Croton (PROSEA Medicinal plants)
- Protologue: Sp. pl. 2: 1004 (1753); Gen. pl. ed. 5: 436(1754).
- Family: Euphorbiaceae
- Chromosome number: x= 9, 10, 14; C. aromaticus, C. caudatus, C. roxburghii, C. tiglium: 2n= 20
Croton argyratus Blume, C. caudatus Geiseler, C. stellatopilosus Ohba, C. tiglium L.
Origin and geographic distribution
Croton is one of the larger genera in the Euphorbiaceae , about 750 species are recognized worldwide in tropical and subtropical regions. The majority of species is found in the Americas and about 75 species in Malesia.
The medicinal uses of Croton are very diverse, varying from strongly purgative qualities to providing aromatic tonics. The aromatic species are mainly found in South America: C. eluteria (L.) W. Wright, C. cascarilla (L.) L. (Cascarilla bark), C. malambo Karsten (Malambo bark), C. pseudo-china Schlechter (Copalchi bark; by some considered a synonym of C. niveus Jacq.). C. aromaticus L. from India is also aromatic. Whereas many species are used for their purgative properties, C. argyratus and C. stellatopilosus are employed to arrest diarrhoea. C. caudatus and C. tiglium have a reputation for their purgative properties. The seed and seed oil of C. tiglium have been widely used as a strong purgative, drastic cathartic and poison throughout South-East Asia. The oil is a strong vesicant but diluted it can be externally applied in liniments as a counterirritant for various skin affections. Caution should be taken with all applications in view of its drastic action. The root has been used as an abortifacient. The wood is said to be diaphoretic when administered in small doses, and purgative and emetic in large doses. An extract of the seed can be used as an insecticide, for field applications as well as in stored cereals and beans. The seed oil of C. tiglium may also be used for production of soap or candles. However, for illumination it can only be used for outdoor applications as the smoke is toxic.
The bark and roots of C. cascarilloides Raeusch (synonym C. cummingii M√ºll. Arg.), from West Malesia, are used as an antipyretic in Thailand. The bark of C. roxburghii N.P. Balakr. (synonym C. oblongifolius Roxb.) is externally applied to sprains. A hot decoction of the leaves is used in Indo-China to treat scabies. The seed oil is very similar to that of C. tiglium , and seeds are likewise purgative and considered poisonous. The leaves of C. kongensis Gagnep. (synonym C. tonkinensis Gagnep.) are used in Indo-China for various stomach disorders including ulcers, and a decoction is externally applied for furuncles and impetigo. The roots of C. crassifolius Geiseler (synonym C. tomentosus (Lour.) M√ºll. Arg.), another species confined to southern China, Indo-China, Burma (Myanmar) and northern Thailand are used to treat cholera, dysentery and to cure an inflamed and painful throat. The leaves of C. flavens L. are a popular ingredient of herbal teas in the Caribbean. Dragon‚Äôs blood, the red, viscous latex of various South American species e.g. C. lechleri M√ºll. Arg., C. draconoides M√ºll. Arg. and C. erythrochilus M√ºll. Arg., is used for various diseases, in particular for wound healing.
Production and international trade
Roots, seeds and seed oil of C. tiglium are locally traded within South-East Asia. Trade with western Europe started in the 16th Century and continued to be important until the beginning of the 20th Century. Recent information is, however, lacking.
The seed of C. tiglium contains 30-45% of a fixed oil named croton oil. Croton seeds contain the toxic proteins croton globulin and croton albumin, croton resin ("crotonol") responsible for the vesicant and irritant properties; a non-volatile unsaturated fatty acid responsible for the purgative properties; crotin, a phytotoxin and blood coagulant with a delayed poisonous effect; and a glucoside, crotonoside, that has no harmful physiological action. The seeds commonly applied as fish poison, show strong molluscicidal activity as well. Several 12,13-diesters, and 12,13,20-triesters of the diterpene phorbol have been isolated from croton resin. Phorbol-12-tiglate-13-decanoate showed antileukaemic activity against lymphocytic leukaemia in mice. In general, however, these phorbol esters as found in C. tiglium (and many other Croton species e.g. C. roxburghii ) are extremely irritant and also tumour promotors. Their presence in C. tiglium and C. flavens means their consumption is sometimes held responsible for certain forms of (nasopharyngeal) cancer as they are able to activate e.g. Epstein-Barr viruses.
A considerable number of compounds, diterpenes, diterpene esters, diterpene lactones and furanoid terpenes have been isolated from various parts of C. stellatopilosus : furanoditerpene A-B, geranylgeraniol ester A-G, planunol A, plaunotol, plaunol A-E, plaunol monoacetate and plaunolide. Furthermore, stem extracts of this Thai medicinal plant yielded ent-3Œ±-hydroxy-13-epimanool and ent-16Œ≤,17-dihydroxykaurene. In earlier studies, 18-hydroxygeranylgeraniol and 5 plaunols were isolated and showed activity against peptic ulcers. The diterpene lactones plaunol A and B also exhibited anti-Shay ulcer activity, as is the case with the acyclic diterpene plaunotol which is used in the clinical treatment of peptic ulcers. The latter compound is marketed under its brand name KelnacFruit¬Æin several countries worldwide. The activity of geranylgeraniol-18-hydroxylase, a novel enzyme catalyzing the C-18 hydroxylation of geranylgeraniol to plaunotol, was demonstrated in a cell-free extract prepared from C. stellatopilosus leaves. This enzyme is involved in the final step of the biosynthetic pathway of plaunotol.
Dragon‚Äôs blood from various South American Croton species contains a dihydrobenzofuran lignan (2-(3‚Äô,4‚Äô-dimethoxyphenyl)-3-hydroxymethyl-2,3-dihydro-7-methoxybenzofuran-5-propan-1-ol), inhibiting cell proliferation, which may well explain its application in folk medicine. (-)-Hardwickiic acid in combination with 3,5-secotrachylobanic acid was found in the resin of the root of the South American C. sonderianus M√ºll. Arg. that shows antimicrobial activity. Cyperenoic acid and (-)-hardwickiic acid have been isolated from the roots of C. aromaticus and displayed moderate insecticidal activity.
In the stem bark of C. levatii Guillaumin, used in Vanuatu as a perfume and aphrodisiac, a diterpenoid levatin has been isolated (ent-15,16-epoxy-18-norcleroda-8(17),13(16)14-triene-19,3:12,12S-diolide).
Adulterations and substitutes
The seed oil of other Euphorbiaceae such as Aleurites moluccana (L.) Willd., Ricinus communis L. and Vernicia spp., can also be used as a purgative. Their effect is less drastic than that of the oil of C. tiglium.
Shrubs to small trees, sometimes lianas, usually monoecious; indumentum usually stellate hairs or peltate scales next to simple hairs. Leaves simple, alternate, in some species with rhythmic growth and leaves crowded, margins often wavy or with teeth and glands, at base usually with two abaxial glands, lower surface in some species completely covered by peltate scales or stellate hairs. Inflorescences usually terminal, bisexual thyrses with basally pistillate flowers and apically staminate flowers. Flowers usually clustered on nodes; sepals 5, freeor slightly fused at base, overlapping; petals 5, usually as long as or shorter than sepals, in pistillate flowers sometimes minute or absent; disk of 5 glands or annular in some pistillate flowers; staminate flowers with 5-30 stamens, strongly inflexed in bud, free, filaments hairy or glabrous, receptacle hairy, pistillode absent; pistillate flowers with a usually 3-locular ovary, one ovule per locule, styles long, slender, stigmas usually deeply forked. Fruit a cylindrical capsule, splitting into 3 (bipartite) or 6 parts, smooth or shortly muricate. Seed without arillode, sometimes carunculate. Seedling with epigeal germination; cotyledons emergent, leafy; hypocotyl elongated; all leaves arranged spirally.
Growth and development
Most Croton species grow fast. C. tiglium raised from seed or cuttings will flower within 15 months. Seedlings of C. stellatopilosus reach a height of 2-4 m in 3-4 years. In areas without a pronounced dry season Croton can be found flowering and fruiting throughout the year. In Prachin Buri, southeastern Thailand, C. stellatopilosus flowers and fruits in February-March, shoot formation is most prominent in April-October, and leaves are shed in November-January.
Other botanical information
Croton is classified in the subfamily Crotonoideae , tribe Crotoneae . The most recent infrageneric classification identifies 40 sections of which two have been subdivided into subsections. The species are often difficult to identify due to minor differences in characters (e.g. different hair types).
Most Croton species are relatively indifferent to their habitat and they are found on a wide range of soils in disturbed and undisturbed vegetation. Some species are more restricted in their ecological range and confined to tidal zones, mangrove, peat swamp or limestone. In general, Croton is found below 1000 m altitude.
Propagation and planting
As most material of Croton is collected from the wild information is rather scarce. In Vietnam, C. crassifolius , C. kongensis and C. tiglium are planted. In other areas planting efforts appear to be limited to C. tiglium , for which small-scale plantings for commercial purposes go back to the beginning of the 20th Century. C. tiglium is propagated from stem cuttings and seed. C. stellatopilosus can be propagated by shoot tip culture technique for rapid multiplication of superior plant material with higher plaunotol content. C. argyratus can be propagated by seed, which shows about 45% germination in 22-73 days. C. crassifolius is propagated by root cuttings in northern Vietnam.
Scions from C. stellatopilosus can be successfully side-grafted onto rootstocks of C. roxburghii , a species not susceptible to root rot under comparable conditions. No root rot was observed in grafted C. stellatopilosus during the year after grafting. Grafting promoted the vegetative growth of C. stellatopilosus and did not affect the plaunotol content of leaves.
In vitro production of active compounds
The production of plaunotol in callus cultures of C. stellatopilosus is enhanced by using media containing high concentrations (>0.8%) of gelling agents, especially gellan gum or agarose. The accumulation of plaunotol was observed within 3 weeks after transfer to the medium and was accompanied by increases in chlorophyll content and in the number and size of regions containing tracheids, and by slow growth. Light and high concentrations of gelling agents were required for plaunotol accumulation in the callus.
During the resting period C. stellatopilosus trees in Thailand should be top-cut at about 2 m above ground; stems with few branches should be thinned and branches with only a few buds cut back. During the growth period only the top part of branches with many leaves should be lightly cut back. Heavy pruning should be avoided to secure an increase in leaf yield and plaunotol content in the leaves of the next harvest. Following this system leaves can be harvested three times a year; at the early stage of vegetative growth late May or late June, a second harvest late July or late August and a third harvest at the late stage of vegetative growth late October or late November. In C. stellatopilosus plantations of less than 2 years old, ploughing and the use of Calopogonium mucunoides Desv. as cover crop were found to be effective methods of weed control, whereas repeated applications of glyphosate at 1.4 kg/ha followed by hoeing and ploughing were suitable in crops of more than 3 years old. Various control measures have been developed to control root rot in C. stellatopilosus plantations. The occurrence of the disease is related to rainfall, frequency of harvesting, ploughing, mulching and soil nutrient status. Control measures include ploughing at the beginning of the dry season in December, sowing a cover crop at the beginning of the rainy season in May followed by mulching 2 months later, supplying sufficient fertilizer together with 60 g dazomet/m2, and harvesting only once or twice annually.
Diseases and pests
Serious diseases or pests have not been reported for the medicinally used Croton species. Root rot, caused by e.g. Fusarium spp., sometimes causes damage in C. stellatopilosus plantations in Thailand. Larvae of Amyna punctum , feeding on the leaves, may attack 3-year-old plantations during the rainy season, but carbaryl (1-naphthylmethylcarbamate) is an effective insecticide to control the pest.
Since the medicinally used Croton species are generally of limited dimensions, the harvesting of fruits, leaves, bark and roots is relatively easy.
By appropriate pruning the dry-weight of 7-year-old C. stellatopilosus can be increased from 341 g to 905 g leaves and from 3.3 g to 6.2 g plaunotol, respectively. Plaunotol content is highest in young leaves. The annual production of a 1200 ha plantation in Thailand was estimated at 1700 t dried leaves.
Handling after harvest
Fruits, leaves, bark and roots can be dried and stored for future use. The seed oil can be stored only for a limited period of time as a result of oxidation.
Genetic resources and breeding
The Croton species of medicinal importance are relatively common and widely distributed. The risk of genetic erosion appears rather limited. No germplasm collections of Croton is known to exist.
The Malesian Croton species are of limited economic importance. Although croton oil is still officially included in several Pharmacopoeias, its use, as well as that of other plant parts (e.g. seeds), should be limited because of their strong purgative action and the presence of phorbol esters with irritant and tumour-promoting activity. C. stellatopilosus seems of interest as a source of plaunotol, a compound used in the treatment of peptic ulcers. However, a patented chemical synthesis is also available for plaunotol.
- Matsunaga, E., Domethong, C. & Boriboon, M., 1990. Studies on the pruning and harvesting systems of a Thai medicinal plant, plau-noi tree (Croton sublyratus Kurz). Japanese Journal of Tropical Agriculture 34(4): 243-249.
- Pieters, L., de Bruyne, T., Claeys, M. & Vlietinck, A., 1993. Isolation of a dihydrobenzofuran lignan from South American dragon‚Äôs blood (Croton spp.) as an inhibitor of cell proliferation. Journal of Natural Products (Lloydia) 56: 899-906.
- Shibata, W., Murai, F., Akiyama, T., Siriphol, M., Matsunaga, E. & Morimoto, H., 1996. Micropropagation of Croton sublyratus Kurz - a tropical tree of medicinal importance. Plant Cell Reports 16(3-4): 147-152.
- Tansakul, P. & De Eknamkul, W., 1998. Geranylgeraniol-18-hydroxylase: the last enzyme on the plaunotol biosynthetic pathway in Croton sublyratus. Phytochemistry 47(7): 1241-1246.
- Webster, G.L., 1993. A provisional synopsis of the sections of the genus Croton (Euphorbiaceae). Taxon 42: 793-823.
- Zeng, Y., Zhong, J.M., Ye, S.W., Ni, Z.Y., Miao, X.Q., Mo, Y.K. & Li, Z.L., 1994. Screening of Epstein-Barr virus early antigen expression inducers from Chinese medicinal herbs and plants. Biomedical and Environmental Sciences 7(1): 50-55.
P.C. van Welzen & H.J. Esser