RESUMO
In this study we evaluate the chemical composition and neuroprotective effects of alkaloid fractions of the Amaryllidaceae species Rhodophiala pratensis, Rhodolirium speciosum, Phycella australis and Phaedranassa lehmannii. Gas chromatography-mass spectrometry (GC/MS) enable the identification of 41 known alkaloids. Rhodolirium speciosum and Rhodophiala pratensis were the most active extracts against acetylcholinesterase (AChE), with IC50 values of 35.22 and 38.13⯵g/mL, respectively. The protective effect of these extracts on human neuroblastoma cells (SH-SY5Y) subjected to mitochondrial oxidative stress with rotenone/oligomycin A (R/O) and toxicity promoted by okadaic acid (OA) was evaluated. Only Phycella australis and Rhodophiala pratensis at 0.75 and 1.5⯵g/mL, tend to reverse the cell death induced by R/O by around 12%. In OA assay, alkaloid fractions of Phycella Australis and Phaedranassa lehmannii displayed a concentration-dependent (0.375-3.0⯵g/mL) effect with a maximum neuroprotective response of 78% and 84%, respectively. Afterwards, neuroprotective effects of Phycella australis (3 and 6⯵g/mL) in mouse hippocampal slices stressed with oxygen glucose deprivation/reoxygenation (OGD/R), shown a protection greater than 14%. Finally, Phycella Australis (6⯵g/mL) reverted the cell viability from 65% to 90% in slices treated with OA, representing a protection of 25% attributable to the alkaloids of this species.
Assuntos
Alcaloides de Amaryllidaceae/farmacologia , Amaryllidaceae/química , Hipocampo/efeitos dos fármacos , Isoquinolinas/farmacologia , Neuroblastoma/metabolismo , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Animais , Linhagem Celular Tumoral , Cromatografia Gasosa-Espectrometria de Massas , Hipocampo/metabolismo , Humanos , Técnicas In Vitro , Camundongos , Camundongos Endogâmicos C57BL , Neuroblastoma/patologiaRESUMO
The persistence of latent HIV-infected cellular reservoirs represents the major hurdle to virus eradication in patients treated with highly active antiretroviral therapy, referred to as HAART. HIV-1 reservoirs are long-lived resting CD4+ memory cells containing the virus latently integrated. Since the HIV-1 reservoirs are not targeted by HAART, reactivation therapy has been suggested to purge viral latency. Bioassay-guided study of an ethyl acetate extract of Euphorbia laurifolia afforded two isomeric diterpenes that showed differential activity over HIV-1 reactivation. A previously reported compound was isolated too from Euphorbia lactea. This compound showed a potent HIV-1 reactivating effect. Bioassays results showed that HIV-1 reactivation activity is influenced by distinct structural characteristics.
Assuntos
Antivirais/farmacologia , Diterpenos/farmacologia , Euphorbia/química , Infecções por HIV/tratamento farmacológico , HIV-1/fisiologia , Extratos Vegetais/farmacologia , Ativação Viral/efeitos dos fármacos , Antivirais/isolamento & purificação , Antivirais/uso terapêutico , Linfócitos T CD4-Positivos/efeitos dos fármacos , Diterpenos/isolamento & purificação , Diterpenos/uso terapêutico , Humanos , Células Jurkat , Látex/química , Fitoterapia , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Latência Viral/efeitos dos fármacosRESUMO
Thirteen alkaloids have been isolated from dried bulbs and leaves of flowering Eucharis amazonica (Amaryllidaceae). The alkaloids, 7-methoxyoxoassoanine, 6-O-methylpretazettine and apohaemanthamine, are reported for the first time from a natural source.