RESUMEN
This study was conducted to confirm the effects of Korean red ginseng on lung and brain dysfunction in a BALB/c mice model exposed to particulate matter (PM)2.5 for 12 weeks. Learning and cognitive abilities were assessed with Y-maze, passive avoidance, and Morris water maze tests. To evaluate the ameliorating effect of red ginseng extract (RGE), the antioxidant system and mitochondrial function were investigated. The administration of RGE protected lung and brain impairment by regulating the antioxidant system and mitochondrial functions damaged by PM2.5-induced toxicity. Moreover, RGE prevented pulmonary fibrosis by regulating the transforming growth factor beta 1 (TGF-ß1) pathway. RGE attenuated PM2.5-induced pulmonary and cognitive dysfunction by regulating systemic inflammation and apoptosis via the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)/c-Jun N-terminal kinases (JNK) pathway. In conclusion, RGE might be a potential material that can regulate chronic PM2.5-induced lung and brain cognitive dysfunction.
Asunto(s)
Encefalopatías , Panax , Animales , Ratones , Antioxidantes , Inflamación/tratamiento farmacológico , Encéfalo , Ratones Endogámicos BALB C , PulmónRESUMEN
In this study, we investigated the anti-amnesic effect of Korean red pine (Pinus densiflora) bark extract (KRPBE) against amyloid beta1-42 (Aß1-42)-induced neurotoxicity. We found that treatment with KRPBE improved the behavioral function in Aß-induced mice, and also boosted the antioxidant system in mice by decreasing malondialdehyde (MDA) content, increasing superoxide dismutase (SOD) activities, and reducing glutathione (GSH) levels. In addition, KRPBE improved the cholinergic system by suppressing reduced acetylcholine (ACh) content while also activating acetylcholinesterase (AChE), regulating the expression of choline acetyltransferase (ChAT), postsynaptic density protein-95 (PSD-95), and synaptophysin. KRPBE also showed an ameliorating effect on cerebral mitochondrial deficit by regulating reactive oxygen species (ROS), mitochondrial membrane potential (MMP) and ATP levels. Moreover, KRPBE modulated the expression levels of neurotoxicity indicators Aß and phosphorylated tau (p-tau) and inflammatory cytokines TNF-α, p-IκB-α, and IL-1ß. Furthermore, we found that KRPBE improved the expression levels of neuronal apoptosis-related markers BAX and BCl-2 and increased the expression levels of BDNF and p-CREB. Therefore, this study suggests that KRPBE treatment has an anti-amnestic effect by modulating cholinergic system dysfunction and neuroinflammation in Aß1-42-induced cognitive impairment in mice.
Asunto(s)
Disfunción Cognitiva , Fármacos Neuroprotectores , Pinus , Acetilcolina/metabolismo , Acetilcolina/farmacología , Acetilcolinesterasa/metabolismo , Adenosina Trifosfato/metabolismo , Péptidos beta-Amiloides , Animales , Antioxidantes/farmacología , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Colina O-Acetiltransferasa/metabolismo , Colina O-Acetiltransferasa/farmacología , Colinérgicos/farmacología , Disfunción Cognitiva/inducido químicamente , Disfunción Cognitiva/tratamiento farmacológico , Glutatión/metabolismo , Malondialdehído/metabolismo , Malondialdehído/farmacología , Ratones , Inhibidor NF-kappaB alfa/metabolismo , Enfermedades Neuroinflamatorias , Fármacos Neuroprotectores/farmacología , Estrés Oxidativo , Corteza de la Planta , Extractos Vegetales/farmacología , Especies Reactivas de Oxígeno/metabolismo , República de Corea , Superóxido Dismutasa/metabolismo , Sinaptofisina/metabolismo , Sinaptofisina/farmacología , Factor de Necrosis Tumoral alfa/metabolismo , Proteína X Asociada a bcl-2/metabolismoRESUMEN
This study was conducted to evaluate the protective effect of Juglans regia (walnut, Gimcheon 1ho cultivar, GC) on high-fat diet (HFD)-induced cognitive dysfunction in C57BL/6 mice. The main physiological compounds of GC were identified as pedunculagin/casuariin isomer, strictinin, tellimagrandin I, ellagic acid-O-pentoside, and ellagic acid were identified using UPLC Q-TOF/MS analysis. To evaluate the neuro-protective effect of GC, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), 2',7'-dichlorodihydrofluorecein diacetate (DCF-DA) analysis were conducted in H2O2 and high glucose-induced neuronal PC12 cells and hippocampal HT22 cells. GC presented significant cell viability and inhibition of reactive oxygen species (ROS) production. GC ameliorated behavioral and memory dysfunction through Y-maze, passive avoidance, and Morris water maze tests. In addition, GC reduced white adipose tissue (WAT), liver fat mass, and serum dyslipidemia. To assess the inhibitory effect of antioxidant system deficit, lipid peroxidation, ferric reducing antioxidant power (FRAP), and advanced glycation end products (AGEs) were conducted. Administration of GC protected the antioxidant damage against HFD-induced diabetic oxidative stress. To estimate the ameliorating effect of GC, acetylcholine (ACh) level, acetylcholinesterase (AChE) activity, and expression of AChE and choline acetyltransferase (ChAT) were conducted, and the supplements of GC suppressed the cholinergic system impairment. Furthermore, GC restored mitochondrial dysfunction by regulating the mitochondrial ROS production and mitochondrial membrane potential (MMP) levels in cerebral tissues. Finally, GC ameliorated cerebral damage by synergically regulating the protein expression of the JNK signaling and apoptosis pathway. These findings suggest that GC could provide a potential functional food source to improve diabetic cognitive deficits and neuronal impairments.
Asunto(s)
Disfunción Cognitiva , Juglans , Acetilcolinesterasa/metabolismo , Animales , Antioxidantes/farmacología , Apoptosis , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/etiología , Disfunción Cognitiva/metabolismo , Dieta Alta en Grasa , Ácido Elágico/farmacología , Peróxido de Hidrógeno/farmacología , Juglans/metabolismo , MAP Quinasa Quinasa 4/metabolismo , Ratones , Ratones Endogámicos C57BL , Mitocondrias/metabolismo , Estrés Oxidativo , Ratas , Especies Reactivas de Oxígeno/metabolismoRESUMEN
This study was performed to investigate the effects of persimmon (Diospyros kaki) on high-fat diet (HFD)-induced hepatic lipotoxicity. The compounds of persimmon water extract (PWE) were identified as gallic acid, glucogallin, 1-O-Galloyl-(2-O-acetyl)-glu, and trihydroxy-octadecadienoic acid. The PWE was ingested by C57BL/6 mice with an HFD for 8 weeks. The PWE improved glucose tolerance and suppressed weight gain by inhibiting increases in the weight of liver and adipose tissues. The results of serum biomarker analysis showed that PWE suppressed biomarkers such as liver injury and dyslipidemia. In ex vivo tests, reduction of oxidative stress and improvement of mitochondrial dysfunction were confirmed in the liver of PWE groups. In a molecular study, it was confirmed that PWE decreased lipid accumulation, insulin resistance, inflammation, and apoptosis in the liver. Finally, in a metabolite analysis of liver tissue using ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS), it was confirmed that PWE has an effect on lipid metabolism. In particular, PWE reduced phosphatidylcholines (PCs) and lysophosphatidylcholines (lysoPCs). Notably, it is presumed that the reduction of lysoPCs and PCs in the PWE group is related to the improvement of liver dysfunction due to lipotoxicity.
Asunto(s)
Diospyros , Enfermedad del Hígado Graso no Alcohólico , Animales , Dieta Alta en Grasa/efectos adversos , Diospyros/química , Metabolismo de los Lípidos , Lípidos , Hígado/metabolismo , Ratones , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Extractos Vegetales/química , Agua/metabolismoRESUMEN
The anti-amnesic effect of a mixture (4:6 = phlorotannin:fucoidan from Ecklonia cava, P4F6) was evaluated on amyloid-beta peptide (Aß)-induced cognitive deficit mice. The cognitive function was examined by Y-maze, passive avoidance, and Morris water maze tests, and the intake of the mixture (P4F6) showed an ameliorating effect on Aß-induced learning and memory impairment. After the behavioral tests, superoxide dismutase (SOD) activity and thiobarbituric acid-reactive substances (TBARS) contents were confirmed in brain tissue, and in the results, the mixture (P4F6) attenuated Aß-induced oxidative stress. In addition, mitochondrial activity was evaluated by mitochondrial reactive oxygen species (ROS) content, mitochondrial membrane potential (MMP), adenosine triphosphate (ATP) content, and mitochondria-mediated apoptotic signaling pathway, and the mixture (P4F6) enhanced mitochondrial function. Furthermore, the mixture (P4F6) effectively regulated tau hyperphosphorylation by regulating the protein kinase B (Akt) pathway, and promoted brain-derived neurotrophic factor (BDNF) in brain tissue. Moreover, in the cholinergic system, the mixture (P4F6) ameliorated acetylcholine (ACh) content by regulating acetylcholinesterase (AChE) activity and choline acetyltransferase (ChAT) expression in brain tissue. Based on these results, we suggest that this mixture of phlorotannin and fucoidan (P4F6) might be a substance for improving cognitive function by effectively regulating cognition-related molecules.
Asunto(s)
Disfunción Cognitiva/tratamiento farmacológico , Kelp , Fármacos Neuroprotectores/administración & dosificación , Polisacáridos/administración & dosificación , Taninos/administración & dosificación , Acetilcolina/metabolismo , Animales , Organismos Acuáticos , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Colinérgicos/metabolismo , Modelos Animales de Enfermedad , Quimioterapia Combinada , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Ratones , Ratones Endogámicos ICR , Mitocondrias/metabolismo , Fármacos Neuroprotectores/farmacología , Fitoterapia , Polisacáridos/farmacología , Taninos/farmacologíaRESUMEN
This study confirmed the ameliorating effect of immature persimmon (Diospyros kaki) ethanolic extract (IPEE) on neuronal cytotoxicity in amyloid beta (Aß)1-42-induced ICR mice. The administration of IPEE ameliorated the cognitive dysfunction in Aß1-42-induced mice by improving the spatial working memory, the short-term and long-term memory functions. IPEE protected the cerebral cholinergic system, such as the acetylcholine (ACh) level and acetylcholinesterase (AChE) activity, and antioxidant system, such as the superoxide dismutase (SOD), reduced glutathione (GSH) and malondialdehyde (MDA) contents. In addition, mitochondrial dysfunction against Aß1-42-induced toxicity was reduced by regulating the reactive oxygen species (ROS), mitochondrial membrane potential and ATP contents. In addition, IPEE regulated the expression levels of tau signaling, such as TNF-α, p-JNK, p-Akt, p-GSK3ß, p-tau, p-NF-κB, BAX and caspase 3. Finally, gallic acid, ellagic acid and quercetin 3-O-(6â³-acetyl-glucoside) were identified as the physiological compounds of IPEE using ultra-performance liquid chromatography ion mobility separation quadrupole time-of-flight/tandem mass spectrometry (UPLC IMS Q-TOF/MS2).
Asunto(s)
Disfunción Cognitiva/prevención & control , Diospyros/química , Frutas/química , Extractos Vegetales/farmacología , Tauopatías/prevención & control , Acetilcolina/metabolismo , Acetilcolinesterasa/metabolismo , Péptidos beta-Amiloides , Animales , Antioxidantes/metabolismo , Disfunción Cognitiva/inducido químicamente , Disfunción Cognitiva/metabolismo , Etanol/química , Aprendizaje por Laberinto/efectos de los fármacos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Memoria a Corto Plazo/efectos de los fármacos , Ratones Endogámicos ICR , Fragmentos de Péptidos , Extractos Vegetales/química , Especies Reactivas de Oxígeno/metabolismo , Tauopatías/inducido químicamente , Tauopatías/metabolismo , Proteínas tau/metabolismoRESUMEN
Here, we investigated the prebiotic and antioxidant effects of Actinidia arguta sprout water extract (AASWE) on lipopolysaccharide (LPS)-induced cognitive deficit mice. AASWE increased viable cell count, titratable acidity, and acetic acid production in Lactobacillus reuteri strain and showed a cytoprotective effect on LPS-induced inflammation in HT-29 cells. We assessed the behavior of LPSinduced cognitive deficit mice using Y-maze, passive avoidance and Morris water maze tests and found that administration of AASWE significantly improved learning and memory function. The AASWE group showed antioxidant activity through downregulation of malondialdehyde levels and upregulation of superoxide dismutase levels in brain tissue. In addition, the AASWE group exhibited activation of the cholinergic system with decreased acetylcholinesterase activity in brain tissue. Furthermore, AASWE effectively downregulated inflammatory mediators such as phosphorylated- JNK, phosphorylated-NF-κB, TNF-α and interleukin-6. The major bioactive compounds of AASWE were identified as quercetin-3-O-arabinopyranosyl(1â2)-rhamnopyranosyl(1â6)-glucopyranose, quercetin-3-O-apiosyl(1â2)-galactoside, rutin, and 3-caffeoylquinic acid. Based on these results, we suggest that AASWE not only increases the growth of beneficial bacteria in the intestines, but also shows an ameliorating effect on LPS-induced cognitive impairment.
Asunto(s)
Actinidia/química , Antioxidantes/farmacología , Disfunción Cognitiva/tratamiento farmacológico , Lipopolisacáridos/efectos adversos , Fitoquímicos/farmacología , Extractos Vegetales/farmacología , Acetilcolinesterasa/metabolismo , Animales , Antiinflamatorios/farmacología , Encéfalo/metabolismo , Disfunción Cognitiva/inducido químicamente , Células HT29 , Humanos , Inflamación/tratamiento farmacológico , Interleucina-6 , Limosilactobacillus reuteri , Masculino , Ratones , FN-kappa B/metabolismo , Fármacos Neuroprotectores/farmacología , Superóxido DismutasaRESUMEN
This study was conducted to assess the protective effect of extract of match (EM) on high-fat diet- (HFD-) induced cognitive deficits in male C57BL/6 mice. It was found that EM improved glucose tolerance status by measuring OGTT and IPGTT with HFD-induced mice. EM protected behavioral and memory dysfunction in Y-maze, passive avoidance, and Morris water maze tests. Consumption of EM reduced fat mass, dyslipidemia, and inflammation in adipose tissue. Also, EM ameliorated hepatic and cerebral antioxidant systems. EM improved the cerebral cholinergic system by regulating ACh contents and expression of AChE and ChAT. Also, EM restored mitochondrial function in liver and brain tissue. EM attenuated hepatic inflammatory effect, lipid synthesis, and cholesterol metabolism by regulating the protein expression of TNF-α, TNFR1, p-IRS-1, p-JNK, IL-1ß, iNOS, COX-2, HMGCR, PPARγ, and FAS. Finally, EM regulated cognitive function and neuroinflammation in the whole brain, hippocampus, and cerebral cortex by regulating the protein expression of p-JNK, p-Akt, p-tau, Aß, BDNF, IDE, COX-2, and IL-1ß. These findings suggest that EM might be a potential source of functional food to improve metabolic disorder-associated cognitive dysfunction.
Asunto(s)
Disfunción Cognitiva , Dieta Alta en Grasa/efectos adversos , Dislipidemias , Trastornos de la Memoria , Paniculitis , Té , Tejido Adiposo/metabolismo , Tejido Adiposo/patología , Animales , Disfunción Cognitiva/inducido químicamente , Disfunción Cognitiva/metabolismo , Disfunción Cognitiva/patología , Disfunción Cognitiva/terapia , Dislipidemias/inducido químicamente , Dislipidemias/metabolismo , Dislipidemias/patología , Dislipidemias/terapia , Regulación de la Expresión Génica , Inflamación/inducido químicamente , Inflamación/metabolismo , Inflamación/patología , Inflamación/terapia , Masculino , Trastornos de la Memoria/inducido químicamente , Trastornos de la Memoria/metabolismo , Trastornos de la Memoria/patología , Trastornos de la Memoria/terapia , Ratones , Paniculitis/inducido químicamente , Paniculitis/metabolismo , Paniculitis/patología , Paniculitis/terapiaRESUMEN
To evaluate possibility as a skin whitening agent of Sorghum bicolor (S. bicolor), its antioxidant activity and anti-melanogenic effect on 3-isobutyl-1-methylxanthine (IBMX)-induced melanogenesis in B16/F10 melanoma cells were investigated. The result of total phenolic contents (TPC) indicated that 60% ethanol extract of S. bicolor (ESB) has the highest contents than other ethanol extracts. Antioxidant activity was evaluated using the 2,2'-azino-bis-(3-ethylbenzothiazolin-6-sulfonic acid) diammonium salt (ABTS)/1,1-diphenyl-2-picryl-hydrazyl (DPPH) radical scavenging activities and malondialdehyde (MDA) inhibitory effect. These results showed ESB has significant antioxidant activities. Inhibitory effect against tyrosinase was also assessed using L-tyrosine (IC50 value = 89.25 µg/mL) and 3,4-dihydroxy-L-phenylalanine (L-DOPA) as substrates. In addition, ESB treatment effectively inhibited melanin production in IBMX-induced B16/F10 melanoma cells. To confirm the mechanism on anti-melanogenic effect of ESB, we examined melanogenesis-related proteins. ESB downregulated melanogenesis by decreasing expression of microphthalmia-associated transcription factor (MITF), tyrosinase and tyrosinase-related protein (TRP)-1. Finally, 9-hydroxyoctadecadienoic acid (9-HODE), 1,3-O-dicaffeoylglycerol and tricin as the main compounds of ESB were analyzed using the ultra-performance liquid chromatography-ion mobility separation-quadrupole time of flight/tandem mass spectrometry (UPLC-IMS-QTOF/MS2). These findings suggest that ESB may have physiological potential to be used skin whitening material.
Asunto(s)
1-Metil-3-Isobutilxantina/farmacología , Melaninas/biosíntesis , Extractos Vegetales/farmacología , Sorghum/química , Animales , Antioxidantes/farmacología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Cromatografía Líquida de Alta Presión , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Metabolismo de los Lípidos/efectos de los fármacos , Peroxidación de Lípido/efectos de los fármacos , Melanoma Experimental , Ratones , Extractos Vegetales/química , Solventes , Espectrometría de Masas en TándemRESUMEN
This study was performed to investigate the effect of the chloroform fraction from Actinidia arguta (CFAA) on cognitive dysfunction in a C57BL/6 mouse model fed a high-fat diet (HFD) for 12 weeks. The CFAA has the protective effect on high glucose-induced neurotoxicity in MC-IXC cell (neuroblastoma cell line). In a C57BL/6 mouse model fed a HFD for 12 weeks, the improved glucose tolerance and cognitive dysfunction were observed in a group ingesting CFAA. In the brain tissue analysis, the impaired cholinergic, antioxidant system and mitochondria functions were improved in the CFAA group. In addition, in a molecular biology study, it was observed that CFAA improves HFD-induced abnormal insulin signaling such as increase of IRS phosphorylation at serine residues and reduction of Akt phosphorylation caused by the increase of JNK phosphorylation and then inhibited apoptosis. In the UPLC Q-TOF/MS analysis, pentacyclic triterpenoids such as asiatic acid (AA), madecassic acid (MA) were identified in CFAA as main compounds. Therefore, these results propose that Actinidia arguta rich in pentacyclic triterpenoids may be effective as preventive matter a therapeutic strategy to improve neurodegenerative disease caused by HFD.
Asunto(s)
Actinidia , Encéfalo/efectos de los fármacos , Fármacos Neuroprotectores/uso terapéutico , Obesidad/fisiopatología , Extractos Vegetales/uso terapéutico , Triterpenos/uso terapéutico , Actinidia/química , Animales , Encéfalo/fisiopatología , Línea Celular Tumoral , Dieta Alta en Grasa/efectos adversos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Obesos , Enfermedades Neurodegenerativas/etiología , Enfermedades Neurodegenerativas/fisiopatología , Enfermedades Neurodegenerativas/prevención & control , Fármacos Neuroprotectores/química , Obesidad/tratamiento farmacológico , Obesidad/etiología , Extractos Vegetales/química , Triterpenos/químicaRESUMEN
This study was performed to investigate the effects of Artemisia argyi and 4,5-dicaffeyolquinic acid (4,5-diCQA) as a main compound of ethyl acetate fraction from Artemisia argyi (EFAA) on high-fat diet (HFD)-induced cognitive dysfunction. Both EFAA and 4,5-diCQA were effective in improving cognitive function on HFD-induced cognitive dysfunction. In brain tissue analysis, it was confirmed that EFAA and 4,5-diCQA inhibited the reduction of neurotransmitters as well as oxidative stress and mitochondrial dysfunction. In addition, they inhibited amyloid ß (Aß) accumulation by increasing the expression of insulin-degrading enzyme and consequently prevented apoptosis. In conclusion, it is presumed that Artemisia argyi may help to improve the cognitive impairment due to the HFD, and it is considered that this effect is closely related to the physiological activity of 4,5-diCQA. PRACTICAL APPLICATIONS: Artemisia argyi is used in traditional herbal medicine in Asia. Type 2 diabetes mellitus has been proven by a variety of epidemiological studies to be a risk factor for cognitive impairment, such as Alzheimer's disease. This study confirmed that 4,5-diCQA is a bioactive compound of Artemisia argyi on improving HFD-induced cognitive dysfunction. Therefore, this study can provide useful information to the effect of Artemisia argyi and related substance.
Asunto(s)
Artemisia , Disfunción Cognitiva/tratamiento farmacológico , Insulisina/efectos de los fármacos , Extractos Vegetales/farmacología , Ácido Quínico/análogos & derivados , Péptidos beta-Amiloides/efectos de los fármacos , Péptidos beta-Amiloides/metabolismo , Apoptosis/efectos de los fármacos , Artemisia/química , Artemisia/metabolismo , Encéfalo/efectos de los fármacos , Encéfalo/fisiopatología , Dieta Alta en Grasa/efectos adversos , Insulisina/metabolismo , Estrés Oxidativo/efectos de los fármacos , Fitoterapia , Plantas Medicinales/metabolismo , Ácido Quínico/farmacologíaRESUMEN
This study was performed to estimate the possibility of using an ethyl acetate fraction from Aruncus dioicus var. kamtschaticus (EFAD) on metabolic syndrome that is induced by a high-fat diet (HFD). It was demonstrated that EFAD suppresses lipid accumulation and improves insulin resistance (IR) caused by Tumor necrosis factor alpha (TNF-α) in in-vitro experiments using the 3T3-L1 cell. In in-vivo tests, C57BL/6 mice were fed EFAD at 20 and 40 mg/kg body weight (BW) for four weeks after the mice were fed HFD for 15 weeks to induce obesity. EFAD significantly suppressed the elevation of BW and improved impaired glucose tolerance in obese mice. Additionally, this study showed that EFAD has an ameliorating effect on obesity-induced cognitive disorder with behavioral tests. The effect of EFAD on peripheral-IR improvement was confirmed by serum analysis and western blotting in peripheral tissues. Additionally, EFAD showed an ameliorating effect on HFD-induced oxidative stress, impaired cholinergic system and mitochondrial dysfunction, which are interrelated symptoms of neurodegeneration, such as Alzheimer's disease and central nervous system (CNS)-IR in brain tissue. Furthermore, we confirmed that EFAD improves CNS-IR by confirming the IR-related factors in brain tissue. Consequently, this study suggests the possibility of using EFAD for the prevention of neurodegeneration by improving metabolic syndrome that is caused by HFD.
Asunto(s)
Trastornos del Conocimiento/tratamiento farmacológico , Cognición/efectos de los fármacos , Dieta Alta en Grasa/efectos adversos , Obesidad/psicología , Extractos Vegetales/farmacología , Células 3T3-L1 , Animales , Peso Corporal/efectos de los fármacos , Trastornos del Conocimiento/etiología , Intolerancia a la Glucosa/tratamiento farmacológico , Intolerancia a la Glucosa/etiología , Resistencia a la Insulina , Ratones , Ratones Endogámicos C57BL , Ratones Obesos , Obesidad/etiologíaRESUMEN
An ethyl acetate fraction from Aralia elata (AEEF) was investigated to confirm its neuronal cell protective effect on ethanol-induced cytotoxicity in MC-IXC cells and its ameliorating effect on neurodegeneration in chronic alcohol-induced mice. The neuroprotective effect was examined by methylthiazolyldiphenyl-tetrazolium bromide (MTT) and 2',7'-dichlorodihydrofluorescein diacetate (DCF-DA) assays. As a result, AEEF reduced alcohol-induced cytotoxicity and oxidative stress. To evaluate the improvement of learning, memory ability, and spatial cognition, Y-maze, passive avoidance, and Morris water maze tests were conducted. The AEEF groups showed an alleviation of the decrease in cognitive function in alcohol-treated mice. Then, malondialdehyde (MDA) levels and the superoxide dismutase (SOD) content were measured to evaluate the antioxidant effect of AEEF in the brain tissue. Treatment with AEEF showed a considerable ameliorating effect on biomarkers such as SOD and MDA content in alcohol-induced mice. To assess the cerebral cholinergic system involved in neuronal signaling, acetylcholinesterase (AChE) activity and acetylcholine (ACh) content were measured. The AEEF groups showed increased ACh levels and decreased AChE activities. In addition, AEEF prevented alcohol-induced neuronal apoptosis via improvement of mitochondrial activity, including reactive oxygen species levels, mitochondrial membrane potential, and adenosine triphosphate content. AEEF inhibited apoptotic signals by regulating phosphorylated c-Jun N-terminal kinases (p-JNK), phosphorylated protein kinase B (p-Akt), Bcl-2-associated X protein (BAX), and phosphorylated Tau (p-Tau). Finally, the bioactive compounds of AEEF were identified as caffeoylquinic acid (CQA), 3,5-dicaffeoylquinic acid (3,5-diCQA), and chikusetsusaponin IVa using the UPLC-Q-TOF-MS system.
Asunto(s)
Trastornos del Sistema Nervioso Inducidos por Alcohol/tratamiento farmacológico , Antioxidantes/farmacología , Apoptosis/efectos de los fármacos , Aralia/química , Encéfalo/metabolismo , Neuronas/metabolismo , Fármacos Neuroprotectores/farmacología , Extractos Vegetales/farmacología , Acetatos/química , Trastornos del Sistema Nervioso Inducidos por Alcohol/metabolismo , Trastornos del Sistema Nervioso Inducidos por Alcohol/patología , Animales , Antioxidantes/química , Encéfalo/patología , Línea Celular , Enfermedad Crónica , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Memoria/efectos de los fármacos , Ratones , Neuronas/patología , Fármacos Neuroprotectores/química , Extractos Vegetales/química , Especies Reactivas de Oxígeno/metabolismoRESUMEN
The aim of this study was to investigate the availability of seeds, one of the byproducts of green tea, and evaluate the physiological activity of seed oil. The ameliorating effect of green tea seed oil (GTO) was evaluated on H2O2-induced PC12 cells and amyloid beta (Aß)1-42-induced ICR mice. GTO showed improvement of cell viability and reduced reactive oxygen species (ROS) production in H2O2-induced PC12 cells by conducting the 2',3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and 2',7'-dichlorofluorescein diacetate (DCF-DA) analysis. Also, administration of GTO (50 and 100 mg/kg body weight) presented protective effects on behavioral and memory dysfunction by conducting Y-maze, passive avoidance, and Morris water maze tests in Aß-induced ICR mice. GTO protected the antioxidant system by reducing malondialdehyde (MDA) levels, and by increasing superoxide dismutase (SOD) and reducing glutathione (GSH) contents. It significantly regulated the cholinergic system of acetylcholine (ACh) contents, acetylcholinesterase (AChE) activities, and AChE expression. Also, mitochondrial function was improved through the reduced production of ROS and damage of mitochondrial membrane potential (MMP) by regulating the Aß-related c-Jun N-terminal kinase (JNK)/protein kinase B (Akt) and Akt/apoptosis pathways. This study suggested that GTO may have an ameliorating effect on cognitive dysfunction and neurotoxicity through various physiological activities.
Asunto(s)
Péptidos beta-Amiloides/metabolismo , Disfunción Cognitiva/tratamiento farmacológico , Fármacos Neuroprotectores/uso terapéutico , Fragmentos de Péptidos/metabolismo , Aceites de Plantas/uso terapéutico , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/efectos de los fármacos , Té , Animales , Antioxidantes/química , Antioxidantes/uso terapéutico , Disfunción Cognitiva/metabolismo , Disfunción Cognitiva/patología , Peróxido de Hidrógeno/metabolismo , Ratones Endogámicos ICR , Fármacos Neuroprotectores/química , Estrés Oxidativo/efectos de los fármacos , Células PC12 , Aceites de Plantas/química , Ratas , Semillas/química , Té/químicaRESUMEN
This study was conducted to assess the antioxidant capacity and protective effect of the ethyl acetate fraction from persimmon (Diospyros kaki) (EFDK) on H2O2-induced hippocampal HT22 cells and trimethyltin chloride (TMT)-induced Institute of Cancer Research (ICR) mice. EFDK had high antioxidant activities and neuroprotective effects in HT22 cells. EFDK ameliorated behavioral and memory deficits in Y-maze, passive avoidance and Morris water maze tests. Also, EFDK restored the antioxidant system by regulating malondialdehyde (MDA), superoxide dismutase (SOD) and reduced gluthathione (GSH), and the cholinergic system by controlling the acetylcholine (ACh) level and acetylcholinesterase (AChE) activity and expression. EFDK enhanced mitochondrial function by regulating reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP), and adenosine triphosphate (ATP). Ultimately, EFDK regulated the c-Jun N-terminal kinase (JNK)/protein kinase B (Akt) pathway and apoptotic pathway by suppressing the expression of tumor necrosis factor-alpha (TNF-α), phosphorylated insulin receptor substrate 1 (IRS-1pSer), phosphorylated JNK (p-JNK), phosphorylated tau (p-tau), phosphorylated nuclear factor kappa-light-chain-enhancer of activated B cells (p-NF-κB), Bcl-2-associated X protein (BAX) and cytosolic cytochrome c, and increasing the expression of phosphorylated Akt (p-Akt) and mitochondrial cytochrome c. This study suggested that EFDK had antioxidant activity and a neuroprotective effect, and ameliorated cognitive abnormalities in TMT-induced mice by regulating the JNK/Akt and apoptotic pathway.
Asunto(s)
Acetatos/farmacología , Cognición/efectos de los fármacos , Diospyros/química , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Neuronas/efectos de los fármacos , Extractos Vegetales/farmacología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/efectos de los fármacos , Animales , Antioxidantes/farmacología , Apoptosis/efectos de los fármacos , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/patología , Recuento de Células , Disfunción Cognitiva , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Ratones , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Neuronas/patología , Fármacos Neuroprotectores/farmacología , Células Piramidales/efectos de los fármacos , Células Piramidales/metabolismo , Células Piramidales/patologíaRESUMEN
This study aimed to investigate the ameliorating effect of an ethyl acetate fraction from the fruit Actinidia arguta (EFAA) on amyloid beta (Aß)-induced neurotoxicity and cognitive deficits in ICR mice. EFAA showed potent protective effects against Aß-induced neurotoxicity through 2',7'-dichlorofluorescein diacetate (DCF-DA), 2',3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) release into the assay medium. EFAA treatment reduced the intracellular ROS level and lactate dehydrogenase (LDH) release in the mitochondria, and increased cell viability in Aß-induced neuroblastoma MC-IXC cells. The administration of EFAA significantly attenuated Aß-induced learning and memory deficits, which were evaluated by Y-maze, passive avoidance, and Morris water maze tests. Furthermore, EFAA showed the ameliorating effect of cholinergic functions by increasing acetylcholine (ACh) levels and decreasing acetylcholinesterase (AChE) activity, and protected antioxidant systems by increasing superoxide dismutase (SOD) and decreasing the oxidized glutathione (GSH)/total GSH and malondialdehyde (MDA) in the brain. Finally, EFAA prevented mitochondrial dysfunction via regulating apoptotic signaling molecules including phosphorylated Akt (p-Akt), phosphorylated tau (p-tau), Bax, and cytochrome c in the brain tissues. Therefore, the present study suggests that EFAA might be a potential source of natural antioxidants with the ability to ameliorate Aß-induced amnesia.
Asunto(s)
Actinidia/química , Enfermedad de Alzheimer/tratamiento farmacológico , Péptidos beta-Amiloides/metabolismo , Extractos Vegetales/administración & dosificación , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/psicología , Péptidos beta-Amiloides/genética , Animales , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Frutas/química , Glutatión/metabolismo , Humanos , Aprendizaje/efectos de los fármacos , Masculino , Malondialdehído/metabolismo , Aprendizaje por Laberinto , Memoria/efectos de los fármacos , Ratones , Ratones Endogámicos ICR , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/aislamiento & purificación , Especies Reactivas de Oxígeno/metabolismo , Superóxido Dismutasa/metabolismoRESUMEN
The ameliorating effects of the ethyl acetate fraction from Hibiscus sabdariffa L. (EFHS)2 against diabetes mellitus (DM)3 and DM-induced cognitive impairment were investigated on streptozotocin (STZ)4-induced DM mice. The EFHS groups showed improved hyperglycemia and glucose tolerance compared to the STZ group. Furthermore, their liver and kidney function and lipid metabolic imbalance in the blood serum were effectively recovered. The EFHS groups significantly ameliorated STZ-induced cognitive impairment in Y-maze, passive avoidance, and Morris water maze (MWM)5 tests. The EFHS groups showed significant improvement in the antioxidant and cholinergic systems of the brain tissue. In addition, EFHS had an excellent ameliorating effect on protein expression levels from the tau hyperphosphorylation pathways, such as phospho-c-Jun N-terminal kinases (p-JNK),6 phospho-tau (p-tau),7 and cleaved poly (ADP-ribose) polymerase (c-PARP).8 The main compounds of EFHS were identified as various phenolic compounds, including hibiscus acid, caffeoylquinic acid (CQA)9 isomers, and quercetin derivates. Therefore, EFHS containing various physiologically active materials can potentially be used for improving DM-induced cognitive impairment via its antioxidant activity, improvement of the cholinergic system, and hyperphosphorylation tau signaling.
Asunto(s)
Acetatos/química , Antioxidantes/farmacología , Conducta Animal/efectos de los fármacos , Encéfalo/efectos de los fármacos , Trastornos del Conocimiento/prevención & control , Cognición/efectos de los fármacos , Diabetes Mellitus Experimental/tratamiento farmacológico , Hibiscus , Hipoglucemiantes/farmacología , Fármacos Neuroprotectores/farmacología , Extractos Vegetales/farmacología , Solventes/química , Acetilcolina/metabolismo , Acetilcolinesterasa/metabolismo , Animales , Antioxidantes/aislamiento & purificación , Biomarcadores/sangre , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Encéfalo/metabolismo , Encéfalo/fisiopatología , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/metabolismo , Trastornos del Conocimiento/psicología , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/complicaciones , Proteínas Ligadas a GPI/metabolismo , Hibiscus/química , Hipoglucemiantes/aislamiento & purificación , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Lípidos/sangre , Masculino , Ratones Endogámicos ICR , Fármacos Neuroprotectores/aislamiento & purificación , Fosforilación , Extractos Vegetales/aislamiento & purificación , Poli(ADP-Ribosa) Polimerasas/metabolismo , Proteínas tau/metabolismoRESUMEN
Spirulina maxima, a microalga containing high levels of protein and many polyphenols, including chlorophyll a and C-phycocyanin, has antioxidant and anti-inflammatory therapeutic effects. However, the mechanisms where by Spirulina maxima ameliorates cognitive disorders induced by amyloid-ß 1-42 (Aß1-42) are not fully understood. In this study, we investigated whether a 70% ethanol extract of Spirulina maxima (SM70EE) ameliorated cognitive impairments induced by an intracerebroventricular injection of Aß1-42 in mice. SM70EE increased the step-through latency time in the passive avoidance test and decreased the escape latency time in the Morris water maze test in Aß1-42-injected mice. SM70EE reduced hippocampal Aß1-42 levels and inhibited amyloid precursor protein processing-associated factors in Aß1-42-injected mice. Additionally, acetylcholinesterase activity was suppressed by SM70EE in Aß1-42-injected mice. Hippocampal glutathione levels were examined to determine the effects of SM70EE on oxidative stress in Aß1-42-injected mice. SM70EE increased the levels of glutathione and its associated factors that were reduced in Aß1-42-injected mice. SM70EE also promoted activation of the brain-derived neurotrophic factor/phosphatidylinositol-3 kinase/serine/threonine protein kinase signaling pathway and inhibited glycogen synthase kinase-3ß phosphorylation. These findings suggested that SM70EE ameliorated Aß1-42-induced cognitive impairments by inhibiting the increased phosphorylation of glycogen synthase kinase-3ß caused by intracerebroventricular injection of Aß1-42 in mice.
Asunto(s)
Glucógeno Sintasa Quinasa 3 beta/metabolismo , Aprendizaje por Laberinto , Trastornos de la Memoria/tratamiento farmacológico , Extractos Vegetales/uso terapéutico , Spirulina/química , Acetilcolinesterasa/metabolismo , Péptidos beta-Amiloides/administración & dosificación , Péptidos beta-Amiloides/toxicidad , Animales , Glutatión/metabolismo , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Inyecciones Intraventriculares , Masculino , Trastornos de la Memoria/etiología , Ratones , Ratones Endogámicos ICR , Fragmentos de Péptidos/administración & dosificación , Fragmentos de Péptidos/toxicidad , Fosforilación , Extractos Vegetales/farmacología , Procesamiento Proteico-PostraduccionalRESUMEN
The cognitive effect of Artemisia argyi H. under liquid-state fermentation by Monascus purpureus (AAFM), which has cellular antioxidant activity and neuronal cell viability, on trimethyltin- (TMT-) induced learning and memory impairment in Institute of Cancer Research (ICR) mice was confirmed. Tests were conducted to determine the neuroprotective effects against H2O2-induced oxidative stress, and the results showed that AAFM has protective effects through the repression of mitochondrial injury and cellular membrane damage against H2O2-induced neurotoxicity. In animal experiments, such as the Y-maze, passive avoidance, and Morris water maze tests, AAFM also showed excellent ameliorating effects on TMT-induced cognitive dysfunction. After behavioral tests, brain tissues were extracted to assess damage to brain tissue. According to the experimental results, AAFM improved the cholinergic system by upregulating acetylcholine (ACh) contents and inhibiting acetylcholinesterase (AChE) activity. AAFM effectively improved the decline of the superoxide dismutase (SOD) level and the increase of the oxidized glutathione (GSH) ratio and lipid peroxidation (malondialdehyde (MDA) production) caused by TMT-induced oxidative stress. The occurrence of mitochondrial dysfunction and apoptosis was also decreased compared with the TMT group. Finally, quinic acid derivatives were identified as the major phenolic compounds in AAFM using ultra-performance liquid chromatography quadrupole-time-of-flight (UPLC-Q-TOF) MS analysis.
RESUMEN
The ameliorating effects of the ethyl acetate fraction from Dendropanax morbifera (EFDM) on cognitive impairment in high-fat diet (HFD)-induced diabetic mice were examined by measuring its possible pharmacological activities. Administration of EFDM (20 and 50mg/kg body weight) in HFD-induced diabetic mice significantly improved glucose tolerance status in the intraperitoneal glucose tolerance test (IPGTT). In animal experiments using Y-maze, passive avoidance and Morris water maze tests, the cognitive and behavioral disorders in HFD-induced diabetic mice were considerably recovered by regulating cholinergic systems, including acetylcholine (ACh) levels and acetylcholinesterase (AChE) inhibition, and antioxidant systems, including superoxide dismutase (SOD), glutathione (GSH), oxidized GSH, and malondialdehyde (MDA) levels. Furthermore, HFD-induced abnormal activity of mitochondria were also significantly protected by the improvement of the c-Jun N-terminal protein kinase (JNK) signaling pathway with phosphorylated JNK (p-JNK), phosphorylated insulin receptor substrate (p-IRS), serine/threonine protein kinase (Akt), phosphorylated Akt (p-Akt), and phosphorylated tau (p-tau). Finally, rutin, orientin, isoorientin, and luteolin-7-O-rutinoside as the main phenolics of EFDM were identified using ultra-performance liquid chromatography/quadrupole time of flight tandem mass spectrometry (UPLC-QTOF/MS(2)). These findings suggest that EFDM may have an effect as a multiple preventive substances to reduce diabetes-associated cognitive dysfunction.