Catharanthus roseus (PROTA)

Plant Resources of Tropical Africa Introduction

List of species

General importance
Geographic coverage Africa
Geographic coverage World
Medicinal
Ornamental
Forage / feed
Climate change

Catharanthus roseus (L.) G.Don

Protologue: Gen. hist. 4(1): 95 (1837).

Family: Apocynaceae

Chromosome number: 2n = 16

Synonyms

• Vinca rosea L. (1759),
• Lochnera rosea (L.) Rchb. ex Endl. (1838).

Vernacular names

• Madagascar periwinkle, rosy periwinkle (En).
• Pervenche de Madagascar, rose amère (Fr).
• Sempre noiva, flor de anjinho, pervinca de Madagascar (Po).
• Mtunda (Sw).

Origin and geographic distribution

Catharanthus roseus originates from Madagascar, but for centuries it has been cultivated as an ornamental throughout the tropics and occasionally in the subtropics; it has become naturalized in many regions. It was brought under cultivation in the first half of the 18^th century in Paris, from seeds collected in Madagascar, and was later distributed from European botanical gardens to the tropics. The antimitotic properties of some of its alkaloids were discovered accidentally in the late 1950s during searches for antidiabetic substances.

Uses

In Africa, especially in the Indian Ocean islands, medicinal uses of Catharanthus roseus are manifold and are similar to those in Asia. A decoction of all parts of Catharanthus roseus is well known as an oral hypoglycaemic agent. The decoction is also taken to treat malaria, dengue fever, diarrhoea, diabetes, cancer and skin diseases. Extracts prepared from the leaves have been applied as antiseptic agents for the healing of wounds, against haemorrhage and skin rash and as a mouthwash to treat toothache. The aerial parts are also considered diaphoretic and diuretic, and decoctions are taken to relieve indigestion, dyspepsia, dysentery, toothache and the effects of wasp stings, and as an emetic, purgative, vermifuge and depurative. In Uganda an infusion of the leaves is taken to treat stomach ulcers. In Botswana the leaves ground in milk are applied to mature abscesses. In Togo a root decoction is taken to treat dysmenorrhoea.

The aerial parts of the plant are used for the extraction of the medicinal alkaloids vincristine and vinblastine. The alkaloids are prescribed in anticancer therapy, usually as part of complex chemotherapy protocols. The dried root is an industrial source of ajmalicine, which increases the blood flow in the brain and peripheral parts of the body. Preparations of ajmalicine are used to treat the psychological and behavioural problems of senility, sensory problems (dizziness, tinnitus), cranial traumas and their neurological complications.

Alkaloids extracted from the aerial parts of Catharanthus roseus are marketed as lyophylisates (solutions of salts) designed for intravenous application. Vindesine and vinorelbine, which are semisynthetic derivatives of vinblastine, are marketed as a sulphate and a bitartrate, respectively. These are prescription drugs in Western countries.

Catharanthus roseus is a popular garden ornamental, grown as a perennial in the tropics and as an annual in temperate regions, although it can overwinter as a pot plant in a conservatory. It is valued for its bushy habit and many large flowers carried above dark green foliage. Catharanthus roseus can also be kept as a cut flower; the branches will last for weeks or even months, producing new, but smaller, flowers all the time.

Production and international trade

The world market consumed 5–10 kg of vincristine and vinblastine in the early 1990s, with a total value of US$ 25–50 million. In 2005 the market was estimated at US$ 150–300 million. In 1991 the world market consumed 3–5 t of ajmalicine, with a total value of US$ 4.5–7.5 million. Two anticancer medicines, Oncovin^® and Velban^®, derived from Catharanthus roseus, are sold for a total of US$ 100 million per year.

Catharanthus roseus is widely cultivated in Spain, United States and China for its pharmaceutical compounds.

Properties

Catharanthus roseus has been found to contain as many as 130 constituents with an indole or dihydroindole structure. The principal component is vindoline (up to 0.5%); other compounds are serpentine, catharanthine, ajmalicine (raubasine), akuammine, lochnerine, lochnericine and tetrahydroalstonine. Ajmalicine and serpentine are essentially present in the roots, whereas catharanthine and vindoline accumulate in aerial parts. The aerial parts contain 0.2–1% alkaloids.

The substances of pharmacological interest are the bisindole alkaloids, most of them containing a plumeran (vindoline) or an ibogan (catharanthine) moiety. Several of these alkaloids have cytostatic properties, but occur in very small amounts: vincristine (leurocristine) in up to 3 g/t of dried plant material and vinblastine (vincaleucoblastine) in a slightly larger amount. Other active compounds are leurosidine (vinrosidine) and leurosine.

Vincristine and vinblastine are highly toxic antimitotics, blocking mitosis in the metaphase. They both also have neurotoxic activity (especially vincristine), affecting neurotransmission. Their peripheral neurotoxic effects are neuralgia, myalgia, paresthesia, loss of the tendon reflexes, depression and headache; their central neurotoxic effects are convulsive episodes and respiratory difficulties. Other side effects are many and include alopecia, gastro-intestinal distress including constipation, ulcerations of the mouth, amenorrhoea and azoospermia. As vinblastine decreases the total number of white blood cells in the blood, its dosage must be carefully controlled. The alkaloids are very irritating; when extravasation accidentally occurs there is a risk of tissue necrosis. It is possible to limit the side effects by careful dosage and administration, and intensively monitoring the treatment. Vindesine, a semisynthetic derivative of vinblastine, is also a potent antimitotic. Its side effects include a transient decrease of the number of granulocytes in the blood and effects comparable to those caused by vincristine and vinblastine, although the neurological symptoms are less obvious. Vinorelbine (noranhydrovinblastine) is synthesized from anhydrovinblastine. It acts preferentially on mitosis and its neurological toxicity is limited. However, its haematotoxic activity is substantial, so its dosage must be carefully controlled. Vincristine (Oncovin^®) is indicated in the treatment of acute leukaemia, Hodgkin’s disease, small-cell lung cancer, cervical and breast cancer and various sarcomas. The indications for vinblastine (Velban^®) are mainly Hodgkin’s disease, non-Hodgkin’s lymphoma, Kaposi’s sarcoma, and renal, testicular, head and neck cancer. Vindesine (Eldisine^®) is indicated in the treatment of acute lymphatic leukaemia (especially in children) and refractory lymphomas and melanomas. Vinorelbine (Navelbine^®) has breast cancer and bronchial cancer as current indications. It is now part of several phase II clinical trials.

Roots to be used in pharmacy must contain at least 0.4% ajmalicine and the closely related serpentine. Ajmalicine (Hydroserpan^®, Lamuran^®) is an α-adrenergic blocking spasmolytic, which at high doses reverses the effects of adrenaline and moderates the activity of the vasomotor centres, especially in the brain stem. It temporarily increases the blood flow to the brain.

Some of the alkaloids (e.g. catharanthine, leurosine and vindoline) exhibit a moderate hypoglycaemic action. The fresh leaf juice though shows considerable hypoglycaemic activity. Vinblastine markedly inhibits the in-vitro reproduction of Trypanosoma cruzi, the organism causing Chagas’ disease. Antiviral activity has been reported in vitro for some Catharanthus alkaloids, e.g. leurocristine, perivine and vincristine. Extracts of the plants have shown fungicidal activity (e.g. against Fusarium solani that causes wilt e.g. in aubergine and Sclerotium rolfsii that causes diseases such as southern blight in tomato) and nematicidal activity (e.g. against Meloidogyne incognita and Meloidogyne javanica). Extracts of the dried flowers, dried leaves or fresh roots have shown antibacterial activity against some human pathogens.

Callus tissue of Catharanthus roseus can be cultured on various media, and can produce a variety of monomeric alkaloids. The alkaloid spectra of root and shoot cultures are similar to those of roots and aerial parts, respectively. In root cultures, ajmalicine and serpentine are usually the major constituents and catharanthine in shoot cultures. Much higher yields of serpentine and ajmalicine can be produced in cell cultures than in whole plants: up to 2% on dry weight basis versus 0.3% in whole plants. The dimeric anticancer alkaloids vinblastine and vincristine are almost undetectable in cultured cells, so attention has turned to the production of catharanthine and vindoline, which can be used as precursors for the synthesis of the dimers. Multiple shoot cultures induced from seedlings produce vindoline and catharanthine in rather higher levels. Another possible method of vindoline production is by cultures of selected hairy roots. These hairy roots can be produced by infecting seedlings with Agrobacterium rhizogenes. Some clones not only produce levels of ajmalicine, serpentine and catharanthine comparable to those of cell suspension cultures, but also about 3 times more vindoline than usually found in cell cultures. Another approach is to produce the alkaloids (or their precursors) in other organisms such as yeast via gene transfer.

Adulterations and substitutes

Vincristine, vinblastine and related compounds prevent mitosis in a different way from colchicine (from Colchicum autumnale L.), another potent antitumour agent. Ajmalicine and derivatives are also found in other Apocynaceae, such as Rauvolfia spp.

Description

• Erect or decumbent, deciduous undershrub up to 1 m tall, usually with white latex and an unpleasant smell; roots up to 70 cm long; stems narrowly winged, green or red, shortly hairy to glabrous, often woody at base.
• Leaves decussately opposite, simple and entire; stipules 2–4 at each side of the leaf base; petiole 3–11 mm long, green or red; blade elliptical to obovate or narrowly obovate, 2.5–8.5 cm × 1–4 cm, base cuneate, apex obtuse or acute with a mucronate tip, herbaceous to thinly leathery, glossy green above and pale green below, sparsely shortly hairy to glabrous on both sides.
• Inflorescence terminal, but apparently lateral, 1–2-flowered.
• Flowers bisexual, 5-merous, regular, almost sessile; sepals slightly fused at base, (2–)3–5 mm long, erect, green; corolla tube cylindrical, 2–3 cm long, widening near the top at the insertion of the stamens, laxly shortly hairy to glabrous outside, with a ring of hairs in the throat and another lower down the tube, greenish, lobes broadly obovate, 1–2(–3) cm long, apex mucronate, glabrous, spreading, pink, rose-purple or white with a purple, red, pink, pale yellow or white centre; stamens inserted just below the corolla throat, included, filaments very short; ovary superior, consisting of 2 very narrowly oblong carpels, style slender, 15–23 mm long, with a cylindrical pistil head provided at base with a reflexed transparent frill and with rings of woolly hairs at base and apex, stigma glabrous.
• Fruit composed of 2 free cylindrical follicles 2–4.5 cm long, striate, laxly shortly hairy to glabrous, green, dehiscent, 10–20-seeded.
• Seeds oblong, 2–3 mm long, grooved at one side, black.
• Seedling with epigeal germination.

Other botanical information

Catharanthus comprises 8 species, all originating from Madagascar except for Catharanthus pusillus (Murr.) G.Don, which is restricted to India and Sri Lanka. Catharanthus is very closely related to Vinca. No consistent qualitative differences have been found in alkaloid composition in relation to the different colours of the corolla of Catharanthus roseus.

Catharanthus coriaceus

Catharanthus coriaceus Markgr. is a rare species of central Madagascar. A leaf decoction is used to treat bilious fevers and dysentery. The bitter flowers are given to people with diabetes, who chew them to lessen their appetite. A decoction of the aerial parts was formerly drunk as an ordeal poison.

Catharanthus longifolius and ovalis

Catharanthus longifolius (Pichon) Pichon and Catharanthus ovalis Markgr. occur in southern-central Madagascar. An extract of the aerial parts of either species is given to humans or calves to expel worms. A concentrated extract was formerly drunk as an ordeal poison. They are both rich in indole alkaloids, including several bisindole alkaloids. Catharanthus ovalis contains the pharmacologically active leurosine, vindoline, vindolinine, coronaridine, catharanthine and vinblastine (vincaleucoblastine), whereas from Catharanthus longifolius e.g. vindolicine was isolated. Natural hybrids exist between Catharanthus longifolius and Catharanthus roseus, and artificial hybrids have been made between Catharanthus ovalis and Catharanthus longifolius.

Growth and development

Catharanthus roseus is usually self-compatible, and intra-flower self-pollination is common, because the stigma may come into contact with the anthers, even after anthesis. The degree of outcrossing may vary with environmental conditions and the presence of seasonal pollinating butterflies. Self-incompatible strains of Catharanthus roseus exist and can be locally common. In warmer climates, Catharanthus roseus will flower and fruit the whole year round. The seeds usually fall close to the mother plant, but are sometimes transported by ants. Within 6–8 weeks after germination the first flowers will appear. At temperatures below 5°C some branches or even the whole plant will die. When the temperature rises, the plant will regrow from basal axillary buds, especially after hard pruning of shoots and roots. Without pruning, the plant regrows mainly from the tops.

Tetraploid plants, induced with colchicine, have been found to have much higher alkaloid content than diploid plants, but the doubling of chromosomes was found to result in reduced pollen fertility and poor seed set.

Ecology

Catharanthus roseus often occurs in sandy locations along the coast, but also inland on river banks, in savanna vegetation and in dry waste places and roadsides, sometimes in open forest or scrub, usually on sandy soils, but sometimes also on rocky soils. It is very salt-tolerant, and is mostly found near sea-level, but occasionally up to 1500 m altitude. It can stand drought well, but not severe heat. Under severe water stress the alkaloid content of mature leaves was found to double, but it did not change in stems and immature leaves and it decreased in roots.

Propagation and planting

Catharanthus roseus is usually propagated by seed. Seed may remain dormant for several weeks after maturity. The optimum temperature for germination is 20–25°C, and the germination rate is in general over 95%. The seeds remain viable for 3–5 years. If the germination rate is low, this might be due to storage under too dry conditions. Seedlings can be potted after 3 weeks. Catharanthus roseus can also be propagated vegetatively by greenwood or semi-ripe cuttings rooted in a closed container with bottom heat. When rooting powder is used, the cuttings will start to root after 4–5 weeks. Putting cuttings in water will also induce rooting but it will take longer than in the soil.

Management

Catharanthus roseus is usually cultivated as an ornamental. It is a fast-growing plant that is easy to cultivate. When the plants become too tall, pruning is necessary. To encourage branching, the top of the seedling can be cut off, resulting in side branches that are always opposite. When the main stem is not topped, it will usually start branching at a height of 20–30 cm, but only one side branch will then develop with subsequent branching. Catharanthus roseus responds well to N fertilizers, but can also grow and persist on poor soils.

Catharanthus roseus is also cultivated for medicinal purposes, in Africa mainly in Madagascar. In India it is mainly cultivated as a 200-day crop for its leaves (for the extraction of vinblastine and vincristine) and its roots (for the extraction of ajmalicine). The crop needs little irrigation or fertilizer. Too excessive watering causes yellowing of the leaves. Plant spacing is 30–40 cm between plants.

Diseases and pests

In Africa no diseases or pests are known, but in Malaysia Catharanthus roseus has been reported to be infected with ‘Malaysian periwinkle yellow’. Symptoms include excessive yellowing of foliage, bunchy top and stunted flowers and leaves, suggesting infection by a mycoplasm-like organism. Similar diseases have been reported from China, Taiwan, North America and Europe. Mycoplasm-like organisms can be transferred to Catharanthus roseus by parasitic plants of the genus Cuscuta, and perhaps also by leafhoppers. Container-grown plants in the United States cultivated as ornamentals have been reported susceptible to Phytophthora parasitica that causes root and stem rot. In glasshouses red spider mite (Tetranychus urticae) is very common.

Harvesting

Catharanthus roseus plants are harvested by uprooting the whole plant after which the roots are separated from the rest of the plant and both parts are separately processed. If only the leaves are harvested, the plants are left in the field for a ratoon crop. Harvesting leaves is done manually or by machine. The alkaloid content of the plants is highest at flowering.

Handling after harvest

The aerial parts and the roots of Catharanthus roseus are cleaned, after which they are dried at low temperatures, then packed for shipment. Potted plants for use as ornamentals are usually traded in sealed packages. They are marketable in this condition for 18 days, and do not require watering during this period.

Genetic resources

Although Catharanthus roseus probably originated from a limited area in south-eastern Madagascar, it is now widely planted and naturalized in all tropical areas, and is certainly not endangered. However, protection of the wild populations in Madagascar is desirable to ensure the conservation of the genetic diversity, which might be of interest for breeding purposes in the future.

Breeding

Catharanthus roseus has been successfully crossed with Catharanthus trichophyllus (Baker) Pichon, with the F₁ having a high seed set and good viability when Catharanthus trichophyllus was the female parent. The alkaloid profiles of the two species are different, and alkaloid production seems to be higher in hybrids than in the parent species.

In breeding, the following characteristics seem to be dominant: purple corolla colour, dark eye of the flower and tall and open habit. Breeding aims at plants of which the corollas drop, because the old corolla will otherwise stick to the young fruit and to the new bud, which cannot develop well. Two large groups of cultivars exist, those with a distinct eye and those with a green to white eye. Subsequent grouping is done by corolla colour, and about 50 cultivars have so far been developed. Although hybrids are only occasionally found in nature, in cultivation many usually fertile hybrids can be made between the different Catharanthus species, which have the same chromosome numbers.

Prospects

The possibility of accessing active dimeric alkaloids by biomimetic synthesis has recently attracted much attention. It is now conceivable that vinblastine could be obtained from starting materials such as catharanthine and vindoline, which are neither rare nor too expensive. These latter two compounds can be produced in sufficient amounts in in-vitro cultures of Catharanthus roseus. Studies on analogues of the well-known alkaloids suggest good prospects for new developments vis-à-vis Catharanthus alkaloids. Horticultural production of Catharanthus roseus for alkaloid production is little studied and deserves more attention. Catharanthus roseus may have good prospects as an ornamental in temperate regions.

Major references

• Gurib-Fakim, A. & Brendler, T., 2004. Medicinal and aromatic plants of Indian Ocean Islands: Madagascar, Comoros, Seychelles and Mascarenes. Medpharm, Stuttgart, Germany. 568 pp.

• Lavergne, R. & Véra, R., 1989. Médecine traditionelle et pharmacopée - Contribution aux études ethnobotaniques et floristiques à la Réunion. Agence de Coopération Culturelle et Technique, Paris, France. 236 pp.

• Mukherjee, A.K., Basu, S., Sarkar, N. & Ghosh, A.C., 2001. Advances in cancer therapy with plant based natural products. Current Medicinal Chemistry 8: 1467–1486.

• Neuwinger, H.D., 2000. African traditional medicine: a dictionary of plant use and applications. Medpharm Scientific, Stuttgart, Germany. 589 pp.

• Plaizier, A.C., 1981. A revision of Catharanthus roseus (L.) G.Don (Apocynaceae). Mededelingen Landbouwhogeschool Wageningen 81–9, Wageningen, Netherlands. 12 pp.

• Ross, I.A., 2003. Medicinal plants of the world. Chemical constituents, traditional and modern uses. Volume 1. 2nd Edition. Humana Press, Totowa NJ, United States. 489 pp.

• Snoeijer, W., 1996. Catharanthus roseus, the Madagascar periwinkle, a review of its cultivars. Series of revisions of Apocynaceae 41. Wageningen Agricultural University Papers 96–3, Wageningen, Netherlands. pp. 47–120.

• Sutarno, H. & Rudjiman, 1999. Catharanthus roseus (L.) G. Don. 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, Netherlands. pp. 185–190.

• van Bergen, M.A., 1996. Revision of Catharanthus G.Don. Series of revisions of Apocynaceae 41. Wageningen Agricultural University Papers 96–3, Wageningen, Netherlands. pp. 9–46.

• van der Heijden, R., Jacobs, D.I., Snoeijer, W., Hallard, D. & Verpoorte, R., 2004. The Catharanthus alkaloids: pharmacognosy and biotechnology. Current Medicinal Chemistry 11(5): 607–628.

Other references

• Bhadra, R., Vani, S. & Shanks, J.V., 1993. Production of indole alkaloids by selected hairy root lines of Catharanthus roseus. Biotechnology and Bioengineering 41(5): 581–592.

• Gurib-Fakim, A., Guého, J. & Bissoondoyal, M.D., 1995. Plantes médicinales de Maurice, tome 1. Editions de l’Océan Indien, Rose-Hill, Mauritius. 495 pp.

• Johns, T., Faubert, G.M., Kokwaro, J.O., Mahunnah, R.L.A. & Kimanani, E.K., 1995. Anti-giardial activity of gastrointestinal remedies of the Luo of East Africa. Journal of Ethnopharmacology 46: 17–23.

• Kulkarni, R.N., Sreevalli, Y., Baskaran, K. & Kumar, S., 2001. The mechanism and inheritance of intraflower self-pollination in self-pollinating variant strains of periwinkle. Plant Breeding 120: 247–250.

• Marfori, E.C. & Alejar, A.A., 1993. Alkaloid yield variation in callus cultures derived from different plant parts of the white and rosy-purple periwinkle, Catharanthus roseus (L.) G. Don. Philippine Journal of Biotechnology 4(1): 1–8.

• Nammi, S., Boini, M.K., Lodagala, S.D. & Behara, R.B., 2003. The juice of fresh leaves of Catharanthus roseus Linn. reduces blood glucose in normal and alloxan diabetic rabbits. BMC Complementary and Alternative Medicine 3: 1–4.

• Ojewole, J.O. & Adewunmi, C.O., 2000. Hypoglycaemic effects of methanolic leaf extract of Catharanthus roseus (Linn.) G. Don (Apocynaceae) in normal and diabetic mice. Acta Medica et Biologica 48(2): 55–58.

• Reda, F., 1978. Distribution and accumulation of alkaloids in Catharanthus roseus G.Don during development. Pharmazie 33(4): 233–234.

• Sevestre-Rigouzzo, M., Nef-Campa, C., Ghesquière, A. & Chrestin, H, 1993. Genetic diversity and alkaloid production in Catharanthus roseus, C. trichophyllus and their hybrids. Euphytica 66: 151–159.

• Singh, S.N., Vats, P., Suri, S., Shyam, R., Kumria, M.M., Ranganathan, S. & Sridharan, K., 2001. Effect of an antidiabetic extract of Catharanthus roseus on enzymic activities in streptozotocin induced diabetic rats. Journal of Ethnopharmacology 76(3): 269–277.

• Tabuti, J.R.S., Lye, K.A. & Dhillion, S.S., 2003. Traditional herbal drugs of Bulamogi, Uganda: plants, use and administration. Journal of Ethnopharmacology 88: 19–44.

• van Wyk, B.E., van Heerden, F. & van Oudtshoorn, B., 2002. Poisonous plants of South Africa. Briza Publications, Pretoria, South Africa. 288 pp.

• Verpoorte, R., Contin, A. & Memelink, J., 2002. Biotechnology for the production of plant secondary metabolites. Phytochemistry Reviews 1: 13–25.

• Yuan, Y.-J., Hu, T.-T. & Yang, Y.-M., 1994. Effects of auxins and cytokinins on formation of Catharanthus roseus G.Don multiple shoots. Plant Cell, Tissue and Organ Culture 37(2): 193–196.

Sources of illustration

• Sutarno, H. & Rudjiman, 1999. Catharanthus roseus (L.) G. Don. 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, Netherlands. pp. 185–190.

Author(s)

• G.H. Schmelzer, PROTA Network Office Europe, Wageningen University, P.O. Box 341, 6700 AH Wageningen, Netherlands

Correct citation of this article

Schmelzer, G.H., 2007. Catharanthus roseus (L.) G.Don. In: Schmelzer, G.H. & Gurib-Fakim, A. (Editors). PROTA (Plant Resources of Tropical Africa / Ressources végétales de l’Afrique tropicale), Wageningen, Netherlands. Accessed 3 April 2025.

• See the Prota4U database.