RESUMEN

Aspirin (AS) has been widely used globally for preventing incidence of cardio-cerebral ischemic disease for nearly 100 years.The people who takes AS for long term may reach several hun-dred million,but many persons were died from interned bleeding.We found salvianolic acids (salvianolic acid B 57％,salvianolic acid A 1％,rosmarinic acid,35％,SA)was much better than AS in preventing in-cidence of cardio-cerebral ischemic disease,and may avoid hemorrhage risk in clinical application.The research are summary briefly as follows: (1) both AS and AS have same anti-platelet aggregation ef-fect,but their mechanism is different.AS inhibited both TXA2 and PGI2,SA inhibited TXA2only;(2)For established thrombosis,SA could dissolved it, AS showed no effect. The thrombolytic mechanism of SA has been elucidated. (3) In SHRSP rats, the incidence of stroke and death rate in SA group was distinct less that of AS group;(4)In MCAO rats,SA and Sal B decreased stroke index and neural im-pairment. AS showed no such ability; (5) There is microcirculatory disturbance in cardio-cerebral isch-emic disease. SA could improve circulatory disturbance induced by LPS, adrenaline, ROS and I/r. there is no any paper reported AS could have beneficial effect on above mentioned microcirculatory dis-turbance models;(6)Hyperlipidemia is an independent risk factor for cardio-cerebral vascular disease. SA could significant hypolipidemic effect which is similar to that of statins(atovastin and simvastin)and ten times stronger than omega-3.AS has no inhibitory effect on hyperlipidemia.(7)Thereis overproduc-tion of ROS induced by ischemic/reperfusion in cardio-cererbal vascular disease.SA showed more ro-bust,anti-oxidant capacity than VitC,Vit E,melatonin,edalavone and resveratrol,etc.SA is one of the most powerful anti-oxidant in the world so far.(8)According to literatures,1/3 patients who take AS for long time will have hemorrhage, we found in normal rats and mice (coagulating and hemodynamics) SA had no apparent effect on coagulation system and this property of SA was confirmed in clinic trial with hundred thousand cases; (9) As well known, neurodegenerative disease are divided into acute and chronic neurodegenerative disease,and both have similar pathogenesis.We proved that SA could inhibit Aβ aggregation and fiber formation, inhibit tau hyperphosphorylation induced by OA and p25/CDK5,as well as increase neurogenesis and angiogenesis.More importantly,SA showed not only pre-ventive effect on cardio-cerebral vascular diseases. SA has been finished clinical trial phase I-IV for treatment of stroke.The therapeutic effect of SA is characterized by inducing multi-target effect and in-hibit pathogenesis of early,middle and late stage of stroke.SA as anti-stroke new drug was approved by the state food and drug administration of China in 2011.

RESUMEN

Clausenamide (clau) is one of seven novel compounds isolated from Clausena lansium (Lour) skeels. Clau is unusual in that it contains 4 chiral centers yielding 8 pairs of enantiomers. After identification of the configuration of these enantiomers, the synthesis of 16 enantiomers, including optically active clau and (+) and (-)clau was carried out. During this study, many stereochemical and synthetic difficulties were solved and the Baldwin principle was updated. Production scale is now sufficient to meet the needs of clinical practice. In a pharmacological study numerous models and indicators showed that (-)clau is the active enantiomer, while (+)clau is inactive and elicits greater toxicity than (-)clau. The principal pharmacological effects of (-)clau are to increase cognition, demonstrated in ten models of memory impairment, as well as to inhibit β-amyloid (Aβ) toxicity, blocking neurofibrillary tangle formation by inhibiting the phosphorylation of tau protein. This anti-dementia effect is characterized by increased synaptic plasticity both in efficacy and in structure and provides new support for the theory that synaptic loss is the main cause of dementia. (-)Clau is considered to be a promising drug candidate for treatment of Alzheimer׳s disease and other neurodegenerative disorders.

RESUMEN

The aim of the study is to investigate the effect of salvianolic acid B (SalB) on blood-brain barrier (BBB) in rats after cerebral ischemia-reperfusion, and to illustrate its possible mechanisms. Cerebral ischemia-reperfusion was induced by middle cerebral artery occlusion in rats. The break-down of BBB was indicated by extravasations of immunoglobulin (IgG) monitored with immunohistochemistry. The expression of MMP-9 and NOS2 in the brain was determined by immunohistochemistry, and the expression of p-p38 and p-ERK1/2 was detected by Western blotting. It was shown that on day 2 after ischemia-reperfusion the IgG accumulated around the vascular boundary zone, suggesting the break-down of BBB, and the expression of MMP-9 and NOS2 up-regulated at the same time. The result of Western blotting suggested that the expression of p-p38 and p-ERK1/2 increased. On day 7 after ischemia-reperfusion the. expression of MMP-9 and NOS2 was about the same level as day 2, the expression of p-p38 was higher than that on day 2 and the expression of p-ERK1/2 was slightly lower than that on day 2. SalB (1 and 10 mg x kg(-1)) significantly alleviated the extravasations of immunoglobulin induced by cerebral ischemia-reperfusion (P < 0.05). On day 2 and day 7 SalB attenuated the expression of MMP-9 and NOS2 (P < 0.05). SalB (10 mg x kg(-1)) reduced the expression of p-p38 and p-ERK1/2 apparently on day 2 and 7 after ischemia-reperfusion (P < 0.05). SalB (1 mg x kg(-1)) inhibited the expression of p-p38 on day 7 after ischemia-reperfusion (P < 0.05). The results indicate that SalB protects blood-brain barrier in rats after cerebral ischemia-reperfusion by inhibiting the MAPK pathway.

Asunto(s)

Animales , Masculino , Ratas , Benzofuranos , Farmacología , Barrera Hematoencefálica , Metabolismo , Isquemia Encefálica , Metabolismo , Patología , Medicamentos Herbarios Chinos , Farmacología , Infarto de la Arteria Cerebral Media , Quinasa 1 de Quinasa de Quinasa MAP , Metabolismo , Sistema de Señalización de MAP Quinasas , Metaloproteinasa 9 de la Matriz , Metabolismo , Óxido Nítrico Sintasa de Tipo II , Metabolismo , Fosforilación , Plantas Medicinales , Química , Distribución Aleatoria , Ratas Sprague-Dawley , Daño por Reperfusión , Metabolismo , Patología , Salvia miltiorrhiza , Química , Proteínas Quinasas p38 Activadas por Mitógenos , Metabolismo

RESUMEN

In recent decades, scientists in Asian and Western countries have been paying great attention to ginseng research. Today, more than 200 ginsenosides and non-saponin constituents have been isolated and identified. Ginsenosides show biological activities only after being deglycosylated by intestinal bacteria. Aglycone protopanaxadiol and protopanaxatriol show the highest bioactivities. According to literature, the noticeable action of ginseng is that of delaying aging and especially increasing the nootropic effect, and it was found for the first time that Rg1 could increase hippocampal neurogenesis in vitro and in vivo under physiological and pathological circumstances. This is one of primary mechanisms underlying many of its pharmacological actions on the central nervous system. Rg1 was further shown to improve learning and memory in normal rats and mice. The nootropic signaling pathway has also been carried out in normal rats, and the Rg1-induced signaling pathway is similar to the memory formation that occurs in mammals, suggesting that Rg1 may have a potential effect in increasing intellectual capacity in normal people. Comparisons of chemical structures and pharmacologic functions between Panax ginseng and Panax quiquefolium were carried out by many scientists. The conclusion is that each has its own characteristics. There is no superiority or inferiority to the other.

Asunto(s)

Animales , Humanos , Ratones , Ratas , Cognición , Ginsenósidos , Farmacología , Aprendizaje , Memoria , Neovascularización Fisiológica , Neurogénesis , Plasticidad Neuronal , Panax , Química , Transducción de Señal

RESUMEN

This study is to investigate the protective effect of (-) clausenamide against the neurotoxicity of okadaic acid in SH-SY5Y cell line, and injection beta-amyloid peptide25-35 (Abeta25-35) to the cerebral ventricle in ovariectomy (OVX) rats. MTT assay, LDH assay, and Hoechst 33258 staining were used to detect the effect of (-) clausenamide on the toxicity of okadaic acid in SH-SY5Y cell line. The animal model was induced by ovariectomized and injection of Abeta25-35 in the cerebroventricle of rats. The effect of (-) clausenamide on learning and memory deficiency was observed by step-through test. Electron microscope, Nissl body staining, and HE staining were used to examine the morphological changes in hippocampus and cerebral cortex neurons. Pretreatment of (-) clausenamide and LiCl decreased the rate of cell death from MTT, LDH release, and apoptosis from Hoechst 33258 staining in SH-SY5Y cell line. The step-through tests showed (-) clausenamide could improve the ability of learning and memory. The Nissl body staining and HE staining experiments also showed the neuroprotective effects of (-) clausenamide on the neurons of hippocampus and cerebral cortex. (-) Clausenamide has the protective effects against the neurotoxicity induced by okadaic acid and Abeta25-35.

Asunto(s)

Animales , Femenino , Humanos , Ratas , Péptidos beta-Amiloides , Toxicidad , Apoptosis , Línea Celular Tumoral , Supervivencia Celular , Corteza Cerebral , Biología Celular , Clausena , Química , Medicamentos Herbarios Chinos , Farmacología , Hipocampo , Biología Celular , L-Lactato Deshidrogenasa , Metabolismo , Lactamas , Farmacología , Aprendizaje , Lignanos , Farmacología , Trastornos de la Memoria , Neuroblastoma , Metabolismo , Patología , Neuronas , Fármacos Neuroprotectores , Farmacología , Ácido Ocadaico , Toxicidad , Ovariectomía , Fragmentos de Péptidos , Toxicidad , Plantas Medicinales , Química , Ratas Sprague-Dawley

RESUMEN

This study is to observe the effect of salvianolic acid B (Sal B) on neural cells damage and neurogenesis in sub-granular zone (SGZ) and sub-ventricular zone (SVZ) after brain ischemia-reperfusion (I/R) in rats. A modified middle cerebral artery occlusion (MCAO) model of focal cerebral ischemia-reperfusion was used. The rats were divided into four groups: sham control group, ischemia-reperfusion group, Sal B 1 and 10 mg x kg(-1) groups. Sal B was consecutively administrated once a day by ip injection after MCAO. The neurogenesis in SGZ and SVZ was investigated by BrdU method 7 days after MCAO. The Nissl staining for neurons in the hippocampal CA1 and cerebral cortex was performed 14 days after MCAO. A beam-walking test was used to monitor the motor function recovery. We found that brain ischemia resulted in an increase of BrdU positive cells both in ipsilateral SGZ and SVZ at 7th day after MCAO. Sal B (10 mg x kg(-1)) significantly increased further the number of BrdU positive cells both in SGZ and SVZ (P < 0.01). Ipsilateral hippocampal neuron damage occurred and CA1 almost lost 14 days after MCAO. Sal B (10 mg x kg(-1)) obviously attenuated the neuron damage and increased the number of neuron both in ipsilateral CA1 and cerebral cortex (P < 0.01). We also observed an obvious improvement of motor function recovery when Sal B (10 mg x kg(-1)) administrated. From the results above we concluded that Sal B stimulated neurogenesis process both in SGZ and SVZ after brain ischemia, and also alleviated neural cells loss and improved motor function recovery after brain ischemia in rats.

Asunto(s)

Animales , Masculino , Ratas , Benzofuranos , Farmacología , Recuento de Células , Corteza Cerebral , Patología , Ventrículos Cerebrales , Patología , Giro Dentado , Patología , Hipocampo , Patología , Infarto de la Arteria Cerebral Media , Actividad Motora , Neurogénesis , Neuronas , Patología , Plantas Medicinales , Química , Distribución Aleatoria , Ratas Sprague-Dawley , Daño por Reperfusión , Patología , Salvia miltiorrhiza , Química

RESUMEN

<p><b>AIM</b>To compare the effects of salvianolic acid B (Sal B) and Ginkgo biloba extract EGb 761 on beta-amyloid peptide (beta-AP) fibril formation and cytotoxicity to PC12 cells.</p><p><b>METHODS</b>The inhibitory effects of Sal B and EGb 761 on beta-AP1-40 fibril formation were determined by using fluorescence analysis with Thioflavin T (ThT) and electron microscopic image. beta-AP25-35 was aged by incubating at 37 degrees C for 7 d, then the protein was incubated with PC12 cells. The protective effects of Sal B and EGb 761 against cytotoxicity induced by aged beta-AP25-35 in PC12 cells were evaluated by MTT reduction assay and flow cytometric analysis. beta-AP25-35-induced accumulation of intracellular reactive oxygen species (ROS) was determined by fluorescence analysis.</p><p><b>RESULTS</b>Both Sal B and EGb 761 inhibited the formation of amyloid fibrils, protected PC12 cells from beta-AP25-35-induced cytotoxicity, and decreased ROS accumulation caused by beta-AP25-35. The effective doses of Sal B were far lower than those of EGb 761.</p><p><b>CONCLUSION</b>Sal B was much more efficient than EGb 761 in inhibiting beta-AP aggregation and in protecting PC12 cells from beta-AP-induced cytotoxicity.</p>

Asunto(s)

Animales , Ratas , Péptidos beta-Amiloides , Química , Toxicidad , Apoptosis , Benzofuranos , Farmacología , Supervivencia Celular , Relación Dosis-Respuesta a Droga , Medicamentos Herbarios Chinos , Farmacología , Citometría de Flujo , Ginkgo biloba , Química , Líquido Intracelular , Metabolismo , Microscopía Electrónica , Fármacos Neuroprotectores , Farmacología , Células PC12 , Fragmentos de Péptidos , Química , Toxicidad , Extractos Vegetales , Farmacología , Plantas Medicinales , Química , Especies Reactivas de Oxígeno , Metabolismo , Salvia miltiorrhiza , Química

RESUMEN

<p><b>AIM</b>To study the mechanism of ginsenosides Rg1 and Rb1 promoting glutamic acid release from PC12 cells.</p><p><b>METHODS</b>The amount of glutamic acid released from PC12 cells was measured by high performance liquid chromatography (HPLC). The effect of Rg1 and Rb1 on the phosphorylation of synapsins was detected with immunofluorescent staining and Western blotting.</p><p><b>RESULTS</b>Both Rg1 (10 micromol x L(-1)) and Rb1 (10 micromol x L(-1)) increased glutamic acid release from PC12 cells. The release of glutamic acid was decreased by pre-incubating with the PKA inhibitor H89. H89 inhibited the release of glutamic acid induced by Rb1, but had no effect on the release of glutamic acid induced by Rg1. Moreover, Rb1 enhanced the phosphorylation of synapsins via PKA pathway, Rg1 was out of touch with this.</p><p><b>CONCLUSION</b>Rb1 may promote release of neurotransmitters by increasing the phosphorylation of synapsins via PKA pathway, whereas the up-regulation of neurotransmitters release induced by Rg1 is independent of the phosphorylation of synapsins.</p>

Asunto(s)

Animales , Ratas , Western Blotting , Proteínas Quinasas Dependientes de AMP Cíclico , Fisiología , Técnica del Anticuerpo Fluorescente , Ginsenósidos , Farmacología , Ácido Glutámico , Secreciones Corporales , Isoquinolinas , Farmacología , Neurotransmisores , Secreciones Corporales , Células PC12 , Fosforilación , Sulfonamidas , Farmacología , Sinapsinas , Metabolismo

RESUMEN

The effects of (+) securinine on behavior and morphological changes after intracerebral ventricle injection of beta-amyloid (25-35) (Abeta(25-35)) in rats were investigated. A single high dose of Abeta(25-35) could impair the spatial cognitive function. The latency of locating the platform was longer in the model group than in the sham-operated group. While chronic administration of D-securinine (40 mg kg(-1)) could significantly shorten the latency. After Morris water maze, the activity of choline acetyltransferase (ChAT) and acetylcholinesterase (AchE) were detected. The results showed that D-securinine could decrease the AchE activity significantly and have no effect on ChAT. Meanwhile, immunohistochemistry analysis revealed that D-securinine could reduce the glial inflammatory responses induced by beta-amyloid protein. These results suggest that the effect of D-securinine in improving the cognitive deficits and neurodegeneration in betaAP(25-35)-treated rats may involve direct and indirect actions on targets. The GABA receptor plays a key role in these therapeutic effects and may be helpful in the treatment of Alzheimer's disease.

Asunto(s)

Alcaloides/uso terapéutico , Péptidos beta-Amiloides/toxicidad , Azepinas/uso terapéutico , Compuestos Heterocíclicos de 4 o más Anillos/uso terapéutico , Lactonas/uso terapéutico , Fármacos Neuroprotectores/uso terapéutico , Síndromes de Neurotoxicidad/etiología , Síndromes de Neurotoxicidad/prevención & control , Fragmentos de Péptidos/toxicidad , Piperidinas/uso terapéutico , Acetilcolinesterasa/metabolismo , Alcaloides/química , Animales , Azepinas/química , Conducta Animal , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/patología , Colina O-Acetiltransferasa/metabolismo , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Proteína Ácida Fibrilar de la Glía/metabolismo , Compuestos Heterocíclicos de 4 o más Anillos/química , Compuestos Heterocíclicos de Anillo en Puente , Inmunohistoquímica/métodos , Lactonas/química , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Síndromes de Neurotoxicidad/fisiopatología , Péptidos/síntesis química , Péptidos/toxicidad , Piperidinas/química , Ratas , Ratas Sprague-Dawley , Factores de Tiempo

RESUMEN

<p><b>AIM</b>To investigate effects of (-), (+)-7-hydroxy-clausenamide (7-OH-Clau) on basal synaptic transmission in the dentate gyrus of anesthetized rats.</p><p><b>METHODS</b>Extracellular recording of the population spike (PS) of hippocampal dentate gyrus following application of low-frequency stimulation (1/30 Hz, 1.0 mA).</p><p><b>RESULTS</b>Fifteen, thirty and sixty minutes after intracerebroventricular (icv) administration of an estimated final brain concentration of 2 x 10(-6) mol.L-1, (-)-7-OH-Clau caused over 30% increase relative to basal PS amplitude before administration, and 27%-41% increase relative to vehicle control (P < 0.05), while (+)-7-OH-Clau exhibited 18%-25% and 11%-20% decrease in the PS amplitude when compared with basal PS amplitude and vehicle control (P < 0.05), respectively.</p><p><b>CONCLUSION</b>The basal synaptic transmission in the dentate gyrus of the rat hippocampus can be potentiated by (-)-7-OH-Clau and attenuated by (+)-7-OH-Clau, indicating that there was a stereoselective difference between the two enantiomers in the modulation of synaptic responses and plasticity.</p>

Asunto(s)

Animales , Masculino , Ratas , Potenciales de Acción , Giro Dentado , Fisiología , Medicamentos Herbarios Chinos , Farmacología , Potenciales Postsinápticos Excitadores , Inyecciones Intraventriculares , Lactamas , Farmacología , Lignanos , Farmacología , Plantas Medicinales , Química , Ratas Sprague-Dawley , Rutaceae , Química , Estereoisomerismo , Transmisión Sináptica

RESUMEN

<p><b>AIM</b>To develop a high throughput screening assay to identify inhibitors of intercellular adhesion molecule-1 (ICAM-1) expression in human umbilical vein endothelial cells (HUVEC).</p><p><b>METHODS</b>ICAM-1 expression in lipopolysaccharide-stimulated endothelial cells was measured by ELISA. The cytotoxicity of the compounds was measured by MTT.</p><p><b>RESULTS</b>Lipopolysaccharide (LPS) increased ICAM-1 expression in HUVEC in a concentration- and time-dependent manner. Two thousand compounds were screened and the hit rate was 1.5%. Among these 30 compounds, 24 were cytotoxic.</p><p><b>CONCLUSION</b>The ELISA method was inexpensive, reproducible and suitable for high throughput primary cell assay. This assay was feasible to identify inhibitors of ICAM-1 and simultaneously discriminate the activity from the cytotoxic effects.</p>

Asunto(s)

Humanos , Moléculas de Adhesión Celular , Células Cultivadas , Química Farmacéutica , Métodos , Evaluación Preclínica de Medicamentos , Métodos , Endotelio Vascular , Biología Celular , Metabolismo , Molécula 1 de Adhesión Intercelular , Metabolismo , Lipopolisacáridos , Farmacología , Venas Umbilicales , Biología Celular , Metabolismo

RESUMEN

<p><b>AIM</b>To investigate the enzyme kinetics of (-)3S,4R,5R,6S-clausenamide[(-)-Clau] and (+)-3R,4S,5S,6R-clausenamide[(+)-Clau] catalyzed by rat liver microsomes and compare their stereoselective differences.</p><p><b>METHODS</b>An in vitro metabolic system was built by using rat liver microsomes and NADPH-generating system. Clau and its metabolites were determined simultaneously by a reversed-phase high performance liquid chromatography. The kinetic parameters, K(m), Vmax, and metabolic rate, Vmax/K(m), were calculated by Eadie-Hofstee plot.</p><p><b>RESULTS</b>In the metabolic system, (-)-Clau was found to be mainly metabolized to 7-hydroxy-, 5-hydoxy- and 4-hydroxy-Clau, and 7-hydroxylation was a preferential pathway which exhibited higher Vmax/K(m) value (0.135 microL.min-1.mg-1) than those of 5- and 4-hydroxylation (0.063 and 0.068 microL.min-1.mg-1, respectively). For (+)-Clau, it was mainly metabolized to 4-hydroxy-Clau, whereas 7-hydroxy- and 4-hydroxy-Clau were so small that they could not be detected systematically. 4-Hydroxylation of (+)-Clau showed highest Vmam/K(m) value (0.547 microL.min-1.mg-1) among all the metabolites tested, which was 8.0 times higher than that of 4-hydroxylation of its antipode.</p><p><b>CONCLUSION</b>The data indicated that there were obvious substrate stereoselective differences in the hydroxylation metabolism of (+)- and (-)-Clau, which provided an explanation of the difference of pharmacokinetic characteristics of Clau enantiomers in rats.</p>

Asunto(s)

Animales , Femenino , Ratas , Medicamentos Herbarios Chinos , Metabolismo , Hidroxilación , Cinética , Lactamas , Química , Metabolismo , Lignanos , Química , Metabolismo , Microsomas Hepáticos , Metabolismo , NADP , Metabolismo , Plantas Medicinales , Química , Ratas Wistar , Rutaceae , Química , Estereoisomerismo

RESUMEN

<p><b>AIM</b>To establish culture procedures of neural stem cells from embryonic rat brain, determine their stem-cell characteristics and observe the effects of several compounds on their proliferation ability.</p><p><b>METHODS</b>Firstly, a stem cell culture system was set up from embryonic rat cortex. The cells were identified as neural stem cells through immunocytochemistry, in which antibodies to neural stem cell specific protein and markers of mature neural cells were used. Then, by using MTT assay, the survival rate of neurospheres incubated with various concentrations of ginsenoside Rg1, (-)-clausenamide and salvianolic acid A were observed. Furthermore, the effect of these drugs was measured with 3[H] thymidine incorporation assay.</p><p><b>RESULTS</b>In this study, a culture model of neural stem cell was successfully set up. In this model, primary cells from E16-18 rat cortex were dissected out, and cultured as floating neurospheres. The results of immunocytochemistry showed that nestin was expressed by the majority of cells within the sphere. After growing for 8 days in differentiation medium, cells from a single neurosphere were shown to differentiate into 3 main kinds of neural cells: neurons, astrocytes and oligodendrocytes. MTT assay revealed that the three drugs all enhanced the survival rate of neural stem cells, but 3[H] thymidine incorporation assay suggested that only Rg1 significantly accelerated the proliferation rate.</p><p><b>CONCLUSION</b>One culture model of neural stem cell was set up successfully. Meanwhile, several drugs were found to increase the proliferation and/or survival rate of neural stem cells. It has been demonstrated that neural stem cells exist in adult mammalian brains. So, these drugs may become promising candidates for the therapy of neurodegenerative diseases; such as Alzheimer's disease and Parkinson's disease.</p>

Asunto(s)

Animales , Ratas , Ácidos Cafeicos , Diferenciación Celular , División Celular , Supervivencia Celular , Células Cultivadas , Corteza Cerebral , Biología Celular , Medicamentos Herbarios Chinos , Farmacología , Embrión de Mamíferos , Ginsenósidos , Farmacología , Lactamas , Lactatos , Lignanos , Ratas Wistar , Células Madre , Biología Celular

RESUMEN

The effect of nimodipine on securinine-induced long-term potentiation in rat hippocampus was studied. The rise of intracellular calcium during the induction of long-term potentiation was measured using Fura-2/AM--a Ca (2+) fluorescent chelator. Results showed that intracerebroventricular injection of nimodipine (4 nmol) blocked the induction of long-term potentiation elicited by securinine (0.4 pmol) and high-frequency stimulation (p < 0.05), but 2-amino-5-phosphonovaleric acid (5 nmol) had no inhibitory effect on securinine-induced long-term potentiation. In addition, securinine-induced intracellular calcium increment was inhibited by nimodipine (10(-6) mol. L(-1), p < 0.01), but not by 2-amino-5-phosphonovaleric acid (10(-6) mol. L(-1), p > 0.05).

Asunto(s)

Alcaloides/farmacología , Azepinas , Calcio/metabolismo , Giro Dentado/efectos de los fármacos , Giro Dentado/metabolismo , Lactonas , Potenciación a Largo Plazo/efectos de los fármacos , Piperidinas , Anestesia , Animales , Bloqueadores de los Canales de Calcio/farmacología , Interacciones Farmacológicas , Euphorbiaceae/química , Compuestos Heterocíclicos de 4 o más Anillos , Compuestos Heterocíclicos de Anillo en Puente , Masculino , Estructura Molecular , Nimodipina/farmacología , Plantas Medicinales/química , Ratas , Ratas Sprague-Dawley , Factores de Tiempo

RESUMEN

Aim The protective effect of total salvianolic acids (Sal) on cerebral hypoxia inmice was studied. Methods Acute cerebral hypoxia was induced by sodium nitrite scand decapitation.The effect of Sal on acute cerebral hypoxia in mice and neuronalhypoxia injury induced by sodium dithionite in primary cultures were ob-served. Results Sal in the doses of 10, 20 mg?kg-1 iv protected mice against theacute cerebral hypoxia and inhibited the production of lipid peroxidation in brain tis-sue of mice caused by cerebral hypoxia. Sal in the doses of 1~10 ?g? L-1 reduced therate of cell death and the content of MDA and lowered LDH content in extra-cellularbathing media in oxygen deprived cortical cultures.Conclusions Sal protects miceagainst cerebral hypoxia by suppressing the generation of lipid peroxide.