RESUMO
Hyperlipidemia is a major contributor for atherosclerosis and hypolipidemic drugs such as statin are highly prescribed to treat elevated lipid level in plasma. Rubus coreanus, which is widely cultivated in south eastern Asia, have been reported to show significant cholesterol lowering action in hyperlipidemic subjects. Our objective was to determine the cellular effect of Rubus coreanus extract (RCE) on cholesterol biosynthesis in human hepatic cells (HepG2) and to elucidate the molecular mechanism by which it causes change in cholesterol metabolism. RCE treatment lowered cholesterol biosynthesis as well as secretion from HepG2 cells. This effect was associated with lowering the release of apolipoproteins from hepatic cells. RCE treatment also showed an increase in phosphorylation of foxhead box protein 01 (FoXo-1) and 5-adenosine monophosphate-activated protein kinase (AMPK), thus lowering expression of phosphoenolpyruvate carboxykinase (PEPCK) and G6Pase, which might be a major pathway for cholesterol biosynthesis inhibition. Apart from this; RCE also lowered sterol regulatory element-binding protein-1 (SREBP-1) expression in HepG2 cells, showing a long term regulation of cholesterol biosynthesis activity. These results indicate that one of the anti-hyperlipidemic actions of RCE is due to inhibition of cholesterol biosynthesis in hepatic cells and provides first documentation of a hypolipidemic bio-molecular action of Rubus coreanus.
Assuntos
Colesterol/metabolismo , Ácidos Graxos/metabolismo , Hipolipemiantes/farmacologia , Extratos Vegetais/farmacologia , Rosaceae , Proteínas Quinases Ativadas por AMP/metabolismo , Apolipoproteína A-I/metabolismo , Apolipoproteínas B/metabolismo , Proteína Forkhead Box O1 , Fatores de Transcrição Forkhead/metabolismo , Glucose-6-Fosfatase/metabolismo , Células Hep G2 , Humanos , Hipolipemiantes/análise , Fígado/citologia , Fígado/metabolismo , Extratos Vegetais/análise , Proteínas Serina-Treonina Quinases/metabolismo , Solventes/química , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Água/químicaRESUMO
OBJECTIVES: Gastrodia elata (GE) Blume (Orchidaceae) has been previously known for its therapeutic benefits against neurodegenerative diseases. Microglial activation and death have been implicated in the pathogenesis of a variety of neurodegenerative diseases, including Alzheimer's disease. In this study, GE and its pure components, gastrodin and 4-hydroxybenzyl alcohol (4HBA), were applied to ß-amyloid-induced BV2 mouse microglial cells. MATERIALS AND METHODS: Cell viability was assessed by the MTT assay and Western blotting was also performed. RESULTS: ß-amyloid-induced cell death was shown to be induced time- and dose-dependently. To examine the cell death mechanism, we confirmed the involvement of ER stress signaling. C/EBP homologous protein (CHOP), a pro-apoptotic ER stress protein, was expressed at high levels but glucose-regulated protein 78 (GRP78), an anti-apoptotic ER stress protein with chaperone activity, was only slightly affected by treatment with ß-amyloid. However, pretreatment with GE and its components inhibited the expression of CHOP but increased that of GRP78 in ß-amyloid-treated cells. This study also showed that a single treatment with GE extracts, gastrodin, or 4HBA induced the expression of GRP78, a marker for enhanced protein folding machinery, suggesting a protective mechanism for GE against ß-amyloid. CONCLUSIONS: This study reveals the protective effects of GE against ß-amyloid-induced cell death, possibly through the enhancement of protein folding machinery of a representative protein, GRP78, and the regulation of CHOP in BV2 mouse microglial cells.
Assuntos
Amiloide/farmacologia , Álcoois Benzílicos/farmacologia , Morte Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Gastrodia/química , Glucosídeos/farmacologia , Microglia/efeitos dos fármacos , Animais , Álcoois Benzílicos/isolamento & purificação , Chaperona BiP do Retículo Endoplasmático , Glucosídeos/isolamento & purificação , CamundongosRESUMO
BACKGROUND: We aimed to investigate the efficacy of the lifestyle intervention (LSI) program in controlling blood glucose regulation and health promotion in type 2 diabetic (T2D) patients. METHODS: Thirty adults with a diagnosed with diabetes were randomly assigned to LSI and control groups. The LSI group maintained their daily routines after participating twice in the LSI program, while control group maintained 4 weeks of daily life without participating in an intervention. RESULTS: HbA1c levels in the LSI group decreased significantly after participation (p = 0.025) compared with levels before the study, but there was no significant difference between the groups. The weight and body mass index (BMI) of the LSI group tended to decrease significantly compared with the control group (p = 0.054 and p = 0.055, respectively), and the waist circumference (WC) of the LSI group decreased significantly compared with that of the control group (p = 0.048). In the effects of the LSI program according to the polymorphism of GCKR genes, changes in glycated albumin (GA) (%), HbA1c, WC, BMI, and weight showed a significant decrease in the non-risk (TT genotype) GCKR group compared with the risk group (CC and TC genotype). CONCLUSION: Application of the four-week LSI program to diabetics revealed positive effects on blood-glucose control and improvement in obesity indicators. In particular, the risk group with variations in the GCKR gene was associated with more genetic effects on indicators such as blood glucose and obesity than was the non-risk group.
RESUMO
Ophiocordyceps sinensis is a natural fungus that has been valued as a health food and used in traditional Chinese medicine for centuries. The fungus is parasitic and colonizes insect larva. Naturally occurring O. sinensis thrives at high altitude in cold and grassy alpine meadows on the Himalayan mountain ranges. Wild Ophiocordyceps is becoming increasingly rare in its natural habitat, and its price limits its use in clinical practice. Therefore, the development of a standardized alternative is a great focus of research to allow the use of Ophiocordyceps as a medicine. To develop an alternative for wild Ophiocordyceps, a refined standardized extract, CBG-CS-2, was produced by artificial fermentation and extraction of the mycelial strain Paecilomyces hepiali CBG-CS-1, which originated from wild O. sinensis. In this study, we analyzed the in vitro immune-modulating effect of CBG-CS-2 on natural killer cells and B and T lymphocytes. CBG-CS-2 stimulated splenocyte proliferation and enhanced Th1-type cytokine expression in the mouse splenocytes. Importantly, in vitro CBG-CS-2 treatment enhanced the killing activity of the NK-92MI natural killer cell line. These results indicate that the mycelial culture extract prepared from Ophiocordyceps exhibits immune-modulating activity, as was observed in vivo and this suggests its possible use in the treatment of diseases caused by abnormal immune function.
RESUMO
Ophiocordyceps sinensis is a natural fungus that has been valued as a health food and traditional Chinese medicine for centuries. The fungus is parasitic and colonizes insect larva. Naturally occurring O. sinensis thrives at high altitude in cold and grassy alpine meadows on the Himalayan mountain ranges. Wild O. sinensis is becoming increasingly rare in its natural habitats, and its price is out of reach for clinical practice. For these reasons, development of a standardized alternative is a great focus of research to allow the use of O. sinensis as a medicine. To develop an alternative for wild O. sinensis, a refined standardized extract, CBG-CS-2, was produced by artificial fermentation and extraction of the mycelial strain Paecilomyces hepiali CBG-CS-1, which originated from wild O. sinensis. In this study, we analyzed the in vivo immune-modulating effect of CBG-CS-2 in mice. Oral administration of CBG-CS-2 supported splenocyte stimulation and enhanced Th1-type cytokine expression from the splenocytes. Importantly, the same treatment significantly enhanced the natural killer cell activity of the splenocytes. Finally, oral administration of CBG-CS-2 enhanced the potential for inflammatory responses. Together, these findings indicate that the mycelial culture extract prepared from O. sinensis exhibited immune-modulating activity and suggest its possible use in the treatment of diseases caused by abnormal immune function.
Assuntos
Ascomicetos/química , Produtos Biológicos/isolamento & purificação , Fatores Imunológicos/farmacologia , Preparações Farmacêuticas/isolamento & purificação , Animais , Produtos Biológicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Citocinas/biossíntese , Hypocreales/química , Células Matadoras Naturais/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Micélio/crescimento & desenvolvimento , Micélio/metabolismo , Baço/citologia , Baço/efeitos dos fármacosRESUMO
The prevalence of metabolic syndrome, hypertension, and diabetes has been increasing rapidly in Korea. The rate of increase has paralleled the replacement of Korean traditional diets (KTD), which emphasize vegetables and fermented foods, with western style dietary patterns that are rich in animal foods and saturated fat. We aimed to investigate the efficacy of the KTD in controlling fasting plasma glucose, blood pressure, and cardiovascular disease risk factors in hypertensive and type 2 diabetic (T2D) patients. Forty-one patients (61.8±1.5 years) who were taking medications prescribed for respective diseases were recruited from the Chonbuk National University Hospital for participation in a 12-week, parallel, controlled clinical trial. The control group (n=20) was advised to "eat as usual," whereas the experimental KTD diet group (n=21) was fed the KTD three times a day for 12 weeks. At the end of the trial, both groups had lower body mass index, % body fat, and waist-hip ratio compared to the baseline values (P<.05). Compared to the control group, the KTD group had a greater mean change (P<.05) from the baseline for glycated hemoglobin (HbA1c) (-0.72% vs. -0.25%) and heart rate (-7.1 vs. +1.6). Regular consumption of the KTD for 12 weeks by hypertensive and T2D patients resulted in favorable changes in cardiovascular risk factors.
Assuntos
Diabetes Mellitus Tipo 2/dietoterapia , Hipertensão/dietoterapia , Idoso , Glicemia/metabolismo , Pressão Sanguínea , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/fisiopatologia , Dieta , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Insulina/sangue , Masculino , Pessoa de Meia-Idade , República da Coreia , Triglicerídeos/sangueRESUMO
Oxidized low-density lipoprotein (oxLDL) contributes to atherosclerosis in part by being taken up into macrophages via scavenger receptors and leading to foam cell formation. Herbal compounds that have been used to treat blood stasis (a counterpart of atherosclerosis) for centuries include extracts of medicinal plants in the Rosaceae and Leguminosae families. In this study, we investigated the effect of the unripe Rubus coreanus (Korean black raspberry) fruit extract on oxLDL uptake by murine macrophage cells. In the presence of Rubus coreanus extract (RCE), Dil-labeled oxLDL uptake was inhibited in a dose-dependent manner. SP600125, a specific JNK inhibitor, inhibited the uptake of Dil-oxLDL into macrophages. RCE also inhibited JNK phosphorylation in a time- and dose-dependent manner in macrophages treated with oxLDL. These results indicate that among the mitogen-activated protein kinases, JNK phosphorylation is inhibited by RCE, which is likely the mechanism underlying the RCE-induced inhibition of oxLDL uptake by macrophages.
Assuntos
Aterosclerose/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Lipoproteínas LDL/metabolismo , Macrófagos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Rosaceae , Animais , Aterosclerose/tratamento farmacológico , Relação Dose-Resposta a Droga , Células Espumosas/efeitos dos fármacos , Células Espumosas/metabolismo , Frutas , Macrófagos/metabolismo , Camundongos , Fosforilação , FitoterapiaRESUMO
OBJECTIVE: Constipation is one of the most common gastrointestinal complaints worldwide. This study examined the effects of fig (Ficus carica L.) paste for the treatment of loperamide-induced constipation in a rat model. METHODS: Animals were divided into one normal control group and four experimental groups (0, 1, 6, and 30 g/kg). Loperamide (2 mg/kg, twice per day) was injected intraperitoneally to induce constipation in the four experimental groups. Fig paste was administered for 4 weeks to assess its anti-constipation effects. RESULTS: Fecal pellet number, weight and water content were increased in the fig-treated groups as compared to the control group. Reductions in body weight and increased intestinal transit length were observed in the fig-treated groups. Fecal pellet number was reduced in the distal colons of the fig-treated rats. Exercise and ileum tension increased in the experimental groups as compared to the control group. According to histological analyses, the thickness of the distal colon and areas of crypt epithelial cells that produce mucin were increased in the fig-treated groups in a dose-dependent manner. CONCLUSION: Constipation was decreased when fig fruit was fed to rats. Specifically, fecal number, weight, and water content, as well as histological parameters such as thickness and mucin areas in the distal colon were improved. Fig treatment may be a useful therapeutic and preventive strategy for chronic constipation.