Expand Document  |  Expand Chapter  |  Full TOC  |  Printable HTML version
WHO Monographs on Selected Medicinal Plants - Volume 1
(1999; 295 pages) View the PDF document
Table of Contents
View the documentAcknowledgements
View the documentIntroduction
View the documentBulbus Allii Cepae
View the documentBulbus Allii Sativi
View the documentAloe
View the documentAloe Vera Gel
View the documentRadix Astragali
View the documentFructus Bruceae
View the documentRadix Bupleuri
View the documentHerba Centellae
View the documentFlos Chamomillae
View the documentCortex Cinnamomi
View the documentRhizoma Coptidis
View the documentRhizoma Curcumae Longae
View the documentRadix Echinaceae
View the documentHerba Echinaceae Purpureae
View the documentHerba Ephedrae
View the documentFolium Ginkgo
View the documentRadix Ginseng
View the documentRadix Glycyrrhizae
View the documentRadix Paeoniae
View the documentSemen Plantaginis
View the documentRadix Platycodi
View the documentRadix Rauwolfiae
View the documentRhizoma Rhei
View the documentFolium Sennae
View the documentFructus Sennae
View the documentHerba Thymi
View the documentRadix Valerianae
View the documentRhizoma Zingiberis
View the documentAnnex. Participants in the WHO Consultation on Selected Medicinal Plants
 

Rhizoma Rhei

Definition

Rhizoma Rhei consists of the underground parts (rhizome and root) of Rheum officinale Baill., or R. palmatum L. (Polygonaceae) (1–7).1

1Rheum tangutium Max., R. coreanum Nakai, R. palmatum L., and R. officinale Baillow, or their interspecific hybrids, are also listed in the Japanese pharmacopoeia (1). R. emodi ("Indian rhubarb") is listed in the Indian pharmacopoeia (7).

Synonyms

None.

Selected vernacular names

Akar kalembak, Chinese rhubarb, chuòng diêp dai hoàng, dai hoàng, daioh, daiou, kot nam tao, rawind, Rhabarberwurzel, rhabarbarum, rhubarb, rhubard de Chine, rhubarb root, turkey rhubarb, ta-huang (8–10).

Description

Rheum species are perennial herbs resembling the common garden rhubarb except for their lower growth and shape of their leaf blades; the underground portion consists of a strong vertical rhizome with fleshy, spreading roots; the portion above ground consists of a number of long petioled leaves that arise from the rhizome in the spring, and flower shoots bearing elongated leafy panicles that are crowded with greenish white, white, to dark purple flowers; the lamina is cordate to somewhat orbicular, entire or coarsely dentate (Rheum officinale) or palmately lobed (R. palmatum). The fruit is an ovoid-oblong or orbicular achene bearing 3 broad membranous wings and the remains of the perianth at the base (9, 11).

Plant material of interest: rhizomes and roots

General appearance

The appearance of the rhizomes and roots varies according to the plant's geographical origin (12). They occur on the market in subcylindrical, barrelshaped, plano-convex or irregularly formed pieces, frequently showing a perforation, or in cubes or rectangular pieces, the last commonly known as "rhubarb fingers". They are hard and moderately heavy. The outer surfaces are smooth, longitudinally wrinkled or sunken, yellowish brown and mottled with alternating striae of greyish white parenchyma and brownish or reddish medullary rays, while here and there may be seen brown cork patches and branched scars, "star spots", of leaf trace fibrovascular bundles. The fracture is uneven and granular, the fractured surface pinkish brown. The smooth transverse surface of the rhizome exhibits a cambium line near the periphery traversed by radial lines that represent medullary rays that project for a short distance within it. The large area within this circle of medullary rays contains stellate vascular bundles 2–4mm in diameter that are arranged in a more or less continuous circle in R. palmatum or scattered irregularly in R. officinale (9).

Organoleptic properties

Odour, characteristic aromatic; taste, slightly astringent and bitter; when chewed, gritty between the teeth; colour, yellow-brown to light brown (1, 2).

Microscopic characteristics

The transverse section of the rhizome shows wavy medullary rays, 2–4 cells in width; the xylem consists of a matrix of wood parenchyma and resembles the phloem and cortex regions in that the cells possess either starch, tannin, or large cluster crystals of calcium oxalate. Large, reticulately thickened vessels occur singly or in small groups. Embedded in the parenchyma near the cambium line and mostly in the pith are a number of compound ("stellate") fibrovascular bundles, each of which consists of a small circle of open collateral bundles separated from each other by yellowish brown medullary rays containing anthraquinone derivatives. The bundles differ from the ordinary open collateral bundle in showing phloem inside and xylem outside the cambium. In R. officinale the compound bundles ("stellate spots") are scattered through the pith, whereas in R. palmatum they are mostly arranged in a ring, the remainder being scattered on either side of the ring (1, 2, 9, 13).

Powdered plant material

Powdered Rhizoma Rhei is dusky yellowish orange to moderate yellowish brown, and coloured red in the presence of alkali. Under the microscope, it shows numerous starch grains, spherical, single or 2–4-compound, 2–25µm in diameter; fragments of non-lignified, reticulate and spiral tracheae, vessels, parenchyma cells containing starch grains or tannin masses; large rosette aggregates of calcium oxalate, 30–60µm, frequently over 100µm, and occasionally attaining a diameter of 190µm; and medullary-ray cells containing an amorphous yellow substance, insoluble in alcohol but soluble in ammonia test solution with a reddish or pink colour; cork, sclerenchymatous cells, and fibres absent (1, 2, 9, 10).

Geographical distribution

Rheum officinale and R. palmatum are cultivated in China (Gansu, Sichuan, and Qinghai provinces), the Democratic People's Republic of Korea and the Republic of Korea. There are several commercial grades (rhizome with or without rootlets, peeled or unpeeled, in transverse or longitudinal cuts) (9, 12, 14).

General identity tests

Macroscopic and microscopic examinations; microchemical colour tests and thin-layer chromatographic analysis for the presence of anthraquinones (1–7).

Purity tests

Microbiology

The test for Salmonella spp. in Rhizoma Rhei products should be negative. The maximum acceptable limits of other microorganisms are as follows (15–17). For preparation of decoction: aerobic bacteria-not more than 107/g; fungi-not more than 105/g; Escherichia coli-not more than 102/g. Preparations for internal use: aerobic bacteria-not more than 105/g or ml; fungi-not more than 104/g or ml; enterobacteria and certain Gram-negative bacteria-not more than 103/g or ml; Escherichia coli-0/g or ml.

Foreign organic matter

Not more than 1.0% (2–7).

Total ash

Not more than 12% (2, 3).

Acid-insoluble ash

Not more than 2.0% (2, 3).

Dilute ethanol-soluble extractive

Not less than 30% (1).

Moisture

Not more than 12% (2, 3).

Pesticide residues

To be established in accordance with national requirements. Normally, the maximum residue limit of aldrin and dieldrin in Rhizoma Rhei is not more than 0.05 mg/kg (17). For other pesticides, see WHO guidelines on quality control methods for medicinal plants (15) and guidelines for predicting dietary intake of pesticide residues (18).

Heavy metals

Recommended lead and cadmium levels are no more than 10 and 0.3mg/kg, respectively, in the final dosage form of the plant material (15).

Radioactive residues

For analysis of strontium-90, iodine-131, caesium-134, caesium-137, and plutonium-239, see WHO guidelines on quality control methods for medicinal plants (15).

Other purity tests

Chemical and water-soluble extractive tests to be established in accordance with national requirements.

Chemical assays

Contains not less than 2.2% hydroxyanthracene derivatives calculated as rhein (2, 3). Quantitative analysis of total hydroxyanthracene glycosides, calculated as rhein, performed by spectrophotometric analysis (2–7). High-performance liquid chromatography is also available (19) for quantitative analysis.

Thin-layer chromatography is employed for the qualitative analysis for the presence of emodin, physcione (emodin 3-methyl ether), chrysophanol (chrysophanic acid), rhein, and aloe-emodin (2, 3).

Major chemical constituents

The major constituents are hydroxyanthracene derivatives (2–5%) including emodin, physcione, aloe-emodin, and chrysophanol glycosides, along with di-O, C-glucosides of the monomeric reduced forms (rheinosides A–D), and dimeric reduced forms (sennosides A–F). The level of the oxidized forms is maximal in the summer and almost nil in the winter (12). Until the 1950s, chrysophanol and other anthraquinones were considered to be the constituents producing the purgative action of rhubarb. Current evidence indicates that the major active principles are the dimeric sennosides A–F (20).

 

R1

R2

chrysophanol

CH3

H

emodin

OH

CH3

physcione

OCH3

CH3

aloe-emodin

CH2OH

H

rhein *

CO2H

H

* same numbering as rheinosides

 

R1

R2

rheinoside A

OH

glc **

rheinoside B

glc **

OH

rheinoside C

H

glc **

rheinoside D

glc **

H

** glc = b-D-glucopyranosyl

Dosage forms

Dried plant material and preparations standardized to contain 10–30mg of hydroxyanthracene derivatives per dose (21, 22). Package in well-closed, lightresistant containers (9, 11).

Medicinal uses

Uses supported by clinical data

Short-term treatment of occasional constipation (20, 23, 24).

Uses described in pharmacopoeias and in traditional systems of medicine

None.

Uses described in folk medicine, not supported by experimental or clinical data

To treat hypotension, increase peripheral vasodilation, and inhibit blood coagulation (8, 20).

Pharmacology

Experimental pharmacology

As shown for senna, the mechanism of action is twofold: (1) stimulation of colonic motility, which augments propulsion and accelerates colonic transit (which in turn reduces fluid absorption from the faecal mass); and (2) an increase in the paracellular permeability across the colonic mucosa probably owing to an inhibition of Na+/K+-exchanging ATPase or to an inhibition of chloride channels (25, 26), which results in an increase in the water content in the large intestine (27). Purgation is followed by an astringent effect owing to the tannins present (11, 12).

Clinical pharmacology

The active constituents of Rhizoma Rhei are the anthraquinone glycosides, sennosides A–F and rheinosides A–D (20). The rheinosides are similar to aloin A and B, the main cathartic principles of aloe. The cathartic action of both the sennosides and rheinosides is limited to the large intestine, where they directly increase motor activity in the intestinal tract (20, 23). Consequently, they are seldom effective before 6 hours after oral administration, and they sometimes do not act before 24 hours.

The mechanism of action is similar to that of other anthraquinone stimulant laxatives. Both the sennosides and rheinosides are hydrolysed by intestinal bacteria and then reduced to the active anthrone metabolite, which acts as a stimulant and irritant to the gastrointestinal tract (28). Preparations of rhubarb are suitable as an occasional aperient, but should not be used in chronic consti- pation. A variable amount is absorbed and imparts a yellowish brown colour to the urine, which is changed to a purplish red on the addition of alkali (11). Rhizoma Rhei preparations have been employed occasionally for their astringent after effects, to check the diarrhoea produced by irritating substances in the intestines (11).

Toxicity

The major symptoms of overdose are griping and severe diarrhoea with consequent losses of fluid and electrolytes (29). Treatment should be supportive with generous amounts of fluid. Electrolytes, particularly potassium, should be monitored, especially in children and the elderly.

Contraindications

As with other stimulant laxatives, products containing Rhizoma Rhei should not be administered to patients with intestinal obstruction and stenosis, atony, severe dehydration states with water and electrolyte depletion, or chronic constipation. Rhizoma Rhei should not be used in patients with inflammatory intestinal diseases, such as appendicitis, Crohn disease, ulcerative colitis, or irritable bowel syndrome, or in children under 10 years of age. Rhizoma Rhei should not be used during pregnancy or lactation except under medical supervision after respective benefits and risks have been considered. As with other stimulant laxatives, Rhizoma Rhei is contraindicated in patients with cramps, colic, haemorrhoids, nephritis, or any undiagnosed abdominal symptoms such as pain, nausea, or vomiting (23, 24).

Warnings

Products containing Rhizoma Rhei should be used only if no effect can be obtained through a change of diet or use of bulk-forming laxatives. Stimulant laxatives should not be used when abdominal pain, nausea, or vomiting are present. Rectal bleeding or failure to have a bowel movement after the use of a laxative may indicate a serious condition (29). Use of stimulant laxatives for longer than the recommended short-term application may increase intestinal sluggishness (28).

The use of stimulant laxatives for more than 2 weeks requires medical supervision.

Chronic use may lead to pseudomelanosis coli (harmless) and to an aggravation of constipation with dependence and possible need for increased dosages.

Chronic abuse with diarrhoea and consequent fluid and electrolyte losses (mainly hypokalaemia) may cause albuminuria and haematuria, and it may result in cardiac and neuromuscular dysfunction, the latter particularly in case of concomitant use of cardiac glycosides (digoxin), diuretics, corticosteroids, or liquorice root (see below, Precautions).

Precautions

General

Laxatives containing anthraquinone glycosides should not be used for periods longer than 1–2 weeks continually, owing to the danger of electrolyte imbalance (29).

Drug interactions

Decreased intestinal transit time may reduce absorption of orally administered drugs (30).

Electrolyte imbalances such as increased loss of potassium may potentiate the effects of cardiotonic glycosides (digitalis, strophanthus). Existing hypokalaemia resulting from long-term laxative abuse can also potentiate the effects of antiarrhythmic drugs, such as quinidine, which affect potassium channels to change sinus rhythm. Simultaneous use with other drugs or herbs which induce hypokalaemia, such as thiazide diuretics, adrenocorticosteroids, or liquorice root, may exacerbate electrolyte imbalance (22).

Drug and laboratory test interactions

Anthranoid metabolites may not be detectable with standard methods. Thus results of measuring faecal excretion may not be reliable (31). Urinary excretion of certain anthranoid metabolites may discolour the urine, which is not clinically relevant but may cause false positive results for urinary urobilinogen and for estrogens when measured by the Kober procedure (30).

Carcinogenesis, mutagenesis, impairment of fertility

Data on the carcinogenicity of Rhizoma Rhei are not available. While chronic abuse of anthranoid-containing laxatives was hypothesized to play a role in colorectal cancer, no causal relationship between anthranoid laxative abuse and colorectal cancer has been demonstrated (32, 33).

Pregnancy: teratogenic effects

The teratogenic effects of Rhizoma Rhei have not been evaluated.

Pregnancy: non-teratogenic effects

Products containing Rhizoma Rhei should not be used by pregnant women because they have a pronounced action on the large intestine and have not undergone sufficient toxicological investigation (28).

Nursing mothers

Anthranoid metabolites appear in breast milk. Rhizoma Rhei should not be used during lactation as there are insufficient data available to assess the potential for pharmacological effects in the breast-fed infant (28).

Paediatric use

Use of Rhizoma Rhei for children under 10 years of age is contraindicated.

Adverse reactions

Single doses may cause cramp-like discomfort of the gastrointestinal tract, which may require a reduction of dosage. Overdoses can lead to colicky abdominal spasms and pain and the formation of thin, watery stools (31).

Chronic abuse of anthraquinone stimulant laxatives can lead to hepatitis (34). Long-term laxative abuse may lead to electrolyte disturbances (hypokalaemia, hypocalcaemia), metabolic acidosis, malabsorption, weight loss, albuminuria, and haematuria (31, 35, 36). Weakness and orthostatic hypotension may be exacerbated in elderly patients when stimulant laxatives are repeatedly used (31). Secondary aldosteronism may occur due to renal tubular damage after aggravated use. Steatorrhoea and protein-losing gastroenteropathy with hypoalbuminaemia have also been reported in laxative abuse (37). Melanotic pigmentation of the colonic mucosa (pseudomelanosis coli) has been observed in individuals taking anthraquinone laxatives for extended time periods (29, 35). The pigmentation is clinically harmless and usually reversible within 4–12 months after the drug has been discontinued (30, 35). Conflicting data exist on other toxic effects such as intestinal-neuronal damage after long-term use (35).

Posology

The individually correct dosage is the smallest dosage necessary to maintain a soft stool. The average dose is 0.5–1.5 g of dried plant material or in decoction; preparations standardized to contain 10–30mg of hydroxyanthracene derivatives, usually taken at bedtime (21, 22, 28).

References

1. The pharmacopoeia of Japan XII. Tokyo, The Society of Japanese Pharmacopoeia, 1991.

2. European pharmacopoeia, 2nd ed. Strasbourg, Council of Europe, 1995.

3. Pharmacopée française. Paris, Adrapharm, 1996.

4. British pharmacopoeia. London, Her Majesty's Stationery Office, 1988.

5. Deutsches Arzneibuch 1996. Stuttgart, Deutscher Apotheker Verlag, 1996.

6. Pharmacopoeia helvetica VII. Berne, Département fédéral de l'intérieur, 1994.

7. Pharmacopoeia of India. New Delhi, The Controller of Publications, 1985.

8. Farnsworth NR, ed. NAPRALERT database. Chicago, University of Illinois at Chicago, IL, March 15, 1995 production (an on-line database available directly through the University of Illinois at Chicago or through the Scientific and Technical Network (STN) of Chemical Abstracts Services).

9. Youngken HW. Textbook of pharmacognosy 6th ed. Philadelphia, Blakiston, 1950.

10. Vietnam materia medica. Hanoi, Ministry of Health, 1972.

11. The Indian pharmaceutical codex. Vol. I. Indigenous drugs. New Delhi, Council of Scientific & Industrial Research, 1953.

12. Bruneton J. Pharmacognosy, phytochemistry, medicinal plants. Paris, Lavoisier, 1995.

13. Jackson BP, Snowden DW. Atlas of microscopy of medicinal plants, culinary herbs and spices. Boca Raton, FL, CRC Press, 1990.

14. Tyler VE, Brady LR, Robbers JE, eds. Pharmacognosy, 9th ed. Philadelphia, Lea & Febiger, 1988.

15. Quality control methods for medicinal plant materials. Geneva, World Health Organization, 1998.

16. Deutsches Arzneibuch 1996. Vol. 2. Methoden der Biologie. Stuttgart, Deutscher Apotheker Verlag, 1996.

17. European pharmacopoeia, 3rd ed. Strasbourg, Council of Europe, 1997.

18. Guidelines for predicting dietary intake of pesticide residues, 2nd rev. ed. Geneva, World Health Organization, 1997 (unpublished document WHO/FSF/FOS/97.7; available from Food Safety, WHO, 1211 Geneva 27, Switzerland).

19. Sagara K, Oshima T, Yoshida T. Rapid and simple determination of sennosides A and B in Rhei Rhizoma by ion-pair high-performance liquid chromatography. Journal of chromatography, 1987, 403:253–261.

20. Nishioka I. Biological activities and the active components of rhubarb. International journal of Oriental medicine, 1991, 16:193–212.

21. Bradley PR, ed. British herbal compendium, Vol. 1. Bournemouth, British Herbal Medicine Association, 1992.

22. German Commission E monograph, Rhei radix. Bundesanzeiger, 1993, 133:21 July.

23. Reynolds JEF, ed. Martindale, the extra pharmacopoeia, 30th ed. London, Pharmaceutical Press, 1993:903.

24. Bisset NG. Max Wichtl's herbal drugs & phytopharmaceuticals. Boca Raton, FL, CRC Press, 1994.

25. Leng-Peschlow E. Dual effect of orally administered sennosides on large intestine transit and fluid absorption in the rat. Journal of pharmacy and pharmacology, 1986, 36:230–236.

26. Yamauchi K et al. Suppression of the purgative action of rhein anthrone, the active metabolite of sennosides A and B, by calcium channel blockers, calmodulin antagonists and indomethacin. Pharmacology, 1993, 47(Suppl. 1):22–31.

27. de Witte P. Metabolism and pharmacokinetics of anthranoids. Pharmacology, 1993, 47(Suppl. 1):86–97.

28. Physicians' desk reference, 49th ed., Montvale, NJ, Medical Economics Company, 1995.

29. Goodman and Gilman's the pharmacological basis of therapeutics, 8th ed. New York, McGraw Hill, 1990.

30. United States pharmacopeia, drug information. Rockville, MD, US Pharmacopeial Convention, 1992.

31. American hospital formulary service. Bethesda, MD, American Society of Hospital Pharmacists, 1990.

32. Siegers CP. Anthranoid laxatives and colorectal cancer. Trends in pharmacological sciences, 1992, 13:229–231.

33. Patel PM et al. Anthraquinone laxatives and human cancer. Postgraduate medical journal, 1989, 65:216–217.

34. Beuers U, Spengler U, Pape GR. Hepatitis after chronic abuse of senna. Lancet, 1991, 337:472.

35. Muller-Lissner SA. Adverse effects of laxatives: facts and fiction. Pharmacology, 1993, 47(Suppl. 1):138–145.

36. Godding EW. Therapeutics of laxative agents with special reference to the anthraquinones. Pharmacology, 1976, 14(Suppl. 1):78–101.

37. Heizer WD et al. Protein-losing gastroenteropathy and malabsorption associated with factitious diarrhoea. Annals of internal medicine, 1968, 68:839–852.

 

to previous section
to next section
 
 
The WHO Essential Medicines and Health Products Information Portal was designed and is maintained by Human Info NGO. Last updated: November 7, 2017