МОНОГРАФИИ ВОЗ Т 4

Fructus Momordicae

tion with a glucose load resulted in a significant improvement in glucose tolerance (p < 0.05) without increasing insulin levels in the blood. In addition, daily consumption of the fried fruit for 8–11 weeks reduced levels of glycosylated haemoglobin by 8% from baseline (29). However, no randomization, blinding or proper controls were used in this study.

In another small case-report study (n = 8) an improvement in blood glucose tolerance and fasting blood glucose levels was observed in male and female patients (38–50 years of age) with uncomplicated type II diabetes. Patients were treated with 50 mg/kg bw of the dried fruit powder twice daily for 1 week (25). In addition, excretion of glucose in the urine was reduced by day 3 and was completely absent after 7 days of treatment. Mean post-treatment blood glucose levels were significantly lower than pre-treatment values. A decrease from 248 mg/dl to 155 mg/dl (p < 0.001) was observed in treated patients and this difference was considerably higher after the administration of 60 g of glucose. No adverse effects were reported.

In a similar case-report study, involving 12 patients with newly diagnosed type II diabetes, the effect of the crude drug on blood glucose levels was assessed. Each patient received one of two crude drug preparations. The first was an aqueous extract prepared by boiling 100 g of the crude drug in 200 ml of water until the volume was reduced to 100 ml. The second preparation was dried fruit powder, administered at a dose of 5 g three times daily. After 3 weeks of treatment the group using the powder preparation showed a reduced post-prandial blood glucose level of 25%, but the result was not statistically significant. However, in the group receiving the aqueous extract, a significant reduction (54%, p < 0.01) in blood glucose was observed, as well as a reduction in glycosylated haemoglobin from 8.37% to 6.95% (p < 0.01) (30).

A series of case-reports involving 18 patients with newly diagnosed type II diabetes assessed the effects of the fruit juice on blood sugar levels (53). The results of oral administration of 100.0 ml of the fruit juice 30 minutes prior to glucose loading for a glucose tolerance test were compared with the results of a glucose tolerance test done the previous day using water as the control test substance. Seventy-three per cent of the patients showed a moderate or significant improvement in glucose tolerance test results after taking the fruit juice before the glucose tolerance test (51). Unfortunately, the study was neither randomized nor blinded, and the patients’ baseline characteristics were poorly described.

In a clinical study, 22 subjects (12 healthy volunteers and 10 patients with type II diabetes) were administered a powder of the fruit after which the serum cholesterol and glucose tolerance were assessed (31). Oral

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administration of the powdered fruit to 10 patients with type II diabetes, at a dose of 2.0 g/day for 11 days, reduced blood glucose and total cholesterol levels by 10.02%. The reduction in blood glucose levels during the glucose tolerance test was 10.64–15.15% in the patients with diabetes, and was highly significant (p < 0.001).

The effects of the crude drug on fasting and post-prandial serum glucose levels (2 hours after oral administration of 75 g glucose) were studied in 100 subjects with moderate non-insulin dependent diabetes mellitus. Drinking the aqueous homogenized suspension of the vegetable pulp led to a significant reduction (p < 0.001) of both fasting and post-prandial serum glucose levels. This hypoglycaemic action was observed in 86 (86%) of the patients. Five patients (5%) showed lowering of fasting serum glucose only (24).

Immune stimulation

Cervical cancer patients have a decreased total white blood cell count, including that of natural killer cells. Natural killer cells, one type of lymphocyte, play a role in eliminating cancer cells by antibody-dependent cell-mediated cytotoxicity. A clinical study assessed the effect of the crude drug in cervical cancer patients undergoing normal treatment (radiotherapy). Subjects were divided into three groups:

—normal control (women aged 35–55 years, n = 35);

—patient control (n = 30); and

—patient treatment (n = 30).

The women in the patient control and patient treatment groups were cervical cancer patients (stage II or III) being treated with radiotherapy (without or with addition of the crude drug). Blood samples from women in the patient control and patient treatment groups were analysed for percentage of natural killer cells and concentration of P-glycoprotein. The results showed an increased percentage of natural killer cells in the patient control and patient treatment groups. The increase in both groups was significant (p < 0.05) when the percentage of natural killer cells from second and third blood samples (taken after radiation with or without addition of the crude drug for 45 and 90 days) was compared with that from the first blood sample (taken before treatment). The results for the women in the patient treatment group also showed a significant decrease of P-glycoprotein level (p < 0.05) in the second and third blood samples when compared with the first blood samples. There was no significant difference in the P-glycoprotein (P-gp) level between the first, second and third blood samples from the women in the patient control group. Ingestion of the crude drug did not affect numbers of natural killer cells, but it did affect the decrease of P-gp level on natural killer cell membrane (52).

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Adverse reactions

The reported adverse effects of the crude drug include hypoglycaemic coma and convulsions in children, increases in Γ-glutamyl transferase and alkaline phosphatase levels, and headaches (53).

Contraindications

Owing to potential abortifacient effects and possible teratogenicity (54, 55), the seeds of the crude drug should not be taken during pregnancy.

Owing to reported adverse events such as severe hypoglycaemia and convulsions in children, the crude drug and its preparations should not be administered to children or taken during breastfeeding (53).

Warnings

Patients with liver disorders should seek advice from their health care professional before taking any crude drug preparation.

Precautions

Drug interactions

The fruit and preparations thereof may have additive effects when taken with other glucose-lowering agents; however these interactions need to be investigated (53).

Pregnancy: teratogenic effects

Momorcharins, isolated from the seeds of the crude drug have been shown to induce early and midterm abortions in mice and were teratogenic in cultured mouse embryos at the early organogenesis stage. Morphological abnormalities were observed in the head, trunk and limbs of the embryos (54, 55).

The genotoxic potential of extracts of the crude drug was assessed in the Salmonella typhimurium microsome activation assay and the alkaline single-cell gel electrophoresis (COMET) assay. The extract did not produce a positive response in strains TA98 and TA100 with or without metabolic activation, but produced an increase above negative control values in the COMET assay (56).

Pregnancy: non-teratogenic effects

See Contraindications.

Breastfeeding mothers

See Contraindications.

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Paediatric use

See Contraindications.

Other precautions

No information was found.

Dosage forms

Crude drug, extracts, fruit juice and tablets.

Posology

(Unless otherwise indicated)

Adult daily oral dose: 10–15 ml of fresh juice (1); 2–15 g of dried crude drug (25, 28, 30).

References

1.The Ayurvedic pharmacopoeia of India, Part I. Vol. II, 1st ed. New Delhi, Ministry of Health & Family Welfare, Department of Indian System of Medicine and Homeopathy, 1999.

2.Perry LM, Metzger J. Medicinal plants of east and southeast Asia: Attributed properties and uses. Cambridge, MA, MIT Press, 1980.

3.de Padua LS, Bunyapraphatsara N, Lemmens RHMJ, eds. Plant resources of South-East Asia, No 12(1): Medicinal and poisonous plants – 1. Leiden, Backhuys Publishers, 1999.

4.Ross IA. Medicinal plants of the world. Totowa, NJ, Humana Press, 1999.

5.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.

6.Nadkarni AK. Dr. K.M. Nadkarni’s Indian materia medica. Bombay, Popular Prakashan, 1976.

7.Medicinal plants in the South Pacific. Manila, World Health Organization Regional Office for the Western Pacific, 1998 (WHO Regional Publications, Western Pacific Series, No. 19).

8.Medicinal plants of India. Vol. II. New Delhi, Indian Council of Medical Research, 1987.

9.Germosén-Robineau L. ed. Farmacopea Vegetal Caribeña. 2nd ed. Leon, Nicaragua, Universitaria, UNAN-Leon, 2005.

10.Medicinal plants in Thailand. Vol. I. Bangkok, Department of Pharmaceutical Botany, Faculty of Pharmacy, Mahidol University, 1996.

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

12.European Pharmacopoeia, 5th ed. Strasbourg, Directorate for the Quality of Medicines of the Council of Europe, 2005.

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

14.Sucrow W. Constituents of Momordica charantia. I. 5, 25-stigmastadien-3- ol and its Β-D-glucoside. Chemische Berichte, 1966, 99:2765–2777.

15.Sucrow W. Constituents of Momordica charantia. II. Two new 7-sterols from Momordica charantia. Chemische Berichte, 1966, 99:3559–3567.

16.Ng T, Yeung H. Bioactive constituents of Cucurbitaceae plants with special emphasis on Momordica charantia and Tricosanthes kirilowii. Proceedings 5th Symposium Medicinal Plants and Spices. Seoul, Korea, 1984.

17.Yeung HW et al. Trichosanthin, Α-momocharin and Β-momocharin: identity of abortifacient and ribosome-inactivating proteins. International Journal of Peptide and Protein Research, 1988, 31:265–268.

18.Tse PMF et al. New ribosome-inactivating proteins from seeds and fruits of the bitter gourd Momordica charantia. International Journal of Biochemistry and Cell Biology, 1999, 31:895–901.

19.Murakami T et al. Medicinal food stuffs. XXI. Structures of new cucurbitanetype triterpene glycosides-a, -b, -c, -d, -e, -f, -g, and -h, and new oleanane-type triterpene saponins, goyasaponins I, II, and III, from the fresh fruit of Japanese

Momordica charantia L. Chemistry and Pharmaceutical Bulletin, 2001, 49:54–63.

20.Xiao ZY, Chen D, Si J. [Chemical constituents of Momordica charantia.] Zhongcaoyao, 2000, 31:571–573 [in Chinese].

21.Okabe H, Miyahara Y, Yamauchi T. Studies on the constituents of Momordica charantia. 3. Characterization of new cucurbitacin glycosides of the im-

mature fruits. (1). Structures of momordicosides G, F1, F2 and I. Chemistry and Pharmaceutical Bulletin, 1982, 30:3977–3986.

22.Okabe H, Miyahara Y, Yamauchi T. Studies on the constituents of Momordica charantia L. IV. Characterization of new cucurbitacin glycosides of the immature fruits. (2). Structures of bitter glycosides, momordicosides K and L. Chemistry and Pharmaceutical Bulletin, 1982, 30:4334–4340.

23.Horax R. et al. Total phenolic contents and phenolic acid constituents in 4 varieties of bitter melons (Momordica charantia) and antioxidant activities of their extracts. Journal of Food Science, 2005, 70:C275–280.

24.Ahmad N et al. Effect of Momordica charantia (Karolla) extracts on fasting and postprandial serum glucose levels in NIDDM patients. Bangladesh Medical Research Council Bulletin, 1999, 25:11–13.

25.Akhtar MS. Trial of Momordica charantia Linn (Karela) powder in patients with maturity-onset diabetes. Journal of the Pakistan Medical Association, 1982, 32:106–107.

26.Baldwa VS et al. Clinical trial in patients with diabetes mellitus of an insulinlike compound obtained from a plant source. Uppsala Journal of Medical Science, 1977, 82:39.

27.Bielenberg J. Bittermelone-Blutzuckersenkung durch ergänzende Bilanziert diät mit Momordica charantia [Bitter melon-reduction of blood sugar levels by supplementary balanced diet with Momordica charantia]. Arztezeitschrift für Naturheilverfahren, 2004, 45:96–101.

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28.Grover JK, Gupta SR. Hypogylcemic effect of seeds of Momordica charantia. European Journal of Pharmacology, 1990, 183:1026–1027.

29.Leatherdale BA et al. Improvement in glucose tolerance due to Momordica charantia (karela). British Medical Journal (Clinical Research Edition), 1981, 282:1823–1824.

30.Srivastava Y. Antidiabetic and adaptogenic properties of Momordica charantia extract: an experimental and clinical evaluation. Phytotherapy Research, 1993, 7:285–289.

31.Upadhyaya GL, Ajai K, Pant MC. Effect of karela as hypoglycemic and hypocholesterolemic agent. Journal of the Diabetic Association of India, 1985, 25:12–15.

32.Sarkar S, Pranava M, Marita R. Demonstration of the hypoglycemic action of Momordica charantia in a validated animal model of diabetes. Pharmacological Research, 1996, 33:1–4.

33.Lin XM et al. [Effects of cactus, aloe vera, Momordica charantia on reducing the blood glucose of diabetic mice.] Wei Sheng Yan Jiu, 2001, 30:203–205 [in Chinese].

34.Rathi SS, Grover JK, Vats V. The effect of Momordica charantia and Mucuna pruriens in experimental diabetes and their effect on key metabolic enzymes involved in carbohydrate metabolism. Phytotherapy Research, 2002, 16:236–243.

35.Patel K, Srinivasan K. Effect of dietary intake of freeze dried bitter gourd (Momordica charantia) in streptozotocin induced diabetic rats. Die Nahrung, 1995, 39:262–268.

36.Virdi J et al. Antihyperglycemic effects of three extracts from Momordica charantia. Journal of Ethnopharmacology, 2003, 88:107–111.

37.Miura T et al. Hypoglycemic activity of the fruit of the Momordica charantia in type 2 diabetic mice. Journal of Nutrition Science and Vitaminology, 2001, 47:340–344.

38.Miura T et al. Suppressive activity of the fruit of Momordica charantia with exercise on blood glucose in type 2 diabetic mice. Biological and Pharmaceutical Bulletin, 2004, 27:248–250.

39.Vikrant V et al. Treatment with extracts of Momordica charantia and Eugenia jambolana prevents hyperglycemia and hyperinsulinemia in fructose fed rats.

Journal of Ethnopharmacology, 2001, 76:139–143.

40.Sitasawad SL, Shewade Y, Bhonde R. Role of bittergourd fruit juice in stzinduced diabetic state in vivo and in vitro. Journal of Ethnopharmacology, 2000, 73:71–79.

41.Ahmed I et al. Effects of Momordica charantia fruit juice on islet morphology in the pancreas of the streptozotocin-diabetic rat. Diabetes Research in Clinical Practice, 1998, 40:145–151.

42.Chen Q, Chan LL, Li ET. Bitter melon (Momordica charantia) reduces adiposity, lowers serum insulin and normalizes glucose tolerance in rats fed a high fat diet. Journal of Nutrition, 2003, 133:1088–1093.

43.Ahmed I et al. Hypotriglyceridemic and hypocholesterolemic effects of antidiabetic Momordica charantia (karela) fruit extract in streptozotocin-induced diabetic rats. Diabetes Research in Clinical Practice, 2001, 51:155–161.

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44.Jayasooriya AP et al. Effects of Momordica charantia powder on serum glucose levels and various lipid parameters in rats fed with cholesterol-free and cholesterol-enriched diets. Journal of Ethnopharmacology, 2000, 72:331–336.

45.Lee-Huang S et al. Inhibition of the integrase of human immunodeficiency virus (HIV) type 1 by anti-HIV plant proteins MAP30 and GAP31. Proceedings of the National Academy of Sciences USA, 1995, 92:8818–8822.

46.Jiratchariyakul W et al. HIV inhibitor from Thai bitter gourd. Planta Medica, 2001, 67:350–353.

47.Raza H et al. Modulation of xenobiotic metabolism and oxidative stress in chronic streptozotocin-induced diabetic rats fed with Momordica charantia fruit extract. Journal of Biochemistry and Molecular Toxicology, 2000, 14:131–139.

48.Raza H et al. Effect of bitter melon (Momordica charantia) fruit juice on the hepatic cytochrome P450-dependent monooxygenases and glutathione S- transferases in streptozotocin-induced diabetic rats. Biochemical Pharmacology, 1996, 52:1639–1642.

49.Tennekoon KH et al. Effect of Momordica charantia on key hepatic enzymes.

Journal of Ethnopharmacology, 1994, 44:93–97.

50.Patel K, Shurpalekar KS, Srinivasan K. Influence of bitter gourd (Momordica charantia) on growth and blood constituents in albino rats. Die Nahrung, 1993, 37:156–160.

51.Welihinda J et al. Effect of Momordica charantia on the glucose tolerance in maturity onset diabetes. Journal of Ethnopharmacology, 1986, 17:277–282.

52.Pongnikorn S et al. Effect of bitter melon (Momordica charantia Linn) on level and function of natural killer cells in cervical cancer patients with radiotherapy. Journal of the Medical Association of Thailand, 2003, 86:61–68.

53.Basch E, Gabardi S, Ulbricht C. Bitter melon (Momordica charantia): A review of efficacy and safety. American Journal of Health System Pharmacy, 2003, 60:356–359.

54.Chan WY et al. Effects of momorcharins on the mouse embryo at the early organogenesis stage. Contraception, 1986, 34:537–544.

55.Yeung HW et al. Purification and partial characterization of momorcharins, abortifacient proteins from the Chinese drug, kuguazi (Momordica charantia seeds). In: Chang HM et al., eds. Advances in Chinese medicinal materials research. Singapore, World Scientific, 1985:311–318.

56.Basaran AA et al. An investigation of some Turkish herbal medicines in Salmonella typhimurium and in the COMET assay in human lymphocytes.

Teratogenesis, Carcinogenesis and Mutagenesis, 1996, 16:125–138.

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Fructus Myrtilli

Definition

Fructus Myrtilli consists of the dried ripe fruits of Vaccinium myrtillus L. (Ericaceae) (1).

Synonyms

Vaccinium angelosums Dulac, V. montanum Salisb., Myrtilis niger Gilib. (2).

Selected vernacular names

Adara, aiges, airadech, airelle myrtille, aires, airolle myrtille, arándano, baceri mirtillo, baggiole, bagolo, Bickbeere, bilberry, bimbelas, blackberry, blaeberry, Blaubeere, Blaubessen, blue berry, blueberry, bog bilberry, brimbelle, burren myrtle, European blueberry, harilik, hei guo yue ju, Heidelbeere, Heidelbeerfruchten, huckleberry, maurettes, mirtillo nero, myrtille, petit myrtle, uva del boschi, uva orsina, waldbeere, whortleberry, wineberry (2–4).

Geographical distribution

Found in Europe and in the North American Rocky Mountains (2, 5).

Description

Trailing shrub forming large colonies from creeping rhizomes, 10–60 cm in height; twigs green, glabrous, 3-angled. Leaves: deciduous, alternate, short petiolate; blade broadly elliptic to ovate, 6–18 mm wide, 10–30 mm long, apex acute to obtuse, base rounded; margin serrulate; bright green, lower surface sparsely glandular with prominent venation. Inflorescence: flowers solitary or paired in leaf axils, bracts 2. Flowers: perfect, radially symmetrical, 5-lobed; calyx lobes very short to almost absent; corolla pale green or white to pink, broadly urceolate to globose, 4–7 mm wide, 3–5 mm long, lobes very short and revolute; stamens 10, filaments glabrous, anthers awned, dehiscent by terminal pores; ovary inferior, style usually included. Fruit: berry, oblate-globose, 5–9 mm diameter, blue to black, rarely glaucous, many-seeded. Chromosome number: 2x = 2n = 24 (2).

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Plant material of interest: dried ripe fruit

General appearance

The dried berry is a dark blue, subglobular, shrunken berry, about 5 mm in diameter, with a scar at the lower end and coarsely wrinkled exocarp. The pedicel may be attached or detached, and often the remains of the style, nectar disc, and calyx are persistent at the apex of the berry, with the calyx appearing as a circular fold. The mesocarp is purple. There are 4–5 locules, each containing many seeds; each seed is approximately 1 mm long with a yellowish brown dimpled surface (1).

Organoleptic properties

Odour: no characteristic odour; taste: sweet and slightly bitter (1).

Microscopic characteristics

The exocarp consists of polygonal, rectangular or quadratic cells with slightly pitted tangential walls. Groups of 2–4 cells occur, each group surrounded by a thick wall, while within the groups the walls are considerably thinner. The mesocarp consists of large parenchymatous cells with scattered solitary sclereids and vascular bundles containing vessels with spiral or helical secondary wall thickenings. The endocarp is composed largely of groups of sclereids similar to those in the mesocarp and having an elongated or nearly quadratic shape. The outer layer of the testa consists of elongated, heavily thickened and pitted sclereids. In cross-section these cells have U-shaped secondary walls with the unthickened side occurring on the outer tangential wall. The endosperm cells are thin-walled and contain droplets of fixed oil. Calcium oxalate crystals may occur occasionally in all tissues (2).

Powdered plant material

Violet-pink sclereids from the endocarp and the mesocarp and testa, usually aggregated, with thick, channelled walls; reddish brown fragments of the epicarp consisting of polygonal cells with moderately thickened walls; brownish yellow fragments of the outer seed testa made up of elongated cells with U-shaped thickened walls; calcium oxalate crystals of various sizes as clusters and prisms. Also present are parenchyma cells, vascular bundles and oil droplets (1).

General identity tests

Macroscopic and microscopic examinations, thin-layer chromatography (1, 2), and high-performance liquid chromatography (6, 7).

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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 (8).

Foreign organic matter

Plant material complies with the test for foreign matter (1).

Total ash

Not more than 5% (1).

Acid-insoluble ash

To be established in accordance with national requirements.

Water-soluble extractive

To be established in accordance with national requirements.

Alcohol-soluble extractive

To be established in accordance with national requirements.

Loss on drying

Not more than 12% (1).

Pesticide residues

The recommended maximum limit of aldrin and dieldrin is not more than 0.05 mg/kg (1). For other pesticides, see the European pharmacopoeia (1) and the WHO guidelines on assessing quality of herbal medicines with reference to contaminants and residues (8) and pesticide residues (9).

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 (8).

Radioactive residues

Where applicable, consult the WHO guidelines on assessing quality of herbal medicines with reference to contaminants and residues (8).

Chemical assays

Not less than 1.0% of tannins, expressed as pyrogallol (1).

Not less than 0.2% of anthocyanins, expressed as cyanidin-3-glucoside chloride (2).

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