RESUMO
Six new bisabolane-type phenolic sesquiterpenoids, including plakordiols A-D (1-4), (7R, 10R)-hydroxycurcudiol (5) and (7R, 10S)-hydroxycurcudiol (6) were isolated from the marine sponge Plakortis simplex collected from the South China Sea. Their structures were determined based on extensive analysis of spectroscopic data. Their configurations were assigned by coupling constant analysis, NOESY correlations, and the modified Mosher's method. Furthermore, their cytotoxic and antibacterial activities were evaluated.
Assuntos
Sesquiterpenos Monocíclicos , Plakortis , Animais , Antibacterianos/farmacologia , China , Estrutura Molecular , Sesquiterpenos Monocíclicos/farmacologia , Oceano Pacífico , Plakortis/químicaRESUMO
Ischemic stroke is the third most common cause of death and the leading cause of disability worldwide in adults. The antiepileptic drug valproic acid (VPA) was reported to protect cerebral ischemia/reperfusion injury. However, the action mechanism of VPA in cerebral ischemia/reperfusion injury has not been fully understood. We explored the action mechanism of VPA in vivo and in vitro. Gerbils were subjected to transient global cerebral ischemic-reperfusion injury, and hippocampal neuron injury was treated with oxygen-glucose deprivation in vitro. Morris water maze test was performed to evaluate the cognitive dysfunction. Histopathological examinations and western blot were performed to evaluate the pyroptosis of neurons. The results showed that VPA attenuated the cognitive dysfunction, pyroptosis of the gerbils suffer from ischemic-reperfusion injury and decreased hippocampal neurons pyroptosis induced by oxygen-glucose deprivation in vitro. In addition, western blot and real-time PCR analysis revealed that VPA modulated the protein expression of apoptosis repressor with caspase recruitment domain (ARC), caspase-1 and IL-1ß/IL-18. Our results suggested that VPA alleviated ischemic/reperfusion injury-mediated neuronal impairment by anti-pyroptotic effects.
Assuntos
Isquemia Encefálica/tratamento farmacológico , Sobrevivência Celular/efeitos dos fármacos , Piroptose/efeitos dos fármacos , Traumatismo por Reperfusão/tratamento farmacológico , Ácido Valproico/uso terapêutico , Animais , Anticonvulsivantes/farmacologia , Anticonvulsivantes/uso terapêutico , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patologia , Sobrevivência Celular/fisiologia , Células Cultivadas , Relação Dose-Resposta a Droga , Gerbillinae , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Piroptose/fisiologia , Distribuição Aleatória , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Ácido Valproico/farmacologiaRESUMO
Five new cyclic peptides (including four heptapeptides and one octapeptide), reniochalistatins A-E (1-5), were isolated and characterized from the marine sponge Reniochalina stalagmitis collected off Yongxing Island in the South China Sea. Their structures were assigned on the basis of HRESIMS, 1D and 2D NMR spectroscopic data, and MALDI-TOF/TOF data for sequence analysis. The absolute configurations of all of the amino acid residues were determined using chiral-phase HPLC and Marfey's analysis. The cyclic octapeptide reniochalistatin E showed biological activity in various cytotoxicity assays employing different tumor cell lines (RPMI-8226, MGC-803, HL-60, HepG2, and HeLa).
