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
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
Ulmus macrocarpa Hance as an oriental medicinal plant has shown enormous potential for the treatment of several metabolic disorders in Korea. Hyperlipidemia, which is characterized by the excess accumulation of lipid contents in the bloodstream, may lead to several cardiovascular diseases. Therefore, in this study, anti-hyperlipidemic potential of U. macrocarpa water extract (UME) was examined in vitro and in vivo using HepG2 cells and experimental rats, respectively. The hyperlipidemia in experimental rats was induced by the high-cholesterol diet (HCD) followed by oral administration of various concentrations (25, 50 and 100 mg/kg) of UME for 6 weeks. As a result, the UME significantly improved the biochemical parameters such as increased the level of triglyceride, total cholesterol, and low-density lipoprotein cholesterol as well as reduced the high-density lipoprotein cholesterol in the HCD-fed rats. In addition, UME also prevented lipid accumulation through regulating AMPK activity and lipid metabolism proteins (ACC, SREBP1 and HMGCR) in the HCD-fed rats as compared to the controls. Moreover, similar pattern of gene expression levels was confirmed in oleic acid (OA)-treated HepG2 cells. Taken together, our results indicate that UME prevents hyperlipidemia via activating the AMPK pathway and regulates lipid metabolism. Thus, based on the above findings, it is estimated that UME could be a potential therapeutic agent for preventing the hyperlipidemia.
Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Dieta Hiperlipídica/efeitos adversos , Regulação da Expressão Gênica/efeitos dos fármacos , Hiperlipidemias/tratamento farmacológico , Metabolismo dos Lipídeos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Ulmus/química , Animais , Células Hep G2 , Humanos , Hiperlipidemias/etiologia , Hiperlipidemias/metabolismo , Hiperlipidemias/patologia , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
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.
Assuntos
Acetatos/farmacologia , Cognição/efeitos dos fármacos , Diospyros/química , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Neurônios/efeitos dos fármacos , Extratos Vegetais/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Contagem de Células , Disfunção Cognitiva , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Neurônios/patologia , Fármacos Neuroprotetores/farmacologia , Células Piramidais/efeitos dos fármacos , Células Piramidais/metabolismo , Células Piramidais/patologiaRESUMO
Recently, research on the processing of raw functional materials with the aim of improving various physiological activities has been conducted. In this study, we investigated the antioxidant activity of royal jelly (RJ) hydrolysates obtained from three commercial proteases. Enzyme-treated royal jelly (ERJ), in which the RJ hydrolysates were converted into easy-to-absorb shorter chain monomers through the removal of two known allergen proteins, showed no difference in the content of (E)-10-hydroxydec-2-enoicacid (10-HDA) or the freshness parameter and showed a significant increase in total free amino acid content. The antioxidant activity of ERJ was determined by 1,1-diphenyl-2-picrylhydrazyl (DPPH) and chemical assays. The ERJ showed about 80% DPPH-radical scavenging activity at same concentration of ascorbic acid. The antioxidant effect of ERJ was confirmed to be due to reduction of intracellular reactive oxidative species (ROS) and nitric oxide (NO) production in LPS-treated macrophages. Moreover, ERJ significantly increased the activity of the antioxidant enzyme superoxide dismutase (SOD) and the level of the antioxidant glutathione (GSH) in a dose-dependent manner. Interestingly, these antioxidant activities of ERJ were stronger than those of non-treated RJ. These findings indicate that ERJ has high potential as an antioxidant agent for use in human and animal diets.