RESUMEN
In addition to beta-amyloid (Aß) plaques and neurofibrillary tangles, Alzheimer's disease (AD) is typically triggered or accompanied by abnormal inflammation, oxidative stress and astrocyte activation. Safflower (Carthamus tinctorius L.) leaf, featuring functional ingredients, is a commonly consumed leafy vegetable. Whether and how dietary safflower leaf powder (SLP) ameliorates cognitive function in an AD mouse model has remained minimally explored. Therefore, we orally administered SLP to APP/PS1 transgenic mice to explore the neuroprotective effects of SLP in preventing AD progression. We found that SLP markedly improved cognitive impairment in APP/PS1 mice, as indicated by the water maze test. We further demonstrated that SLP treatment ameliorated inflammation, oxidative stress and excessive astrocyte activation. Further investigation indicated that SLP decreased the Aß burden in APP/PS1 mice by mediating excessive astrocyte activation. Our study suggests that safflower leaf is possibly a promising, cognitively beneficial food for preventing and alleviating AD-related dementia.
Asunto(s)
Astrocitos/efectos de los fármacos , Carthamus tinctorius/química , Cognición/efectos de los fármacos , Extractos Vegetales/farmacología , Enfermedad de Alzheimer/metabolismo , Animales , Disfunción Cognitiva/metabolismo , Modelos Animales de Enfermedad , Femenino , Ratones , Ratones Transgénicos , Prueba del Laberinto Acuático de Morris/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Hojas de la Planta/químicaRESUMEN
Free radical scavenging activity of the extracts of petals (bud, early stage, full blooming and ending stage), leaf, stem, root and seeds of Mogami-benibana (safflower, Carthamus tinctorius Linne), the contents of the major active components of carthamin and polyphenols, and neuroprotective effect of the petal extracts and carthamin in the brain of mice and rats were examined. Water extracts of Mogami-benibana petals scavenged superoxide, hydroxyl and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals and singlet oxygen. The scavenging activities of the extract of safflower petals with various colors showed the order of orange, yellow and white from high to low. This order is consistent with the contents of carthamin, which is a pigment of orange color and is found highest in orange petals and lowest in white petals. There was also a relationship between DPPH radical scavenging activity and carthamin content in the petal extracts of safflower. The neuroprotective effects were examined in cellular and animal models. Mogami-benibana petal extract inhibited glutamate-induced C6 glia cell death, significantly decreased the formation of malondialdehyde in mouse cerebrum, and inhibited the increase in thiobarbituric acid reactive substances and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in the cerebral cortex of rats subjected to an injection of FeCl(3) solution into the sensory motor cortex. Carthamin showed similar effects in inhibiting 8-OHdG by the petal extract in rats. These results suggest that the petal extract of Mogami-benibana has free radical scavenging activity and neuroprotective effect and carthamin is one of the major active components.
Asunto(s)
Antioxidantes/farmacología , Carthamus tinctorius , Fármacos Neuroprotectores/farmacología , Preparaciones de Plantas/farmacología , 8-Hidroxi-2'-Desoxicoguanosina , Animales , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Muerte Celular/efectos de los fármacos , Línea Celular , Chalcona/análogos & derivados , Chalcona/farmacología , Desoxiguanosina/análogos & derivados , Desoxiguanosina/metabolismo , Depuradores de Radicales Libres/farmacología , Radicales Libres/metabolismo , Glucósidos/farmacología , Peroxidación de Lípido/efectos de los fármacos , Masculino , Ratones , Neuroglía/citología , Neuroglía/efectos de los fármacos , Neuroglía/metabolismo , Extractos Vegetales/farmacología , Estructuras de las Plantas , Ratas , Ratas Wistar , Oxígeno Singlete/metabolismoRESUMEN
Toki-shakuyaku-san (TJ-23), a Japanese traditional herbal medicine, has a long history in Asia for the treatment of neurodegenerative, immune, and airway diseases. However, the effect of TJ-23 on heart function has not been elucidated. This study was designed to examine the effect of TJ-23 on ventricular contractile function at the single cardiomyocyte level. Ventricular cardiomyocytes from adult rat hearts were stimulated to contract at 0.5 Hz, and mechanical properties were evaluated using an IonOptix Myocam system. Contractile properties analyzed included peak shortening (PS), time-to-PS (TPS), time-to-90% relengthening (TR(90)), and maximal velocity of shortening/relengthening (+/-dL/dt). TJ-23 (10(-)(8) - 10(-)(5) mg/ml) exhibited significant augmentation in PS, with a maximal response of 27.2%. TJ-23 at 10(-)(7) - 10(-)(5) mg/ml also increased +/-dL/dt, shortened TR(90), while had no effect on TPS. Pretreatment with the Na(+)-K(+)-ATPase inhibitor ouabain (1 microM), removal of extracellular sodium from contractile buffer (which inhibits Na(+)/Ca(2+) exchanger), or both concurrently abolished the positive effect of TJ-23 in cell shortening without inhibiting the baseline cell shortening. This study demonstrated a direct cardiac stimulatory action of TJ-23 at the cardiomyocyte level, which may be related to, at least in part, a Na(+)/K(+)-ATPase and/or Na(+)/Ca(2+) exchanger-dependent mechanism.
Asunto(s)
Medicamentos Herbarios Chinos/farmacología , Miocitos Cardíacos/efectos de los fármacos , Animales , Tamaño de la Célula/efectos de los fármacos , Células Cultivadas , Ventrículos Cardíacos/citología , Ventrículos Cardíacos/efectos de los fármacos , Ventrículos Cardíacos/metabolismo , Técnicas In Vitro , Japón , Masculino , Contracción Muscular/efectos de los fármacos , Contracción Miocárdica/efectos de los fármacos , Miocitos Cardíacos/citología , Miocitos Cardíacos/metabolismo , Ouabaína/farmacología , Ratas , Ratas Sprague-Dawley , Sodio/metabolismo , Intercambiador de Sodio-Calcio/metabolismo , ATPasa Intercambiadora de Sodio-Potasio/antagonistas & inhibidores , ATPasa Intercambiadora de Sodio-Potasio/metabolismoRESUMEN
Guanidino compounds of guanidinoethanesulfonic acid, guanidinoacetic acid, guanidinosuccinic acid, N-acetylarginine, beta-guanidinopropionic acid, creatinine, gamma-guanidinobutyric acid, arginine, guanidine, methylguanidine, homoarginine and alpha-guanidinoglutaric acid are present in the mammalian brain. These guanidino compounds except for arginine and guanidine induce seizures and convulsions in rat, rabbit and cat by intracisternal injection. Hirudonine, audonine, alpha-keto-delta-guanidinovaleric acid, N,N'-dibenzoylguanidine and phenylethylguanidine are also convulsants. Levels of creatinine, guanidinoethanesulfonic acid, creatinine, guanidinoacetic acid and methylguanidine in animal brain were changed at pre- and during convulsions induced by pentylentetrazol, amygdala kindling, iron-induced epileptogenesis and so on. These convulsions are thought to be due to depressed functions of serotonergic neurons and accumulated free radicals. Arginine is a substrate of nitric oxide production by nitric oxide synthase. alpha-Guanidinoglutaric acid is a generator of superoxide, hydroxyl radicals and nitric oxide, and induced C6 glial cell death. On the other hand, aminoguanidine is a free radical scavenger. Energy formation by creatine metabolism may inhibit apoptosis induced by pathogenesis. Free radical generation/ reaction and energy generation by guanidino compounds must be important key role in the brain.