Coptis chinensis

Rhizoma Coptidis WHO

Rhizoma Coptidis is the dried rhizome of Coptis chinensis Franch, Coptis deltoides C.Y. Cheng et Hsiao, Coptis japonica Makino (Ranunculaceae), or other berberine-containing species of the same genus (1, 2).

Selected vernacular names

Coptis chinensis Franch

Chinese goldthread, ch'uan-lien, coptis, coptis rhizome, gold thread, huang lian, huang-lien, huánglián, oren, Perlenschnur, weilian (1–6).

Coptis deltoides C.Y. Cheng et Hsiao

Coptis, gold thread, huang lian, huang-lien, huánglián, yalian (1, 4, 7).

Coptis japonica Makino

Coptis, coptis rhizome, oren (2, 5).

Description

Coptis chinensis Franch

A perennial stemless herb, 20–50 cm high. Leaves basal, long petiolate; blade triangular-ovate, 3–8 cm long by 2.5–7 cm wide, ternatisect; leaflets pinnatifid, lobes incised, the terminal leaflet longer than the others. Peduncles 1–2, 12– 25cm long, bracts resembling leaves. Inflorescence a terminal cyme with 3–8 whitish green flowers; sepals narrow-ovate, 9–12 mm long; petals small, oblanceolate, 5–7mm long; stamens numerous, 3–6mm long; carpels 8–12, with carpophores, follicles many-seeded. Seeds with black crustaceous testa. Rhizome shaped like a cockspur, 5–6 cm long, brownish yellow, densely covered with numerous nodes and often with rootlets; interior yellow-orange; in transverse section, the central pith deeper in colour (4).

Plant material of interest: dried rhizome

Coptis chinensis Franch

The rhizome is curved, gathered in a cluster and resembles "chicken feet", 3– 6cm long and 3–8mm in diameter. Rough, greyish yellow or yellowish brown surface, bearing irregular protrusions, rootlets, and rootlet remnants. Apex often bearing remains of stem or petiole. Texture is hard and fracture uneven. Bark is orange-red or dark brown; wood brightly yellow or orange-yellow. Pith, sometimes hollowed (1).

Coptis deltoides C.Y. Cheng et Hsiao

Frequently single, somewhat cylindrical, slightly curved, 4–8cm long and 0.5– 1cm in diameter. Internodes smooth and relatively long. Apex with some stem remains (1).

Coptis japonica Makino

Irregular, cylindrical rhizome, 2–4cm, rarely up to 10 cm in length, 0.2–0.7 cm in diameter, slightly curved and often branched; externally greyish yellow-brown, with ring nodes, and with numerous remains of rootlets; generally remains of petiole at one end; fractured surface rather fibrous; cork layer light greyish brown, cortex yellow-brown, xylem yellow, and pith yellow-brown in colour (2).

Organoleptic properties

Odour, slight; taste, very bitter; colour, greyish yellow to yellowish brown, drug when chewed colours saliva yellow (1, 2).

Microscopic characteristics

Coptis chinensis Franch

In transverse section cork cells occupy several layers. Cortex broader than others; stone cells singly or grouped together; pericycle fibres yellow, in bundles or accompanied by stone cells; collateral vascular bundles arranged in a ring. Interfascicular cambium indistinct. Xylem yellow, lignified with well developed fibres. Pith consisting of parenchyma cells and devoid of stone cells (1).

Coptis deltoides C.Y. Cheng et Hsiao

Transverse section shows pith with stone cells (1).

Coptis japonica Makino

Transverse section reveals a cork layer composed of thin-walled cork cells; cortex parenchyma usually contains groups of stone cells near the cork layer and yellow phloem fibres near the cambium; xylem consists chiefly of vessels, tracheae and wood fibres; medullary ray distinct; pith large; in pith, stone cells or sometimes stone cells with thick and lignified cells are recognized; parenchyma cells contain minute starch grains (2).

Powdered plant material

Coptis japonica Makino

Almost all elements are yellow. The powder shows mainly fragments of vessels, tracheids, and xylem fibres; parenchyma cells containing starch grains; polygonal cork cells. Usually, round to obtuse polygonal stone cells and their groups, and phloem fibres, 10–20µm in diameter, and fragments of their bundles. Occasionally, polygonal and elongated epidermal cells, originating from the petiole, having characteristic thickened membranes. Starch grains are single grains 1–7µm in diameter (2).

Coptis chinensis Franch and Coptis deltoides C.Y. Cheng et Hsiao

Descriptions to be established by appropriate national authorities.

Geographical distribution

Coptis chinensis Franch. and Coptis deltoides C.Y. Cheng et Hsiao

China (3, 4).

Coptis japonica Makino

Japan (2).

Coptis teeta Wall.

Indigenous in India, where it is considered an endangered species (7). Coptis teeta Wall. has compendial status in China (1), where it is cultivated commercially (2).

General identity tests

Macroscopic, microscopic, and microchemical examinations; thin-layer chromatographic analysis for the presence of berberine (1, 2).

Purity tests

Microbiological

The test for Salmonella spp. in Rhizoma Coptidis products should be negative. The maximum acceptable limits of other microorganisms are as follows (8–10). 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.

Total ash

Not more than 5.0% (1, 2).

Pesticide residues

To be established in accordance with national requirements. Normally, the maximum residue limit of aldrin and dieldrin for Rhizoma Coptidis is not more than 0.05 mg/kg (10). For other pesticides, see WHO guidelines on quality control methods for medicinal plants (8) and guidelines for predicting dietary intake of pesticide residues (11).

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 (8).

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 (8).

Other purity tests

Chemical tests and tests for acid-insoluble ash, dilute ethanol-soluble extractive, foreign organic matter, moisture and water-soluble extractive are to be established in accordance with national requirements.

Chemical assays

Should contain not less than 4.2% of berberine, calculated as berberine chloride, assayed by means of thin-layer chromatography or high-performance liquid chromatography (2).

Major chemical constituents

The major constituents are berberine and related protoberberine alkaloids (3, 8, 10). Berberine occurs in the range of 4–8% (C. chinensis: 5–7%; C. deltoides: 4– 8%; C. japonica: 7–9%), followed by palmatine (C. chinensis: 1–4%; C. deltoides: 1–3%; C. japonica: 0.4–0.6%), coptisine (C. chinensis: 0.8–2%; C. deltoides: 0.8–1%; C. japonica: 0.4–0.6%), berberastine (C. chinensis: 1%; C. deltoides: 1%; C. japonica: trace) among others (12).

Dosage forms

Crude plant material, decoction, and powder. Store in a well-ventilated dry environment protected from light (1).

Medicinal uses

Uses supported by clinical data

None.

Uses described in pharmacopoeias and in traditional systems of medicine

To manage bacterial diarrhoeas (1, 4). The drug is also used in the treatment of acute conjunctivitis, gastroenteritis, boils, and cutaneous and visceral leishmaniasis ("oriental sore") (1, 4, 13, 14).

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

Treatment of arthritis, burns, diabetes, dysmenorrhoea, toothache, malaria, gout, and renal disease (13).

Pharmacology

Experimental pharmacology

Numerous reports support the antimicrobial activity of Rhizoma Coptidis. In vitro studies have shown that the crude drug and its active constituent, berberine, have a similar spectrum of antibacterial action (3, 15). Both inhibit the in vitro growth of staphylococci, streptococci, pneumococci, Vibrio cholerae, Bacillus anthracis, and Bacillus dysenteriae, but they do not inhibit Escherichia coli, Proteus vulgaris, Salmonella typhi, S. paratyphi, Pseudomonas aeruginosa, and Shigella sonnei (3). Berberine was also active in vitro against Entamoeba histolytica, Giardia lamblia, and Trichomonas vaginalis (16).

In vitro studies have demonstrated that V. cholerae can grow in a medium containing berberine, but it fails to produce toxins (17). It has been hypothesized that the antidysenteric activity of berberine is due to local effects on the intestinal tract and not due to its bactericidal activity. The mechanism by which berberine exerts its antidiarrhoeal effects is thought to be activation of α2-adrenoceptors and inhibition of cyclic AMP accumulation (18), which in turn decrease intestinal motility (19). However, in vitro studies of the drug on guineapig ileum contractility have demonstrated that berberine (≥1µmol/l) inhibits acetylcholinesterase, which decreases the breakdown of acetylcholine and increases the contractility of the ileum (20). This study suggests that the antidiarrhoeal activity of berberine may be due to its antisecretory (21) as well as its antimicrobial actions (20). Berberine inhibits in vivo and in vitro intestinal secretions induced by cholera toxin (22–24). In addition, berberine reduces intestinal secretion induced by the heat-labile toxin of Escherichia coli in rabbit ileal loop by 70% and it markedly inhibits the secretory response of the heatstable toxin of E. coli in rats (25, 26).

Intragastric administration of berberine to mice produces hypoglycaemic effects with doses of 50–100mg/kg (27–29).

Local injection of berberine into lesions caused by Leishmania braziliensis panamensis in hamsters reduced lesion size by approximately 50% (30).

Clinical pharmacology

Despite the large number of published clinical studies, only two have examined the effect of berberine in comparison with a positive control, such as tetracycline, on fluid loss caused by diarrhoea in patients with cholera or in noncholera diarrhoea (14, 31–33). In the first study, berberine chloride 100mg was administered orally four times daily. The alkaloid did not have any signifi- cant vibriostatic effect; instead it only slightly reduced stool volume, and possibly reduced the vibriostatic effect of tetracycline (32). Berberine or tetracycline was no better than a placebo in patients with non-cholera diarrhoea of unspeci- fied etiologies (32). A randomized controlled trial of 165 patients utilized a 400mg single-bolus dose of berberine sulfate for enterotoxigenic Escherichia coli-induced diarrhoea and either 400 mg as a single oral dose or 1200mg of berberine sulfate (400 mg every 8 hours) for the treatment of cholera (33). Berberine significantly reduced stool volume during enterotoxigenic E. coli (ETEC) diarrhoea regardless of strain and had a slight antisecretory activity in patients with cholera. No adverse effects were observed in the patients receiving berberine. The results of this study indicated that berberine was an effective and safe antisecretory drug for ETEC diarrhoea, but that it had only a modest antisecretory effect in cholera patients, where the activity of tetracycline alone was superior (33).

Berberine has been used therapeutically in the treatment of cutaneous leishmaniasis ("oriental sore") by direct injection of the drug into local lesions. In humans, injection of a preparation containing 2% berberine into lesions caused by Leishmania tropica was an effective treatment (34–36).

Contraindications

The safety of berberine or extracts of Rhizoma Coptidis in pregnancy has not been established (14). Therefore, until such data are available the use of berberine during pregnancy is contraindicated.

Precautions

Carcinogenesis, mutagenesis, impairment of fertility

The safety of berberine or extracts of Rhizoma Coptidis has not been established with respect to fertility (14). There are conflicting reports as to the mutagenicity of Rhizoma Coptidis and berberine (37–43).

Pregnancy: non-teratogenic effects

The safety of berberine or extracts of Rhizoma Coptidis has not been established with respect to pregnancy. See Contraindications, above.

Nursing mothers

Excretion of berberine or Rhizoma Coptidis into breast milk, and its effects on the newborn have not been established; therefore, use of the herb during lactation is not recommended.

Paediatric use

The safety and efficacy of Rhizoma Coptidis or berberine in children have not been established.

Other precautions

No information available concerning general precautions, drug interactions, drug and laboratory test interactions, or teratogenic effects on pregnancy.

Adverse reactions

Berberine was reported to be well tolerated in therapeutic doses of 500mg, and no serious intoxication was reported in humans (44). One report of nausea, vomiting, enterocinetic sound, abdominal distortion, diarrhoea, polyuria, and erythropenia after administration of oral Rhizoma Coptidis to human adults (45) does not state the dosage used. No systematic studies have assessed organ function during acute or chronic administration of berberine salts or extracts of Rhizoma Coptidis (14).

Posology

Maximum daily oral dosage of crude plant material: 1.5–6g (1, 3).

References

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