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

Abstract

Several species of Aspidosperma plants 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, yellow peroba, coffee-peroba andmatiambu, grows in the Atlantic Forest of Brazil in the South to the Southeast regions. Through a guided biofractionation of A. ramiflorum extracts, the plant activity against Plasmodium falciparum was 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 berghei in 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.

Aspidosperma pyrifolium, a medicinal plant from the Brazilian caatinga, displays a high antiplasmodial activity and low cytotoxicity

“…The high selectivity index of A. pyrifolium was comparable to that of other species of Aspidosperma published before [ 29 – 31 ]. Aspidosperma pyrifolium was the second-best species for in vitro activity against malaria parasites, only preceded by A. nitidum , a species highly used as anti-malarial treatment in Brazilian malaria-endemic areas [ 29 ].…”

“…The A. pyrifolium was the second-best Aspidosperma species for in vitro activity against malaria parasites, only preceded by A. nitidum , a species highly used as anti-malarial treatment in Brazilian malaria-endemic areas [ 29 ]. The two other species A. olivaceum [ 30 ] and A. ramiflorum [ 31 ] showed higher toxicities, resulting in lower selectivity indexes when compared to A. pyrifolium . This plant species is likely to be useful for further development of an anti-malarial drug, but supplementary chemical and pharmacological studies are still needed.…”

“…The half-maximal drug inhibitory concentration (IC 50 ) was estimated by curve fitting with the software Origin (OriginLab Corporation, USA) compared to parasite growth in drug-free medium. Fractions with IC 50 values bellow 10 µg/ml were considered active; between 10 e 20 µg/ml as partially active, and above 20 µg/ml as inactive as demonstrated before [ 30 , 31 ]. The chloroquine was used as anti-malarial control in all assays.…”

Characterizing Casca d´anta: an Apocynaceae used to treat tropical diseases in the Amazonian region

“…Aspidosperma ramiflorum Müll. Arg., for example, showed efficiency in the treatment against P. falciparum, from extracts of the stem and leaves (Aguiar et al 2015). Ethanol extracts from the roots, stem bark and leaves of A. macrocarpon tested in vitro also showed promising results for inhibition of P. falciparum (de Mesquita et al 2007), with better results for root extracts.…”

Unraveling the leaf-dropping behavior behind bat folivory: do bats use biological control against roost parasites?

“…Diverse biological effects (e.g. controlling, repellant) against several organisms that include fungus, bacteria, protozoans, helminths, insects and/or mites have been reported for species of Aspidosperma Martius & Zuccarini (Aguiar et al 2015, de Almeida et al 2019, Tapura Aublet (Taljaard 2014), Erythrina Linnaeus (Sato et al 2003, Kumari et al 2017, Brosimum Swartz (Coqueiro et al 2014, Borges et al 2017 and Ficus Linnaeus (de Amorin et al 1999, Romeh 2013, Wan et al 2017. Plant volatiles from leaves are extremely common and very diverse (Pichersky et al 2006, Courtois et al 2009.…”