1199

12(2): Medicinal and poisonous plants 2

Micromelum minutum (J.G. Forster) Wight & Arn.

Prodr. fl. Ind. orient.: 448, 468 (1834).

RUTACEAE

2n = 18

Micromelum pubescens Blume (1825), Micromelum ceylanicum Wight (1840), Micromelum compressum (Blanco) Merr. (1918).

Lime berry (En). Indonesia: sesi (Lampung), ki mangkok (Sundanese), mentanen (Javanese). Malaysia: chememar, cherek, kematu (Peninsular). Philippines: piris (Tagalog), makabangon (Bikol), basar basar (Iloko). Thailand: samui (chaang) (peninsular), saam sok (northern), sabaek (eastern). Vietnam: cam n[us]i, kim s[uw][ow]ng.

Micromelum minutum is found from India throughout South-East Asia to Australia and the Pacific.

In Peninsular Malaysia, the pounded leaves of Micromelum minutum are an ingredient of a poultice used to relieve skin irritation. A poultice of boiled roots is applied for ague. Magical powers are also attributed to it for warding off evil spirits. In the Philippines, the young shoots are heated with oil and used as a medicine for infantile convulsions. The leaves and roots are used as a febrifuge. The roots in decoction or infusion are given for diarrhoea in children, and as a carminative. The roots are also good for toothache. It is further reported as a remedy for stomach-ache and headache. In southern Sumatra, pieces of the root are chewed with betel for coughs. In Indo-China the leaves are rubbed on the skin to relieve irritations caused by scabies. In Fiji the leaves or inner bark of the twigs are used in various ways for headache and stomach-ache, to cure coughs and a sore tongue, to arrest profuse menstruation, to treat gonorrhoea, and as a remedy for thrush. The leaves are further taken as a general tonic. The wood is used for furniture and handles, but is of little economic interest.

Micromelum minutum is an ingredient of herbal supplements traded in Malaysia and the Middle East. Production and trade statistics, however, are not available.

Micromelum species are well known for the presence of coumarins, especially of the 6- or 8-prenylated-7-methoxy type. For example, from an acetone extract of the bark of Micromelum minutum, 12 coumarins were isolated: micromarin A, B, C, F, G and H, micromelin, murralonginol-isovalerate, microminutinin, 6-methoxymicrominutinin, microminutin and murrangatin. Furthermore, the hexane/diethyl ether extract of the bark yielded the coumarin phebalosin. Micromelin, microminutinin and 6-methoxymicrominutinin are also reported to be present in the leaves and twigs of this species collected in Malaysia, together with 1,2-seco-dihydromicromelin. Additionally, the aboveground parts of Micromelum minutum collected in India yielded coumarins including osthol, micromelin, murralongin, murrangatin, dihydromicromelin-A and -B and acetyldihydromicromelin A. Furthermore, the furoquinoline alkaloid flindersine has been reported for Micromelum minutum.
Of the isolated compounds, both micromelin and microminutin showed in-vivo activity in the P-388 lymphocytic leukaemia assay. In addition, the coumarin phebalosin showed significant toxicity in the brine shrimp lethality assay (LC₅₀ 47 ppm) and significantly inhibited the development of crown gall tumours on potato discs. However, insignificant cytotoxic activity was observed in the 9KB and 9 PS cell lines (ED₅₀> 20 µg/ml, ED₅₀ 27 µg/ml, respectively), and no activity was observed in the 9ASK astrocytoma reversal assay. In the P-388 in vivo murine leukaemia system, phebalosin was inactive in doses up to 25 mg/kg, but insufficient material was available for testing at higher doses.
Extracts of Micromelum integerrimum (Buch.-Ham.) Roem. have been fractionated based on in-vivo activity by using the P-388 lymphocytic leukemia assay in mice. Subsequent chomatography led to the isolation of the coumarins micromelin and scopoletin, which both demonstrated antitumour activities as crystalline compounds. Micromelin was furthermore converted into the corresponding butenolide (deoxymicromelin), which was inactive in the 9KB assay however.

The alkaloid flindersine has been found in other Rutaceae, including Zanthoxylum australe (Cunn.) G. Don. Phebalosin was previously isolated from Phebalium drummondii Benth.

A small to medium-sized, unarmed tree up to 20 m tall, with stem up to 15 cm in diameter; twigs and buds densely short-hairy. Leaves alternate, imparipinnate, up to 30 cm long including petiole with 9—15 alternate leaflets; stipules absent; leaflets ovate-lanceolate, 3—12 cm x 1.5—6 cm, base obtuse and asymmetrical, apex attenuate-acuminate, rarely obtuse or emarginate, margin entire to irregularly undulate-crenate; petiolule 3—5 mm long. Inflorescence terminal, cymose-paniculate, (3—)15—20 cm long. Flowers bisexual, 5-merous, calyx cupular, shallowly 5-toothed; petals valvate, linear-oblong, 7 mm x 1.5 mm, pale green to yellowish-white, densely appressed hairy outside; stamens 10; ovary superior, cylindrical, hairy, 5-celled, cells bi-ovulate, with a twisting of the radial follicle walls. Fruit an ellipsoid, oblong berry, 6—10 mm long, with 1—3 developed locules, each one-seeded. Seed glabrate, yellow to red when ripe, with flat and folded cotyledons. Seedling with epigeal germination; emergent cotyledons green; hypocotyl elongated.

Micromelum minutum flowers and fruits throughout the year. However, in areas with a pronounced dry season, flowering is restricted to the wet season.

Micromelum belongs to the tribe Clauseneae, together with Clausena, Glycosmis and Murraya but is classified on its own in the subtribe Micromelinae. Micromelum comprises some 9 species distributed from West Pakistan, India, Sri Lanka to southern China and throughout South-East Asia to Australia, New Caledonia and the South Pacific. The circumscription of the species varies among specialists of this group. Here, a broad circumscription of Micromelum minutum is adopted, including many variable forms distinguished as separate species by others. In Peninsular Malaysia, the leaves of Micromelum hirsutum Oliv. are an ingredient of a poultice to relieve skin irritation caused by caterpillars. It is, however, more linked to magical powers to ward off evil spirits. In Indo-China the leaves are rubbed on the skin to relieve irritations caused by scabies. Micromelum falcatum (Lour.) Tanaka (synonym Micromelum octandrum Turcz.) from southern China, Indo-China, Thailand, Burma (Myanmar) and the Andaman Islands, is used in folk medicine in Indo-China. A decoction of the leaves and roots is used as an emmenagogue, analgesic and anti-arthritic. The leaves are applied as a wound disinfectant. A tincture prepared from the leaves or roots is also prescribed in embrocation for rheumatism and arthritis. The bark of Micromelum integerrimum, a closely related species from northern India, Burma (Myanmar) and the Andaman Islands, is used for pulmonary affections.

Micromelum minutum is found on a wide range of soils in both primary and secondary forest, from sea-level up to 1000 m altitude.

In a seedling trial in Peninsular Malaysia seeds of Micromelum minutum germinated in 12—47 days.

Bark, leaves and fruits of Micromelum minutum are collected whenever the need arises.

Micromelum minutum is widespread and common throughout South-East Asia, and therefore not endangered. Apart from collections in botanical gardens no breeding programmes exist.

Cytostatics and antitumour treatments constitute a dynamic field of modern pharmaceutical research, which traditionally has been strongly based on natural products. There is always a need for new constituents with potential activity, to serve as lead compounds for future developments. Therefore, the coumarins from Micromelum which showed activity in the P-388 in vivo assay merits further research, in order to fully evaluate their potential.

Cambie, R.C. & Ash, J., 1994. Fijian medicinal plants. Commonwealth Scientific and Industrial Research Organisation, Canberra, Australia. pp. 276—277.
Cassady, J.M., Ojima, N., Chang, C. & McLaughlin, J.L., 1979. An investigation of the antitumor activity of Micromelum integerrimum (Rutaceae). Journal of Natural Products 42(3): 274—278.
Ito, C., Otsuka, T., Ruangrungsi, N. & Furukawa, H., 2000. Chemical constituents of Micromelum minutum. Isolation and structural elucidation of new coumarins. Chemical and Pharmaceutical Bulletin 48(3): 334—338.
Jones, D.T., 1995. Rutaceae. In: Soepadmo, E. & Wong, K.M. (Editors): Tree flora of Sabah and Sarawak. Vol 1. Sabah Forestry Department, Forest Research Institute Malaysia and Sarawak Forestry Department, Kepong, Malaysia. pp. 351—419.
Rahmani, M., Taufiq-Yap, Y.H., Ismail, H.B.M., Sukari, A. & Waterman, P.G., 1994. New coumarin and dihydrocinnamic acid derivatives from two Malaysian populations of Micromelum minutum. Phytochemistry 37(2): 561—564.
Tantishaiyakul, V., Pummangura, S., Chaichantipyuth, C., Ma, W.W. & McLaughlin, J.L., 1986. Phebalosin from the bark of Micromelum minutum. Journal of Natural Products 49(1): 180—181.

[74] Backer, C.A. & Bakhuizen van den Brink Jr, R.C., 1964—1968. Flora of Java. 3 volumes. Noordhoff, Groningen, the Netherlands. Vol. 1 (1964) 647 pp., Vol. 2 (1965) 641 pp., Vol. 3 (1968) 761 pp.
[128] Brown, W.H., 1951—1957. Useful plants of the Philippines. Reprint of the 1941—1943 edition. 3 volumes. Technical Bulletin 10. Department of Agriculture and Natural Resources. Bureau of Printing, Manila, the Philippines. Vol. 1 (1951) 590 pp
[135] Burkill, I.H., 1966. A dictionary of the economic products of the Malay Peninsula. Revised reprint. 2 volumes. Ministry of Agriculture and Co-operatives, Kuala Lumpur, Malaysia. Vol. 1 (A—H) pp. 1—1240, Vol. 2 (I—Z) pp. 1241—2444.
[207] Corner, E.J.H., 1988. Wayside trees of Malaya. 3rd Edition. 2 volumes. The Malayan Nature Society, Kuala Lumpur, Malaysia. 774 pp.
[215] Council of Scientific and Industrial Research, 1948—1976. The wealth of India: a dictionary of Indian raw materials & industrial products. 11 volumes. Publications and Information Directorate, New Delhi, India.
[220] Croft, K.D. & Toia, R.F., 1989. Coumarins from Micromelum minutum. Planta Medica 55(4): 401.
[231] Das, S., Baruah, R.H., Sharma, R.P., Barua, J.N., Kulanthaivel, P. & Herz, W., 1984. 7-Methoxycoumarins from Micromelum minutum. Phytochemistry 23(10): 2317—2322
[407] Heyne, K., 1950. De nuttige planten van Indonesië [The useful plants of Indonesia]. 3rd Edition. 2 volumes. W. van Hoeve, 's-Gravenhage, the Netherlands/Bandung, Indonesia. 1660 + CCXLI pp.
[523] Kessler, P.J.A. (Editor), 2000. Secondary forest trees of Kalimantan, Indonesia. A manual to 300 selected species. Tropenbos Kalimantan Series 3. MOFEC Tropenbos-Kalimantan Project, Wanariset Samboja, Balikpapan, Indonesia. 404 pp.
[671] Merrill, E.D., 1923—1926. An enumeration of Philippine flowering plants. 4 volumes. Bureau of Printing, Manila, the Philippines.
[730] Ng, F.S.P., 1991—1992. Manual of forest fruits, seeds and seedlings. 2 volumes. Malayan Forest Record No 34. Forest Research Institute Malaysia, Kepong, Malaysia. 997 pp.
[739] Nguyen Van Duong, 1993. Medicinal plants of Vietnam, Cambodia and Laos. Mekong Printing, Santa Ana, California, United States. 528 pp.
[786] Perry, L.M., 1980. Medicinal plants of East and Southeast Asia. Attributed properties and uses. MIT Press, Cambridge, Massachusetts, United States & London, United Kingdom. 620 pp.
[788] Pételot, A., 1952—1954. Les plantes médicinales du Cambodge, du Laos et du Vietnam [The medicinal plants of Cambodia, Laos and Vietnam]. 4 volumes. Centre National de Recherches Scientifiques et Techniques, Saigon, Vietnam.
[810] Quisumbing, E., 1978. Medicinal plants of the Philippines. Katha Publishing Co., Quezon City, the Philippines. 1262 pp.
[819] Rahmani, M., Taufiq-Yap, Y.H., Ismail, H.B.M., Sukari, A. & Manas, A.S., 1993. Microminutinin: a novel coumarin from Micromelum minutum. Planta Medica 59(1): 93—94.
[976] Swingle, W.T. & Reece, P.C., 1967. The botany of Citrus and its wild relatives. In: Reuther, W., Webber, H.J. & Batchelor, L.D. (Editors): The citrus industry. Revised edition. Vol. 1. History, world distribution, botany and varieties. University of California Publications, Riverside, United States. pp. 190—430.

M.A. Nor Azah

Nor Azah, M.A., 2001. Micromelum minutum (J.G. Forster) Wight & Arn.. In: van Valkenburg, J.L.C.H. and Bunyapraphatsara, N. (Editors): Plant Resources of South-East Asia No 12(2): Medicinal and poisonous plants 2. PROSEA Foundation, Bogor, Indonesia. Database record: prota4u.org/prosea