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 Coptidis

Definition

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).

Synonyms

None.

Selected vernacular names

Coptis chinensis Franch

Chinese goldthread, ch'uan-lien, coptis, coptis rhizome, gold thread, huang lian, huang-lien, huánglián, oren, Perlenschnur, weilian (16).

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).

Coptis deltoides C.Y. Cheng et Hsiao and Coptis japonica Makino

Descriptions to be established by appropriate national authorities.

Plant material of interest: dried rhizome

General appearance

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 (810). 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, 3133). 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 (3436).

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.

Warnings

No information available.

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 (3743).

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

1. Pharmacopoeia of the People's Republic of China (English ed.). Guangzhou, Guangdong Science and Technology Press, 1992.

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

3. Chang HM, But PPH, eds. Pharmacology and applications of Chinese materia medica, Vol. 2. Singapore, World Scientific Publishing, 1987.

4. Medicinal plants in China. Manila, World Health Organization, 1989 (WHO Regional Publications, Western Pacific Series, No. 2).

5. Hsu HY. Oriental materia medica, a concise guide. Long Beach, CA, Oriental Healing Arts Institute, 1986.

6. 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).

7. Pandit MK, Babu CR. Cytology and taxonomy of Coptis teeta Wall. (Ranunculaceae). Botanical journal of the Linnean Society, 1993, 111:371–378.

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

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

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

11. 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).

12. Ikuta A, Kobayashi A, Itokawa H. Studies on the quantitative analysis of protoberberine alkaloids in Japanese, Chinese and other countries Coptis rhizomes by thin-layer chromatography-densitometry. Shoyakugaku zasshi, 1984, 38:279– 282.

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

14. Lampe KF, Berberine. In: De Smet PAGM et al., eds. Adverse effects of herbal drugs, Vol. 1. Berlin, Springer-Verlag, 1992:97–104.

15. Simeon S, Rios JL, Villar A. Pharmacological activities of protoberberine alkaloids. Plantes médicinales et phytothérapie, 1989, 23:202–250.

16. Kaneda Y et al. In vitro effects of berberine sulfate on the growth and structure of Entamoeba histolytica, Giardia lamblia, and Trichomonas vaginalis. Annals of tropical medicine and parasitology, 1991, 85:417–425.

17. Hah FE, Ciak J. Berberine. Antibiotics, 1975, 3:577.

18. Uebaba K et al. Adenylate cyclase inhibitory activity of berberine. Japanese journal of pharmacology, 1984, 36(Suppl. 1):352.

19. Hui KK et al. Interaction of berberine with human platelet alpha-2 adrenoceptors. Life sciences, 1989, 49:315–324.

20. Shin DH et al. A paradoxical stimulatory effect of berberine on guinea-pig ileum contractility: possible involvement of acetylcholine release from the postganglionic parasympathetic nerve and cholinesterase inhibition. Life sciences, 1993, 53:1495– 1500.

21. Sack RB, Froehlich JL. Berberine inhibits intestinal secretory response of Vibrio cholerae and Escherichia coli enterotoxins. Infection and immunity, 1989, 35:471–475.

22. Gaitonde BB, Marker PH, Rao NR. Effect of drugs on cholera toxin induced fluid in adult rabbit ileal loop. Progress in drug research, 1975, 19:519–526.

23. Sabir M, Akhter MH, Bhide NK. Antagonism of cholera toxin by berberine in the gastrointestinal tract of adult rats. Indian journal of medical research, 1977, 65:305–313.

24. Swabb EA, Tai YH, Jordan L. Reversal of cholera toxin-induced secretion in rat ileum by luminal berberine. American journal of physiology, 1981, 241:G248–G252.

25. Tai YH et al. Antisecretory effects of berberine in rat ileum. American journal of physiology, 1981, 241:G253–G258.

26. Guandalini S et al. Berberine effects on ion transport in rabbit ileum. Pediatric research, 1983, 17:423.

27. Shen ZF, Xie MZ. Determination of berberine in biological specimens by high performance TLC and fluoro-densitometric method. Yao hsueh hsueh pao, 1993, 28:532–536.

28. Chen QM, Xie MZ. Studies on the hypoglycemic effect of Coptis chinensis and berberine. Yao hsueh hsueh pao, 1986, 21:401–406.

29. Chen QM, Xie MZ. Effect of berberine on blood glucose regulation of normal mice. Yao hsueh hsueh pao, 1987, 22:161–165.

30. Vennerstrom JL et al. Berberine derivatives as antileishmanial drugs. Antimicrobial agents and chemotherapy, 1990, 34:918–921.

31. Lahiri SC, Dutta NK. Berberine and chloramphenicol in the treatment of cholera and severe diarrhea. Journal of the Indian Medical Association, 1967, 48:1–11.

32. Khin-Maung U et al. Clinical trial of berberine in acute watery diarrhoea. British medical journal, 1986, 291:1601–1605.

33. Rabbani GH et al. Randomized controlled trial of berberine sulfate therapy for diarrhea due to enterotoxigenic Escherichia coli and Vibrio cholerae. Journal of infectious diseases, 1987, 155:979–984.

34. Devi AL. Berberine sulfate in oriental sore. Indian medical gazette, 1929, 64:139.

35. Das Gupta BM. The treatment of oriental sore with berberine acid sulfate. Indian medical gazette, 1930, 65:683.

36. Das Gupta BM, Dikshit BB. Berberine in the treatment of Oriental boil. Indian medical gazette, 1929, 67:70.

37. Lee HK et al. Effect of bacterial growth-inhibiting ingredients on the Ames mutagenicity of medicinal herbs. Mutation research, 1987, 192:99–104.

38. Pasqual MS et al. Genotoxicity of the isoquinoline alkaloid berberine in prokaryotic and eukaryotic organisms. Mutation research, 1993, 286:243–252.

39. Faddejeva MD et al. Possible intercalative bindings of alkaloids sanguinarine and berberine to DNA. IRCS medical science and biochemistry, 1980, 8:612.

40. Nozaka T et al. Mutagenicity of isoquinoline alkaloids, especially the aporphine type. Mutation research, 1990, 240:267–279.

41. Morimoto I et al. Mutagenicity screening of crude drugs with Bacillus subtilis Rec-assay and Salmonella/microsome reversion assay. Mutation research, 1982, 97:81– 102.

42. Yamamoto K, Mizutani T, Nomura H. Studies on the mutagenicity of crude drug extracts. I. Yakugaku zasshi, 1982, 102:596–601.

43. Watanabe F et al. Mutagenicity screening of hot water extracts from crude drugs. Shoyakugaku zasshi, 1983, 37:237–240.

44. Roth L, Daunderer M, Kormann K. Giftpflanzen. Pflanzengifte, 3rd ed. Landsberg, Ecomed, 1988:145–146, 810.

45. Bao Y. Side effects of Coptis chinensis and berberine. Chinese journal of integrated and traditional western medicine, 1983, 3:12–13.

 

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: March 20, 2014