RESUMO
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.
Assuntos
Disfunção Cognitiva/tratamento farmacológico , Kelp , Fármacos Neuroprotetores/administração & dosagem , Polissacarídeos/administração & dosagem , Taninos/administração & dosagem , Acetilcolina/metabolismo , Animais , Organismos Aquáticos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Colinérgicos/metabolismo , Modelos Animais de Doenças , Quimioterapia Combinada , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos ICR , Mitocôndrias/metabolismo , Fármacos Neuroprotetores/farmacologia , Fitoterapia , Polissacarídeos/farmacologia , Taninos/farmacologiaRESUMO
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).
Assuntos
Disfunção Cognitiva/prevenção & controle , Diospyros/química , Frutas/química , Extratos Vegetais/farmacologia , Tauopatias/prevenção & controle , Acetilcolina/metabolismo , Acetilcolinesterase/metabolismo , Peptídeos beta-Amiloides , Animais , Antioxidantes/metabolismo , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/metabolismo , Etanol/química , Aprendizagem em Labirinto/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Memória de Curto Prazo/efeitos dos fármacos , Camundongos Endogâmicos ICR , Fragmentos de Peptídeos , Extratos Vegetais/química , Espécies Reativas de Oxigênio/metabolismo , Tauopatias/induzido quimicamente , Tauopatias/metabolismo , Proteínas tau/metabolismoRESUMO
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.
Assuntos
Actinidia/química , Antioxidantes/farmacologia , Disfunção Cognitiva/tratamento farmacológico , Lipopolissacarídeos/efeitos adversos , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Acetilcolinesterase/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Encéfalo/metabolismo , Disfunção Cognitiva/induzido quimicamente , Células HT29 , Humanos , Inflamação/tratamento farmacológico , Interleucina-6 , Limosilactobacillus reuteri , Masculino , Camundongos , NF-kappa B/metabolismo , Fármacos Neuroprotetores/farmacologia , Superóxido DismutaseRESUMO
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.
Assuntos
1-Metil-3-Isobutilxantina/farmacologia , Melaninas/biossíntese , Extratos Vegetais/farmacologia , Sorghum/química , Animais , Antioxidantes/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Melanoma Experimental , Camundongos , Extratos Vegetais/química , Solventes , Espectrometria de Massas em TandemRESUMO
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.
Assuntos
Artemisia , Disfunção Cognitiva/tratamento farmacológico , Insulisina/efeitos dos fármacos , Extratos Vegetais/farmacologia , Ácido Quínico/análogos & derivados , Peptídeos beta-Amiloides/efeitos dos fármacos , Peptídeos beta-Amiloides/metabolismo , Apoptose/efeitos dos fármacos , Artemisia/química , Artemisia/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/fisiopatologia , Dieta Hiperlipídica/efeitos adversos , Insulisina/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fitoterapia , Plantas Medicinais/metabolismo , Ácido Quínico/farmacologiaRESUMO
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.
Assuntos
Transtornos do Sistema Nervoso Induzidos por Álcool/tratamento farmacológico , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Aralia/química , Encéfalo/metabolismo , Neurônios/metabolismo , Fármacos Neuroprotetores/farmacologia , Extratos Vegetais/farmacologia , Acetatos/química , Transtornos do Sistema Nervoso Induzidos por Álcool/metabolismo , Transtornos do Sistema Nervoso Induzidos por Álcool/patologia , Animais , Antioxidantes/química , Encéfalo/patologia , Linhagem Celular , Doença Crônica , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Memória/efeitos dos fármacos , Camundongos , Neurônios/patologia , Fármacos Neuroprotetores/química , Extratos Vegetais/química , Espécies Reativas de Oxigênio/metabolismoRESUMO
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.
Assuntos
Transtornos Cognitivos/tratamento farmacológico , Cognição/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos , Obesidade/psicologia , Extratos Vegetais/farmacologia , Células 3T3-L1 , Animais , Peso Corporal/efeitos dos fármacos , Transtornos Cognitivos/etiologia , Intolerância à Glucose/tratamento farmacológico , Intolerância à Glucose/etiologia , Resistência à Insulina , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/etiologiaRESUMO
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.
Assuntos
Peptídeos beta-Amiloides/metabolismo , Disfunção Cognitiva/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Fragmentos de Peptídeos/metabolismo , Óleos de Plantas/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Chá , Animais , Antioxidantes/química , Antioxidantes/uso terapêutico , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/patologia , Peróxido de Hidrogênio/metabolismo , Camundongos Endogâmicos ICR , Fármacos Neuroprotetores/química , Estresse Oxidativo/efeitos dos fármacos , Células PC12 , Óleos de Plantas/química , Ratos , Sementes/química , Chá/químicaRESUMO
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.