Aspidosperma (Apocynaceae) plant cytotoxicity and activity towards malaria parasites. Part II: experimental studies withAspidosperma ramiflorum in vivo and in vitro

Several species of Aspidospermaplants are used to treat diseases in the tropics, including Aspidosperma ramiflorum, which acts against leishmaniasis, an activity that is experimentally confirmed. The species, known as guatambu-yellow, yellowperoba, coffee-peroba andmatiambu, grows in the Atlantic Forest of Brazil in the South to the Southeast regions. Through a guided biofractionation of A. ramiflorumextracts, the plant activity against Plasmodium falciparumwas evaluated in vitro for toxicity towards human hepatoma G2 cells, normal monkey kidney cells and nonimmortalised human monocytes isolated from peripheral blood. Six of the seven extracts tested were active at low doses (half-maximal drug inhibitory concentration < 3.8 µg/mL); the aqueous extract was inactive. Overall, the plant extracts and the purified compounds displayed low toxicity in vitro. A nonsoluble extract fraction and one purified alkaloid isositsirikine (compound 5) displayed high selectivity indexes (SI) (= 56 and 113, respectively), whereas compounds 2 and 3 were toxic (SI < 10). The structure, activity and low toxicity of isositsirikine in vitro are described here for the first time in A. ramiflorum, but only the neutral and precipitate plant fractions were tested for activity, which caused up to 53% parasitaemia inhibition of Plasmodium bergheiin mice with blood-induced malaria. This plant species is likely to be useful in the further development of an antimalarial drug, but its pharmacological evaluation is still required.

Multiplicação in vitro de Aspidosperma ramiflorum Muell. Arg. (Apocynaceae) / In vitro multiplication of Aspidosperma ramiflorum Muell. Arg. (Apocynaceae)

O presente estudo relata um método simples e promissor para multiplicação in vitro de Aspidosperma ramiflorum, uma espécie encontrada no sudeste do Brasil e seriamente ameaçada de extinção, utilizada com propósitos medicinais e como fonte de compostos que podem ser usados para desenvolver novos fármacos sintéticos. O trabalho teve como objetivo o estabelecimento de um protocolo de multiplicação in vitro de Aspidosperma ramiflorum (guatambu), a partir de segmentos apicais de material juvenil originários de plântulas obtidos a partir de sementes. A avaliação da multiplicação in vitro foi realizada em meio de cultura Woody Plant Médium (WPM), suplementado com concentrações variadas de ácido naftalenoacético (ANA) e 6-Benzilaminopurina (6-BAP). A multiplicação de A. ramiflorum foi positivamente influenciada principalmente nas combinações aonde as concentrações de 6-BAP foram relativamente maiores do que as do ANA, nessas concentrações houve a indução de múltiplas brotações.

The present study described a simple and promissory method for in vitro multiplication of Aspidosperma ramiflorum, a species found in the South of Brazil and seriously extinction menaced. The method was used for medicinal proposes and as a source of compounds to develop new synthetic drugs. The objective of this work was to establish an in vitro multiplication protocol of Aspidosperma ramiflorum (guatambu), from apical segments of juvenile material of plantlets obtained from seeds. The in vitro multiplication evaluation was done in WPM medium, supplemented with variable concentrations of Naphthalene acetic acid (NAA) and 6- Benzyl aminopurine (6-BAP). The multiplication of A. ramiflorum was positively influenced mainly in the combinations when 6-BAP concentrations were relatively higher than NAA. In these concentrations multiple shoots were induced.