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

Aguiar AC, Cunha AC, Ceravolo IP, Gonçalves RA, Oliveira AJ, Krettli AU - Mem. Inst. Oswaldo Cruz (2015)

Bottom Line: 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.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).This plant species is likely to be useful in the further development of an antimalarial drug, but its pharmacological evaluation is still required.

View Article: PubMed Central - PubMed

Affiliation: Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, MG, Brasil.

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 and matiambu, 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.

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Related in: MedlinePlus

off-line ESI-MS of crude extract from stem bark ofAspidospermaramiflorum. Ion at m/z467 corresponding toramiflorine A (1) and ramiflorine B (2), ion at m/z 327corresponding to 10-methoxy-geissoschizol (3) and ion at m/z355 corresponding to β-yohimbine (4) and isositsikine (5).
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f03: off-line ESI-MS of crude extract from stem bark ofAspidospermaramiflorum. Ion at m/z467 corresponding toramiflorine A (1) and ramiflorine B (2), ion at m/z 327corresponding to 10-methoxy-geissoschizol (3) and ion at m/z355 corresponding to β-yohimbine (4) and isositsikine (5).

Mentions: The mass peaks observed in the chemical characterisation of the crude extract from thebarks of A. ramiflorum used in the ESI-MS analysis are shown inFig. 3. A new molecule was identified, isositsirikine(5) at m/z 355 [M + H]+ (TableIII). The other isolated compounds were ramiflorine A (1) and B (2) atm/z 467 [M + H]+, 10-methoxy-geissoschizol (3) at 327 [M + H]+ andβ-yohimbine (4) and these compounds correspond to compounds previously described in thespecies (Marques et al. 1996, Tanaka et al. 2007). All of the fractions from thestem bark had similar mass spectra profiles.


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

Aguiar AC, Cunha AC, Ceravolo IP, Gonçalves RA, Oliveira AJ, Krettli AU - Mem. Inst. Oswaldo Cruz (2015)

off-line ESI-MS of crude extract from stem bark ofAspidospermaramiflorum. Ion at m/z467 corresponding toramiflorine A (1) and ramiflorine B (2), ion at m/z 327corresponding to 10-methoxy-geissoschizol (3) and ion at m/z355 corresponding to β-yohimbine (4) and isositsikine (5).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4660620&req=5

f03: off-line ESI-MS of crude extract from stem bark ofAspidospermaramiflorum. Ion at m/z467 corresponding toramiflorine A (1) and ramiflorine B (2), ion at m/z 327corresponding to 10-methoxy-geissoschizol (3) and ion at m/z355 corresponding to β-yohimbine (4) and isositsikine (5).
Mentions: The mass peaks observed in the chemical characterisation of the crude extract from thebarks of A. ramiflorum used in the ESI-MS analysis are shown inFig. 3. A new molecule was identified, isositsirikine(5) at m/z 355 [M + H]+ (TableIII). The other isolated compounds were ramiflorine A (1) and B (2) atm/z 467 [M + H]+, 10-methoxy-geissoschizol (3) at 327 [M + H]+ andβ-yohimbine (4) and these compounds correspond to compounds previously described in thespecies (Marques et al. 1996, Tanaka et al. 2007). All of the fractions from thestem bark had similar mass spectra profiles.

Bottom Line: 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.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).This plant species is likely to be useful in the further development of an antimalarial drug, but its pharmacological evaluation is still required.

View Article: PubMed Central - PubMed

Affiliation: Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, MG, Brasil.

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 and matiambu, 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.

Show MeSH
Related in: MedlinePlus