . 2005;45(2):203-210.

38. Ernst E. Herbal medicinal products during pregnancy: are they safe? BJOG . 2002;109(3):227-235.

39. Mahmoud BM, Ali HM, Homeida MM, Bennett JL. Significant reduction in chloroquine bioavailability following coadministration with Sudanese beverages Aradaib, Karkadi, and Lemon. J Antimicrob Chemother . 1994;33(5):1005-1009.

40. Fakeye TO, Adegoke AO, Omoyeni OC, Famakinde AA. Effects of water extract of Hibiscus sabdariffa , Linn (Malvaceae) 'Roselle' on excretion of a diclofenac formulation. Phytother Res . 2007;21(1):96-98.

41. Amin A, Hamza AA. Hepatoprotective effects of Hibiscus, Rosmarinus and Salvia on azathioprine-induced toxicity in rats. Life Sci . 2005;77(3):266-278.

Hibiscus sabdariffa / Family: Malvaceae

Native to parts of North Africa and Southeast Asia, Hibiscus sabdariffa is a shrubby tropical plant that produces light yellow flowers with reddish-purple centers.1 After the petals drop from the flower, its remaining deep red calyces (the cup-like structures formed by the sepals) grow into seed-containing pods that look like flower buds. Most of the hibiscus plant’s economic value, particularly as an ingredient in herbal teas, comes from the red calyx, although the leaves, seeds, and flowers are also used in local forms of traditional medicine.1 In commerce the calyces are known by the names hibiscus and roselle.

History and Cultural Significance

Hibiscus is now widely cultivated for its flowers, fruit, and calyces in the tropical and subtropical regions of almost every continent. The hibiscus plant has many medicinal, decorative, and culinary uses. In Egypt and Sudan the deep red tea from the calyces, called karkade, is popular as a “refrigerant,” i.e., a beverage that helps lower body temperature. In Egypt preparations from the calyx have been used to treat cardiac and nerve diseases and also to stimulate diuresis (increased production of urine).1 Elsewhere in North Africa, calyx preparations are used to treat cough, sore throat, and genital problems, and the emollient leaf pulp is used for treating external wounds and abscesses.2 In Europe dried calyces and epicalyces (a group of bracts simulating a calyx) are used primarily as a caffeine-free beverage tea.3 In 1990 the German Commission E evaluated various European uses of hibiscus and determined that efficacy for the claimed uses has not been substantiated, including its uses to stimulate appetite, for colds, catarrhs of the upper respiratory tract, to dissolve phlegm, as a gentle laxative, diuretic, and for circulatory disorders.4 Still, hibiscus is used in many medicinal herbal products in the German-speaking countries. It is used particularly in medicinal teas in combination with lemon balm leaf (Melissa officinalis, Lamiaceae) and St. John’s wort herb (Hypericum perforatum, Clusiaceae) for nervous restlessness and difficulty falling asleep.5 In Iran, sour hibiscus tea is a traditional treatment for hypertension.6 The stalks are used in making rope in Africa and the seeds are expressed for the oil.7

Modern Research

The traditional uses of hibiscus for its blood pressure (BP)-lowering effect have been clinically researched. A standardized extract of hibiscus was shown effective in lowering BP in hypertensive humans in a controlled Mexican trial.8 A clinical study in Iran also investigated the BP-lowering effects of sour tea (hibiscus tea) and found it superior to placebo in hypertensive patients.9 A recent double-blind, reference-controlled trial demonstrated a significant reduction in BP in the hibiscus group when compared directly with the antihypertensive drug lisinopril.8 Animal research suggests potential antioxidant and cholesterol-lowering effects of hibiscus teas.10 A recent clinical trial supports this activity.11

Animal research has tested the potential use of topical hibiscus extract from a different species, H. rosa-sinensis, as a cancer chemopreventive agent,12,13 but there are no human clinical studies supporting this activity.

An official quality control standards monograph for the whole or cut calyces and epicalyces collected during fruiting is published in the 5th edition of the European Pharmacopoeia under the European common name Roselle (Hibisci sabdariffae flos).14

Future Outlook

The main supply of hibiscus comes from Thailand, Sudan, China, and Mexico and is known as jamaica (ha-my-kah).15 Sudanese hibiscus, formerly the primary source of hibiscus sold in herbal teas in the United States, is considered by many in the herb trade as the preferred product. Due to the US trade embargo on agricultural goods from Sudan due to the conflict in Darfur, Sudanese hibiscus is now sold through brokers in Germany at a substantial price mark-up. Therefore, the majority of hibiscus in the United States now comes from China and Thailand. Germany and the United States are the main importers of hibiscus products. There is a growing industry of hibiscus production in the African nations of Gambia (where it is called wanjo), Mali, Namibia (omutete), Nigeria (zobo), Senegal (bissap), Tanzania, and Uganda, plus the Tamil Nadu area of South India, as well as in the Caribbean islands. Some of the African hibiscus production has focused on organically grown material, based on initiatives by the Swedish International Development Agency (SIDA) and a group called the Export Promotion of Organic Products from Africa (EPOPA).7 Additionally, the United States Agency for International Development (USAID)-backed Agriculture in Sustainable African Plant Products (ASNAPP) supports initiatives in which over 4000 rural farmers, mostly women, are growing the herb, mainly in the west-African area around Senegal.16

In 1999, reports from the Food and Agriculture Organization of the United Nations stated that the demand for hibiscus had been increasing steadily. At that time, about 15,000 metric tons of hibiscus were involved in international trade over a period of one year.15

—Gayle Engels

References

    1. Leung AY, Foster S, eds. Encyclopedia of Common Natural Ingredients Used in Food, Drugs, and Cosmetics. 2nd ed. New York: John Wiley and Sons; 1996.

    2. Neuwinger HD. African Traditional Medicine. Stuttgart: Medpharm Scientific Publication; 2000.

    3. Wichtl M, ed., Brinckmann JA, Lindenmaier MP, trans. Herbal Drugs and Phytopharmaceuticals: A Handbook for Practice on a Scientific Basis. Stuttgart: Medpharm Scientific Publishers; 2004.

    4. Blumenthal M, Busse WR, Goldberg A, Gruenwald J, Hall T, Riggins CW, Rister RS, eds. Klein S, Rister RS, trans. The Complete German Commission E Monographs Therapeutic Guide to Herbal Medicines. Austin, TX: American Botanical Council; Boston: Integrative Medicine Communication; 1998.

    5. Meyer-Buchtela E. Tee-Rezepturen: Ein Handbuch für Apotheker und Ärzte, 3. Ergänzungslieferung 2004. Stuttgart: Duetscher Apotheker Verlag; 2004.

    6. Burnham T, Wickersham R, Novak K, et al. The Review of Natural Products. 3rd ed. St. Louis, MO: Facts and Comparisons; 2002.

    7. Burke V. Nile Teas Uganda Ltd. exports dried hibiscus; hope for the farmer, health for the consumer. EPOPA Newsletter. June 2006;2:4. Available at: http://www.grolink.se/epopa/Publications/Newsletter/EPOPA-newsletter-no2.pdf. Accessed March 29, 2007.

    8. Herrera-Arellano A, Flores-Romero S, Chavez-Soto MA, 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. July 2004;11(5):375-382.

    9. Haji Faraji M, Haji Tarkhani A. The effect of sour tea (Hibiscus sabdariffa) on essential hypertension. J Ethnopharmacol. June 1999;65(3):231-236.

    10. Hirunpanich V, Utaipat A, Noppawan PM, et al. Hypocholesterolemic and antioxidant effects of aqueous extracts from the dried calyx of Hibiscus sabdariffa L. in hypercholesterolemic rats. J Ethnopharmacol. January 16, 2006;103(2):252-260.

    11. Lin TL, Lin HH, Chen CC, Lin MC, Chou MC, Wang CJ. Hibiscus sabdariffa extract reduces serum cholesterol in men and women. Nutrition Research. 2007;27(3):140-145.

    12. Tseng TH, Hsu JD, Lo MH, Chu CY, Chou FP, Huang CL, Wang CJ. Inhibitory effect of Hibiscus protocatechuic acid on tumor promotion in mouse skin. Cancer Lett. April 24, 1998;126(2):199-207.

    13. Sharma S, Khan N, Sultana S. Study on prevention of two-stage skin carcinogenesis by Hibiscus rosa sinensis extract and the role of its chemical constituent, gentisic acid, in the inhibition of tumour promotion response and oxidative stress in mice. Eur J Cancer Prev. February 2004;13(1):53-63.

    14. European Pharmacopoeia Commission. European Pharmacopoeia 5th Edition, Supplement 5.8. Strassbourg, France: European Directorate for the Quality of Medicines and Healthcare. 2006;2376-2377.

    15. Plotto A. Hibiscus: Post-Production Management for Improved Market Access for Herbs and Spices. Compendium on Postharvest Operations. 1999. Available at: http://www.fao.org/inpho/content/compend/text/ch28/ch28.htm. Accessed April 13, 2006.

    16. Country Programs: Senegal. Agribusiness in Sustainable Natural African Plant Products Web site. Available at: http://www. asnapp.org/country-progs/senegal.html. Accessed March 29, 2007.