МОНОГРАФИИ ВОЗ Т 4

Cortex Berberidis

Dosage forms

Crude drug and dried extracts, fluidextracts, and tinctures (1, 75). Store in a tightly sealed container away from heat and light.

Posology

(Unless otherwise indicated)

Daily dose: crude drug 0.5–1.0 g three times daily, or by decoction; liquid extract 1:1 in 60% ethanol, 0.3–1.0 ml three times daily; tincture 1:10 60% ethanol, 2–4 ml three times daily (1).

References

1.British herbal pharmacopoeia, Vol. 1. Exeter, British Herbal Medicine Association, 1996.

2.Farmacopea homeopática de los estados unidos mexicanos. Mexico City, Secretaría de salud, Comisión permanente de la farmacopea de los Estados Unidos Mexicanos, 1998 [in Spanish].

3.Bedevian AK. Illustrated polyglottic dictionary of plant names. Cairo, Medbouly Library, 1994.

4.Farnsworth NR, ed. NAPRALERT database. Chicago, University of Illinois at Chicago, IL (an online database available directly through the University of Illinois at Chicago or through the Scientific and Technical Network [STN] of Chemical Abstracts Services), 30 June 2005.

5.Youngken HW. Textbook of pharmacognosy. Philadelphia, Blakiston, 1950.

6.PDR for herbal medicine. Montvale, New Jersey, Medical Economics Company, 1998.

7.WHO guidelines on assessing quality of herbal medicines with reference to contaminants and residues. Geneva, World Health Organization, 2007.

8.European Pharmacopoeia, 5th ed. Strasbourg, Directorate for the Quality of Medicines of the Council of Europe (EDQM), 2005.

9.Guidelines for predicting dietary intake of pesticide residues, 2nd rev. ed. Geneva, World Health Organization, 1997 (unpublished document WHO/FSF/ FOS/97.7).

10.The United States Pharmacopoeia, 29. Rockville, MD, United States Pharmacopeia Convention, 2005.

11.Drost-Karbowska K, Kowalewski Z, Szaufer M. Determination of protoberberine alkaloid complex in various organs of Berberis vulgaris. Acta Poloniae Pharmaceutica, 1974, 31:683–687.

12.Slavik J, Slavikova L. Quaternary isoquinoline alkaloids and some diterpenoid alkaloids in plants of the Czech Republic. Collection Czechoslovakian Chemical Communication, 1995, 60:1034–1041 [in English].

13.Velluda CC et al. Effect of Berberis vulgaris extract, and of berberine, berbamine and oxyacanthine alkaloids on liver and bile function. Lucrarile prezentate. Conference Nationale Farmacia Bucharest, 1958:351–354.

43

WHO monographs on selected medicinal plants

14.Khin-Maung U et al. Clinical trial of berberine in acute watery diarrhoea.

British Medical Journal, 1986, 291:1601–1605.

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

16.Chauhan RK, Jain AM, Bhandari B. Berberine in the treatment of childhood diarrhoea. Indian Journal of Pediatrics, 1970, 37:577–579.

17.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.

18.Sharda DC. Berberine in the treatment of diarrhoea in infancy and childhood. Journal of the Indian Medical Association, 1970, 54:22–24.

19.Sharma R, Joshi CK, Goyal RK. Berberine tannate in acute diarrhoea. Indian Journal of Pediatrics, 1970, 7:496–501.

20.Tang W, Eisenbrand G. Chinese drugs of plant origin. London, Springer-Ver- lag, 1992.

21.Mohan M et al. Berberine in trachoma. Indian Journal of Ophthalmology, 1982, 30:69–75.

22.Das Gupta BM. The treatment of oriental sore with berberine acid sulfate.

Indian Medical Gazette, 1930, 65:683–685.

23.Das Gupta BM, Dikshit BB. Berberine in the treatment of Oriental boil. Indian Medical Gazette, 1929, 67:70.

24.Devi AL. Berberine sulfate in oriental sore. Indian Medical Gazette, 1929, 64:139.

25.Peirce A. The APhA practical guide to natural medicines. New York, NY, Stonesong Press, Wm. Morrow & Co., 1999.

26.Kupeli E et al. A comparative study on the anti-inflammatory, antinociceptive and antipyretic effects of isoquinoline alkaloids from the roots of Turkish Berberis species. Life Sciences, 2002, 72:645–657.

27.Zolotnitskaya SY, ed. Pharmaceutical resources of Armenian Flora, Vol. 2. Yerevan, Armenia, SSR AN Publishers, 1965.

28.Hahn FE, Ciak J. Berberine. Antibiotics, 1975, 3:577–588.

29.Uebaba K et al. Adenylate cyclase inhibitory activity of berberine. Japanese Journal of Pharmacology, 1984, 36 (Suppl.1):352.

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

31.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.

32.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.

33.Sack RB, Froehlich JL. Berberine inhibits intestinal secretory response of

Vibrio cholerae and Escherichia coli enterotoxins. Infection and Immunity, 1982, 35:471–475.

44

Cortex Berberidis

34.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.

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

36.Tai YH et al. Antisecretory effects of berberine in rat ileum. American Journal of Physiology, 1981, 241:G253–G258.

37.Taylor CT et al. Berberine inhibits ion transport in human colonic epithelia.

European Journal of Pharmacology, 1999, 368:111–118.

38.Ivanovska N, Philipov S, Hristova M. Influence of berberine on T-cell mediated immunity. Immunopharmacology and Immunotoxicology, 1999, 21:771– 786.

39.Zhou H, Mineshita S. The effect of berberine chloride on experimental colitis in rats in vivo and in vitro. Journal of Pharmacology and Experimental Therapeutics, 2000, 294:822–829.

40.Iizuka N et al. Inhibitory effect of Coptidis Rhizoma and berberine on the proliferation of human esophageal cancer cell lines. Cancer Letters, 2000, 148:19–25.

41.Ivanovska N, Philipov S. Study on the anti-inflammatory action of Berberis vulgaris root extract, alkaloid fractions and pure alkaloids. International Journal of Immunopharmacology, 1996, 18:553–561.

42.Huang CG et al. Effect of berberine on arachidonic acid metabolism in rabbit platelets and endothelial cells. Thrombosis Research, 2002, 106:223–227.

43.Mahady GB et al. In vitro susceptibility of Helicobacter pylori to isoquinoline alkaloids from Sanguinaria canadensis and Hydrastis canadensis. Phytotherapy Research, 2003, 17:217–221.

44.Stermitz FR et al. Two flavonols from Artemisia annua which potentiate the activity of berberine and norfloxacin against a resistant strain of Staphylococcus aureus. Planta Medica, 2002, 68:1140–1141.

45.Gentry EJ et al. Antitubercular natural products: berberine from the roots of commercial Hydrastis canadensis powder. Isolation of inactive 8-oxotetrahy- drothalifendine, canadine, Β-hydrastine, and two new quinic acid esters, hycandinic acid esters-1 and -2. Journal of Natural Products, 1998, 61:1187– 1193.

46.Chi HJ, Woo YS, Lee YJ. Effect of berberine and some antibiotics on the growth of microorganisms. Korean Journal of Pharmacognosy, 1991, 22:45–50.

47.Cernakova M, Kostalova D. Antimicrobial activity of berberine – a constituent of Mahonia aquifolium. Folia Microbiologia (Praha), 2002, 47:375–378.

48.Iwasa K et al. Structure-activity relationships of protoberberines having antimicrobial activity. Planta Medica, 1998, 64:748–751.

49.Kaneda Y et al. In vitro effects of berberine sulphate on the growth and structure of Entamoeba histolytica, Giardia lamblia, and Trichomonas vaginalis. Annals of Tropical Medicine and Parasitology, 1991, 85:417–425.

45

WHO monographs on selected medicinal plants

50.Pan JF et al. Identification of three sulfate-conjugated metabolites of berberine chloride in healthy volunteers’ urine after oral administration. Acta Pharmacologia Sinica, 2002, 23:77–82.

51.Pan GY et al. The involvement of P-glycoprotein in berberine absorption.

Pharmacology and Toxicology, 2002, 91:193–197.

52.Zhou Z, Xu J, Lan T. [Protective effect of berberine on isolated perfused heart in heart failure.] Huaxi Yike Daxue Xuebao, 2001, 32:417–418.

53.Wong KK. Mechanism of the aorta relaxation induced by low concentrations of berberine. Planta Medica, 1998, 64:756–757.

54.Chiou WF, Yen MH, Chen CF. Mechanism of vasodilatory effect of berberine in rat mesenteric artery. European Journal of Pharmacology, 1991, 204:35–40.

55.Ko WH et al. Vasorelaxant and antiproliferative effects of berberine. European Journal of Pharmacology, 2000, 399:187–196.

56.Chiou WF, Chen J, Chen CF. Relaxation of corpus cavernosum and raised intracavernous pressure by berberine in rabbit. British Journal of Pharmacology, 1998, 125:1677–1684.

57.Baldazzi C et al. Effects of the major alkaloid of Hydrastis canadensis L., berberine, on rabbit prostate strips. Phytotherapy Research, 1998, 12:589– 591.

58.Cao JW et al. Effects of berberine on intracellular free calcium in smooth muscle cells of guinea pig colon. Digestion, 2001, 64:179–183.

59.Rehman J et al. Increased production of antigen-specific immunoglobulins G and M following in vivo treatment with the medicinal plants Echinacea angustifolia and Hydrastis canadensis. Immunology Letters, 1999, 68:391–395.

60.Marinova EK et al. Suppression of experimental autoimmune tubulointerstitial nephritis in BALB/c mice by berberine. Immunopharmacology, 2000, 48:9–16.

61.Xu X, Malave A. Protective effect of berberine on cyclophosphamide-in- duced haemorrhagic cystitis in rats. Pharmacological Toxicology, 2001, 88:232–237.

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

63.Janbaz KH, Gilani AH. Studies on preventive and curative effects of berberine on chemical-induced hepatotoxicity in rodents. Fitoterapia, 2000, 71:25–33.

64.Supek Z, Tomic D. Pharmacological and chemical investigations of barberry (Berberis vulgaris). Lijec vjesnic, 1946, 68:16.

65.Haginiwa J, Harada M. Pharmacological studies on crude drugs. V. Comparison of the pharmacological actions of berberine type alkaloid containing plants and their components. Yakugaku Zasshi, 1962, 82:726.

66.Cometa MF, Abdel-Haq H, Palmery M. Spasmolytic activities of Hydrastis canadensis L. on rat uterus and guinea pig trachea. Phytotherapy Research, 1998, 12(Suppl 1):S83–S85.

46

Cortex Berberidis

67.Maeng HJ et al. P-glycoprotein-mediated transport of berberine across Caco-2 cell monolayers. Journal of Pharmaceutical Sciences, 2002, 91:2614– 2621.

68.Tsai PL, Tsai TH. Simultaneous determination of berberine in rat blood, liver and bile using microdialysis coupled to high-performance liquid chromatography. Journal of Chromatography A, 2002, 961:125–130.

69.Blumenthal M et al., eds. The complete German Commission E monographs. Austin, TX, American Botanical Council, 1998.

70.Inbaraj JJ et al. Photochemistry and photocytotoxicity of alkaloids from Goldenseal (Hydrastis canadensis L.) 1. Berberine. Chemical Research Toxicology, 2001, 14:1529–1534.

71.Lin HL et al. Up-regulation of multidrug resistance transporter expression by berberine in human and murine hepatoma cells. Cancer, 1999, 85:1937– 1942.

72.Lin HL et al. Berberine modulates expression of mdr1 gene products and the responses of digestive tract cancer cells to Paclitaxel. British Journal of Cancer, 1999, 81:416–422.

73.Li Q et al. Clinical study on coadministration of cyclosporin A and berberine hydrochloride in renal transplant recipients. China Journal of Clinical Pharmacology, 2001, 17:114–117.

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

75.Bradley PR ed. British herbal compendium, Vol. 1. London, British Herbal Medicine Association, 1992.

47

Gummi Boswellii

Definition

Gummi Boswellii consists of the dried gum resin of Boswellia serrata Roxb. ex Colebr. (Burseraceae) (1).

Synonyms

Boswellia glabra Roxb., B. thurifera (Colebr.) Roxb. (2, 3).

Selected vernacular names

Alberodell’incenso, anduga, arbore à encerns, boswellia, boswellie-dent- elee, chilakdupa, dhupelio, dhup-gugali, dhupdo, fan hun hsiang, fan hun shu, gajabhakshya, gandhabiroz, gobahr shalla, gugal, guggul, guggula, husn-e-lubban, Indian frankincense tree, Indian olibanum, Indischerweihrauch, kapitthaprani, kondagugi tamu, kondor, koonkanadhoopam, kundre, kundrikam, kundur, kundur luban, kunduru, kunthreekan, kunturukkam, labana, loban, loban zakar, lobhan, luban, luban-dacar-hindi, luban dhakar, maddi, madi, madimar, pahadi, parangisambrani, parangisampirani, saladi, salai, Salaibaum, salai cha dink, salai gonad, salai guggal, salakhi, saleda, saledhi, saledo, salgai, sallaki, sambrani, samprani, sanlaki, shaledum, shallaki, susrava, tallaki, vishesha dhoop, visheshdhup, zarw (1, 2, 4–7).

Geographical distribution

Native to India (3, 6, 7).

Description

A medium to large deciduous tree, up to 18 m in height and 2.4 m in girth. Leaves imparipinnate, leaflets ovate or ovate-lanceolate, variable. Flowers small, white, in axillary racemes or panicles. Drupes 12 mm long, trigonous, scarlet when young, turn white at maturity. Bark thick and aromatic. When cut, a secretion exudes and becomes gum-like after exposure to air (1, 2, 7).

48

Gummi Boswellii

Plant material of interest: dried gum-resin

General appearance

The gum solidifies slowly with time. It is reddish brown, greenish yellow, or dull yellow to orange in colour. It occurs in small, ovoid, fragrant tears. Sometimes the tears form agglomerated masses up to 5 cm long and 2 cm thick. Fracture is brittle, fractured surface is waxy and translucent. Burns readily and emanates an agreeable characteristic balsamic resinous odour (1, 2).

Organoleptic properties

Odour: aromatic, characteristically balsamiferous; taste: agreeable (1, 2).

Microscopic characteristics

Debris of fibres, rectangular cork cells, very few yellowish oil globules and numerous, small or large, oval to round or rhomboidal crystalline fragments present (2).

Powdered plant material

Not applicable.

General identity tests

Macroscopic examinations (1, 2), microchemical and fluorescence tests and thin-layer chromatography (1), high-performance liquid chromatography (8, 9) and gas chromatography–mass spectrometry for the presence of boswellic acids (10), as well as gas chromatography–mass spectrometry analysis for volatile and semi-volatile terpenes (11).

Purity tests

Microbiological

Tests for specific microorganisms and microbial contamination limits are as described in the WHO guidelines on assessing quality of herbal medicines with reference to contaminants and residues (12).

Foreign organic matter

Not more than 5% (1).

Total ash

Not more than 10% (1).

Acid-insoluble ash

Not more than 8% (1).

Water-soluble extractive

Not less than 28% (1).

49

WHO monographs on selected medicinal plants

Alcohol-soluble extractive

Not less than 45% (1).

Loss on drying

To be established in accordance with national requirements.

Pesticide residues

The recommended maximum limit of aldrin and dieldrin is not more than 0.05 mg/kg (13). For other pesticides see the European Pharmacopoeia (13) and the WHO guidelines on assessing quality of herbal medicines with reference to contaminants and residues (12) and pesticide residues (14).

Heavy metals

For maximum limits and analysis of heavy metals, consult the WHO guidelines on assessing quality of herbal medicines with reference to contaminants and residues (12).

Radioactive residues

Where applicable, consult the WHO guidelines on assessing quality of herbal medicines with reference to contaminants and residues (12).

Chemical assays

To be established in accordance with national requirements.

Major chemical constituents

Contains 5–9% essential oil with major constituents being Α-thujene (50– 61%), sabinene (5%), Α-pinene (8%) and Α-phellandrene (2%). Major triterpene constituents of biological interest are members of the boswellic acids (more than 12) including 11-oxo-Β-boswellic acid, 3-O-acetyl-11- oxo-Β-boswellic acid, Α-boswellic acid, Β-boswellic acid, 3-O-acetyl-Α- boswellic acid, and 3-O-acetyl Β-boswellic acid (3, 15–17). The structures of representative boswellic acids are presented below.

Medicinal uses

Uses supported by clinical data

Orally for the management of arthritis, bronchial asthma, Crohn’s disease and ulcerative colitis (18–22).

Uses described in pharmacopoeias and well established documents

Orally for the treatment of rheumatism and arthritis (1, 2, 23).

50

Gummi Boswellii

Uses described in traditional medicine

Treatment of abdominal pain, asthma, coughs, dysentery, fever, jaundice, kidney stones, pimples, sores and stomach disorders (5). Also used as an antivenin and an emmenagogue (24, 25).

Pharmacology

Experimental pharmacology

Analgesic activity

Intragastric administration of the gum at doses ranging from 100.0– 500.0 mg/kg body weight (bw) had no analgesic effects in dogs, rabbits or rats (26–28). However, administration of a non-phenolic fraction of the crude drug produced analgesia in 60% of rats treated with a dose of 60.0 mg/kg bw. A dose of 150.0 mg/kg bw induced analgesia in 70% of rats (29). The degree of analgesia was comparable to a dose of 3–4.5 mg/ kg bw of morphine. A dose of 150.0 mg/kg bw also caused a 70% reduction in spontaneous motor activity that lasted for 2 hours (29).

Anticomplementary activity

Boswellic acids exhibited anticomplementary activity in vitro, as assessed by the reduction of immune-induced haemolysis of antibody-coated sheep erythrocytes by pooled guinea-pig serum (30). The decrease in im- mune-induced haemolysis was due to inhibition of C3-convertase of the classical complement pathway. The threshold concentration for inhibiting C3-convertase was found to be 100.0 μg/ml (30).

51

WHO monographs on selected medicinal plants

Anti-inflammatory activity

The anti-inflammatory activity of an aqueous extract of the crude drug was assessed in vivo. The extract significantly inhibited both the maximal oedema response and the total oedema response during 6 hours of carra- geenan-induced rat paw oedema (31). Intragastric administration of the gum or an aqueous methanol extract of the gum (9:1) to rats, at a dose of 50.0–200.0 mg/kg bw reduced carrageenanor adjuvant-induced pedal oedema by 34–73% (26, 32). An ethanol extract of the crude drug, administered at a dose of 50.0–200.0 mg/kg bw, exhibited anti-inflammatory activity in carrageenan-induced oedema in rats and mice and dextran-in- duced oedema in rats (28). The extract also had considerable anti-arthritic activity but no significant effect was observed in the cotton pellet-induced granuloma test. Treatment with the extract inhibited inflammation-in- duced increase in serum transaminase levels and leukocyte counts, but lacked any analgesic or antipyretic effects in rats (28).

The anti-inflammatory effects of the crude drug and boswellic acids were assessed in rats with adjuvant-induced arthritis. The animals were treated with 100.0 mg/kg bw of the crude drug or 200.0 mg/kg bw of boswellic acid administered by gastric lavage for 2 weeks (33). The activity of Β-glucuronidase was used to assess lysosomal stability, which is an important factor in the arthritic syndrome. Induction of arthritis reduced lysosome stability, but treatment with either the extract or boswellic acid increased stability and had a protective effect on lysosomal integrity (33). Specific boswellic acids inhibit elastase in leukocytes, inhibit proliferation, induce apoptosis and inhibit topoisomerases of leukaemia and glioma cell lines (23).

A methanol extract of the crude drug, containing boswellic acids and their structural derivatives, was applied topically to the backs of mice to determine its anti-inflammatory effects (23). The treatment markedly inhibited 12-O-tetradecanoylphorbol-13-acetate-induced skin inflammation, epidermal proliferation, the number of epidermal cell layers and tumour promotion in 7,12-dimethylbenz[a]anthracene-initiated mice. Feeding 0.2% of crude drug in the diet to CF-1 mice for 10–24 weeks reduced the accumulation of parametrial fat pad weight under the abdomen, and inhibited azoxymethane-induced formation of aberrant crypt foci by 46% (22).

Boswellic acids (15.0 μg/ml) inhibit the biosynthesis of the pro-inflam- matory leukotrienes in neutrophilic granulocytes by a non-redox, noncompetitive inhibition of 5-lipoxygenase, an enzyme in the pro-inflamma- tory arachidonic acid cascade (34–36). The extract and its derivatives caused a concentration-dependent decrease in the formation of leukotriene

52