1017

12(2): Medicinal and poisonous plants 2

Combretum Loefl.

Iter Hispan. App.: 308 (1758).

COMBRETACEAE

x = 13; Combretum erythrophyllum, Combretum micranthum: 2n = 26; polyploidy is observed in several species.

Major species Combretum quadrangulare Kurz.

Combretum comprises about 250 species, throughout the tropics, and is most abundant in Africa; about 13(—17) species are present in South-East Asia.

In South-East Asia Combretum is best known as a vermifuge and for poulticing. Seeds or sometimes other parts of Combretum quadrangulare and Combretum trifoliatum are widely used as a vermifuge or for other intestinal disorders. The leaves or roots of Combretum quadrangulare and Combretum sundaicum are employed for poulticing wounds and boils. The fruits of Combretum tetralophum C.B. Clarke are applied as a substitute for Combretum trifoliatum. Both species are called 'sonsong harus' in Malay. This also applies to Combretum acuminatum Roxb., a third species of which the leaves are employed as a vermifuge; either as a decoction for adults, or as an externally applied plaster on the abdomen of children. In Peninsular Malaysia, the leaves of Combretum nigrescens King are used for poulticing wounds. In Indo-China, the astringent fruits of Combretum latifolium Blume are considered a tonic. In West Africa Combretum micranthum G. Don is traditionally used as an antimalarial. It is locally cultivated in Vietnam as a reputed remedy for bilious fever and haematuria. Several non-indigenous Combretum species have been introduced for their ornamental value, e.g. Combretum constrictum (Benth.) Rawson, Combretum grandiflorum G. Don, Combretum quadrangulare and Combretum roxburghii Spreng. (synonym Combretum decandrum Roxb.).

Combretum is only used at the local level in South-East Asia, and data on trade for medicinal use are lacking.

The vermifugal properties of the ripe fruits of Combretum quadrangulare were evaluated in buffalo calves after a single oral administration. A dosage of 18—54 mg/kg body weight decreased the number of Neoascaris vitulorum eggs in faeces to zero in 1—3 weeks. In a further in vivo study on the anthelmintic activity of Combretum quadrangulare, the ethereal and 95% alcohol extracts of dried roots were as active as the seed extract. However, in a clinical experiment for the treatment of threadworm-infested children, negative results were obtained for moderate doses, and at a high dose negative side effects were observed.
Ripe seeds of Combretum quadrangulare produced no acute toxicity in albino rats and mice when administered orally at a single dose of about 0.6 and 2 g/kg respectively. The LD₅₀ of a 80% methanol extract, given orally to male and female mice and male and female rats, was reported to be 3.95, 3.9, 4.4 and 3.5 g/kg respectively. In a subchronic toxicity test, female rats, given the extract at 1 g/kg/day for 4 weeks, had significantly less weight gain without any changes in SGOT, SGAT, alkalinephosphatase, BUN or in serum albumin levels compared to controls.
Extracts of the seeds furthermore showed antibacterial activity against Staphylococcus aureus (ATCC 25923), Bacillus subtilis (ATCC 6633), Salmonella typhosa (Bangkok), Escherichia coli (ATCC 25922) and Pseudomonas aeruginosa (ATCC 10045) in vitro.
Triterpene glucosides (e.g. quadranosides I, II, V), isolated from the seeds of Combretum quadrangulare, showed significant hepatoprotective effects against D-galactosamine/tumour necrosis factor-'ALFA'(TNF-'ALFA')-induced cell death in primary cultured mouse hepatocytes. Cycloartane-type triterpenes and flavonoids from the methanolic leaf extract showed significant hepatoprotective effects on D-galactosamine/lipopolysaccharide-induced experimental liver injury in mice in vivo, together with in vitro activity in the previously mentioned assay. A potent inhibition was found to TNF-'ALFA'-induced cell death for the triterpenes quadrangularol B (IC₅₀ 34.3 µM), methyl quadrangularates A, I, N (IC₅₀ 45.7, 33.7, 89.3 µM, respectively), norquadrangularic acid B (IC₅₀ 67.6 µM), and the flavonoids vitexin (IC₅₀ 40.1 µM), kamatakenin (IC₅₀ 13.3 µM), 5,7,4'-trihydroxy-3,3'-dimethoxyflavone (IC₅₀ 22.4 µM), 5,4'-dihydroxy-3,7,3'-trimethoxyflavone (IC₅₀ 13.4 µM) and isokaempferide (IC₅₀ 22.8 µM), when compared to silibin (IC₅₀ 39.6 µM) as a clinically-used reference.
Methyl quadrangularate B and D also exhibit strong cytotoxicity against murine colon 26-L5 carcinoma cells, having ED₅₀ values of 9.54 and 5.42 µM, respectively; all flavonoids showed ED₅₀ values equal to or less than 6 µM.
Reported constituents for the roots include sterols and triterpenes, e.g. combretol, daucosterol, 3,6-diketo-olean-12-en-28-oic acid, olean-12-en-28-oic acid, 'BETA'-sitosterol and 3'BETA',6'BETA',18'BETA'-trihydro-urs-12-en-30-oic acid. The 95% alcohol extracts of dried roots showed in vitro antimicrobial activity against several bacteria.
An infusion or decoction of Combretum micranthum shows in vitro antimalarial activity against strains of Plasmodium falciparum sensitive to chloroquine (F32-Tanzania) and resistant to chloroquine (FcB1-Colombia)at IC₅₀ values lower than that of Azadirachta indica A.H.L. Juss.
The methanol extract of Combretum micranthum showed potent acaricidal activity against the two-spotted spider mite (Tetranychus urticae) using the leaf dipping method.
A methanolic extract of the leaves of Combretum micranthum, left standing for 7 days, shows in vitro antiviral activity against herpes simplex virus 1 and 2 (HSV-1,HSV-2). EC₅₀s of catechinic acid auto-oxidation products against HSV-1 and HSV-2 replication were 2 µg/ml and 4 µg/ml, respectively, when cell cultures were treated with the compound during virus infection. Several compounds including flavonoids (e.g. myricetin glycosides, vitexin), alkaloids ( e.g. stachydrine, 4-hydroxystachydrine) have been isolated from Combretum micranthum)

Small trees, scandent shrubs or large woody climbers up to 30 m tall. Leaves opposite, verticillate or rarely alternate, simple, entire, glabrous or hairy, often scaly and often with domatia; usually petiolate; stipules absent. Inflorescence an elongated or subcapitate, axillary or extra-axillary spike or raceme, or a terminal and/or axillary, often leafy, panicle. Flowers usually bisexual, actinomorphic, 4—5-merous; calyx tube (receptacle) glabrous or hairy, usually divided into a lower part adnate to the ovary and an upper part terminating in 4—5 calyx lobes; petals small or showy, white, yellow, orange, red or purple; stamens usually twice as many as petals, usually exserted; intrastaminal disk present; ovary inferior, unilocular. Fruit a pseudocarp, 4—5-winged, ridged or angled, usually indehiscent, 1-seeded, sessile or stipitate.

In Java, Combretum sundaicum flowers from January-February, and Combretum trifoliatum from May—November. Dry, indehiscent winged fruits may indicate dispersal by wind. Seed dispersal of narrow-winged or angled fruits of riverine species may be by water.

Quisqualis is closely related to Combretum and the most recent view is that both genera should be united. The name Combretum has priority over Quisqualis. However, for the Malesian species so far only Quisqualis indica L. has been recombined in Combretum indica (L.) Jongkind.

South-East Asian Combretum are found in habitats ranging from riverine and swampy, flood-plains (Combretum acuminatum, Combretum tetralophum, Combretum trifoliatum) to savanna woodlands and monsoon forest (Combretum trifoliatum) and evergreen forest (Combretum nigrescens), quite often in forest borders and secondary forest.

Combretum is propagated by seed or semi-ripe cuttings kept under mist spray or in a closed case to prevent excessive evaporation.

Fruits of Combretum quadrangulare are collected when mature; bark or leaves are collected whenever the need arises.

The Combretum species of medicinal importance are relatively widespread in South-East Asia and are also found in disturbed habitats, and therefore certainly not endangered. There are no known breeding programmes of South-East Asian Combretum.

The flavonoids and triterpenes from Combretum show interesting in vitro/in vivo effects, e.g. in the field of hepato-protection. Further experimental data will, however, be necessary for their total evaluation. The vermifugal effects which are well-known from traditional medicine were also found in cattle, and further research is therefore merited to fully investigate the possibilities.

Adnyana, I.K., Tezuka, Y., Banskota, A.H., Xiong, Q., Tran, K.Q. & Kadota, S., 2000. Quadranosides I-V, new triterpene glucosides from the seeds of Combretum quadrangulare. Journal of Natural Products 63(4): 496—500.
Aguilar, N.O., 1999. Quisqualis L. In: de Padua, L.S., Bunyapraphatsara, N. & Lemmens, R.H.M.J. (Editors): Plant Resources of South-East Asia No 12(1). Medicinal and poisonous plants 1. Backhuys Publishers, Leiden, the Netherlands. pp. 421—424.
Banskota, A.H., Tezuka, Y., Adnyana, I.K., Xiong, Q., Hase, K., Tran, K.Q., Tanaka, K., Saiki, I. & Kadota, S., 2000. Hepatoprotective effect of Combretum quadrangulare and its constituents. Biological and Pharmaceutical Bulletin 23(4): 456—460.
Banskota, A.H., Tezuka, Y., Phung, L.K., Tran, K.Q., Saiki, I., Miwa, T., Taga, T. & Kadota, S., 1998. Cytotoxic cycloartane-type triterpenes from Combretum quadrangulare. Bioorganic and Medicinal Chemistry Letters 8(24): 3519—3524.
Exell, A.W., 1954. Combretaceae. In: van Steenis, C.G.G.J. (Editor): Flora Malesiana. Series 1, Vol. 4. Noordhoff-Kolff N.V., Djakarta, Indonesia. pp. 533—548.
Farnsworth, N.R. & Bunyapraphatsara, N. (Editors), 1992. Thai medicinal plants. Medicinal Plant Information Center, Prachachon Co., Bangkok, Thailand. pp. 124—125.

Noorma Wati Haron

Combretum quadrangulare
Combretum sundaicum
Combretum trifoliatum

Haron, N.W., 2001. Combretum Loefl.. 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

The following species in this genus are important in this commodity group and are treated separatedly in this database:
Combretum quadrangulare
Combretum sundaicum
Combretum trifoliatum