RESUMO
Two similarly sulfated triterpene saponins from Pearsonothuria graeffei were prepared to investigate the anti-obesity effects of echinoside A (EA) and holothurin A (HA). The in vitro inhibitory activities of EA and HA toward pancreatic lipase were investigated, and two in vivo studies were performed: (i) Male Wistar rats were orally administered the lipid emulsion with or without a saponin (HA or EA). The serum's total triglyceride concentration was measured at various times. (ii) C57BL/6 mice were assigned to four groups, high fat (HF), EA (0.03%), HA (0.04%), and orlistat (0.01%), and the weight of adipose tissue and level of fatty acids excreted in the feces were determined. Both EA and HA repressed the pancreatic lipase activity and increased fatty acid excretion in the feces. Treatment with EA and HA significantly decreased the adipose tissue accumulation in mice. EA and HA manifested different inhibitory activities in vitro, but each of them dramatically inhibited lipid absorption in vivo and showed strong anti-obesity activity.
Assuntos
Absorção Fisico-Química/efeitos dos fármacos , Gorduras na Dieta/metabolismo , Holoturina/análogos & derivados , Obesidade/tratamento farmacológico , Animais , Peso Corporal/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Holoturina/química , Holoturina/metabolismo , Holoturina/farmacologia , Holoturina/uso terapêutico , Lipase/antagonistas & inibidores , Lipase/química , Lipase/metabolismo , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Camundongos , Simulação de Acoplamento Molecular , Obesidade/metabolismo , Obesidade/patologia , Tamanho do Órgão/efeitos dos fármacos , Pâncreas/enzimologia , Conformação Proteica , RatosRESUMO
BACKGROUND: Echinoside A (EA) and ds-echinoside A (DSEA) are triterpene glycosides isolated from the sea cucumber Pearsonothuria graeffei. DSEA, the desulfurisation product of EA, has the following structure: ß-D-xylopyranosyl-holost-8(9),11(12)-diene-3ß,17α-diol. In the present study, we examined the anti-tumour activities-in particular, the structure-activity relationships-of EA and DSEA in vitro and in vivo. RESULTS: Both EA and DSEA exhibited an inhibitory effect on cell proliferation, along with apoptosis-inducing activity, in HepG2 cells. Moreover, they significantly arrested the cell cycle in the G0/G1 phase. A reverse transcriptase-polymerase chain reaction assay revealed that EA and DSEA significantly increased the expression of the cell-cycle-related genes, namely, p16, p21 and c-myc, and decreased that of cyclin D1. Western blotting analysis demonstrated that they down-regulated the expression of Bcl-2, and enhanced mitochondria cytochrome c release, caspase-3 activation, and poly(adenosine diphosphate ribose) polymerase, cleavage. Nuclear factor kappa B (NF-κB) expression was significantly decreased by DSEA, but was unaffected by EA. EA and DSEA (2.5 mg kg⻹) treatment of mice bearing H22 hepatocarcinoma tumours reduced the tumour weight by 49.8% and 55.0%, respectively. CONCLUSION: EA and DSEA exhibit marked anti-cancer activity in HepG2 cells, by blocking cell-cycle progression and inducing apoptosis through the mitochondrial pathway. DSEA-induced apoptosis was more potent than EA-induced apoptosis. Furthermore, the two triterpene glycosides derived from P. graeffei may induce apoptosis of HepG2 cells in an NF-κB-dependent or NF-κB-independent manner, depending on their structure.
Assuntos
Antineoplásicos/farmacologia , Holoturina/análogos & derivados , Neoplasias Hepáticas/tratamento farmacológico , Pepinos-do-Mar/química , Animais , Antineoplásicos/efeitos adversos , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Holoturina/efeitos adversos , Holoturina/química , Holoturina/farmacologia , Holoturina/uso terapêutico , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/genética , NF-kappa B/metabolismo , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , RNA Mensageiro/metabolismo , Distribuição Aleatória , Fase de Repouso do Ciclo Celular/efeitos dos fármacos , Relação Estrutura-AtividadeRESUMO
In the search of new antileishmanial drugs from marine resources, we have investigated Actinopyga lecanora, a coral reef sea cucumber, for its in vitro and in vivo activities. Methanol extract and n-butanol fraction of A. lecanora exhibited excellent Leishmania donovani inhibition. Among the two glycosides isolated from n-butanol fraction, holothurin B (2) displayed excellent in vitro and moderate in vivo leishmanicidal activity, whereas holothurin A (1) revealed only moderate action. These findings provide an important marine lead toward the development of new antileishmanial drugs and necessitate the further exploration of rich and diverse marine resources for more potent bioactive molecules.