МОНОГРАФИИ ВОЗ Т 4

Semen Cardamomi

ner epidermis of flattened cells. Perisperm of thin-walled cells, packed with minute starch grains, 1–6 μm in diameter, and containing 1–7 small prisms of calcium oxalate, about 10–20 μm long. Endosperm, of small thin-walled parenchymatous cells, each filled with a hyaline or granular mass of protein but no starch; embryo, of small thin-walled cells containing aleurone grains; fibrous sclerenchyma and large vessels present in pericarp (2, 3).

Powdered plant material

Reddish to greyish-brown, characterized by numerous fragments of perisperm cells, each filled with starch granules and containing one or more prisms of calcium oxalate, 10–25 μm long; polyhedral masses of adherent starch granules from perisperm, individual granules, up to 4 μm in diameter; numerous fragments of yellowish to reddish-brown sclereids; occasional particles of epidermal cells, often crossed at right angles by the cells of the collapsed layer (2).

General identity tests

Macroscopic and microscopic examinations (1–3, 5–8, 14).

Purity tests

Microbiology

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 (16).

Chemical

To be established in accordance with national requirements.

Foreign organic matter

Not more than 3% (2, 17).

Total ash

Not more than 6% (3, 6–8, 17).

Acid-insoluble ash

Not more than 4% (1, 3, 5–8).

Water-soluble extractive

Not less than 10% (3).

Alcohol-soluble extractive

Not less than 2% (3).

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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 (18). For other pesticides, see the European Pharmacopoeia (18) and the WHO guidelines on assessing quality of herbal medicines with reference to contaminants and residues (16) and pesticide residues (19).

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 (16).

Radioactive residues

Where applicable, consult the WHO guidelines on assessing quality of herbal medicines with reference to contaminants and residues (16).

Chemical assay

Contains not less than 3.3% essential oil (v/w) (5–8).

Major chemical constituents

Contains 2–8% essential oil, the major constituents of which are 1,8-cin- eole (20–40%), (+)-Α-terpinyl acetate (30–42%), Α-terpineol (4–45%), limonene (6%), and smaller amounts of linalool and linalool acetate, among others (13, 20–22). The structures of 1,8-cineole, (+)-Α-terpinyl acetate and Α-terpineol are presented below.

CH3			CH3				CH3
	O	H	and enantiomer	H3C			H
	CH3	HO					O
	CH3	H3C CH3			O H3C CH3
1,8-Cineole			-Terpineol	(+)- -Terpinyl acetate

Medicinal uses

Uses supported by clinical data

None.

Uses described in pharmacopoeias and well-established documents

Orally for the treatment of dyspepsia (23, 24).

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Uses described in traditional medicine

Treatment of asthma, bronchitis, colic, coughs, fainting, fever, rheumatism, stomach cramps and urinary stones. Also used as an aphrodisiac, appetizer, diuretic and emmenagogue (13, 24).

Pharmacology

Experimental pharmacology

Anti-inflammatory and analgesic activities

An in vivo study was performed to compare the anti-inflammatory activity of the essential oil of the seed, at doses of 175 and 280 μl/kg body weight (bw) with that of indometacin at a dose of 30.0 mg/kg bw against acute carrageenan-induced plantar oedema in rats. Intraperitoneal administration of 280 μl/kg bw of the essential oil to rats or 233 μl/kg bw to mice suppressed carrageenan-induced pedal oedema (25).

One study assessed the analgesic activity of the essential oil from the seed using 1,4-benzoquinone as a chemical stimulus for pain in mice. Intragastric administration of a dose of 233 μl/kg bw of the essential oil produced a 50% reduction in writhing (stretching syndrome) induced by intraperitoneal administration of a 0.02% solution of 1,4-benzoquinone (25). Butanol and ether extracts of the seeds had anti-inflammatory activity in vitro, as assessed in the albumin stabilizing assay (concentration not stated). The aqueous extract of the seeds, however, was not active (26).

Antimicrobial effects

At a concentration of 500 ppm, the essential oil from the seed weakly inhibited the growth of the fungi Arthroderma simii, Chaetomium indicum, Microsporum canis and Trichophyton mentagrophytes in vitro (27).

Antispasmodic activity

A 95% ethanol extract of the crude drug at a concentration of 200 μg/ml reduced histamine-induced and barium chloride-induced contractions in guinea-pig ileum in vitro (28). Administration of essential oil from the seed to rabbits, at a dose of 0.4 ml/kg bw, inhibited acetylcholine-induced intestinal spasms (25). However, an aqueous extract of the crude drug was reported to stimulate the rectus abdominus muscle of the frog and rat jejunum in vitro at a concentration of 10% of the bath media (29).

Smooth-muscle relaxant activity

The essential oil from the seed relaxed isolated guinea-pig ileum and trachea in vitro with a median effective dose of 15 mg and 27 mg/l, respectively. An aqueous ethanol seed extract (10 mg/ml in bath medium) relaxed guinea-pig ileum in vitro (30).

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Antiulcer activity

Intragastric administration of dried aqueous or methanol extracts of the seeds to mice, at a dose of 53.0–126.9 mg/kg bw, reduced the secretion of gastric juice (31). A methanol extract of the dried seeds (5:1) at a concentration of 100 μg/ml inhibited the growth of Helicobacter pylori in vitro (32).

Choleretic activity

Intraduodenal administration of a dried acetone extract of the dried seed to rats at a dose of 50.0–500.0 mg/kg bw, had significant choleretic effects (p < 0.01–0.05) (33).

Central nervous system depressant activity

Intraperitoneal administration of the essential oil from the seed, at a dose of 1.6 ml/kg bw, induced drowsiness and a staggering gait in mice (25).

Dermatological effects

Application of the essential oil from the seed at a concentration of 1.0% to rabbit skin enhanced the dermal penetration of piroxicam, indometacin and diclofenac sodium (34). Application of the essential oil from the seed, at a dose of 1.0 ml/per square inch enhanced the dermal penetration of indometacin in rats, rabbits and humans (34, 35). External pre-application of the essential oil from the seed, at a concentration of 5%, to rabbit skin increased the bioavailability of piroxicam gel (34).

Toxicity

Intragastric or subcutaneous administration of an aqueous ethanol (1:1) extract of the seed, at a dose of 10 g/kg bw had no observed toxicity in mice (36).

Miscellaneous activities

An aqueous ethanol (1:1) extract of the seed, at a concentration of 10.0 mg/ ml had histaminergic activity in guinea-pig ileum in vitro (30). Aqueous extracts (10% w/v) of the crude drug were used for an ex vivo study of their effect on gastric secretion. The stomach of pentobarbitone-anaes- thetized rats was perfused at 0.15 ml/min with aqueous extracts of cardamom or acetylcholine (1.0 μg/ml or 10.0 μg/ml solutions, in 40-minute time periods, twice in each experiment) followed by saline perfusions. The acid content in the samples was estimated by titration with 0.1 N sodium hydroxide with phenolphthalein as indicator. Acute gastric mucosal injury was induced by leaving aspirin 125.0 mg/kg bw in the stomach for 2 h before perfusion. The aqueous extract significantly increased gastric secretion from 0.10 to 0.28 (p < 0.005) (37).

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Semen Cardamomi

Adverse reactions

Contact dermatitis has been reported (38).

Contraindications

Hypersensitivity or allergy to the crude drug.

Warnings

No information was found.

Precautions

General

Patients with gallstones should consult their health care provider before using preparations of Semen Cardamomi (23).

Drug interactions

None reported.

Drug and laboratory test interactions

None reported.

Carcinogenesis, mutagenesis, impairment of fertility

A hot aqueous or methanol extract of the crude drug at concentrations of 50 mg/disc was not mutagenic in the Ames test in Salmonella typhimurium strains TA98 and TA100 (39). The essential oil inhibited formation of DNA adducts with aflatoxin B1 by inhibiting activation in rat liver microsomes, thus demonstrating antimutagenic activity. The median inhibitory concentration was 10 μl/disc (40).

Drug interactions

No information was found.

Drug and laboratory test interactions

None reported.

Pregnancy: teratogenic effects

No information was found.

Pregnancy: non-teratogenic effects

No information was found.

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Nursing mothers

No information was found.

Paediatric use

No information was found.

Dosage forms and storage

Crude drug, extracts and tinctures (23).

Posology

(Unless otherwise indicated)

Average daily dosage: 1.5 g of drug; equivalent preparations. Tincture: daily dosage equivalent to 12 g (23).

References

1.The National Formulary 20th ed, 1st Suppl. Rockville, MD, The United States Pharmacopeia Convention, 2002.

2.African pharmacopoeia, Vol. 1. Lagos, Nigeria, Organization of African Unity, Scientific Technical & Research Commission, 1985.

3.The API Pharmacopoeia of India, Part I. Vol. I, 1st ed. New Delhi, Government of India Ministry of Health and Family Welfare, Department of Indian Systems of Medicine and Homeopathy, 1990 (reprinted 2001).

4.Nadkarni AK, ed. Dr. K.M. Nadkarni’s Indian materia medica, Vol. 1. Bombay, Popular Prakshan, 1976.

5.The Japanese pharmacopeia, 14th ed. (English ed.). Tokyo, Ministry of Health, Labour and Welfare, 2001 (http://jpdb.nihs.go.jp/jp14e/).

6.Pharmacopoeia of the Republic of Korea, 7th ed. (English ed.). Seoul, Korea Food and Drug Administration, and Korean Association of Official Compendium for Public Health, 1998.

7.Asian crude drugs, their preparations and specifications. Asian Pharmacopeia. Manila, Federation of Asian Pharmaceutical Associations, 1978.

8.The Japanese standards for herbal medicines. Tokyo, Yakuji Nippon, 1993.

9.British herbal pharmacopoeia. Exeter, British Herbal Medicine Association, 1996.

10.Reynolds JEF, ed. Martindale, the extra pharmacopoeia. London, Pharmaceutical Press, 1996.

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

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

13.Farnsworth NR, ed. NAPRALERT database. Chicago, University of Illinois at Chicago, IL (an online database available directly through the University

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of Illinois at Chicago or through the Scientific and Technical Network [STN] of Chemical Abstracts Services), 30 June 2005.

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

15.Evans WC. Trease and Evans pharmacognosy, 15th ed. Edinburgh, WB Saunders, 2002.

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

17.British pharmacopoeia. London, Her Majesty’s Stationery Office, 1993.

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

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

20.Hänsel R, Sticher O, Steinegger E. Pharmakognosie-phytopharmazie. Berlin, Springer-Verlag, 1999 [in German].

21.Shaban MAE et al. The chemical composition of the volatile oil of Elettaria cardamomum seeds. Pharmazie, 1987, 42:207–208.

22.Marongiu B, Piras A, Porcedda S. Comparative analysis of the oil and super-

critical CO2 extract of Elettaria cardomomum (L) Maton. Journal of Agricultural Chemistry, 2004, 52:6278–6282.

23.Blumenthal M et al. The complete German Commission E monographs: Therapeutic guide to herbal medicines. Austin, TX, American Botanical Council, 1998.

24.Govindarajan VS et al. Cardamom – production, technology, chemistry, and quality. Critical Reviews in Food Science Nutrition, 1982, 16:229–326.

25.Al-Zuhair H et al. Pharmacological studies of cardamon oil in animals. Pharmacological Research, 1996, 34:79–82.

26.Han BH et al. Screening of the anti-inflammatory activity of crude drugs.

Korean Journal of Pharmacognosy, 1972, 4:205–209.

27.El-Kady IA, El-Maraghy SSM, Mostafa E. Antibacterial and antidermatophyte activities of some essential oils from spices. Qatar University Science Journal, 1993, 13:63–69.

28.Itokawa H et al. Studies on the constituents of crude drugs having inhibitory activity against contraction of the ileum caused by histamine or barium chloride. Shoyakugaku Zasshi, 1983, 37:223–228.

29.Haranath PSRK, Akther MH, Sharif SI. Acetylcholine and choline in common spices. Phytotherapy Research, 1987, 1:91–92.

30.Mokkhasmit M, Swatdimongkol K, Satrawaha P. Study on toxicity of Thai medicinal plants. Bulletin of the Department of Medical Sciences, 1971, 12:36–65.

31.Sakai K et al. Effect of extracts of Zingiberaceae herbs on gastric secretion in rabbits. Chemical and Pharmaceutical Bulletin, 1989, 37:215–217.

32.Mahady GB et al. In vitro susceptibility of Helicobacter pylori to botanicals used traditionally for the treatment of gastrointestinal disorders. Phytotherapy Research, 2005, 19:988–991.

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33.Yamahara J et al. Biologically active principles of crude drugs. Cholagogic substances in cardamon seeds and its properties. Yakugaku Zasshi, 1983, 103:979–985.

34.Huang YB et al. Cardomom oil as a skin permeation enhancer for indomethacin, piroxicam and diclofenac. International Journal of Pharmaceutics, 1995, 126:111–117.

35.Huang YB et al. Crude drug (Zingiberaceae) enhancement of percutaneous absorption of indomethacin: in vitro and in vivo permeation. Gaoxiong Yi Xue Ke Xue Za Zhi, 1993, 9:392–400.

36.Mokkhasmit M et al. Pharmacological evaluation of Thai medicinal plants.

Journal of the Medical Association of Thailand, 1971, 54:490–504.

37.Vasudevan K et al. Influence of intragastric perfusion of aqueous spice extracts on acid secretion in anesthetized albino rats. Indian Journal of Gastroenterology, 2000, 19:53–56.

38.Seetharam KA, Pasricha JS. Condiments and contact dermatitis of the finger tips. Indian Journal of Dermatology, Venerology, and Leprology, 1987, 53:325–328.

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

40.Hashim S et al. Modulatory effects of essential oils from spices on the formation of DNA adducts by aflatoxin B1 in vitro. Nutrition in Cancer, 1994, 21:169–175.

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Fructus Chebulae

Definition

Fructus Chebulae consists of the dried fruits of Terminalia chebula Retz. or T. chebula Retz. var. tomentella Kurt. (Combretaceae) (1–3).

Selected vernacular names

Abhaya, ahlilaj kâbuli, alalekai, alayla, amagola, arabi, aralu, areyra, aridadi, badamier chebule, bal har, black myrobalan, bush kaduka, chebulic myrobalan, Chebulische Myrobalane, divya, Ga ja, Habra, hacha, halela, halela kabuli, halela zard, halileh, halileh kaboli, halilehsiyâh, halileh zard, hallilaj, harad, harar, harda, hardo, harir, haritaki, harra, harro, harroh, haser, helikha, hezi, himaja, hirda, hirdo, hireda, hlilej khel, hlijej sfer, hokikha, ihlilaj kabuli, inknut tree, jivathi, kabuli-harda, hora, kadukka, kadukkai, kale har, karaka, karakkaya, kashi, katukka, kãyasthã, kot- pung-pla, kurka, medicine terminalia, mirobalan de caboul, mirobalano, myrobalan, myrobalano nero, myrobalans, myrobaran, pathyã, pile har, pilo-harde, post-e-haleela kabli, post-e-haleela siyah, post-e-haleela zard, pulo-harda, rispiger Myrobalanenbaum, rong mao he zi, silikha, sa-mo- thai, samo-thai, shajar shiir hindi, sirri hindi, silikha, sivã, sringitiga, suddha, terminaalia, vayastha, vijayã, yellow myrobalan, yellow myrobalan plum, zama, zangli har (2–11).

Geographical distribution

Native to Cambodia, China, India, Lao People’s Democratic Republic, Malaysia, Myanmar, Philippines, Thailand and Viet Nam and cultivated elsewhere (4, 9, 10, 12).

Description

A tropical shade tree, usually 15–20 m high, but can be up to 30 m in height, and up to 1.3 m in girth; bark rough, scaly; shoots and young leaves usually rusty villous. Leaves simple, opposite, coriaceous, broadly ovate to ovate-elliptic, 7–15 cm in width by 8–25 cm in length, glabrescent; veins obscure above, slightly raised and usually brownish pubescent beneath;

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apex acute or abruptly acuminate; base cuneate, slightly cordate or rounded; petiole 1–3 cm long, glabrous or sparsely pubescent with a pair of nodular glands near leaf base. Inflorescences axillary or terminal panicles, usually with 3–6 spikes (each 3–6 cm long); rachis pubescent; flowers 2 mm long, 3–4 mm in diameter; bracts nearly glabrous, 1.5–2.0 mm long; calyx outside glabrous, inside densely villous, calyx-segments triangular; stamens 3–4 mm long; ovary glabrous, ovoid, 1 mm long; style glabrous, 2.5–3.0 mm long; disc lobed, densely villous. Fruit a drupe, glabrous, subglobose to ellipsoid, 2.5–5.0 cm by 1.5–2.5 cm, usually smooth or frequently 5-angulate, ridged, wrinkled, turning blackish when dry. Seed: one, rough, ellipsoid, 1.0–2.0 cm by 0.2–0.7 cm, and without ridges (9).

Plant material of interest: dried fruits

General appearance

Oblong or ovoid, 2.5–5.0 cm in length, 1.5–2.5 cm in diameter. Externally yellowish-brown or dark brown, somewhat lustrous, marked with 5 or 6 longitudinal ribs and irregular wrinkles, base with a rounded fruit stalk scar. Texture compact. Sarcocarp 2–5 mm thick, yellowish-brown or dark yellowish-brown; kernels 1.5–2.5 cm long, 1.0–1.5 cm in diameter, pale yellow, rough and hard. One seed, narrowly fusiform, 1.0–2.0 cm by 0.2– 0.7 cm; testa yellowish-brown, cotyledons 2, white, overlapping and convolute (1, 2, 8).

Organoleptic properties

Odour: slight and characteristic (8); taste: bitter, sour, astringent, then sweet (1, 8).

Microscopic characteristics

Transverse section of the fruit shows epicarp composed of a layer of epidermal cells, the outer tangential wall and upper portion of the thick radial walls. Mesocarp, 2 or 3 layers of collenchyma followed by a broad zone of parenchyma with fibres and sclereids in groups, and vascular bundles, scattered; fibres, simple-pitted walls; porous parenchyma; sclereids, various shapes and sizes, mostly elongated; tannins and aggregate crystals of calcium oxalate in parenchyma; starch grains simple rounded or oval in shape, measuring 2–7 μm in diameter. Endocarp consists of thick-walled sclereids of various shapes and sizes, mostly elongated. Fibres, sclereids and vessels, lignified. Testa, one layer of large cubical cells, followed by a zone of reticulate parenchyma and vessels; tegmen consists of collapsed parenchyma. Cotyledon folded and containing aleurone grains, oil globules and some rosette aggregate crystals (2).

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