Indole alkaloids from Catharanthus roseus: bioproduction and their effect on human health

Abstract

Catharanthus roseus is a medicinal plant belonging to the family Apocynaceae which produces terpenoid indole alkaloids (TIAs) of high medicinal importance. Indeed, a number of activities like antidiabetic, bactericide and antihypertensive are linked to C. roseus. Nevertheless, the high added value of this plant is based on its enormous pharmaceutical interest, producing more than 130 TIAs, some of which exhibit strong pharmacological activities. The most striking biological activity investigated has been the antitumour effect of dimeric alkaloids such as anhydrovinblastine, vinblastine and vincristine which are already in pre-, clinical or in use. The great pharmacological importance of these indole alkaloids, contrasts with the small amounts of them found in this plant, making their extraction a very expensive process. To overcome this problem, researches have looked for alternative sources and strategies to produce them in higher amounts. In this sense, intensive research on the biosynthesis of TIAs and the regulation of their pathways has been developed with the aim to increase by biotechnological approaches, the production of these high added value compounds. This review is focused on the different strategies which improve TIA production, and in the analysis of the beneficial effects that these compounds exert on human health.

Figure 1

Chemical structures of the four Vinca alkaloids vincristine (A), vinblastine (B), vinorelbine (C) and vinflunine (D). The arrow indicates the principal difference between vincristine (A) and vinblastine (B). The arrow heads indicate the principal difference between vinorelbine (C) and vinflunine (D).

Figure 2

Gene regulation scheme of transcription factors involved in the TIA biosynthethic pathways. AS, anthranilate synthase; TDC, tryptophan decarboxylase; G10H, geraniol 10-hydroxilase; SLS, secologanin synthase; STR, strictosidine synthase; SGD, strictosidine β-D-glucosidase, T16H, tabersonine 16-hydroxylase, OMT, 16-hydoxytabersonine 16-O-methyltransferase; NMT, N-methyltransferase; D4H, desacetoxyvindoline 4-hydroxylase; DAT, deacetylvindoline 4-O-acetyltransferase; Prx, peroxidase.