Physical characteristics

Is a species of Catharanthus native and endemic to Madagascar? Synonyms include Vinca rosea (the basionym), Ammocallis rosea, and Lochnera rosea; other English names occasionally used include Cape Periwinkle, Rose Periwinkle, Rosy Periwinkle, and "Old-maid".

In the wild, it is an endangered plant; the main cause of decline is habitat destruction by slash and burn agriculture. It is also however widely cultivated and is naturalised in subtropical and tropical areas of the world. It is an evergreen subshrub or herbaceous plant growing to 1 m tall. The leaves are oval to oblong, 2.5–9 cm long and 1–3.5 cm broad, glossy green, hairless, with a pale midrib and a short petiole 1–1.8 cm long; they are arranged in opposite pairs. The flowers are white to dark pink with a darker red centre, with a basal tube 2.5-3 cm long and a corolla 2–5 cm diameter with five petal-like lobes. The fruit is a pair of follicles 2–4 cm long and 3 mm broad.

Composition

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.

Medicinal uses

The species has long been cultivated for herbal medicine and as an ornamental plant. In traditional Chinese medicine, extracts from it have been used to treat numerous diseases, including diabetes, malaria and Hodgkin's disease. The substances vinblastine and vincristine extracted from the plant are used in the treatment of leukaemia. This conflict between historical indigenous use, and recent patents on C.roseus-derived drugs by western pharmaceutical companies, without compensation, has led to accusations of biopiracy. It can be dangerous if consumed orally.[3] It can be hallucinogenic, and is cited (under its synonym Vinca rosea) in the Louisiana State Act 159.

Other uses

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

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