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To probe the functions of Aster glehni (AG) extract containing various caffeoylquinic acids on dyslipidemia, obesity, and skeletal muscle-related diseases focused on the roles of skeletal muscle, we measured the levels of biomarkers involved in oxidative phosphorylation and type change of skeletal muscle in C2C12 cells and skeletal muscle tissues from apolipoprotein E knockout (ApoE KO) mice. After AG extract treatment in cell and animal experiments, western blotting, immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA) were used to estimate the levels of proteins that participated in skeletal muscle type change and oxidative phosphorylation. AG extract elevated protein expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), phosphorylated 5'-AMP-activated protein kinase (p-AMPK), peroxisome proliferator-activated receptor beta/delta (PPARß/δ), myoblast determination protein 1 (MyoD), and myoglobin in skeletal muscle tissues. Furthermore, it elevated the ATP concentration. However, protein expression of myostatin was decreased by AG treatment. In C2C12 cells, increments of MyoD, myoglobin, myosin, ATP-producing pathway, and differentiation degree by AG were dependent on PPARß/δ and caffeoylquinic acids. AG extract can contribute to the amelioration of skeletal muscle inactivity and sarcopenia through myogenesis in skeletal muscle tissues from ApoE KO mice, and function of AG extract may be dependent on PPARß/δ, and the main functional constituents of AG are trans-5-O-caffeoylquinic acid and 3,5-O-dicaffeoylquinic acid. In addition, in skeletal muscle, AG has potent efficacies against dyslipidemia and obesity through the increase of the type 1 muscle fiber content to produce more ATP by oxidative phosphorylation in skeletal muscle tissues from ApoE KO mice.
Assuntos
Camundongos Knockout , Desenvolvimento Muscular , Músculo Esquelético , PPAR delta , PPAR beta , Extratos Vegetais , Ácido Quínico , Animais , Camundongos , Ácido Quínico/análogos & derivados , Ácido Quínico/farmacologia , Extratos Vegetais/farmacologia , PPAR beta/metabolismo , PPAR beta/genética , Músculo Esquelético/metabolismo , Músculo Esquelético/efeitos dos fármacos , Desenvolvimento Muscular/efeitos dos fármacos , PPAR delta/metabolismo , PPAR delta/genética , Masculino , Apolipoproteínas E/genética , Apolipoproteínas E/metabolismo , Humanos , Proteína MyoD/metabolismo , Proteína MyoD/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Camundongos Endogâmicos C57BL , Proteínas Quinases Ativadas por AMP/metabolismoRESUMO
Humulus japonicus has been used to treat obesity, hypertension, and nonalcoholic fatty liver and to alleviate inflammation and oxidative stress. In the present study, we aimed to investigate the effects of H. japonicus ethanol extracts (HE) and luteolin 7-O-ß-d-glucoside (LU), which is identified as a major active component of H. japonicus, on ethanol-induced oxidative stress and lipid accumulation in primary hepatocytes. Mouse primary hepatocytes were treated with HE and stimulated with ethanol. The MTT test was used to determine cell viability. By using Western blotting, the effects of HE on the expression of different proteins were investigated. Experimental mice were given a 5% alcohol liquid Lieber-DeCarli diet to induce alcoholic fatty liver. We found that both HE and LU individually attenuated ethanol-induced lipid accumulation, lipogenic protein expression, and cellular oxidative stress in hepatocytes. Treatment with HE or LU increased PPARα and SOD1 expression and catalase activity in a dose-dependent manner. Small interfering RNA of PPARα reduced the effects of HE on oxidative stress, lipid metabolism, and levels of antioxidants. We also observed that orally administered HE treatment alleviated hepatic steatosis in a diet containing ethanol-fed mice. This study suggests HE as a functional food that can improve hepatic steatosis, thereby preventing hepatic injury caused by alcohol consumption.
Assuntos
Humulus , Hepatopatia Gordurosa não Alcoólica , Animais , Camundongos , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Etanol/metabolismo , Hepatócitos/metabolismo , Lipídeos , Fígado/metabolismo , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Estresse Oxidativo , PPAR alfa/genética , PPAR alfa/metabolismoRESUMO
Humulus japonicus (HJ) is an herbal medicine, which has been reported as being antioxidative and anti-inflammatory. The present study aimed to investigate the effect of oral administration of HJ water extract (HJW) on cognitive function through the cholinergic system in Alzheimer's disease (AD) mouse models. Institute of Cancer Research mice injected with beta-amyloid (Aß) (1-42) (i.c.v.) and APP/PS1 transgenic (TG) mice were orally administered with HJW at 500 mg/kg/day for 3 weeks. Aß-injected mice and APP/PS1 TG mice showed cognitive dysfunction, which was evaluated by various behavioral tests. HJW treatment significantly attenuated memory impairments in Aß-injected mice and APP/PS1 TG mice. Aß injection decreased acetylcholine (ACh) concentrations and choline acetyltransferase (ChAT) activity, and increased acetylcholinesterase (AChE) activity. These cholinergic impairments were also found in APP/PS1 TG mice. HJW significantly attenuated cholinergic alterations in Aß-injected mice and TG mice. In addition, HJW significantly decreased Aß plaque deposition in the cerebral cortex and hippocampus of TG mice. Therefore, the present study demonstrated that HJW protected against AD-related memory impairments via enhancing the cholinergic system and inhibiting Aß plaque deposition.
Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humulus , Animais , Camundongos , Doença de Alzheimer/tratamento farmacológico , Acetilcolinesterase , Colina O-Acetiltransferase/metabolismo , Colina O-Acetiltransferase/farmacologia , Acetilcolina , Peptídeos beta-Amiloides/metabolismo , Placa Amiloide , Camundongos Transgênicos , Modelos Animais de Doenças , Hipocampo , Transtornos da Memória , Água , Colinérgicos/farmacologiaRESUMO
Brain-computer interface (BCI) is challenging to use in practice due to the inter/intra-subject variability of electroencephalography (EEG). The BCI system, in general, necessitates a calibration technique to obtain subject/session-specific data in order to tune the model each time the system is utilized. This issue is acknowledged as a key hindrance to BCI, and a new strategy based on domain generalization has recently evolved to address it. In light of this, we've concentrated on developing an EEG classification framework that can be applied directly to data from unknown domains (i.e. subjects), using only data acquired from separate subjects previously. For this purpose, in this paper, we proposed a framework that employs the open-set recognition technique as an auxiliary task to learn subject-specific style features from the source dataset while helping the shared feature extractor with mapping the features of the unseen target dataset as a new unseen domain. Our aim is to impose cross-instance style in-variance in the same domain and reduce the open space risk on the potential unseen subject in order to improve the generalization ability of the shared feature extractor. Our experiments showed that using the domain information as an auxiliary network increases the generalization performance. Clinical relevance-This study suggests a strategy to improve the performance of the subject-independent BCI systems. Our framework can help to reduce the need for further calibration and can be utilized for a range of mental state monitoring tasks (e.g. neurofeedback, identification of epileptic seizures, and sleep disorders).
Assuntos
Interfaces Cérebro-Computador , Neurorretroalimentação , Calibragem , Eletroencefalografia/métodos , HumanosRESUMO
Resolvin D3 (RD3), an endogenous lipid mediator derived from omega-3 fatty acids, has been documented to attenuate inflammation in various disease models. Although it has been reported that omega-3 fatty acids attenuate metabolic disorders, the roles of RD3 in insulin signaling in skeletal muscle and hepatic lipid metabolism remain unclear. In the current study, we examined the role of RD3 in skeletal muscle insulin resistance and hepatic steatosis using in vitro and in vivo obesity models. In mouse primary hepatocytes, RD3 treatment reduced lipid accumulation and the production of lipogenic proteins (processed SREBP1 and SCD1) while improving insulin signaling in C2C12 myocytes. Furthermore, RD3 treatment ameliorated palmitate-induced ER stress markers (phospho-eIF2α and CHOP) in mouse primary hepatocytes and C2C12 myocytes. Treatment with RD3 increased phospho-AMPK expression and autophagy markers (LC3 conversion, p62 degradation, and autophagosome formation). AMPK siRNA or 3-MA reduced the effects of RD3 on C2C12 myocytes and mouse primary hepatocytes treated with palmitate. Finally, we confirmed the therapeutic effects of RD3 on skeletal muscle insulin resistance and hepatic lipid metabolism in high-fat diet (HFD)-fed mice. In vivo transfection-mediated suppression of AMPK restored all these changes in animal models. The results of the present study suggest that RD3 alleviates insulin resistance in skeletal muscle and hepatic steatosis via AMPK/autophagy signaling and provides an effective and safe therapeutic approach for treating metabolic disorders, including insulin resistance, type 2 diabetes, and NAFLD.
Assuntos
Diabetes Mellitus Tipo 2 , Ácidos Graxos Ômega-3 , Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Autofagia , Diabetes Mellitus Tipo 2/metabolismo , Dieta Hiperlipídica , Estresse do Retículo Endoplasmático , Ácidos Graxos Ômega-3/metabolismo , Ácidos Graxos Insaturados/metabolismo , Insulina/metabolismo , Metabolismo dos Lipídeos , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Músculo Esquelético , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Palmitatos/metabolismo , Palmitatos/farmacologia , Palmitatos/uso terapêuticoRESUMO
Chronic stress can cause the gastrointestinal disorders characterized by an altered bowel movement and abdominal pain. Studies have shown that Humulus japonicus extract (HJE) has anti-inflammatory and antidiarrheal effects, and Phragmites rhizoma extract (PEP) has antioxidative and antistress effects. The present study aimed to investigate the possible effects of HJE and PEP in rat models with stress-induced gastrointestinal dysfunctions. The rats were exposed to water avoidance stress (WAS, 1 h/day) for 10 days to induce gastrointestinal disorders. We found that WAS significantly increased fecal pellet output during 1 h stress, gastric emptying, colonic contractility, and permeability compared to the normal rats. Pretreatment with HJE and PEP (0.25 and 0.5 mL/kg, both administered separately) improved the increased gastric emptying and colonic contractility induced by electrical field stimulation, acetylcholine, and serotonin and also alleviated the increased colonic permeability. HJE and PEP also increased the claudin-1 and occludin expressions, reduced by WAS. WAS increased the concentration of TNF-α and TBARS and reduced FRAP. HJE and PEP recovered these effects. HJE and PEP improved the gastrointestinal disorders induced by WAS by upregulating the tight junction protein, possibly acting on cholinergic and serotonergic receptors to abolish the colonic hypercontractility and hyperpermeability and degradation of inflammatory cytokines via an antioxidant effect.
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A new kind of sequence-to-sequence model called a transformer has been applied to electroencephalogram (EEG) systems. However, the majority of EEG-based transformer models have applied attention mechanisms to the temporal domain, while the connectivity between brain regions and the relationship between different frequencies have been neglected. In addition, many related studies on imagery-based brain-computer interface (BCI) have been limited to classifying EEG signals within one type of imagery. Therefore, it is important to develop a general model to learn various types of neural representations. In this study, we designed an experimental paradigm based on motor imagery, visual imagery, and speech imagery tasks to interpret the neural representations during mental imagery in different modalities. We conducted EEG source localization to investigate the brain networks. In addition, we propose the multiscale convolutional transformer for decoding mental imagery, which applies multi-head attention over the spatial, spectral, and temporal domains. The proposed network shows promising performance with 0.62, 0.70, and 0.72 mental imagery accuracy with the private EEG dataset, BCI competition IV 2a dataset, and Arizona State University dataset, respectively, as compared to the conventional deep learning models. Hence, we believe that it will contribute significantly to overcoming the limited number of classes and low classification performances in the BCI system.
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It has been recognized that serotonin 2A receptor (5-HT2A) agonist 2,5-dimethoxy-4-iodo-amphetamine (DOI) impairs serotonergic homeostasis. However, the mechanism of DOI-induced serotonergic behaviors remains to be explored. Moreover, little is known about therapeutic interventions against serotonin syndrome, although evidence suggests that ginseng might possess modulating effects on the serotonin system. As ginsenoside Re (GRe) is well-known as a novel antioxidant in the nervous system, we investigated whether GRe modulates 5-HT2A receptor agonist DOI-induced serotonin impairments. We proposed that protein kinase Cδ (PKCδ) mediates serotonergic impairments. Treatment with GRe or 5-HT2A receptor antagonist MDL11939 significantly attenuated DOI-induced serotonergic behaviors (i.e., overall serotonergic syndrome behaviors, head twitch response, hyperthermia) by inhibiting mitochondrial translocation of PKCδ, reducing mitochondrial glutathione peroxidase activity, mitochondrial dysfunction, and mitochondrial oxidative stress in wild-type mice. These attenuations were in line with those observed upon PKCδ inhibition (i.e., pharmacologic inhibitor rottlerin or PKCδ knockout mice). Furthermore, GRe was not further implicated in attenuation mediated by PKCδ knockout in mice. Our results suggest that PKCδ is a therapeutic target for GRe against serotonergic behaviors induced by DOI.
Assuntos
Ginsenosídeos/farmacologia , Proteína Quinase C-delta/metabolismo , Antagonistas da Serotonina/farmacologia , Síndrome da Serotonina/prevenção & controle , Acetofenonas/farmacologia , Anfetaminas/toxicidade , Animais , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/fisiologia , Benzopiranos/farmacologia , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Piperidinas/farmacologia , Proteína Quinase C-delta/deficiência , Proteína Quinase C-delta/genética , Inibidores de Proteínas Quinases/farmacologia , Serotonina/fisiologia , Agonistas do Receptor de Serotonina/farmacologia , Síndrome da Serotonina/induzido quimicamente , Síndrome da Serotonina/fisiopatologiaRESUMO
Attention deficit hyperactivity disorder (ADHD) is a psychiatric disorder commonly found in children, which is recognized by hyperactivity and aggressive behavior. It is known that the pathophysiology of ADHD is associated with neurobiological dysfunction. Although psychostimulants are recognized as the therapeutic drugs of choice for ADHD patients, the side effects might be of great concern. Ginkgo biloba is a promising herbal, complementary supplement that may modulate the neuronal system in an ADHD-like condition. The beneficial effect of Ginkgo biloba on ADHD-like symptoms may be related to the modulation of the system by novel molecular mechanisms. Ginkgo biloba is known to modulate dopamine, serotonin, and norepinephrine signaling. Flavonoid glycosides and terpene trilactones are the two major phytochemical components present in the Ginkgo biloba preparations, which can exhibit antioxidant and neuroprotective activities. The pharmacological mechanisms of the phytochemical components may also contribute to the neuroprotective activity of Ginkgo biloba. In this review, we have summarized recent findings on the potential of various Ginkgo biloba preparations to treat ADHD-like symptoms. In addition, we have discussed the pharmacological mechanisms mediated by Ginkgo biloba against an ADHD-like condition.
Assuntos
Antioxidantes/química , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Ginkgo biloba/química , Fármacos Neuroprotetores/química , Extratos Vegetais/farmacologia , Animais , Antioxidantes/farmacologia , Dopamina/metabolismo , Descoberta de Drogas , Flavonoides/química , Glicosídeos/química , Humanos , Fármacos Neuroprotetores/farmacologia , Norepinefrina/metabolismo , Serotonina/metabolismo , Transdução de Sinais , Terpenos/químicaRESUMO
Glutathione peroxidase (GPx) acts in co-ordination with other signaling molecules to exert its own antioxidant role. We have demonstrated the protective effects of GPx,/GPx-1, a selenium-dependent enzyme, on various neurodegenerative disorders (i.e., Parkinson's disease, Alzheimer's disease, cerebral ischemia, and convulsive disorders). In addition, we summarized the recent findings indicating that GPx-1 might play a role as a neuromodulator in neuropsychiatric conditions, such as, stress, bipolar disorder, schizophrenia, and drug intoxication. In this review, we attempted to highlight the mechanistic scenarios mediated by the GPx/GPx-1 gene in impacting these neurodegenerative and neuropsychiatric disorders, and hope to provide new insights on the therapeutic interventions against these disorders.
Assuntos
Glutationa Peroxidase/metabolismo , Transtornos Mentais/metabolismo , Doenças Neurodegenerativas/metabolismo , Neuroproteção/fisiologia , Animais , Azóis/uso terapêutico , Glutationa Peroxidase/genética , Humanos , Raios Infravermelhos , Isoindóis , Transtornos Mentais/tratamento farmacológico , Transtornos Mentais/terapia , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neurodegenerativas/terapia , Óxido Nítrico Sintase Tipo III/metabolismo , Compostos Organosselênicos/uso terapêutico , Fototerapia , Proteína Quinase C-delta/metabolismo , Receptor Muscarínico M1/metabolismo , Regulação para Cima/efeitos da radiação , Glutationa Peroxidase GPX1RESUMO
Inflammation and endoplasmic reticulum (ER) stress have been documented to contribute to the development of atherosclerosis. Ginsenoside Rb2 has been reported to exhibit antidiabetic effects. However, the effects of Rb2 on atherosclerotic responses such as inflammation and ER stress in endothelial cells and monocytes remain unclear. In this study, the expression of inflammation and ER stress markers was determined using a Western blotting method. Concentrations of tumor necrosis factor alpha (TNF[Formula: see text]) and monocyte chemoattractant protein-1 (MCP-1) in culture media were assessed by enzyme-linked immunosorbent assay (ELISA) and apoptosis was evaluated by a cell viability assay and a caspase-3 activity measurement kit. We found that exposure of HUVECs and THP-1 monocytes to Rb2 attenuated inflammation and ER stress, resulting in amelioration of apoptosis and THP-1 cell adhesion to HUVECs under lipopolysaccharide (LPS) condition. Increased AMPK phosphorylation and heme oxygenase (HO)-1 expression, including GPR120 expression were observed in Rb2-treated HUVECs and THP-1 monocytes. Downregulation of both, AMPK phosphorylation and HO-1expression rescued these observed changes. Furthermore, GPR120 siRNA mitigated Rb2-induced AMPK phosphorylation. These results suggest that Rb2 inhibits LPS-mediated apoptosis and THP-1 cell adhesion to HUVECs by GPR120/AMPK/HO-1-associated attenuating inflammation and ER stress. Therefore, Rb2 can be used as a potential therapeutic molecule for treatment of atherosclerosis.
Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Aterosclerose/tratamento farmacológico , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Estresse do Retículo Endoplasmático/genética , Ginsenosídeos/farmacologia , Ginsenosídeos/uso terapêutico , Lipopolissacarídeos/efeitos adversos , Fitoterapia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Apoptose/efeitos dos fármacos , Apoptose/genética , Aterosclerose/induzido quimicamente , Aterosclerose/genética , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Expressão Gênica/efeitos dos fármacos , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Células Endoteliais da Veia Umbilical Humana , Humanos , Inflamação , Fosforilação/efeitos dos fármacos , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Células THP-1 , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BACKGROUND: Taekkyon, a Korean form of martial arts, has been trained for a long period. However, it is not yet known whether the Taekkyon exercise has better effects on functional mobility or balance in older adults than other types of well-investigated exercise programs such as Tai Chi (TC). OBJECTIVE: This study aimed to compare the effects of TC and Taekkyon exercise programs on the lower-extremity strength, balance, and gait ability of community-dwelling older women as a fall prevention method. METHODS: Community-dwelling older women were randomly allocated into the TC group (n1= 23) and the Taekkyon group (n2= 23). Both groups completed 1 h of either TC or Taekkyon exercises twice weekly for 12 consecutive weeks (24 sessions in total). We measured the Timed Up and Go test (TUG), Functional Reach test (FR), one-leg standing test (OLS), Five Times Sit-to-Stand test (5 × STS), 30 Second Sit-to-Stand test (30 s STS), and spatiotemporal gait parameters (gait velocity, step length, step width, stride time, and cadence) before and after the intervention. RESULTS: Both groups similarly showed statistically significant improvements in balance (TUG, FR, and OLS), lower-extremity strength (5 × STS and 30 s STS), and spatiotemporal gait parameters except for step width (P< 0.05). Moreover, the TC group showed greater improvement in the OLS test than the Taekkyon group (P< 0.05). CONCLUSIONS: The results from this study support the efficacy of the TC and Taekkyon exercise programs at improving mobility in this population of older women. However, this study did not clarify which exercise program is more effective as general balance and mobility training program for older women.
Assuntos
Terapia por Exercício/métodos , Marcha/fisiologia , Artes Marciais , Equilíbrio Postural/fisiologia , Amplitude de Movimento Articular/fisiologia , Tai Chi Chuan , Acidentes por Quedas/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Exercício Físico/fisiologia , Feminino , Humanos , Vida Independente , Método Simples-Cego , Estudos de Tempo e MovimentoRESUMO
An aqueous extract of Humulus japonicus (AH) has been documented to ameliorate hypertension and non-alcoholic fatty liver disease (NAFLD). Here, we investigated the effects of an aqueous extract of AH on thermogenesis and palmitate-induced oxidative stress in adipocytes. To verify the effect of AH on browning, we measured the expression levels of specific markers in 3T3-L1 adipocytes using qPCR and Western blotting, respectively. To assess the role of oxidative stress, cells were stained with DCFDA and observed by fluorescence microscopy. AH increased the expression of brown adipose tissue-specific markers. Additionally, it induced fatty acid oxidation and lipolysis and suppressed both lipogenic markers and lipid accumulation. Furthermore, AH ameliorated hydrogen peroxide-induced oxidative stress. Enhanced expression of these markers contributed to fat browning, fatty acid oxidation and lipolysis of 3T3-L1 adipocytes via the AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor delta (PPARδ) signaling pathways. Moreover, AMPK and PPARδ resulting in protective effects of AH against oxidative stress. In sum, AH could promote the browning, lipolysis and thermogenesis in 3T3-L1 adipocytes and would suppress the hydrogen peroxide-induced oxidative stress and lipogenesis during differentiation. We therefore suggest that AH could be used as a potential candidate for treating obesity and related metabolic disorders.
Assuntos
Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Termogênese/efeitos dos fármacos , Células 3T3-L1 , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Ácidos Graxos/metabolismo , Humulus , Lipogênese/efeitos dos fármacos , Lipólise/efeitos dos fármacos , Camundongos , Microscopia de Fluorescência , PPAR delta/metabolismoRESUMO
Our study aimed to investigate the effects of the polysaccharide-rich extract of Phragmites rhizoma (PEP) against water immersion restraint (WIR) stress and forced swimming-induced fatigue. Exposure to WIR stress significantly increased the ulcer index, bleeding score, the weight of the adrenal gland, blood glucose concentrations, total cholesterol, cortisol, and creatine kinase (CK). The weight of the spleen decreased significantly. In addition, myeloperoxidase (MPO) and thiobarbituric acid-reactive substance (TBARS) were significantly upregulated by WIR stress. The antioxidative factors such as glutathione (GSH) and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) in the stomach were decreased by WIR stress. Alterations induced by WIR stress were effectively reversed by pretreatment with PEP. The swimming endurance capacity of mice was significantly prolonged by the oral administration of PEP. Swimming-induced fatigue significantly reduced the body weight; however, the injection of PEP inhibited the decrease of body weight. The PEP-treated group had significantly lower CK levels in plasma, an indicator of muscle damage. These results indicated that PEP has anti-stress and anti-fatigue effects, which are mediated by suppressing the hyperactivation of the hypothalamus-pituitary-adrenal axis, and antagonism of the oxidative damages induced by WIR stress and prolonged swimming times.
Assuntos
Fadiga/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Poaceae/química , Polissacarídeos/administração & dosagem , Animais , Catalase/metabolismo , Modelos Animais de Doenças , Fadiga/metabolismo , Fadiga/fisiopatologia , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Peroxidase/metabolismo , Extratos Vegetais/química , Polissacarídeos/química , Rizoma/química , Estresse Fisiológico/efeitos dos fármacos , Superóxido Dismutase/metabolismo , NataçãoRESUMO
Serotonin syndrome is an adverse reaction due to increased serotonin (5-hydroxytryptophan: 5-HT) concentrations in the central nervous system (CNS). The full 5-HT1A receptor (5-HT1AR) agonist (±)-8-hydroxy-dipropylaminotetralin (8-OH-DPAT) has been recognized to elicit traditional serotonergic behaviors. Treatment with 8-OH-DPAT selectively increased PKCδ expression out of PKC isoforms and 5-HT turnover rate in the hypothalamus of wild-type mice. Treatment with 8-OH-DPAT resulted in oxidative burdens, co-immunoprecipitation of 5-HT1AR and PKCδ, and phosphorylation and membrane translocation of p47phox. Importantly, p47phox also interacted with 5-HT1AR or PKCδ in the presence of 8-OH-DPAT. Consistently, the interaction and oxidative burdens were attenuated by 5-HT1AR antagonism (i.e., WAY100635), PKCδ inhibition (i.e., rottlerin and genetic depletion of PKCδ), or NADPH oxidase/p47phox inhibition (i.e., apocynin and genetic depletion of p47phox). However, WAY100635, apocynin, or rottlerin did not exhibit any additive effects against the protective effect by inhibition of PKCδ or p47phox. Furthermore, apocynin, rottlerin, or WAY100635 also significantly protected from pro-inflammatory/pro-apoptotic changes induced by 8-OH-DPAT. Therefore, we suggest that 8-OH-DPAT-induced serotonergic behaviors requires oxidative stress, pro-inflammatory, and pro-apoptotic changes, that PKCδ or p47phox mediates the serotonergic behaviors induced by 8-OH-DPAT, and that the inhibition of PKCδ-dependent p47phox activation is critical for protecting against serotonergic behaviors.
Assuntos
NADPH Oxidases/metabolismo , Proteína Quinase C-delta/metabolismo , Receptor 5-HT1A de Serotonina/metabolismo , Agonistas do Receptor 5-HT1 de Serotonina/administração & dosagem , Síndrome da Serotonina/tratamento farmacológico , Serotonina/metabolismo , 8-Hidroxi-2-(di-n-propilamino)tetralina , Animais , Comportamento Animal/efeitos dos fármacos , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , NADPH Oxidases/genética , Fosforilação/efeitos dos fármacos , Ligação Proteica , Proteína Quinase C-delta/genética , Receptor 5-HT1A de Serotonina/genética , Síndrome da Serotonina/genética , Síndrome da Serotonina/metabolismo , Síndrome da Serotonina/psicologiaRESUMO
In this study, the effects of Humulus japonicus (HJ) aqueous extract on 3T3-L1 preadipocytes and HepG2 cells (in vitro model) as well as on C57BL/6 mice fed on high-fat diet (HFD) (in vivo model) were evaluated. Mice fed on HFD for 12-weeks were taken the HJ water extract (HJW) at various doses, 50, 150, and 250 mg/kg, orally for 8 weeks. We have noticed the accumulation of fat globules in preadipocytes and HepG2 cells using Oil Red O staining. In addition, supplementation with HJW considerably inhibited the weight gain, lipid accumulation, and adipogenesis and decreased the size of subcutaneous adipocytes in 3T3-L1 adipocytes. Furthermore, treatment with HJW improved hyperlipidemia via decreasing the levels of serum triglyceride (TG) and low-density lipoproteins as well as the atherogenic index. Supplementation with HJW could attenuate HFD-induced lipid accumulation, increase the mRNA expressions of fatty acid synthase (FAS) and stearoyl-CoA desaturase (SCD1), and would elevate the levels of serum aspartate aminotransferase and alanine aminotransferase in mice liver. The levels of TG and FAS mRNA in HepG2 cells treated with palmitate were reduced in a dose-dependent manner. In sum, HJW could alleviate the HFD-induced obesity and decrease the dyslipidemia profiles; the keys that could contribute to cardiovascular and nonalcoholic liver diseases.
Assuntos
Fármacos Antiobesidade/administração & dosagem , Humulus/química , Hiperlipidemias/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Obesidade/tratamento farmacológico , Adipogenia/efeitos dos fármacos , Animais , Dieta Hiperlipídica/efeitos adversos , Ácido Graxo Sintases/genética , Ácido Graxo Sintases/metabolismo , Humanos , Hiperlipidemias/genética , Hiperlipidemias/metabolismo , Hiperlipidemias/fisiopatologia , Lipoproteínas LDL/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Hepatopatia Gordurosa não Alcoólica/metabolismo , Obesidade/genética , Obesidade/metabolismo , Obesidade/fisiopatologia , PPAR gama/genética , PPAR gama/metabolismo , Estearoil-CoA Dessaturase/genética , Estearoil-CoA Dessaturase/metabolismo , Triglicerídeos/sangueRESUMO
Obesity is the most common metabolic disease in developed countries and has become a global epidemic in recent years. Obesity is associated with various metabolic abnormalities, including glucose intolerance, insulin resistance, type 2 diabetes, dyslipidemia, and hypertension. Leaves from the plant Dendropanax morbiferus are beneficial to health as they contain high levels of vitamin C and tannin. There have been seminal studies on the anticancer, antimicrobial, antidiabetes, and antihyperglycemic effects of treatments with D. morbiferus trees. Herein, we investigated the toxicity of D. morbiferus water (DLW) extracts in vitro, and demonstrated no toxicity at 5-500 µg/mL in 24-72-h experiments with 3T3-L1 cells. The DLW increased cell viability at 48 h and inhibited adipogenesis in 3T3-L1 cells by reducing intracellular triglyceride levels and glucose uptake. In addition, mRNA and protein expression levels of adipogenesis-related genes were lowered by DLW, suggesting antiobesity effects in mouse 3T3-L1 cells. Because few studies have demonstrated cholesterol-lowering effects of D. morbiferus, we investigated the activities of adipogenic transcriptional factors following treatments of 3T3-L1 cells with D. morbiferus and observed increased CEBPα, CEBPß, PPARγ, and SREBP1 activities in the cells, indicating that DLW extracts inhibit adipogenesis.
Assuntos
Células 3T3-L1/efeitos dos fármacos , Fármacos Antiobesidade/farmacologia , Araliaceae , Obesidade/tratamento farmacológico , Extratos Vegetais/farmacologia , Células 3T3-L1/metabolismo , Animais , Fármacos Antiobesidade/uso terapêutico , Colesterol/metabolismo , Camundongos , Fitoterapia , Extratos Vegetais/uso terapêutico , Triglicerídeos/metabolismoRESUMO
Herein we describe fluorescence resonance energy transfer (FRET) for a pH/redox-activatable fluorescent carbon dot (FNP) to realize "off-on" switched imaging-guided controllable photothermal therapy (PTT). The FNP is a carbonized self-crosslinked polymer that allows IR825 loading (FNP[IR825]) via hydrophobic interactions for cancer therapy. Fluorescence bioimaging was achieved by the internalization of FNP(IR825) into tumor cells, wherein glutathione (GSH) disulfide bonds are reduced, and benzoic imine groups are cleaved under acidic conditions. The release of IR825 from the FNP core in this system may be used to efficiently control PTT-mediated cancer therapy via its photothermal conversion after near-infrared (NIR) irradiation. In vitro and in vivo cellular uptake studies revealed efficient uptake of FNP(IR825) by tumor cells to treat the disease site. In this way we demonstrated in mice that our smart nanocarrier can effectively kill tumor cells under exposure to a NIR laser, and that the particles are biocompatible with various organs. This platform responds sensitively to the exogenous environment inside the cancer cells and may selectively induce the release of PTT-mediated cytotoxicity. Furthermore, this platform may be useful for monitoring the elimination of cancer cells through the fluorescence on/off switch, which can be used for various applications in the field of cancer cell therapy and diagnosis.
Assuntos
Benzoatos/uso terapêutico , Corantes/uso terapêutico , Preparações de Ação Retardada/química , Indóis/uso terapêutico , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Pontos Quânticos/química , Animais , Benzoatos/administração & dosagem , Carbono/química , Linhagem Celular Tumoral , Corantes/administração & dosagem , Cães , Feminino , Transferência Ressonante de Energia de Fluorescência/métodos , Humanos , Concentração de Íons de Hidrogênio , Hipertermia Induzida/métodos , Indóis/administração & dosagem , Raios Infravermelhos , Células Madin Darby de Rim Canino , Camundongos Endogâmicos BALB C , Camundongos Nus , Imagem Óptica/métodos , Oxirredução , Fototerapia/métodosRESUMO
We investigated whether a specific serotonin (5-HT) receptor-mediated mechanism was involved in dextromethorphan (DM)-induced serotonergic behaviors. We firstly observed that the activation of 5-HT1A receptor, but not 5-HT2A receptor, contributed to DM-induced serotonergic behaviors in mice. We aimed to determine whether the upregulation of 5-HT1A receptor induced by DM facilitates the specific induction of certain PKC isoform, because previous reports suggested that 5-HT1A receptor activates protein kinase C (PKC). A high dose of DM (80 mg/kg, i.p.) induced a selective induction of PKCδ out of PKCα, PKCßI, PKCßII, PKCξ, and PKCδ in the hypothalamus of wild-type (WT) mice. More importantly, 5-HT1A receptor co-immunoprecipitated PKCδ in the presence of DM. Consistently, rottlerin, a pharmacological inhibitor of PKCδ, or PKCδ knockout significantly protected against increases in 5-HT1A receptor gene expression, 5-HT turnover rate, and serotonergic behaviors induced by DM. Treatment with DM resulted in an initial increase in nuclear factor erythroid-2-related factor 2 (Nrf2) nuclear translocation and DNA-binding activity, γ-glutamylcysteine (GCL) mRNA expression, and glutathione (GSH) level. This compensative induction was further potentiated by rottlerin or PKCδ knockout. However, GCL mRNA and GSH/GSSG levels were decreased 6 and 12 h post-DM. These decreases were attenuated by PKCδ inhibition. Our results suggest that interaction between 5-HT1A receptor and PKCδ is critical for inducing DM-induced serotonergic behaviors and that inhibition of PKCδ attenuates the serotonergic behaviors via downregulation of 5-HT1A receptor and upregulation of Nrf2-dependent GSH synthesis.
Assuntos
Comportamento Animal , Regulação para Baixo , Glutationa/biossíntese , Fator 2 Relacionado a NF-E2/metabolismo , Proteína Quinase C-delta/metabolismo , Receptor 5-HT1A de Serotonina/metabolismo , Serotonina/metabolismo , Regulação para Cima , Acetofenonas/farmacologia , Animais , Benzopiranos/farmacologia , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Dextrometorfano , Glutamato-Cisteína Ligase/genética , Glutamato-Cisteína Ligase/metabolismo , Dissulfeto de Glutationa/metabolismo , Hipotálamo/metabolismo , Hipotermia Induzida , Isoenzimas/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fármacos Neuroprotetores/farmacologia , Fosforilação/efeitos dos fármacos , Piperazinas/farmacologia , Piridinas/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptor 5-HT2A de Serotonina/metabolismo , Antagonistas do Receptor 5-HT1 de Serotonina/farmacologia , Fatores de TempoRESUMO
We developed nanoparticles comprising a photothermal dye (IR825)-loaded carbonized zwitterionic polymer [FNP-I] as "switch-on" pH-responsive fluorescence probes to sense intracellular cancer cells and for near-infrared (NIR) controllable photothermal therapy (PTT) in vivo and in vitro. The fluorescent "off" of FNP-I was activated after reaching the cancer cell environment, where the zwitterionic compartment of FNP lost its hydrophobicity to induce PTT-mediated heat release of IR825 under NIR irradiation in the tumor. Approximately 100% of the IR825 was released from the FNP core to generate high thermal conversion to completely kill the cancer cells. Furthermore, after intravenous treatment of FNP-I into MDAMB-231-cell bearing mice, pH-responsive photothermal therapy was observed, achieving marked ablation of tumor cells with release of IR825 under tumor environment conditions. In addition, fluorescent signals were clearly found at the tumor site after 3 h, decreasing at the 6 h time point. The in vitro and in vivo detection system demonstrated good cellular uptake and biocompatibility as a potential imaging-guided photothermal therapy nanotool for cancer treatment. Interestingly, the synergism of the biosensor and PTT in single FNP-I platform led to more effective cancer cell killing than either monotherapy, providing a new approach for cancer treatment.