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Rhizoma Rhei

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

Synonyms
None.

Selected vernacular names

Akar kalembak, Chinese rhubarb, chuong diep dai hoilng, dai hoilng, daioh, aiou, kot nam tao, rawind, Rhabarberwurzel, rhabarbarum, rhubarb, rhubard de Chine, rhubarb root, turkey rhubarb, ta-huang.

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 offinale) 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.

Plant material of interest: rhizomes and roots
General appearance

The appearance of the rhizomes and roots varies according to the plant's geographical origin. They occur on the market in sub cylindrical. barrel-shaped, 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 whitc parenchyma and brownish or reddish medullary ray.s, while here and there may be secn 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 2-4 mm in diameter that are arranged in a more or less continuous circle in R. palmatum or scattcrcd irregularly in R. officinale.

Organoleptic propeties
Odour, characteristic aromatic; taste, slightly astringent and bitter; when chewed, gritty bctwcen thc tecth; colour, yellow-brown to light brown.

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 anti raquinone 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.

Powdered plant mateiral
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, 1-25 um 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, 30-60um, frequently over 100um, and occasionally attaining a diameter of 190 um 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.

Geographical distribution
Rheum officinale and R. palmatum are cultivated in China (Gansu, Sichuan. and Oinghai provinces), the Democratic People's Republic of Korea and the Republic of Korea. There are several commercial grades (rhizomr with or without rootlets, peeled or unreeled. in transverse or longitudinal cuts)

General identity tests
Macroscopic and microscopic examinations: microchemical colour tests and  thin-layer chromatographic analysis for the presence of anthraquinones.

Purity tests
Microbiology

The test for Salmonella spp. in Rhizoma Rhei products shoul dbe negative.  The maximum acceptable limits of other microorganisms are as follows.  For preparation of decoction: aerobic bacteria--not more thatn 10 4/g: fungi--not more than 10 5/g; Escherichia coli--not more than 10 2/g.  Preparations for internal use: aerobic bacteria--not more than 10 5/g or ml: fungi--not more than 10 4/g or ml; enterobacteria and certain Gram-negative bacteria--not more than 10 3/g or ml: Esscherichia coli--o/g or ml.
          
Foreign Organic Matter
Not more than 1.0%

Total ash
Not more than 12% (2, 3).

Acid-insoluble ash
Not more than 2.0%.

Dilute ethanol-soluble extractive
Not less than 30%.

Moisture
Not more than l2%.

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. For other pesticides, see WHO guidelines on quality control methods for medicinal plants and guidelines for predicting dietary intake of pesticide residues.
                                                                                              
Heavy metals
Recommended lead an dcadmium levels are no more than 10 and 0.3mg/kg, respectively, in the final dosage form of the plant material.

Radioactive residues
For analysis of strontium-90, iodine-131, caesium-134, caesium-137, and   plutonium-239, see WHO guidelincs on quality control methods for medicinal plants.

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.   Quantittive analysis of total hydroxyanthracene glycosides,calculated as rhein, perofrmed by spectophotometric analysis.  High-performance liquid chromatography is also vailable for quantitative analysis hydroxyanthracene derivatives calculated as rhein.

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

Major chemical constituents
The major constituents arc 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. 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.

Dosage forms
Dried plant material and preparations standardized to contain 10-30 mg of hydroxyanthracene derivatives per dose.. Package in well-closed, light-resistant containers.

Medicinal uses
Uses supported by clinical data
Short-term treatment of occasional constipation.

Uses described in pharmacopoeias and in traditonal systems of medicine
None.

Uses described in folk medicine, not supported by eperimental or clinical data
To treat hypotension, increase peripheral vasodilation, and inhibit blood coagulation.

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 which results in an increase in the water content in the large intestine. Purgation is followed by an astringent effect owing to the tannins present.

Clinical pharmacology
The active constituents of Rhizoma Rhei are the anthraquinone glycosides, sennosides A-F and rheinosides A-D. 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. 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. Preparations of rhubarb, are suitable as an occasional aperient, but should not be used in chronic constipation. A variable amount is absorbed and imparts a yellowish brown colour to the urine, which is changed toa purplish red on the addition of alkali. Rhizoma Rhei preparations have becn emrloyed occasionally for their astrinent after effects, to check the diarrhoea produced by irritating substances in the intestines.

Toxicity
The major symptoms of overdose are griping and severe diarrhoea with consequent losses of fluid and electrolytes. rreatment 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 Rehi should not be used during pregnancy or lactation except under medical supervision after respective benefits and risks have been cosnidered.  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.

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 seriolls condition. Use of stimulant laxatives for longer than the recommended short-term application may increasc intestillal sluggishness.

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 neuromilscufar 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 gylcosides hould not be used for periods longer than 1-2 weeks continually, owing to the danger of electrolyte imbalance.

Drug interactions
Decreased intestinal transit time may reduce absorption of orally administered drugs.

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 qunidine, 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.

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

Carcinogenesis, mutagenesis, impairment of fertility
Data on the carcinogenicity of Rhzoma 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.

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.

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.

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 gastointestinal tract, which may require a reduction of dosage.  Overdoses can lead to colicky  abdominal spasms and pain and the formation f thin, watery stools.

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

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

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