RESUMO
BACKGROUND: Severe intracranial atherosclerotic stenosis (ICAS) is a major cause of stroke. Although percutaneous transluminal angioplasty and stenting (PTAS) treatment methods have increased over the last decade as alternative therapies, there is debate regarding the best method of treatment, with medical and surgical therapies often suggested. METHODS: We analyzed the long-term follow-up results from 5 years of intracranial stenting for intracranial stenosis from three stroke centers. The primary endpoints were early stroke complications or death within 30 days after stent insertion, and the secondary endpoint was a recurrent stroke between 30 days and 60 months. Correlating factors and Kaplan-Meier survival curves for recurrent stroke and in-stent restenosis (ISR) were also obtained. RESULTS: Seventy-three PTAS in 71 patients were examined in this study. The primary and secondary endpoints were all 8.2% (n = 6), and restenosis was 13.7% (n = 10) during the 5-year follow-up. The primary endpoints were significantly frequent in the high National Institutes of Health Stroke Scale (NIHSS) and early stent (≤ 7 days after dual antiplatelet medication) groups. Secondary endpoint and ISR were identically frequent in the younger age group and in the presence of tandem stenosis in other major intracranial arteries. The cumulative probability of recurrent stroke and ISR at 60 months was 16.4% and 14.1%, respectively. CONCLUSIONS: This study shows that PTAS is safe and effective for major ICAS. Reducing the early complication rate is still an important factor, despite the fact that long-term stroke recurrence was low.
Assuntos
Arteriosclerose Intracraniana , Acidente Vascular Cerebral , Angioplastia/efeitos adversos , Constrição Patológica/diagnóstico por imagem , Constrição Patológica/cirurgia , Humanos , Arteriosclerose Intracraniana/diagnóstico por imagem , Arteriosclerose Intracraniana/cirurgia , Stents/efeitos adversos , Acidente Vascular Cerebral/etiologia , Resultado do Tratamento , Estados UnidosRESUMO
Given the worldwide burden of neglected tropical diseases, there is ongoing need to develop novel anthelmintic agents to strengthen the pipeline of drugs to combat these burdensome infections. Many diseases caused by parasitic flatworms are treated using the anthelmintic drug praziquantel (PZQ), employed for decades as the key clinical agent to treat schistosomiasis. PZQ activates a flatworm transient receptor potential (TRP) channel within the melastatin family (TRPMPZQ) to mediate sustained Ca2+ influx and worm paralysis. As a druggable target present in many parasitic flatworms, TRPMPZQ is a promising target for a target-based screening campaign with the goal of discovering novel regulators of this channel complex. Here, we have optimized methods to miniaturize a Ca2+-based reporter assay for Schistosoma mansoni TRPMPZQ (Sm.TRPMPZQ) activity enabling a high throughput screening (HTS) approach. This methodology will enable further HTS efforts against Sm.TRPMPZQ as well as other flatworm ion channels. A pilot screen of ~16,000 compounds yielded a novel activator of Sm.TRPMPZQ, and numerous potential blockers. The new activator of Sm.TRPMPZQ represented a distinct chemotype to PZQ, but is a known chemical entity previously identified by phenotypic screening. The fact that a compound prioritized from a phenotypic screening campaign is revealed to act, like PZQ, as an Sm.TRPMPZQ agonist underscores the validity of TRPMPZQ as a druggable target for antischistosomal ligands.
Assuntos
Anti-Helmínticos/farmacologia , Proteínas de Helminto/antagonistas & inibidores , Praziquantel/farmacologia , Schistosoma mansoni/metabolismo , Esquistossomose mansoni/parasitologia , Canais de Potencial de Receptor Transitório/antagonistas & inibidores , Animais , Anti-Helmínticos/química , Cálcio/metabolismo , Avaliação Pré-Clínica de Medicamentos , Feminino , Proteínas de Helminto/genética , Proteínas de Helminto/metabolismo , Humanos , Masculino , Camundongos , Praziquantel/química , Schistosoma mansoni/efeitos dos fármacos , Schistosoma mansoni/genética , Esquistossomose mansoni/tratamento farmacológico , Esquistossomose mansoni/metabolismo , Canais de Potencial de Receptor Transitório/genética , Canais de Potencial de Receptor Transitório/metabolismoRESUMO
Phosphatidylserine is one of the phospholipids present in cell membranes, especially in brain and nervous system. The phosphatidylserine content is reduced with aging and age-related decrease in phosphatidylserine is known to contribute to cognitive impairment and Alzheimer's disease in the elderly. In the present study, we examined the effect of supplementation with phosphatidylserine on the response to oxidative stress and aging using C. elegans as a model system. Dietary supplementation with phosphatidylserine significantly increased resistance to oxidative stress and extended lifespan accompanying reduced fertility as a trade-off. Age-related decline in motility was also delayed by supplementation with phosphatidylserine. The cellular levels of reactive oxygen species and the expression of stress-responsive genes were increased by phosphatidylserine treatment, suggesting a hormetic effect. The extension of lifespan by phosphatidylserine overlaps with reduced insulin/IGF-1-like signaling and requires DAF-16. The effect of phosphatidylserine on age-related diseases was examined using animal model of disease. Supplementation with phosphatidylserine significantly suppressed amyloid beta-induced toxicity in Alzheimer's disease model. Reduced survival in diabetes mellitus due to high-glucose diet was reversed by supplementation with phosphatidylserine. This study reports the anti-oxidative stress and anti-aging effect of phosphatidylserine for the first time at the organismal level and proposes possible underlying mechanisms.
Assuntos
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/efeitos dos fármacos , Suplementos Nutricionais , Fatores de Transcrição Forkhead/metabolismo , Hormese , Longevidade/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Fosfatidilserinas/administração & dosagem , Fatores Etários , Animais , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Fatores de Transcrição Forkhead/genética , Movimento/efeitos dos fármacos , Fosfatidilserinas/metabolismoRESUMO
Curcumin, a compound found in Indian yellow curry, is known to possess various biological activities, including anti-oxidant, anti-inflammatory, and anti-cancer activities. Cur2004-8 is a synthetic curcumin derivative having symmetrical bis-alkynyl pyridines that shows a strong anti-angiogenic activity. In the present study, we examined the effect of dietary supplementation with Cur2004-8 on response to environmental stresses and aging using Caenorhabditis elegans as a model system. Dietary intervention with Cur2004-8 significantly increased resistance of C. elegans to oxidative stress. Its anti-oxidative-stress effect was greater than curcumin. However, response of C. elegans to heat stress or ultraviolet irradiation was not significantly affected by Cur2004-8. Next, we examined the effect of Cur2004-8 on aging. Cur2004-8 significantly extended both mean and maximum lifespan, accompanying a shift in time-course distribution of progeny production. Age-related decline in motility was also delayed by supplementation with Cur2004-8. In addition, Cur2004-8 prevented amyloid-beta-induced toxicity in Alzheimer's disease model animals which required a forkhead box (FOXO) transcription factor DAF-16. Dietary supplementation with Cur2004-8 also reversed the increase of mortality observed in worms treated with high-glucose-diet. These results suggest that Cur2004-8 has higher anti-oxidant and anti-aging activities than curcumin. It can be used for the development of novel anti-aging product.
Assuntos
Envelhecimento/efeitos dos fármacos , Catecóis/administração & dosagem , Curcumina/análogos & derivados , Longevidade/efeitos dos fármacos , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/prevenção & controle , Peptídeos beta-Amiloides/toxicidade , Animais , Caenorhabditis elegans , Catecóis/química , Catecóis/farmacologia , Curcumina/administração & dosagem , Curcumina/farmacologia , Suplementos Nutricionais , Modelos Animais de Doenças , Estrutura Molecular , Estresse Oxidativo/efeitos dos fármacosRESUMO
Phosphatidylcholine is one of the major phospholipids comprising cellular membrane and is known to have several health-promoting activities, including the improvement of brain function and liver repair. In this paper, we examine the in vivo effect of dietary supplementation with phosphatidylcholine on the response to environmental stressors and aging in C. elegans. Treatment with phosphatidylcholine significantly increased the survival of worms under oxidative stress conditions. However, there was no significant difference in response to stresses caused by heat shock or ultraviolet irradiation. Oxidative stress is believed to be one of the major causal factors of aging. Then, we examined the effect of phosphatidylcholine on lifespan and age-related physiological changes. Phosphatidylcholine showed a lifespan-extending effect and a reduction in fertility, possibly as a tradeoff for long lifespan. Age-related decline of motility was also significantly delayed by supplementation with phosphatidylcholine. Interestingly, the expressions of well-known longevity-assuring genes, hsp-16.2 and sod-3, were significantly upregulated by dietary intervention with phosphatidylcholine. DAF-16, a transcription factor modulating stress response genes, was accumulated in the nucleus by phosphatidylcholine treatment. Increase of the ROS level with phosphatidylcholine suggests that the antioxidant and lifespan-extending effects are due to the hormetic effect of phosphatidylcholine. Phosphatidylcholine also showed a protective effect against amyloid beta-induced toxicity in Alzheimer's disease model animals. Experiments with long-lived mutants revealed that the lifespan-extending effect of phosphatidylcholine specifically overlapped with that of reduced insulin/IGF-1-like signaling and required DAF-16. These findings showed the antioxidant and antiaging activities of phosphatidylcholine for the first time in vivo. Further studies focusing on the identification of underlying cellular mechanisms involved in the antiaging effect will increase the possibility of using phosphatidylcholine for the development of antiaging therapeutics.
Assuntos
Peptídeos beta-Amiloides/toxicidade , Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/efeitos dos fármacos , Fatores de Transcrição Forkhead/metabolismo , Longevidade/efeitos dos fármacos , Fosfatidilcolinas/farmacologia , Animais , Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/efeitos da radiação , Proteínas de Caenorhabditis elegans/antagonistas & inibidores , Proteínas de Caenorhabditis elegans/genética , Núcleo Celular/metabolismo , Fatores de Transcrição Forkhead/antagonistas & inibidores , Fatores de Transcrição Forkhead/genética , Insulina/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Interferência de RNA , RNA de Cadeia Dupla/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Raios Ultravioleta , Regulação para Cima/efeitos dos fármacosRESUMO
Recently, there have been reports that chronic insomnia acts as an insult in the brain, causing memory loss through the production of ROS, inflammation, and, Alzheimer's disease if persistent. Insomnia remains the leading cause of sleep disturbance and as such has serious implications for public health. Patients with Alzheimer's disease are also known to suffer from severe sleep disturbance. Meanwhile, vitexin is a key ingredient in Passiflora incarnata L (passion flower, PF) extract, which is known to help with sleep. This medicinal plant has been used as a folk remedy for sedation, anxiety and sleep since centuries ago, but the standardization work has not been done and the extent of the effect has not been clearly demonstrated. For this reason, we tried to test the possibility that repeated administration of PF could improve the memory by promoting hippocampal neurogenesis at the DBA/2 mice known have inherited sleep disorders, as well as preventive effects of Alzheimer's disease. Here, we found that vitexin, which is the main bioactive component of ethanol extracts from leaves and fruits (ratio; 8:2) of PF, confirmed the improvement of neurogenesis (DCX) of DBA/2 mice repeated PF oral administration by immunohistochemistry (IHC) and western blot analysis. PF-treated group showed increased the neurotrophic factor (BDNF) in the hippocampus compared with that of vehicle-treated group, but the inflammation markers Iba-1 (microglial marker) and COX-2 were inconsistent between the groups. However, we found COX-2 signal is essential for hippocampal neurogenesis according to the additional IHC experiments using COX-2 inhibitor and pIkappaB have shown. In addition, although prescription sleeping pills have been reported to show significant changes in appetite and metabolic rate from time to time, no changes in the feeding behavior, body weight, metabolic rate and body composition of the animals were observed by administration of PF. Interestingly, we found that short-term oral administration of PF displayed improved memory according to the water maze test. Quantitative analysis of Tau protein, which is a marker of Alzheimer's disease, was performed in the SD rats and DBA/2 mice by repeated PF oral administration and pTau/Tau values were significantly decreased in PF-treated group than vehicle-treated group. In conclusion, our results suggest that PF lead high hippocampal neurogenesis in the animals even in inherited sleep-disturbed animals. The increased hippocampal neurogenesis functionally enhanced memory and learning functions by repeated PF oral administration. These results identify PF as a potential therapy for enhancing memory functions and prevention of Alzheimer's disease through actions on the hippocampus.
Assuntos
Memória/efeitos dos fármacos , Neurogênese/efeitos dos fármacos , Passiflora , Extratos Vegetais/farmacologia , Transtornos do Sono-Vigília , Animais , Proteína Duplacortina , Hipocampo/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos DBA , Camundongos Endogâmicos ICR , Ratos , Ratos Sprague-DawleyRESUMO
The purpose of this study was to investigate the bioactive substances and extraction conditions of lipid-soluble green tee extract using supercritical CO extraction from green tea leaves growing in Boseong-gun, Jeollanam-do and to demonstrate cell safety and effects on inflammatory response of the nano-encapsulated lipid-soluble green tee extract. The polyphenol content of green tea extract using supercritical CO2 extraction was analyzed. The highest polyphenol was extracted in the condition of 400 bar/50 °C. A total of polyphenol content was 2.47 mg/g. The lipid-soluble vitamin content of supercritical extracts of lipid-soluble green tea was analyzed. Beta-carotene, a vitamin A precursor (4.131 mg/100 g) and vitamin E (537.9 mg/100 g) were detected. ECG content was the highest of catechin of lipid-soluble green tea extract. For cell safety and NO inhibition, human skin cell-derived HaCaT cells and RBL-2H3 mast cells did not have cytotoxicity in 1% of the nano-encapsulated lipid-soluble green tea leaf extract. RAW 264.7 cells did not show cytotoxicity in 5%. NO production was significantly decreased in RAW 264.7 cells in a concentration-dependent manner and within the concentration range. Based on the findings, this study suggested the extraction standards and ingredients of polyphenol according to temperature and pressure in extracting green tea leaf ingredients using supercritical CO2 extraction. This study also objectively demonstrated the safety and anti-inflammatory effect of the nano-encapsulated lipid-soluble green tea leaf extract which is used as functional materials in the cosmetic industry.
Assuntos
Catequina , Óxido Nítrico , Catequina/análise , Catequina/farmacologia , Humanos , Lipídeos , Extratos Vegetais/farmacologia , Polifenóis , CháRESUMO
The vine stem of Spatholobus suberectus Dunn (SS) is used as a traditional herbal medicine in China. Chinese herbal medicines are well known as natural bioactive compounds that can be used as new medicines, and their antioxidant and anticancer effects have also been reported. This study aimed to examine the anticancer effect of a high-pressure hot-water SS extract on rat C6 glioma cells. The SS extract effectively suppressed the viability and proliferation of C6 glioma cells through an antioxidant effect. Reactive oxygen species (ROS) levels in cancer cells are higher than that in normal cells. If the ROS level falls below that required for the growth of cancer cells, their rapid proliferation and growth can be suppressed. We also measured the induction of mitochondrial membrane depolarization and cell cycle arrest effect caused by the SS extract in C6 glioma cells through a FACS analysis. In addition, we observed an increase in STAT3, p53, E2F1, and p21 mRNA expression and a decrease in Bcl-2 mRNA expression by quantitative PCR. An increase in p21 protein expression of over 83% was observed through western blot analysis. All these data support the fact that the high-pressure hot-water SS extract has the potential to be used for glioma treatment.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Fabaceae/química , Glioma/tratamento farmacológico , Mitocôndrias/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Catequina/análise , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Inibidor de Quinase Dependente de Ciclina p21/genética , Regulação da Expressão Gênica , Glioma/metabolismo , Camundongos , Mitocôndrias/patologia , Fenóis/análise , Caules de Planta/química , Ratos , Espécies Reativas de Oxigênio/metabolismoRESUMO
Previous studies show that nutritional interventions with anti-oxidants have various healthpromoting effects in several model organisms. Here, we examine the effects of S-allyl cysteine on resistance to environmental stressors and age-related physiological changes using C. elegans as a model system. S-allyl cysteine is a modified amino acid found in aged garlic extracts and known to have strong anti-oxidant activity. The survival of worms under oxidative-stress conditions significantly increased with supplementation of S-allyl cysteine. In addition, pretreatment of S-allyl cysteine significantly increased resistance to both heat stress and ultraviolet irradiation. However, lifespan was not affected by S-allyl cysteine treatment. We also examined the effect of S-allyl cysteine on motility of C. elegans and found that S-allyl cysteine can retard the age-related decline of muscle tissue locomotive activity. S-allyl cysteine also significantly suppressed amyloid -induced paralysis in Alzheimer's disease model animals. Taken together, our study indicates that dietary supplementation of S-allyl cysteine can improve health span and suggests that S-allyl cysteine can be used to develop novel health-promoting pharmaceuticals.
Estudos anteriores mostram que intervenções nutricionais com antioxidantes têm vários efeitos promotores da saúde em vários organismos-modelo. Aqui, examinamos os efeitos da S-alil cisteína sobre a resistência a estressores ambientais e alterações fisiológicas relacionadas com a idade usando C. elegans como um sistema modelo. Salil cisteína é um aminoácido modificado encontrado em extratos de alho envelhecido e conhecido por ter forte atividade antioxidante. A sobrevivência de vermes sob condições de estresse oxidativo aumentou significativamente com a suplementação de S-alil cisteína. Além disso, o pré-tratamento com S-alil cisteína aumentou significativamente a resistência tanto ao estresse térmico como à irradiação ultravioleta. No entanto, o tempo de vida não foi afetado pelo tratamento com S-alil cisteína. Nós também examinamos o efeito da S-alil cisteína na motilidade de C. elegans e descobrimos que a S-alil cisteína pode retardar o declínio relacionado à idade da atividade locomotora do tecido muscular. A S-alil cisteína também suprimiu significativamente a paralisia induzida por amilóide em animais-modelo da doença de Alzheimer. Tomados em conjunto, o nosso estudo indica que a suplementação dietética de S-alil cisteína pode melhorar a duração da saúde e sugere que S-alil cisteína pode ser usada para desenvolver novos produtos farmacêuticos de promoção da saúde.
Assuntos
Caenorhabditis elegans , Cisteína , Alho , AntioxidantesRESUMO
Hippophae rhamnoides L., also known as sea buckthorn (SBT), possesses a wide range of biological and pharmacological activities. However, the underlying mechanism is largely unknown. The present study examined whether SBT leaf extract could inhibit proliferation and promote apoptosis of rat glioma C6 cells. The results revealed that the treatment with SBT leaf extract inhibited proliferation of rat C6 glioma cells in a dose-dependent manner. SBT-induced reduction of C6 glioma cell proliferation and viability was accompanied by a decrease in production of reactive oxygen species (ROS), which are critical for the proliferation of tumor cells. SBT treatment not only significantly upregulated the expression of the pro-apoptotic protein Bcl-2-associated X (Bax) but also promoted its localization in the nucleus. Although increased expression and nuclear translocation of Bax were observed in SBT-treated C6 glioma cells, the induced nuclear morphological change was distinct from that of typical apoptotic cells in that most of SBT-treated cells were characterized by convoluted nuclei with cavitations and clumps of chromatin. All of these results suggest that SBT leaf extract could inhibit the rapid proliferation of rat C6 glioma cells, possibly by inducing the early events of apoptosis. Thus, SBT may serve as a potential therapeutic candidate for the treatment of glioma.
Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Glioma/patologia , Hippophae/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Espécies Reativas de Oxigênio/metabolismo , Transporte Ativo do Núcleo Celular/efeitos dos fármacos , Animais , Antineoplásicos/química , Catequina/análise , Linhagem Celular Tumoral , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Espaço Intracelular/efeitos dos fármacos , Espaço Intracelular/metabolismo , Fenóis/análise , Extratos Vegetais/química , Ratos , Proteína X Associada a bcl-2/metabolismoRESUMO
Recently, we reported that Artemisia annua (AA) has anti-adipogenic properties in vitro and in vivo. Reduction of adipogenesis by AA treatment may dampen systemic inflammation and protect neurons from cytokine-induced damage. Therefore, the present study was undertaken to assess whether AA increases neuronal maturation by reducing inflammatory responses, such as those mediated by cyclooxygenase 2 (COX-2). Mice were fed normal chow or a high-fat diet with or without chronic daily oral administration of AA extract (0.2 g/10 mL/kg) for 4 weeks; then, changes in their hippocampal dentate gyri were measured via immunohistochemistry/immunofluorescence staining for bromodexoxyuridine, doublecortin, and neuronal nuclei, markers of neuronal maturation, and quantitative western blotting for COX-2 and Iba-1, in order to assess correlations between systemic inflammation (interleukin-6) and food type. Additionally, we tested the effect of AA in an Alzheimer's disease model of Caenorhabditis elegans and uncovered a potential benefit. The results show that chronic AA dosing significantly increases neuronal maturation, particularly in the high-fat diet group. This effect was seen in the absence of any changes in COX-2 levels in mice given the same type of food, pointing to the possibility of alternate anti-inflammatory pathways in the stimulation of neurogenesis and neuro-maturation in a background of obesity.
Assuntos
Ciclo-Oxigenase 2/efeitos dos fármacos , Giro Denteado/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Obesidade/veterinária , Extratos Vegetais/farmacologia , Transdução de Sinais/efeitos dos fármacos , Adipogenia/efeitos dos fármacos , Administração Oral , Animais , Artemisia annua , Diferenciação Celular/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos , Dieta Hiperlipídica/veterinária , Imunofluorescência/veterinária , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , Extratos Vegetais/administração & dosagemRESUMO
Tenebrio molitor are large insects and their larvae are consumed as food in many countries. The nutritional composition of T. molitor has been studied and contains high amounts of proteins, unsaturated fatty acids, and valuable minerals. However, the bioactivity of T. molitor has not been fully understood. We examined the effects of T. molitor extracts on resistance to oxidative stress and organism's lifespan using Caenorhabditis elegans as a model system. The response to heat shock and ultraviolet (UV) irradiation was monitored in vivo. The extracts from T. molitor showed significant effects on resistance to oxidative stress and UV irradiation and extend both mean and maximum lifespan of C. elegans. The number of progeny produced significantly increased in animals supplemented with T. molitor extracts. In addition, the expression of hsp-16.2 and sod-3 was markedly upregulated by supplementation with T. molitor extracts. These findings suggest that T. molitor extracts can increase response to stressors and extend lifespan by the induction of longevity assurance genes in C. elegans.
RESUMO
The anti-obesity effect of Korean traditional food, Memilmuk, was examined through inhibition of differentiation of 3T3-L1 preadipocytes by buckwheat flour extract. Oil-Red O staining showed that lipid accumulation in adipocytes was reduced upon adding buckwheat flour extract, indicating effective inhibition of adipocyte differentiation. Buckwheat flour extract also inhibited the expression of adipogenic transcription factor, peroxisome proliferator-activated receptor γ (PPARγ), and AMP-activated protein kinase (AMPK), an intracellular regulator of energy balance. Overall, the anti-obesity effect of Korean Memilmuk might be mediated through down-regulation of PPARγ expression via AMPK activation by buckwheat flour.
Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Adipócitos/efeitos dos fármacos , Fagopyrum/química , Alimento Funcional , Obesidade/tratamento farmacológico , Células 3T3-L1 , Proteínas Quinases Ativadas por AMP/genética , Adipócitos/enzimologia , Adipócitos/metabolismo , Animais , Sobrevivência Celular , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Camundongos , República da CoreiaRESUMO
Policosanol (PC) is a mixture of health promoting bioactive long-chain aliphatic alcohols. Here, we report that green tea (Camellia sinensis) leaves are the exceptionally rich plant-sources of PC. Young and tender leaves and old and turf leaves of C. sinensis were hand-picked in spring and autumn. The total contents of PC in the leaves were in the range of 726.2-1363.6mg/kg as determined by a GC-MS/MS. The compositions of PC in the leaves were different with harvest season and types. The total contents of PC in commercial green tea leaves were found to be in the range of 856.7-1435.1mg/kg. Interestingly, the infused green tea leaves contained the higher PC than the non-infused green tea product, reaching to 1629.4mg/kg. This represents the first report on the contents and compositions of PC in green tea leaves, showing unambiguous evidence of their potential as rich sources of PC.
Assuntos
Camellia sinensis/química , Álcoois Graxos/química , Chá/química , Folhas de Planta/química , Estações do Ano , Espectrometria de Massas em TandemRESUMO
Obesity has increased continuously in western countries during the last several decades and recently become a problem in developing countries. Currently, anti-obesity drugs originating from natural products are being investigated for their potential to overcome adverse effects associated with chemical drugs. Artemisinic acid, which was isolated from the well-known anti-malaria herb Artemisia annua (AA) L., was recently shown to possess anti-adipogenic effects in vitro. However, the anti-adipogenic effects of AA in animal models have not yet been investigated. Therefore, we conducted daily oral administration with AA water extract in a diet-induced obesity animal model and treated 3T3-L1 cells with AA to confirm the anti-adipogenic effects in the related protein expressions. We then evaluated the physiology, adipose tissue histology and mRNA expressions of many related genes. Inhibition of adipogenesis by the AA water extract was observed in vitro. In the animal model, weight gain was significantly lower in the AA treated group, but there were no changes in food intake volume or calories. Reductions in lipid droplet size and mRNA expression associated with adipogenesis were also observed in animal epididymal fat. This study is the first to report that AA has an anti-obese effects in vivo.
Assuntos
Adipogenia/efeitos dos fármacos , Fármacos Antiobesidade/farmacologia , Artemisia annua/química , Expressão Gênica/efeitos dos fármacos , Camundongos Endogâmicos C57BL/fisiologia , Células 3T3-L1 , Tecido Adiposo/citologia , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Administração Oral , Animais , Compostos Azo/química , Western Blotting , Camundongos , Extratos Vegetais/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
OBJECTIVE: This study was performed to determine the effect of N-acetyl-L-cysteine, a modified sulfur-containing amino acid that acts as a strong cellular antioxidant, on the response to environmental stressors and on aging in C. elegans. METHOD: The survival of worms under oxidative stress conditions induced by paraquat was evaluated with and without in vivo N-acetyl-L-cysteine treatment. The effect of N-acetyl-L-cysteine on the response to other environmental stressors, including heat stress and ultraviolet irradiation (UV), was also monitored. To investigate the effect on aging, we examined changes in lifespan, fertility, and expression of age-related biomarkers in C. elegans after N-acetyl-L-cysteine treatment. RESULTS: Dietary N-acetyl-L-cysteine supplementation significantly increased resistance to oxidative stress, heat stress, and UV irradiation in C. elegans. In addition, N-acetyl-L-cysteine supplementation significantly extended both the mean and maximum lifespan of C. elegans. The mean lifespan was extended by up to 30.5% with 5 mM N-acetyl-L-cysteine treatment, and the maximum lifespan was increased by 8 days. N-acetyl-L-cysteine supplementation also increased the total number of progeny produced and extended the gravid period of C. elegans. The green fluorescent protein reporter assay revealed that expression of the stress-responsive genes, sod-3 and hsp-16.2, increased significantly following N-acetyl-L-cysteine treatment. CONCLUSION: N-acetyl-L-cysteine supplementation confers a longevity phenotype in C. elegans, possibly through increased resistance to environmental stressors.
Assuntos
Acetilcisteína/farmacologia , Envelhecimento/efeitos dos fármacos , Caenorhabditis elegans/efeitos dos fármacos , Longevidade/efeitos dos fármacos , Envelhecimento/genética , Animais , Antioxidantes/farmacologia , Caenorhabditis elegans/fisiologia , Fertilidade/efeitos dos fármacos , Proteínas de Fluorescência Verde/fisiologia , Estresse Oxidativo/efeitos dos fármacos , Estresse Fisiológico/efeitos dos fármacos , Fatores de Transcrição/genéticaRESUMO
BACKGROUND/OBJECTIVES: Acanthopanax sessiliflorus is a native Korean plant and used as traditional medicine or an ingredient in many Korean foods. The free radical theory of aging suggests that cellular oxidative stress caused by free radicals is the main cause of aging. Free radicals can be removed by cellular anti-oxidants. MATERIALS/METHODS: Here, we examined the anti-oxidant activity of Acanthopanax sessiliflorus extract both in vitro and in vivo. Survival of nematode C. elegans under stress conditions was also compared between control and Acanthopanax sessiliflorus extract-treated groups. Then, anti-aging effect of Acanthopanax sessiliflorus extract was monitored in C. elegans. RESULTS: Stem extract significantly reduced oxidative DNA damage in lymphocyte, which was not observed by leaves or root extract. Survival of C. elegans under oxidative-stress conditions was significantly enhanced by Acanthopanax sessiliflorus stem extract. In addition, Acanthopanax sessiliflorus stem increased resistance to other environmental stresses, including heat shock and ultraviolet irradiation. Treatment with Acanthopanax sessiliflorus stem extract significantly extended both mean and maximum lifespan in C. elegans. However, fertility was not affected by Acanthopanax sessiliflorus stem. CONCLUSION: Different parts of Acanthopanax sessiliflorus have different bioactivities and stem extract have strong anti-oxidant activity in both rat lymphocytes and C. elegans, and conferred a longevity phenotype without reduced reproduction in C. elegans, which provides conclusive evidence to support the free radical theory of aging.
RESUMO
UV is a major environmental factor inducing and worsening the symptoms of hyperpigmentation disorders such as freckles, melasma and solar lentigines. During UV-induced skin inflammatory reactions, pro-inflammatory mediators initiate the production of various paracrine melanogenic factors (α-MSH, SCF, ET-1, bFGF and NO) in keratinocytes. These paracrine factors activate melanin synthase in melanocytes through the paracrine network between melanocytes and keratinocytes. Glechoma hederacea (GH) is a herbal plant used in oriental medicine to treat inflammation. Its anti-inflammatory effects, through inhibition of NO synthesis (NOS) as well as the pro-inflammatory cytokine TNF-α, have been reported. However, there has not yet been any report of a depigmenting effect. In this study of placebo-controlled, 8 week topical treatment with a 1% GH extract lotion on UV-induced pigmented spots in female Asian subjects, significant effects of anti-inflammation and depigmenting were proven. The depigmenting effect of GH seems to be related to inhibiting the secretion of pro-inflammatory cytokines and melanogenic paracrine factors from keratinocytes, rather than to direct inhibition of melanogenic activities in melanocytes.
Assuntos
Lamiaceae , Fitoterapia , Extratos Vegetais/uso terapêutico , Pigmentação da Pele/efeitos dos fármacos , Adulto , Povo Asiático , Método Duplo-Cego , Feminino , Humanos , Pessoa de Meia-Idade , Espectrofotometria , Adulto JovemRESUMO
Ginseng has been reported to ameliorate hyperglycemia in experimental and clinical studies; however, its mechanism of action remains unclear. In this study, we investigated the metabolic effects and putative molecular mechanisms of Korean red ginseng (KRG, Panax ginseng) in animal models for type 2 diabetes mellitus (T2DM) and peripheral insulin-responsive cell lines. Korean red ginseng was administered orally at a dose of 200 mg/(kg d) to Otsuka Long-Evans Tokushima fatty rats for 40 weeks. Initially, chronic administration of KRG reduced weight gain and visceral fat mass in the early period without altering food intake. The KRG-treated Otsuka Long-Evans Tokushima fatty rats showed improved insulin sensitivity and significantly preserved glucose tolerance compared with untreated control animals up to 50 weeks of age, implying that KRG attenuated the development of overt diabetes. KRG promoted fatty acid oxidation by the activation of adenosine monophosphate-activated protein kinase (AMPK) and phosphorylation of acetyl-coenzyme A carboxylase in skeletal muscle and cultured C2C12 muscle cells. Increased expression of peroxisome proliferator-activated receptor-gamma coactivator-1alpha, nuclear respiratory factor-1, cytochrome c, cytochrome c oxidase-4, and glucose transporter 4 by KRG treatment indicates that activated AMPK also enhanced mitochondrial biogenesis and glucose utilization in skeletal muscle. Although these findings suggest that KRG is likely to have beneficial effects on the amelioration of insulin resistance and the prevention of T2DM through the activation of AMPK, further clinical studies are required to evaluate the use of KRG as a supplementary agent for T2DM.
Assuntos
Diabetes Mellitus Tipo 2/prevenção & controle , Hipoglicemiantes/farmacologia , Resistência à Insulina , Insulina/metabolismo , Gordura Intra-Abdominal/efeitos dos fármacos , Obesidade/metabolismo , Panax , Preparações de Plantas/farmacologia , Animais , Western Blotting , Teste de Tolerância a Glucose , Transportador de Glucose Tipo 4/efeitos dos fármacos , Transportador de Glucose Tipo 4/metabolismo , Hipoglicemiantes/administração & dosagem , Masculino , Obesidade/complicações , Obesidade/fisiopatologia , Preparações de Plantas/administração & dosagem , Ratos , Ratos Endogâmicos OLETFRESUMO
We used high-density oligonucleotide arrays to measure transcriptional alterations in the heart and brain (neocortex) of 30-mo-old B6C3F(1) mice supplemented with alpha-tocopherol (alphaT) and gamma-tocopherol (gammaT) since middle age (15 mo). Gene expression profiles were obtained from 5- and 30-mo-old control mice and 30-mo-old mice supplemented with alphaT (1 g/kg) or a mixture of alphaT and gammaT (500 mg/kg of each tocopherol) from middle age (15 mo). In the heart, both tocopherol-supplemented diets were effective in inhibiting the expression of genes previously associated with cardiomyocyte hypertrophy and increased innate immunity. In the brain, induction of genes encoding ribosomal proteins and proteins involved in ATP biosynthesis was observed with aging and was markedly prevented by the mixture of alphaT and gammaT supplementation but not by alphaT alone. These results demonstrate that middle age-onset dietary supplementation with alphaT and gammaT can partially prevent age-associated transcriptional changes and that these effects are tissue and tocopherol specific.