RESUMO
This study mainly investigated the ameliorative effect of lotus seedpod proanthocyanidins (LSPC) and the mechanism underlying such effect on cognitive impairment and brain aging induced by d-galactose. Aging mice induced by d-galactose (150 mg/kg, sc injection daily for 6 weeks) were chosen for the experiment. LSPCs (30, 60, and 90 mg/kg, ig) were provided after d-galactose injection. Learning and memory functions were detected by Y-maze and step-down avoidance tests. Then, some biochemical indexes related to cognitive ability and aging were measured. Histopathological feature and P53 protein expression in the hippocampus were observed. Results showed that the three different doses of LSPC could significantly ameliorate the learning and memory abilities impaired by d-galactose. LSPC significantly reduced the levels of malondialdehyde and nitric oxide (i.e. 90 mg/kg LSPC group vs. model group, P=0.008), reduced the content of ß-amyloid peptide 1-42 (i.e. 90 mg/kg LSPC group vs. model group, P=0.009), decreased the activities of acetylcholinesterase, monoamine oxidase B, total nitric oxide synthase (i.e. 90 mg/kg LSPC group vs. model group, P=0.006), and neuronal nitric oxide synthase and synchronously increased the activities of superoxide dismutase and glutathione peroxidase in the brain. Furthermore, LSPC could prevent neuron damage and could lessen the expression of P53 protein in the hippocampus. These findings demonstrated that LSPC effectively attenuated cognitive damage and improved parameters related to brain aging in senescent mice induced by d-galactose, and may be used to treat Alzheimer's disease.
Assuntos
Comportamento Animal/efeitos dos fármacos , Transtornos Cognitivos/tratamento farmacológico , Cognição/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Lotus/química , Fármacos Neuroprotetores/farmacologia , Extratos Vegetais/farmacologia , Proantocianidinas/farmacologia , Fatores Etários , Envelhecimento , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Biomarcadores/metabolismo , Transtornos Cognitivos/induzido quimicamente , Transtornos Cognitivos/metabolismo , Transtornos Cognitivos/patologia , Transtornos Cognitivos/fisiopatologia , Transtornos Cognitivos/psicologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Galactose , Hipocampo/metabolismo , Hipocampo/patologia , Hipocampo/fisiopatologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Memória/efeitos dos fármacos , Camundongos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Fármacos Neuroprotetores/isolamento & purificação , Fitoterapia , Extratos Vegetais/isolamento & purificação , Plantas Medicinais , Proantocianidinas/isolamento & purificação , Sementes , Fatores de TempoRESUMO
Research in the field of procyanidins is always hindered by the lack of procyanidin standards, and the preparation of procyanidins, especially in large scale, remains difficult and time-consuming. Commercial sources of procyanidin standards are scarce. In this study, a rapid preparation method of procyanidins by using low-pressure column chromatography was developed. Procyanidins in Granny Smith apples were extracted with boiled water and purified on an ADS-17 macroporous resin column to obtain a Granny Smith apple procyanidin extract (GSE). GSE was fractionated according to its degree of polymerization on a Toyopearl TSK HW-40s column. Procyanidins B2 (epicatechin-(4beta-8)-epicatechin) and C1 (epicatechin-(4beta-8)-epicatechin-(4beta-8)-epicatechin) were prepared without HPLC separation. Oligomeric procyanidins from Granny Smith apples were also identified by liquid chromatography-electrospray ionization-mass spectrometry.