RESUMEN
Bangle (Zingiber purpureum) is a tropical ginger that is used as a spice in Southeast Asia. Phenylbutenoid dimers isolated from Bangle have exhibited neurotrophic effects in primary cultured rat cortical neurons and PC12 cells. Furthermore, chronic treatment with phenylbutenoid dimers enhances hippocampal neurogenesis in olfactory bulbectomized mice. In this study, we investigated the effects of Bangle extract on behavior and hippocampal neurogenesis in vivo. SAMP8 mice, which are an established model for accelerated aging, with age-related learning and memory impairments, were given a Bangle-containing diet for 1 month, and subsequent behavioral tests and immunohistochemistry for Ki67, a proliferating cell marker, were performed. We found that the Bangle-containing diet improved spatial learning and memory deficits in the Morris water maze and significantly increased the numbers of Ki67-positive cells in the dentate gyrus of the SAMP8 mice. In addition, the Bangle extract exhibited a neurotrophin-like activity as indicated by the induction of neurite sprouting in PC12 cells. Our results suggest that Bangle is beneficial for the prevention of age-related progression of cognitive impairment.
Asunto(s)
Envejecimiento/efectos de los fármacos , Trastornos de la Memoria/tratamiento farmacológico , Neurogénesis/efectos de los fármacos , Neuronas/efectos de los fármacos , Aprendizaje Espacial/efectos de los fármacos , Zingiberaceae/química , Envejecimiento/psicología , Animales , Giro Dentado/efectos de los fármacos , Giro Dentado/fisiopatología , Modelos Animales de Enfermedad , Humanos , Masculino , Memoria/efectos de los fármacos , Trastornos de la Memoria/fisiopatología , Trastornos de la Memoria/psicología , Ratones , Ratones Transgénicos , Neuronas/citología , Células PC12 , RatasRESUMEN
Angiogenesis is a promising target for cancer prevention and treatment. This study aimed to determine the antiangiogenic effects of melinjo (Gnetum gnemon L.) seed extract and its resveratrol derivative components, such as gnetin C (GC), gnetin L (GL), gnemonoside A (GMA), gnemonoside C (GMC), and gnemonoside D (GMD). An ethanol extract of melinjo seeds (EEMS) and the two gnetins markedly inhibited the proliferation and tube formation of human umbilical vein endothelial cells (HUVEC) stimulated with vascular endothelial growth factor and basic fibroblast growth factor. The inhibitory effects of GC and GL were much stronger than those of resveratrol. GMC and GMD inhibited only proliferation, whereas GMA had almost no effect on the two endothelial cell functions. The EEMS and GC also reduced the cell viability of tube-forming HUVEC, with accompanying ERK1/2 inactivation, and suppressed the migration of HUVEC. Furthermore, dietary intake of EEMS significantly inhibited tumor angiogenesis in a mouse dorsal air sac assay. In conclusion, we found that the EEMS and its resveratrol derivatives, particularly GC, suppress multiple angiogenesis-related endothelial cell functions and/or tumor angiogenesis, indicating that the melinjo seeds and the natural resveratrol derivatives may be useful for cancer prevention and treatment.
Asunto(s)
Inhibidores de la Angiogénesis/farmacología , Antineoplásicos Fitogénicos/farmacología , Descubrimiento de Drogas , Gnetum/química , Neovascularización Patológica/tratamiento farmacológico , Extractos Vegetales/farmacología , Estilbenos/farmacología , Inhibidores de la Angiogénesis/química , Animales , Antineoplásicos Fitogénicos/química , Bioensayo , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Femenino , Glucósidos/química , Glucósidos/farmacología , Células Endoteliales de la Vena Umbilical Humana/citología , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/fisiología , Humanos , Ratones , Ratones Endogámicos ICR , Extractos Vegetales/química , Resveratrol , Semillas/química , Estilbenos/químicaRESUMEN
A 50% EtOH extract of the dried endosperms of melinjo (Gnetum gnemon L.) was purified by a combination of column chromatography, including highly porous polymer, octadecylated silica (ODS), hydroxypropylated dextran (LH-20), and silica gel, resulting in the isolation of a new stilbenoid 1, named gnetin L, along with five previously identified stilbenoids 2-6 (gnetin C, gnemonosides A, C, and D, and resveratrol). All of these stilbenoids showed 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity similar to that of ascorbic acid and dl-alpha-tocopherol. With the exception of gnemonoside A (3), these stilbenoids showed moderate antimicrobial activity. Inhibition of lipase from porcine pancreas was recognized in four stilbenoids excluding gnemonoside A (3) and resveratrol (6). Gnetin C (2), gnemonoside C (4), and gnemonoside D (5) inhibited the hydrolysis of starch by alpha-amylase from porcine pancreas. An EtOH extract containing these stilbenoids also showed DPPH radical scavenging effect, lipase and alpha-amylase inhibition activity, and antimicrobial activity against food microorganisms and enterobacteria. The present study indicates that melinjo and extracts containing these constituents are useful as health supplements.