RESUMEN
We previously prepared and pharmaceutically evaluated ginger orally disintegrating (OD) tablets, optimized the base formulation, and carried out a clinical trial in healthy adults in their 20 s and 50s to measure their effect on salivary substance P (SP) level and improved swallowing function. In this study, we conducted clinical trials using the ginger OD tablets in older people to clinically evaluate the improvements in swallowing function resulting from the functional components of the tablet. The ginger OD tablets were prepared by mixing the excipients with the same amount of mannitol and sucrose to a concentration of 1% ginger. Eighteen healthy older adult volunteers aged 63 to 90 were included in the swallowing function test. Saliva was collected before and 15 min after administration of the placebo and ginger OD tablets. Swallowing endoscopy was performed by an otolaryngologist before administration and 15 min after administration of the ginger OD tablets. A scoring method was used to evaluate the endoscopic swallowing. Fifteen minutes after taking the ginger OD tablets, the salivary SP amount was significantly higher than prior to ingestion or after taking the placebo (p<0.05). Among 10 subjects, one scored 1-3 using the four evaluation criteria. Overall, no aspiration occurred and a significant improvement in the swallowing function score was observed (p<0.05) after taking the ginger OD tablets. Our findings showed that the ginger OD tablets increased the salivary SP amount and improved swallowing function in older people with appreciably reduced swallowing function.
Asunto(s)
Deglución/efectos de los fármacos , Preparaciones de Plantas/administración & dosificación , Zingiber officinale , Administración Oral , Anciano , Anciano de 80 o más Años , Catecoles/administración & dosificación , Catecoles/análisis , Catecoles/farmacología , Excipientes/química , Alcoholes Grasos/administración & dosificación , Alcoholes Grasos/análisis , Alcoholes Grasos/farmacología , Femenino , Humanos , Masculino , Manitol/química , Persona de Mediana Edad , Preparaciones de Plantas/química , Preparaciones de Plantas/farmacología , Polvos , Saliva/metabolismo , Solubilidad , Sustancia P/metabolismo , Sacarosa/química , Canales Catiónicos TRPV/agonistas , ComprimidosRESUMEN
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
Trans-3-(3'4'-dimethoxyphenyl)-4-[(E)-3",4"-dimethoxystyryl]cyclohex-1-ene (Comp.1) and cis-3-(3'4'-dimethoxyphenyl)-4-[(E)-3",4"-dimethoxystyryl]cyclohex-1-ene (Comp.2), phenylbutenoid dimers, have been isolated as neurotrophic molecules from an Indonesian medicinal plant, Zingiber purpureum. The aim of this study was to explore the neurotrophic effects of Comp.1 and Comp.2 in vitro and in vivo. Comp.1 (10-30 µM) or Comp.2 (30 µM) significantly induced neurite sprouting in PC12 cells. Comp.1 (0.03-3 µM) or Comp.2 (0.3-3 µM) significantly increased the neurite length and number of neurites in primary cultured rat cortical neurons. Comp.1 (30 µM) and Comp.2 (3-30 µM) also provided significant protection against cell death caused by deprivation of serum. The in vivo effects of both Comp.1 and Comp.2 were evaluated on hippocampal neurogenesis in olfactory bulbectomized (OBX) mice, an experimental depression and dementia animal model. Comp.1 (50mg/kg p.o.), Comp.2 (50mg/kg p.o.), or fluoxetine (10mg/kg i.p.), an antidepressant, were administrated once a day on days 15-28 after OBX. Neurogenesis was assessed by analysis of cells expressing NeuN, a neuronal marker, and 5-bromo-2'-deoxyuridine (BrdU) uptake. Immunohistochemical analysis showed that the number of BrdU/NeuN double-labeled cells in the dentate gyrus was significantly decreased 30 days after OBX. Chronic treatment with Comp.1, Comp.2 or fluoxetine significantly increased the number of BrdU/NeuN double-labeled cells. These results indicate that Comp.1 and Comp.2 have neurotrophic effects, and have the potential for disease modification in depression and dementia.
Asunto(s)
Butiratos/farmacología , Hipocampo/efectos de los fármacos , Hipocampo/crecimiento & desarrollo , Neurogénesis/efectos de los fármacos , Neuronas/efectos de los fármacos , Bulbo Olfatorio/fisiología , Zingiber officinale/química , Animales , Butiratos/aislamiento & purificación , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Cromatografía Líquida de Alta Presión , Femenino , Hipocampo/citología , Inmunohistoquímica , Espectroscopía de Resonancia Magnética , Ratones , Neuritas/efectos de los fármacos , Fármacos Neuroprotectores , Células PC12 , Raíces de Plantas/química , Embarazo , Ratas , Ratas Sprague-DawleyRESUMEN
The methanolic extract and its EtOAc-soluble fraction from the rhizomes of Zingiber cassumunar inhibited invasion of human fibrosarcoma HT 1080 cells. From the EtOAc-soluble fraction, eight new phenylbutanoids, cassumunols A-H, were isolated together with 30 known constituents. The structures of new phenylbutanoids were elucidated on the basis of chemical and physicochemical evidence. Principal constituents were examined the inhibitory effects on the invasion of HT 1080 cells. Among them, phlain I and III, (E)-1-(3,4-dimethoxyphenyl)buta-1,3-diene, (E)-1-(2,4,5-trimethoxyphenyl)buta-1,3-diene, and (-)-ß-sesquiphellandrene showed anti-invasion effects. Interestingly, (E)-1-(2,4,5-trimethoxyphenyl)buta-1,3-diene [inhibition (%) 46.8 ± 7.2 (p<0.05) at 30 µM] significantly inhibited the invasion, and only a weak cytotoxic effect was observed.