Study of pharmacological activities of compounds isolated from Rheedia brasiliensis (Cluseaceae) and its synthetic analog in rat nervous system
Beatriz Rocha Adaime1, Leida Calegário Oliveira2, Marcelo Henrique dos Santos3, Denise Carmona Cara4, Maria Salete de Abreu Castro 1 e Maria Elena de Lima5.
1Depto.Fisiologia e Biofísica, 4Depto Patologia Geral, 5Depto. Bioquímica e Imunologia – Universidade Federal de Minas Gerais. 2Faculdade Newton de Paiva, - Belo Horizonte, MG. 3Escola de Farmácia e Odontologia de Alfenas – Alfenas, MG.
The species Rheedia brasiliensis is native in the Amazonian regions. It is widely distributed in the Brazilian territory. This plant is also known as bacuparí, bacuparé or bacoparí miúdo. The phytochemical investigation of the fruits from Rheedia brasiliensis led to isolation of various compounds, including a benzofenone poliprenylated (M6), identified as 7-epiclusianone. A biflavonoid (M7), identified as fukugentin has bee isolated as well. A new compound has been synthetized by adding an aminoguanidine radical into the molecule (7-epiclusianone) sentencing a guanylilhidrazone, known as M12. This molecule has some structural similarity with amiloryde and it is known to be active on ionic channels, ion pumps and to modify the activity of some enzymes of nervous system (i.e.monoamine oxidase, acetylcolinesterase) involved in neurotransmission. In this study, we investigated the effects of M12 and of some other compounds isolated from the fruits of Rheedia brasiliensis. The M12 administered by intraperitoneal or intracerebrally in mice did not present apparent toxicity. Animals were monitored for 24h. The histological analysis from several organs (liver, heart, lung, brain, kidney, spleen, stomach and intestine) after 1, 7, 14 and 60 days after injections with M12 did not show any important visible alteration. In other experimental approach, the 3[H]glutamate uptake by rat cerebral cortex synaptosomes was inhibited by M12 and also by the other compounds from Rheedia (M6, M7 and M11). The IC50 of glutamate uptake ihibition calculated for M12 was 2.68 μM. Prior studies showed that M12 in concentrations greater than 6μM might damage synaptosome. We also observed that M6, M12 and crude extract from Rheedia are able to inhibit the acetyl-cholinesterase enzyme from finger extensor long muscle preparation of mice. The inhibition of this enzyme by M12 reaches up to 60%, at the verified dose. The knowledge of the pharmacological actions of the compounds obtained from Rheedia brasiliensis can indicate new drugs with new therapeutical potential or can be used as tools in neurobiology investigation.
|