Rhubarb

Scientific Name(s): Rheum officinale Baillon, Rheum palmatum L., and Rheum rhabarbarum L. Family: Polygonaceae (Buckwheat family).

Common Name(s): Rhubarb , rheum , rhaptonic , Chinese rhubarb , bo ye da huang , da-huang , ta-huang , radix et rhizoma rhei , and Turkey rhubarb . Rhubarb is also one of the ingredients in Danning Pian and Number Ten preparations.

Uses

Rhubarb is extensively used in traditional Chinese medicine. Rhubarb has been studied for the management of GI and renal function disorders, and for the treatment of hyperlipidemia and cancer. However, sound clinical evidence for its use is lacking.

Dosing

Dried rhubarb extract 20 to 50 mg/kg daily has been used in clinical trials.

Contraindications

Contraindications have not been identified.

Pregnancy/Lactation

Avoid dosages higher than those found in food because safety and efficacy are unproven.

Interactions

Interaction with cardiac glycosides (digoxin) and a reduction in the absorption of orally administered drugs have been noted when rhubarb is taken in large quantities.

Adverse Reactions

A few reactions, primarily GI effects, have been reported in clinical trials.

Toxicology

The leaf blades (but not the stalks) of rhubarb contain enough oxalic acid to cause poisoning. Acute renal failure has been associated with long-term anthraquinone use.

Botany

Rhubarb is derived from several Rheum species. The perennial herb has a conical rootstock, that is fleshy and yellow inside and produces large, cordate, 7-lobed leaves 30 to 46 cm long. The blade or green leaves of the plant are often considered the most poisonous due to high oxalic acid concentration; however, other chemical constituents of the plant are also toxic. The edible stalks are up to 45 cm long and 2.5 to 5 cm in diameter, and are used in pies, jams, jellies, sauces, and juices. 1 , 2

Medicinal rhubarb consists of the dried rhizome and root of R. officinale Baillon or R. palmatum , of related species/hybrids grown in China (Chinese rhubarb), or of Rheum emodi or Rheum webbianum native to India, Pakistan, or Nepal (Indian rhubarb). 3

History

Rhubarb was first recorded and rated as one of the inferior remedies in the oldest Chinese herbal books, from 22 to 250 AD. 4 In the 1780s, the active constituents responsible for the root's cathartic action and astringency were still unknown. Initially, researchers learned that the medicinal root came from several varieties or species of rhubarb. By the end of the 19th century, it became clear that the particular medicinal characteristics of rhubarb were affected by conditions under which the roots grew, such as soil composition and climate. 5

Rhubarb has been used medicinally in Europe since the 13th century. The herb was brought from the eastern Mediterranean by way of the Silk Road, which stretches from China across central Asia. The first reported sighting of the plant in situ was in the mountains of Bulgaria. In 1731, a rhubarb commission was set up at the Mongolian border to import the best possible root at a fixed price. At the same time, the British East India Company secured their positions in Chinese ports. Both companies supplied Europe with rhubarb. 5

In the 1830s and 1840s, the cooked stems of rhubarb emerged as a culinary delight, especially in Britain and the United States. 5 , 6

Chemistry

The Rheum species contains a number of anthraquinone derivatives. The free anthraquinones—rhein, emodin, physcion, and chrysophamol—are present in nearly all species. 7 Stilbene glycosides, including rhaponticin and the metabolite rhapontigenin, have been identified in the root. 4 , 7 , 8 , 9 Tannins, sennosides, catechins, gallic acid, and cinnaminic acid have been identified. 7 Lindleyin, a phytochemical with estrogenic activity, has also been described. 10

Oxalic acid is present in the leaf blades, as well as 2-methylbutanol and 4-methylhexanol. 2 , 11

Uses and Pharmacology

Rhubarb is widely used in traditional Chinese medicine. Most reported clinical trials have been small and poorly designed, and in some studies, a number of different herbs were coadministered with rhubarb, making it difficult to evaluate which herb contributed to the outcomes.

Cancer

The actions of emodin and hydroxyanthraquinones in managing cancer have been reviewed. 12 , 13 Cell cycle inhibition of many human cancer lines has been observed in vitro; however, a mechanism of action is unclear. 12 , 13 , 14 , 15 , 16 Apoptosis, as well as antitumor action, has been demonstrated, and rhubarb extract has been suggested as an adjunct to chemotherapy. 12 , 13 , 17 Antiangiogenic action has also been shown 12 , 13 ; clinical trials are lacking.

Rhubarb extract 20 mg/kg daily administered for 6 weeks to patients undergoing radiation therapy for cancer resulted in a reduction in radiation-induced lung toxicity in a randomized clinical trial. Evaluation of anti-inflammatory markers suggests that an anti-inflammatory action of rhubarb is responsible for the effect. 18

GI effects

In addition to the sennosides present in rhubarb extracts, which have been traditionally used as a laxative, emodin and other anthraquinones exert action on the GI tract. Emodin is metabolized in the large intestine by intestinal bacteria and converted to aglycone, which exerts various effects on absorption, secretion, and motility in the tract, and is also suggested to increase peristalsis without affecting the stomach or duodenum. 12 It has been used in cases of GI bleeds to eliminate extravasated blood. 12 , 19

In a study among patients with septicemia, crude rhubarb extract powder 9 g daily was used to preserve GI function. The investigators suggest that increased perfusion of gastric mucosal blood flow, increased excretion of bacteria and toxins, and decreased permeability of intestinal mucous membranes contributed to the positive effects. 20

Lipid-lowering effects

Rhubarb appears to be a potential source of dietary fiber with a lipid-lowering effect. It has been proposed that rhubarb exerts its effects on cholesterol by inhibition of squalene epoxidase. 21 This enzyme is thought to catalyze the rate-limiting step in cholesterol biogenesis. An anti-inflammatory action has also been suggested. 22

Animal data

Experiments in mice and rats receiving a cholesterol-enriched diet or with induced diabetic nephropathy/hyperlipidemia showed an improved lipid profile with rhubarb extract compared with control animals. 23 , 24 , 25 Rabbits with induced atherosclerotic plaques and fed a high-cholesterol diet demonstrated a decrease in plaque rupture with either administration of rhubarb extract or simvastatin compared with control. Lipid profiles were improved in the two experimental arms. 22

Clinical data

Treating hypercholesterolemia in men with rhubarb stalk fiber for 4 weeks lowered serum total cholesterol and low-density lipoproteins (LDL), while high-density lipoproteins remained unchanged. 26 In 103 patients with atherosclerosis randomized to receive the extract for 6 months, rhubarb extract improved the lipid profile in patients with chronic renal failure (CRF) compared with control. 25 Individuals taking rhubarb reported decreased LDL compared with those taking placebo and compared with the pretreatment levels. 27

Renal effects

Large, randomized clinical trials are lacking. Acute renal failure has been associated with long-term anthraquinone use. 28

Animal data

A number of studies have observed the effects of rhubarb in rats with CRF. Low molecular weight tannins, purified from rhubarb, produced an increase in glomerular filtration rate, decreased levels of uremic toxins, and increased blood flow to the kidneys. 25 , 29 , 30 , 31 , 32

Clinical data

Use of rhubarb extract in patients with elevated serum creatinine has been reported to prevent progression of CRF. Trials have been conducted comparing captopril and rhubarb. Allocation to rhubarb or captopril produced a slower progression to CRF when compared with controls, and synergism of rhubarb with captopril was demonstrated. 32 , 33 Other clinical studies have evaluated rhubarb extracts, either alone or with other herbs, in patients with CRF and report reduced uremic symptoms and reduced blood urea nitrogen. 34 , 35

Mechanisms of action have been proposed and include inhibition of protein decomposition, accelerated reutilization of certain amino acids, reduction of the formation of free radicals, inhibition of overexpression of plasminogen activator inhibitor-1, and suppression of cytokines. 32 , 34 , 36

Other effects
Alzheimer disease

Traditional Chinese medicine suggests rhubarb improves the memory in senile patients. 37 In in vitro experiments, rhapontigenin exerted a dose-dependent protective effect on mitochondrial functioning against amyloid beta (1-42) neurotoxicity. 8 Clinical trials are lacking.

Antimicrobial

The anthraquinone derivatives of rhubarb have been used as antifungal 38 , 39 and molluscicidal 40 agents. Rhein has in vitro antimicrobial activity against a wide spectrum of gram-negative and gram-positive bacteria. 13 , 39 , 41

Dental

An extract of rhubarb stalk has been used as a dental desensitizer. Calcium oxalate crystals form and occlude the dentinal tubules responsible for sensitization. 42

Estrogen

In vitro studies and in vivo experiments in fish show that rhubarb extract possesses estrogenic activity, which has been suggested to be caused by the chemical lindleyin. 10

Heptoprotective effects

R. officinale has been used in China to treat neonatal jaundice. 43 In rats with induced cholestatic hepatitis, total bilirubin was decreased and the liver enzyme profile was improved with administration of emodin. 44 A growth-promoting effect, resulting in liver regeneration, has been demonstrated by emodin. 12

Other properties attributed to rhubarb include antiplatelet properties, 45 antihypertensive effects, 46 anti-inflammatory action, 47 and glucose homeostasis. 48

Dosage

Crude rhubarb extract 9 g powder was given daily to patients with sepsis. 20 Rhubarb extract 20 mg/kg daily was administered for 6 weeks to patients undergoing radiation therapy. 18 Patients with atherosclerosis were given rhubarb extract 50 mg/kg for 6 months. 27

In Kampo medicine (the practice and adaptation of traditional Chinese medicine in Japan), long-term (12 months) use of rhubarb extract has been administered to improve Oketsu (blood stagnation), and short-term (2 weeks) use has been administered for lazy bowel syndrome. 28 , 49

Pregnancy/Lactation

Avoid dosages higher than those found in food because safety and efficacy are not proven. Rhubarb extract has been evaluated in pregnancy-related hypertension at 0.75 g daily 50 ; however, anthraquinones may have uterine-stimulant and genotoxic effects. 51 , 52

Interactions

Information is lacking.

With long-term overuse, rhubarb may increase the toxic effects of cardiac glycosides. An effect on antiarrhythmics is possible because of the loss of potassium. Potassium deficiency can be increased by concurrent use of thiazide diuretics, corticosteroids, or licorice root. Additionally, deceased intestinal transit time may reduce the absorption of orally administered drugs. 53

Adverse Reactions

Clinical trials using rhubarb extract report few adverse reactions; most relate to mild GI symptoms that resolve without treatment. 18 , 27

Localized oxalosis was noted in a case report. A small amount of rhubarb may have adhered to the wall of the tracheobronchial tree, producing a localized area of oxalosis with accompanying necrosis. 54 Consumption of rhubarb in patients with renal stones is not advised because of the oxalate content. 13

Toxicology

The leaf blades, but not the stalks, of rhubarb contain enough oxalic acid to cause poisoning. 2 Acute renal failure has been associated with long-term anthraquinone use. 28

Emodin was mutagenic in several Salmonella typhimurium strains, and has been demonstrated to be phototoxic in vitro. 12

Bibliography

1. Rheum officinale Baile . USDA, NRCS. 2007. The PLANTS Database (http://plants.usda.gov; January, 2009). National Plant Data Center, Baton Rouge, LA 70874-4490 USA.
2. Lust JB. The Herb Book . New York: Bantam Books; 1974.
3. Robbers JE, Tyler VE. Tyler's Herbs of Choice: The Therapeutic Use of Phytomedicinals . New York, NY: Haworth Herbal Press; 1999.
4. Peigen X, Liyi H, Liwei W. Ethnopharmacologic study of Chinese rhubarb. J Ethnopharmacol . 1984;10(3):275-293.
5. Foust CM. That elusive rhubarb: some botanical and horticultural aspects before the twentieth century. J Nal Assoc . 1985;10(1-4):7-21.
6. López-Muñoz F, Alamo C, García-García P. “The herbs that have the property of healing ...,”: the phytotherapy in Don Quixote. J Ethnopharmacol . 2006;106(3):429-441.
7. Zhu W, Wang XM, Zhang L, Li XY, Wang BX. Pharmacokinetic of rhein in healthy male volunteers following oral and retention enema administration of rhubarb extract: a single dose study. Am J Chin Med . 2005;33(6):839-850.
8. Misiti F, Sampaolese B, Mezzogori D, et al. Protective effect of rhubarb derivatives on amyloid beta (1-42) peptide-induced apoptosis in IMR-32 cells: a case of nutrigenomic. Brain Res Bull . 2006;71(1-3):29-36.
9. Li Y, Liu H, Ji X, Li J. Optimized separation of pharmacologically active anthraquinones in Rhubarb by capillary electrochromatography. Electrophoresis . 2000;21(15):3109-3115.
10. Usui T, Ikeda Y, Tagami T, et al. The phytochemical lindleyin, isolated from Rhei rhizoma, mediates hormonal effects through estrogen receptors. J Endocrinol . 2002;175(2):289-296.
11. Dregus M, Schmarr HG, Takahisa E, Engel KH. Enantioselective analysis of methyl-branched alcohols and acids in rhubarb ( Rheum rhabarbarum L.) stalks. J Agric Food Chem . 2003;51(24):7086-7091.
12. Srinivas G, Babykutty S, Sathiadevan PP, Srinivas P. Molecular mechanism of emodin action: transition from laxative ingredient to an antitumor agent. Med Res Rev . 2007;27(5):591-608.
13. Huang Q, Lu G, Shen HM, Chung MC, Ong CN. Anti-cancer properties of anthraquinones from rhubarb. Med Res Rev . 2007;27(5):609-630.
14. Cai J, Razzak A, Hering J, et al. Feasibility evaluation of emodin (rhubarb extract) as an inhibitor of pancreatic cancer cell proliferation in vitro. JPEN J Parenter Enteral Nutr . 2008;32(2):190-196.
15. Wang C, Wu X, Chen M, et al. Emodin induces apoptosis through caspase 3-dependent pathway in HK-2 cells. Toxicology . 2007;231(2-3):120-128.
16. Cui XR, Tsukada M, Suzuki N, et al. Comparison of the cytotoxic activities of naturally occurring hydroxyanthraquinones and hydroxynaphthoquinones. Eur J Med Chem . 2008;43(6):1206-1215.
17. Lin S, Fujii M, Hou DX. Rhein induces apoptosis in HL-60 cells via reactive oxygen species-independent mitochondrial death pathway. Arch Biochem Biophys . 2003;418(2):99-107.
18. Yu HM, Liu YF, Cheng YF, Hu LK, Hou M. Effects of rhubarb extract on radiation induced lung toxicity via decreasing transforming growth factor-beta-1 and interleukin-6 in lung cancer patients treated with radiotherapy. Lung Cancer . 2008;59(2):219-226.
19. Jiao DH, Ma YH, Chen SJ, Liu CT, Shu HN, Chu CM. Résumé of 400 cases of acute upper digestive tract bleeding treated by rhubarb alone. Pharmacology . 1980;20(suppl 1):128-130.
20. Fang XL, Fang Q, Luo JJ, Zheng X. Effects of crude rhubarb on intestinal permeability in septic patients. Am J Chin Med . 2007;35(6):929-936.
21. Abe I, Seki T, Noguchi H, Kashiwada Y. Galloyl esters from rhubarb are potent inhibitors of squalene epoxidase, a key enzyme in cholesterol biosynthesis. Planta Med . 2000;66(8):753-756.
22. Liu Y, Yan F, Liu Y, et al. Aqueous extract of rhubarb stabilizes vulnerable atherosclerotic plaques due to depression of inflammation and lipid accumulation. Phytother Res . 2008;22(7):935-942.
23. Basu TK, Ooraikul B, Garg M. The lipid-lowering effects of rhubarb stalk fiber: a new source of dietary fiber. Nutr Res . 1993;13:1017-1024.
24. Goel V, Cheema SK, Agellon LB, Ooraikul B, Basu TK. Dietary rhubarb ( Rheum rhaponticum ) stalk fibre stimulates cholesterol 7 alpha-hydroxylase gene expression and bile acid excretion in cholesterol-fed C57BL/6J mice. Br J Nutr . 1999;81(1):65-71.
25. Yarnell E. Botanical medicines for the urinary tract. World J Urol . 2002;20(5):285-293.
26. Goel V, Ooraikul B, Basu TK. Cholesterol lowering effects of rhubarb stalk fiber in hypercholesterolemic men. J Am Coll Nutr . 1997;16(6):600-604.
27. Liu YF, Yu HM, Zhang C, et al. Treatment with rhubarb improves brachial artery endothelial function in patients with atherosclerosis: a randomized, double-blind, placebo-controlled clinical trial. Am J Chin Med . 2007;35(4):583-595.
28. Kwan TH, Tong MK, Leung KT, et al. Acute renal failure associated with prolonged intake of slimming pills containing anthraquinones. Hong Kong Med J . 2006;12(5):394-397.
29. Zhang G, el Nahas AM. The effect of rhubarb extract on experimental renal fibrosis. Nephrol Dial Transplant . 1996;11(1):186-190. Erratum in: Nephrol Dial Transplant 1996;11(4):753.
30. Yokozawa T, Suzuki N, Okuda I, Oura H, Nishioka I. Changes in the urinary constituents in rats with chronic renal failure during oral administration of rhubarb extract. Chem Pharm Bull (Tokyo) . 1985;33(10):4508-4514.
31. Yokozawa T, Fujioka K, Oura H, Nonaka G, Nishioka I. Effects of rhubarb tannins on renal function in rats with renal failure. Nippon Jinzo Gakkai Shi . 1993;35(1):13-18.
32. Peng A, Gu Y, Lin SY. Herbal treatment for renal diseases. Ann Acad Med Singapore . 2005;34(1):44-51.
33. Zhang JH, Li LS, Zhang M. Clinical effects of rheum and captopril on preventing progression of chronic renal failure. Chin Med J (Engl) . 1990;103(10):788-793.
34. Kang Z, Bi Z, Ji W, Zhao C, Xie Y. Observation of therapeutic effect in 50 cases of chronic renal failure treated with rhubarb and adjuvant drugs. J Tradit Chin Med . 1993;13(4):249-252.
35. Bi ZQ, Zheng FL, Kang ZQ. Treatment of chronic renal failure by retention-enema with rhizoma rhei compound decoction. J Tradit Chin Med . 1982;2(3):211-214.
36. Wojcikowski K, Stevenson L, Leach D, Wohlmuth H, Gobe G. Antioxidant capacity of 55 medicinal herbs traditionally used to treat the urinary system: a comparison using a sequential three-solvent extraction process. J Altern Complement Med . 2007;13(1):103-109.
37. Tian J, Du H, Yang H, Liu X, Li Z. A clinical study on compound da huang (radix et Rhizoma rhei) preparations for improvement of senile persons' memory ability. J Tradit Chin Med . 1997;17(3):168-173.
38. Agarwal SK, Singh SS, Verma S, Kumar S. Antifungal activity of anthraquinone derivatives from Rheum emodi . J Ethnopharmacol . 2000;72(1-2):43-46.
39. Tegos G, Stermitz FR, Lomovskaya O, Lewis K. Multidrug pump inhibitors uncover remarkable activity of plant antimicrobials. Antimicrob Agents Chemother . 2002;46(10):3133-3141.
40. Liu SY, Sporer F, Wink M, et al. Anthraquinones in Rheum palmatum and Rumex dentatus ( Polygonaceae ), and phorbol esters in Jatropha curcas ( Euphorbiaceae ) with molluscicidal activity against the schistosome vector snails Oncomelania, Biomphalaria and Bulinus. Trop Med Int Health . 1997;2(2):179-188.
41. Cyong J, Matsumoto T, Arakawa K, Kiyohara H, Yamada H, Otsuka Y. Anti- Bacteroides fragalis substance from rhubarb. J Ethnopharmacol . 1987;19(3):279-283.
42. Sauro S, Gandolfi MG, Prati C, Mongiorgi R. Oxalate-containing phytocomplexes as dentine desensitisers: an in vitro study. Arch Oral Biol . 2006;51(8):655-664.
43. Ho NK. Traditional Chinese medicine and treatment of neonatal jaundice. Singapore Med J . 1996;37(6):645-651.
44. Ding Y, Zhao L, Mei H, et al. Exploration of Emodin to treat alpha-naphthylisothiocyanate-induced cholestatic hepatitis via anti-inflammatory pathway. Eur J Pharmacol . 2008;590(1-3):377-386.
45. Ko SK, Lee SM, Whang WK. Anti-platelet aggregation activity of stilbene derivatives from Rheum undulatum . Arch Pharm Res . 1999;22(4):401-403.
46. Chen HC, Hsieh MT, Tsai HY, Chang HH, Wang TF, Shibuya T. Studies on the "San-Huang-Hsieh-Hsin-Tang" in the treatment of essential hypertension. Taiwan Yi Xue Hui Za Zhi . 1984;83(4):340-346.
47. Li C, Zhou J, Gui P, He X. Protective effect of rhubarb on endotoxin-induced acute lung injury. J Tradit Chin Med . 2001;21(1):54-58.
48. Reimer RA, Thomson AB, Rajotte RV, Basu TK, Ooraikul B, McBurney MI. A physiological level of rhubarb fiber increases proglucagon gene expression and modulates intestinal glucose uptake in rats. J Nutr . 1997;127(10):1923-1928.
49. Mantani N, Kogure T, Sakai S, et al. A comparative study between excess-dose users and regular-dose users of rhubarb contained in Kampo medicines. Phytomedicine . 2002;9(5):373-376.
50. Zhang ZJ, Cheng WW, Yang YM. Low-dose of processed rhubarb in preventing pregnancy induced hypertension [in Chinese]. Zhonghua Fu Chan Ke Za Zhi . 1994;29(8):463-464, 509.
51. Newall CA, Anderson LA, Phillipson JD, eds. Herbal Medicines: A Guide for Health-Care Professionals . London, UK: Pharmaceutical Press; 1996.
52. Ernst E. Herbal medicinal products during pregnancy: are they safe? BJOG . 2002;109(3):227-235.
53. Blumenthal M. Interactions between herbs and conventional drugs: Introductory considerations. HerbalGram . 2000;49:52-63.
54. Weiner ES, Hutchins GM. Localized endotracheal oxalosis probably secondary to aspiration of rhubarb. Arch Intern Med . 1979;139(5):602.

Copyright © 2009 Wolters Kluwer Health

Hide
(web4)