RESUMEN
Previously we have demonstrated that a Rhodiola crenulata extract (RCE), containing a potent antioxidant salidroside, promotes neurogenesis in the hippocampus of depressive rats. The current study was designed to further investigate the protective effect of the RCE on neurogenesis in a rat model of Alzheimer's disease (AD) induced by an intracerebroventricular injection of streptozotocin (STZ), and to determine whether this neuroprotective effect is induced by the antioxidative activity of salidroside. Our results showed that pretreatment with the RCE significantly improved the impaired neurogenesis and simultaneously reduced the oxidative stress in the hippocampus of AD rats. In vitro studies revealed that (1) exposure of neural stem cells (NSCs) from the hippocampus to STZ strikingly increased intracellular reactive oxygen species (ROS) levels, induced cell death and perturbed cell proliferation and differentiation, (2) hydrogen peroxide induced similar cellular activities as STZ, (3) pre-incubation of STZ-treated NSCs with catalase, an antioxidant, suppressed all these cellular activities induced by STZ, and (4) likewise, pre-incubation of STZ-treated NSCs with salidroside, also an antioxidant, suppressed all these activities as catalase: reduction of ROS levels and NSC death with simultaneous increases in proliferation and differentiation. Our findings indicated that the RCE improved the impaired hippocampal neurogenesis in the rat model of AD through protecting NSCs by its main ingredient salidroside which scavenged intracellular ROS.
Asunto(s)
Glucósidos/farmacología , Hipocampo/efectos de los fármacos , Hipocampo/lesiones , Neurogénesis/efectos de los fármacos , Fenoles/farmacología , Extractos Vegetales/farmacología , Rhodiola/química , Estreptozocina , Animales , Catalasa/metabolismo , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Depuradores de Radicales Libres/farmacología , Hipocampo/metabolismo , Hipocampo/patología , Inyecciones , Masculino , Células-Madre Neurales/efectos de los fármacos , Células-Madre Neurales/metabolismo , Células-Madre Neurales/patología , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Neuronas/patología , Fármacos Neuroprotectores/farmacología , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismoRESUMEN
The purpose of the present study was to investigate the effect of Ganoderma spores lipid (GSL) on Bax, Bcl-xl and Caspase-3 expression in damaged retina and to address the effect of GSL on photoreceptor cell lesions induced by N-methyl-N-nitrosourea (MNU). Thirty 50-day-old female Sprague-Dawley rats were divided randomly into five groups to detect the dose-response effect of GSL by electroretinogram (ERG) analysis. Four groups received different daily GSL doses (0.5, 1, 2 and 4 g/kg, respectively) and one control group received no treatment. Sixty rats were divided randomly into an untreated MNU model control group and the GSL treatment group. Retina tissue samples were obtained sequentially 0 h before and 1, 3, 7 and 10 d after MNU injection. Expressions of Bax, Bcl-xl and Caspase-3 were detected by RT-PCR and immunofluorescence assays, then photoreceptor cell apoptosis was confirmed by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-digoxigenin nick-end labeling (TUNEL) signals. GSL had a dose-response effect on retina ERG and reversed retinal photoreceptor damage induced by MNU. RT-PCR analysis demonstrated that transcription levels of Bax, Bcl-xl and Caspase-3 in MNU control group and GSL treatment group were all upregulated on 1 d (p < 0.01) and peaked on 3 d (p < 0.01) after MNU injection compared to before MNU injection. GSL treatment significantly decreased mRNA levels of Bax on 1, 3, 7 and 10 d vs. MNU group (all p < 0.01) and mRNA levels of Caspase-3 on 1, 3, 7 d (p < 0.01) and 10 d (p < 0.05) vs. MNU group. Bcl-xl was clearly upregulation on 1, 3, 7 and 10 d vs. MNU group (all p < 0.01). Expression ratios of Bax/Bcl-xl were raised after MNU injection on 1 and 3 d vs. 0 h before MNU (both p < 0.01), peaked on 3 d, then dropped after GSL treatment on 1, 3, 7 and 10 d vs. MNU group (all p < 0.01). Immunofluorescence assays showed GSL decreased Bax and Caspase-3 positive staining levels in retina and increased Bcl-xl level. TUNEL-positive cells were evoked only in the outer nuclear layer and peaked on 3 d in rats receiving MNU (p < 0.01 vs. 0 h before MNU). GSL administration decreased apoptosis levels significantly, and the apoptotic indexes (AIs) of the GSL group were lower than those of MNU group on 1 and 3 d (both p < 0.01). Taken together, these data suggest that GSL may regulate the expressions of Bax, Bcl-xl and Caspases-3, inhibiting MNU-induced rat photoreceptor cell apoptosis and protecting retinal function.
Asunto(s)
Apoptosis/efectos de los fármacos , Medicamentos Herbarios Chinos/administración & dosificación , Metilnitrosourea/toxicidad , Células Fotorreceptoras de Vertebrados/efectos de los fármacos , Reishi , Retinitis Pigmentosa/prevención & control , Animales , Caspasa 3/genética , Caspasa 3/metabolismo , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Electrorretinografía/efectos de los fármacos , Femenino , Técnica del Anticuerpo Fluorescente Indirecta , Etiquetado Corte-Fin in Situ , Células Fotorreceptoras de Vertebrados/metabolismo , Células Fotorreceptoras de Vertebrados/patología , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Retinitis Pigmentosa/inducido químicamente , Retinitis Pigmentosa/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Proteína X Asociada a bcl-2/genética , Proteína X Asociada a bcl-2/metabolismo , Proteína bcl-X/genética , Proteína bcl-X/metabolismoRESUMEN
OBJECTIVE: To explore the effects of Rhodiola rosea on the body weight and the intake of sucrose and water in depressive rats induced by chronic mild stress.dz METHODS: A total of 70 male SD rats were divided into seven groups, including normal control group (treated with 0.5% sodium carboxymethycellulose), untreated group, negative control group (treated with 0.5% sodium carboxymethycellulose), positive control group (treated with fluoxetine), low-, medium- and high-dose Rhodiola rosea group (treated with 1.5, 3, 6 g/kg Rhodiola rosea respectively). Except for rats in normal control group, the other sixty rats endured chronic stress for 4 weeks to establish the depression model. After that, rats were administered Rhodiola rosea for 3 weeks. During the whole experiment, the body weight, and sucrose intake, tap water intake of all rats were examined once a week. RESULTS: After the termination of the stress regime, compared with the normal control group, the body weight and 1% sucrose intake in depressive rats were decreased. After 3-week Rhodiola rosea treatment, the body weight and 1% sucrose intake increased in rats of the low-dose Rhodiola rosea group and recovered to the level of the normal control group. CONCLUSION: Low-dose Rhodiola rosea can increase the body weight and sucrose intake of depressive rats, making them recover to normal status.
Asunto(s)
Peso Corporal/efectos de los fármacos , Depresión/tratamiento farmacológico , Ingestión de Líquidos/efectos de los fármacos , Fitoterapia , Rhodiola/química , Animales , Depresión/etiología , Depresión/metabolismo , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Masculino , Ratas , Ratas Sprague-Dawley , Estrés Psicológico/tratamiento farmacológico , Sacarosa/administración & dosificaciónRESUMEN
OBJECTIVE: To explore the effects of Valerian on the level of 5-hydroxytryptamine (5-HT), cell proliferation and neuron number in cerebral hippocampus of rats with depression induced by chronic mild stress. METHODS: Seventy rats were divided into 7 groups: normal control, untreated, negative control, positive control, and low-, medium- and high-dose Valerian-treated groups. There were 10 rats in each group. Except for the normal control group, depression was induced in rats by chronic mild stress. The depressive rats in the other six groups were intragastrically administered with sodium carboxymethycellulose, fluoxetine, and low, medium and high-dose Valerian, respectively for 3 weeks. After the treatment, the proliferating cells in the hippocampus were labeled by injecting bromodeoxyuridine (BrdU) in 7 groups. The content of 5-hydroxytryptamine (5-HT) in the hippocampus was detected by high-performance liquid chromatography (HPLC), and the number of hippocampal neurons was counted by morphometry. RESULTS: Compared with the normal control group, the levels of 5-HT in the hippocampus in the low- and medium-dose Valerian-treated groups were increased and recovered to normal level. After the administration of low-dose Valerian for 3 weeks, the number of BrdU positive cells and neurons in the hippocampus of the depressive rats were recovered to the normal status. CONCLUSION: Minidose Valerian may promote the level of 5-HT and cell proliferation in the hippocampus of the depressive rats, and may play a role in saving injured neurons of the hippocampus.
Asunto(s)
Depresión/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Hipocampo/metabolismo , Fitoterapia , Serotonina/metabolismo , Valeriana/química , Animales , Proliferación Celular/efectos de los fármacos , Depresión/etiología , Depresión/metabolismo , Hipocampo/patología , Masculino , Neuronas/patología , Ratas , Ratas Sprague-Dawley , Estrés Psicológico/complicacionesRESUMEN
OBJECTIVE: To explore the effects of Rhodiola rosea on the level of 5-hydroxytryptamine (5-HT), cell proliferation and differentiation, and number of neuron in cerebral hippocampus of rats with depression induced by chronic mild stress. METHOD: Fifty rats were divided into 5 groups: normal control, untreated, negative control, positive control and Rhodiola rosea-treated groups. There were 10 rats in each group. Except for normal control group, depression was induced in rats by chronic mild stress. The depressive rats in the other four groups were intragastrically administered with 0.5% sodium carboxymethycellulose, fluoxetine and Rhodiola rosea for 3 weeks. After the treatment, the content of 5-HT in the hippocampus was detected by high-performance liquid chromatography. The proliferating cells and differentiated cells in the hippocampus were labeled by bromodeoxyuridine (BrdU) or/and beta-tubulin III immunohistochemistry, and the number of hippocampal neurons was counted by morphometry. RESULT: Compared with the normal control group, the content of 5-HT, number of BrdU positive cells, percentage of BrdU and beta-tubulin III double labeled cells and number of neurons in cerebral hippocampus in the Rhodiola rosea-treated group were increased and recovered to normal level. CONCLUSION: Rhodiola rosea may enhance the level of 5-HT and promote the proliferation and differentiation of neural stem cells in the hippocampus of the depressive rats, and may play a role in saving injured neurons of the hippocampus.
Asunto(s)
Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Depresión/tratamiento farmacológico , Medicamentos Herbarios Chinos/administración & dosificación , Hipocampo/citología , Neuronas/efectos de los fármacos , Rhodiola/química , Serotonina/metabolismo , Animales , Depresión/metabolismo , Depresión/fisiopatología , Medicamentos Herbarios Chinos/química , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Humanos , Masculino , Neuronas/citología , Neuronas/metabolismo , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Estrés Psicológico/tratamiento farmacológico , Estrés Psicológico/metabolismo , Estrés Psicológico/fisiopatologíaRESUMEN
OBJECTIVE: To study the anticancer activity of Rhodiola sachalinensis in vitro and in vivo experiments. METHODS: The effect of Rhodiola sachalinensis extracts at various concentrations on T241 fibrosarcoma cells proliferation and cytotoxic potential were measured. We divided T241 fibrosarcoma-bearing C57Bl6/J mice into two groups, the tumor inhibition rate were observed. RESULTS: Rhodiola sachalinensis extracts inhibited T241 tumor cells growth in a dose-dependent manner. The concentrations of Rhodiola sachalinensis extracts from 50 microg/ml to 250 microg/ml did not reduced the survival rate of T241 tumor cells. The daily administration of Rhodiola sachalinensis resulted in a significant suppression of the growth of primary tumors, compared to control group, tumor inhibition rate in Rhodiola sachalinensis group reached 70.9%. CONCLUSION: Rhodiola sachalinensis can inhibit T241 tumor cells growth and does not cause a direct cytotoxicity against tumor cells in vitro and in vivo.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Proliferación Celular/efectos de los fármacos , Fibrosarcoma/patología , Extractos Vegetales/farmacología , Rhodiola , Animales , Antineoplásicos Fitogénicos/uso terapéutico , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Fibrosarcoma/tratamiento farmacológico , Ratones , Ratones Endogámicos C57BL , Trasplante de Neoplasias , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/uso terapéutico , Plantas Medicinales/química , Rhodiola/químicaRESUMEN
OBJECTIVE: To investigate the effects of Ganoderma spores on mitochondria-related molecular substances in hippocampus of young rats birthed by rats with gestational hypertension. METHODS: Nitric oxide synthase (NOS) inhibitor Nw-nitro-L-arginine methylester (L-NAME) was intraperitoneally injected into pregnant rats to induce gestational hypertension, and Ganoderma spores were administered orally. The effects of Ganoderma spores on levels of mitochondria-related molecular substances in hippocampus of young rats birthed by the rats with gestational hypertension were evaluated with immunoradiometric assay of cAMP, RT-PCR analysis of related genes, and detection of enzyme activity. RESULTS: In hippocampus of the new-born rats birthed by rats with gestational hypertension, the cAMP level, mitochondrial DNA (mtDNA) level and adenosine triphosphatase (ATPase) activity were decreased, and the expression level of peroxisome proliferator activated receptor gamma coactivator 1 alpha (pgc1 alpha) was unchanged compared to the normal control group. The cAMP level, mtDNA level, ATPase activity and pgc1 alpha expression level in hippocampus of 30-day post-natal rats were lower than those of the rats in normal control group. After oral administration of Ganoderma spores, the cAMP and mtDNA levels in hippocampus of the new-born rats and 30-day post-natal rats recovered almost to the levels of normal control rats, and the ATPase activity and pgc1 alpha expression level were also increased significantly. CONCLUSION: Ganoderma spores may regulate the levels of mitochondria-related molecular substances in hippocampus of young rats birthed by rats with gestational hypertension.
Asunto(s)
ADN Mitocondrial/metabolismo , Ganoderma/fisiología , Hipocampo/metabolismo , Hipertensión Inducida en el Embarazo/fisiopatología , Proteínas Mitocondriales/metabolismo , Animales , Animales Recién Nacidos , AMP Cíclico/metabolismo , ADN Mitocondrial/genética , Femenino , Ganoderma/química , Hipertensión Inducida en el Embarazo/inducido químicamente , Masculino , Proteínas Mitocondriales/genética , NG-Nitroarginina Metil Éster , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma , Embarazo , Proteínas de Unión al ARN , Ratas , Ratas Sprague-Dawley , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Esporas/química , Esporas/fisiología , Factores de Transcripción/metabolismoRESUMEN
OBJECTIVE: To explore whether pre-administration of Ganoderma lucidum spore (GASP) can reduce incidence of neural tube defects (NTDs) induced by all-trans retinoic acid (ATRA) in pregnant mice. METHODS: Twenty pregnant mice were randomly divided into four groups: normal control group, solvent-treated group, ATRA-induced group, and GASP-treated plus ATRA-induced group. GASP solution, which was prepared with solvent (sodium carboxymethyl cellulose), was fed to the pregnant mice in the GASP-treated plus ATRA-induced group twice a day from embryo (E) 0 d to E10.5 d. The same dose of solvent was given to the pregnant mice in the solvent-treated group. At E7.75 d, ATRA (50 mg/kg) was given to the pregnant mice in both ATRA-induced group and GASP-treated plus ATRA-induced group for single time. Embryos were sampled from pregnant mice at E10.5 d. Then the incidence rate of NTDs in mouse embryo was calculated and the crown-rump length of mouse embryo was measured. The positive rate of nestin expression and the distribution of cell cycle of embryonic neural tube neuroepithelial cells were detected by histochemical staining technique and flow cytometry respectively. Reverse transcription-polymerase chain reaction method was used to detect the gene expressions of cyclin-dependent protein kinase 2 (Cdk2) and Cdk4 mRNAs. RESULTS: The incidence rates of NTDs in mouse embryos in the ATRA-induced group and the GASP-treated plus ATRA-induced group were 79.41% and 21.67% respectively, while the crown-rump length of mouse embryos in these two groups were (3.62+/-1.27) mm and (5.84+/-0.92) mm respectively. The positive rate of nestin expression in embryonic neural tube neuroepithelial cells of mouse embryo at E10.5 d in the ATRA-induced group was 32.44%, while that in the GASP-treated plus ATRA-induced group was 77.65%. The cell cycle of embryonic neural tube neuroepithelial cells was obviously arrested at G(0)/G(1) phase in the ATRA-induced group as compared with that in the GASP-treated plus ATRA-induced group. The Cdk4 mRNA was transcripted at a high level in embryonic neural tube in the GASP-treated plus ATRA-induced group, but the Cdk2 mRNA was not detected in this group. CONCLUSION: Pre-administration of GASP can reduce the incidence of NTDs induced by ATRA in pregnant mice.