RESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: The seeds of Zizyphus jujuba var. spinosa (Bunge) Hu ex H.F. Chow (Rhamnaceae) have long been treated as hypnotic agent for sleep disturbances in traditional Chinese and Korean medicine and many previous studies have focused on its effect in central nervous system. AIMS OF STUDY: The present study aimed to provide evidence showing that the ethanol extract of Zizyphus jujuba var. spinosa seeds (EEZS), which may regulate plasmin activity, has the potential to serve as a therapeutic agent for AD. MATERIALS AND METHODS: Synaptic function was determined by measuring long-term potentiation (LTP) in Shaffer-collateral pathway of the hippocampus. Protein levels of plasmin or plasminogen were examined using western blotting. Plasmin activity was measured using ELISA. Cognitive functions were measured using passive avoidance and object recognition tests in the 5XFAD mice. RESULTS: Our in vitro analysis revealed that EEZS-treated hippocampal slices from 5XFAD mice, a mouse model of AD, showed significantly higher long-term potentiation levels than did vehicle-treated hippocampal slices from 5XFAD mice (Pâ¯<â¯0.05). Additionally, EEZS significantly elevated the plasmin level and activity in the hippocampal slices from 5XFAD mice (Pâ¯<â¯0.05). Co-treating the slices with EEZS and 6-aminocaproic acid, a plasmin inhibitor, blocked the ameliorating effects of EEZS on the synaptic deficits that were present in 5XFAD mice. Compatible with the in vitro study, the results of our in vivo investigation showed that administering EEZS orally to 5XFAD mice ameliorated their memory impairments. Orally administered EEZS also elevated the plasmin level and activity in the hippocampus of 5XFAD mice. CONCLUSIONS: Collectively, our findings suggest that EEZS alleviates the AD-like symptoms in 5XFAD mice by regulating of plasmin activity and EEZS may be a suitable treatment for AD.
Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Trastornos de la Memoria/tratamiento farmacológico , Extractos Vegetales/uso terapéutico , Ziziphus , Enfermedad de Alzheimer/metabolismo , Animales , Reacción de Prevención/efectos de los fármacos , Conducta Animal/efectos de los fármacos , Modelos Animales de Enfermedad , Etanol , Fibrinolisina/metabolismo , Hipocampo/efectos de los fármacos , Masculino , Trastornos de la Memoria/metabolismo , Ratones , Ratones Transgénicos , Extractos Vegetales/farmacología , Semillas , Sinapsis/efectos de los fármacosRESUMEN
In attempting to identify effective anticancer drugs from natural products that are harmless to humans, we found that the gomisin J from Schisandra chinensis fruit has anticancer activity. Schisandra chinensis fruits are used in traditional herbal medicine and gomisin J is one of their chemical constituents. In the present study, we examined the anticancer activity of gomisin J in MCF7 and MDA-MB-231 breast cancer cell lines and in MCF10A normal cell line, in a time- and concentration-dependent manner. Our data revealed that gomisin J exerted a much stronger cytotoxic effect on MCF7 and MDA-MB-231 cancer cells than on MCF10A normal cells. Gomisin J suppressed the proliferation and decreased the viability of MCF7 and MDA-MB-231 cells at relatively low (<10 µg/ml) and high (>30 µg/ml) concentrations, respectively. Our data also revealed that gomisin J induced necroptosis, a programmed form of necrosis, as well as apoptosis. Notably, gomisin J predominantly induced necroptosis in MCF7 cells that are known to have high resistance to many pro-apoptotic anticancer drugs, while MDA-MB-231 exhibited a much lower level of necroptosis but instead a higher level of apoptosis. This data indicated the possibility that it may be used as a more effective anticancer drug, especially in apoptosis-resistant malignant cancer cells. In an extended study, gomisin J exhibited a strong cytotoxic effect on all tested various types of 13 cancer cell lines, indicating its potential to be used against a wide range of different types of cancer cells.
Asunto(s)
Lignanos/farmacología , Neoplasias/tratamiento farmacológico , Compuestos Policíclicos/farmacología , Schisandra/química , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Frutas/química , Humanos , Lignanos/uso terapéutico , Compuestos Policíclicos/uso terapéuticoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Aubang Gahl Soo (AGS) is a Korean traditional drink manufactured from medicinal plants and fruits using sugar or honey. Although traditional old book stated its effects on body, there is no scientific evidence yet. Therefore, in the present study, we tested AGS on brain functions. AIM OF THIS STUDY: In this study, we tried to uncover the effect of on brain functions. To do this we examined the action of AGS on the hippocampal synaptic function and memory in mice. MATERIALS AND METHODS: To examine the effect of AGS on synaptic plasticity, we observed input-output curves (I/O curve), paired-pulse facilitation (PPF), and long-term potentiation (LTP) using mouse hippocampal slices. Moreover, to investigate the functional relevance of the effect of AGS on synaptic plasticity, we conducted passive avoidance, Y-maze and Morris water maze tests. To examine relevant mechanism, acetylcholinesterase (AChE) activity and acetylcholine (ACh) level assay were also conducted. RESULTS: In the basal synaptic transmission study, we found that AGS did not affect I/O curves and PPF. However, AGS facilitated hippocampal LTP in a concentration-dependent manner. Moreover, AGS blocked AChE activity (IC50 = 485⯵g/ml). Moreover, ACh level was increased by AGS (100⯵g/ml) treatment. Along with this, facilitating effect of AGS on hippocampal LTP also blocked by scopolamine, a muscarinic acetylcholine receptor antagonist. Moreover, AGS also ameliorated memory impairments induced by scopolamine in passive avoidance, Y-maze, and Morris water maze tests. CONCLUSIONS: These results suggest that AGS facilitates hippocampal LTP through activating cholinergic system and ameliorates cholinergic dysfunction-induced memory deficit.