RESUMEN
Mountain ginseng (Panax ginseng) has been used for cancer patient therapy in Northeast Asia. Although it is well known that cancer cells are able to induce angiogenesis, the effect of mountain ginseng on angiogenesis is still unknown. In the present study, we investigated whether ethanolic extract of mountain ginseng (MGE) could inhibit angiogenesis in in vitro and in vivo models. In comparison with farmcultivated ginseng extract (FGE), MGE more strongly inhibited cell migration and formation of capillarylike network within noncytotoxic ranges in SVEC410 cells. In addition, MGE dosedependently suppressed Transwell cell migration of the cells. Moreover, MGE reduced the phosphorylation and expression of VEGFR2 as well as the phosphorylation of FAK, Src, Akt and ERK, the intermediate proteins in the VEGFR2 signaling cascade, in the cells. As expected, MGE dramatically decreased hemoglobin content in Matrigel plugs in mice. In conclusion, MGE possesses stronger antiangiogenic properties than FGE in vascular endothelial cells. Such effect of MGE is correlated with inhibition of activation of the VEGFR2 signaling pathway. Therefore, the novel features of MGE may be helpful for understanding its anticancer mechanism for the treatment of cancer patients.
Asunto(s)
Movimiento Celular/efectos de los fármacos , Extractos Vegetales/farmacología , Receptor 2 de Factores de Crecimiento Endotelial Vascular/efectos de los fármacos , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo , Inhibidores de la Angiogénesis/farmacología , Animales , Línea Celular , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Hemoglobinas/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Neovascularización Patológica/tratamiento farmacológico , Neovascularización Patológica/metabolismo , Panax/química , Fosforilación/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND: Many Type 2 diabetes (T2DM) patients in Korea take Korean Red Ginseng (KRG) for various reasons. In this study, we investigated the effects of KRG administration on diabetic peripheral neuropathy in T2DM patients. METHODS: This study was a randomized, double-blind, placebo-controlled trial. Participants were randomly allocated to either the placebo or KRG group and took corresponding tablets for 24 weeks. The primary outcomes were changes in current perception threshold (CPT) at week 24. Secondary outcomes were altered fasting plasma glucose, HbA1c, and various metabolic and inflammatory markers at week 24. RESULTS: Sixty-one patients completed the study. The CPT of the lower extremities at various frequencies exhibited significant improvements at week 24 in the KRG group. Other metabolic parameters were not altered after 24 weeks in both groups. In the subgroup analysis, CPT levels were improved in those with a longer diabetes duration or who already had neuropathy at the beginning of the study, and insulin resistance was improved in patients with a shorter diabetes duration. CONCLUSION: Twenty-four week administration of KRG in T2DM patients resulted in a significant improvement in neuropathy, especially in those with a longer diabetes duration. A further, larger population study with a longer follow-up period is warranted to verify the effects of KRG on diabetic neuropathy.
Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Neuropatías Diabéticas/tratamiento farmacológico , Medicina Tradicional Coreana , Panax , Extractos Vegetales/uso terapéutico , Umbral Sensorial/fisiología , Percepción del Tacto/fisiología , Anciano , Glucemia , Diabetes Mellitus Tipo 2/fisiopatología , Neuropatías Diabéticas/fisiopatología , Método Doble Ciego , Femenino , Humanos , Resistencia a la Insulina/fisiología , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
BACKGROUND: Metformin can cause serum vitamin B12 deficiency, but studies on the influence of its duration and dose are lacking. We investigated vitamin B12 deficiency in patients with type 2 diabetes using metformin, in conjunction with other related factors. METHOD: This cross-sectional study included 1111 patients with type 2 diabetes who took metformin for at least 6 months. Serum vitamin B12 levels were quantified using a competitive-binding immunoenzymatic assay, and vitamin B12 deficiency was defined as serum B12 <300âpg/mL. Information on metformin use and confounding variables were collected from records or questionnaires and interviews. RESULT: Serum vitamin B12 deficiency occurred in 22.2% of patients (nâ=â247). After adjusting for confounders, a 1âmg increase in daily metformin dose was associated with a 0.142âpg/mL decrease in vitamin B12 (Pâ<â.001). Compared with a daily dose of <1000âmg, the adjusted odds ratios for 1000 to 1500, 1500 to 2000, and ≥2000âmg metformin were 1.72 (Pâ=â.080), 3.34 (Pâ<â.001), and 8.67 (Pâ<â.001), respectively. Vitamin B12 deficiency occurred less often in patients taking multivitamins (odds ratio 0.23; Pâ<â.001). After adjusting for confounding factors, there was no correlation between B12 deficiency and duration of metformin use. Serum homocysteine levels showed significant negative correlation with vitamin B12. CONCLUSION: Metformin at ≥1500âmg/d could be a major factor related to vitamin B12 deficiency, whereas concurrent supplementation of multivitamins may potentially protect against the deficiency. Serum homocysteine levels were negatively correlated with vitamin B12 levels, suggesting that B12 deficiency due to metformin use may occur at the tissue level. However, this hypothesis will require further study.
Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Metformina/uso terapéutico , Deficiencia de Vitamina B 12/inducido químicamente , Factores de Edad , Anciano , Consumo de Bebidas Alcohólicas/epidemiología , Anemia/epidemiología , Estudios Transversales , Diabetes Mellitus Tipo 2/epidemiología , Relación Dosis-Respuesta a Droga , Femenino , Ácido Fólico/sangre , Homocisteína/sangre , Humanos , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/efectos adversos , Masculino , Metformina/administración & dosificación , Metformina/efectos adversos , Persona de Mediana Edad , Oportunidad Relativa , República de Corea , Factores de Tiempo , Vitamina B 12/sangre , VitaminasRESUMEN
BACKGROUND: Hovenia dulcis (Rhamnaceae) fruits are popularly used as herbal medicines or dietary supplements in Asian countries due to functions such as liver protection and detoxification from alcohol poisoning. Accordingly, it is very likely for dietary supplemental products, including H. dulcis fruit extracts, to be taken with prescription drugs. OBJECTIVE: In this study, possible food-drug interactions involving H. dulcis fruit extracts were evaluated based on the inhibition of cytochrome P450 (CYP) enzyme activity. MATERIAL AND METHODS: The water extract of H. dulcis fruit extracts was incubated in human liver microsomes with CYP-specific substrates. The formation of the CYP-specific metabolites was measured using liquid chromatography-tandem mass spectrometry. RESULTS: H. dulcis fruit extracts showed negligible effects on seven CYP isozyme activities at all concentrations tested. CONCLUSION: This result suggests that H. dulcis fruit extracts may have minimal pharmacokinetic interactions with coadministered drugs through the modulation of CYP enzymes. SUMMARY: Food-drug interactions involving H. dulcis fruit extracts were evaluated.The inhibition of CYPs by H. dulcis extracts was tested.H. dulcis extracts showed negligible effects on CYP activities.H. dulcis extracts may have minimal pharmacokinetic interactions with co-administered drugs. Abbreviations Used: CYP: cytochrome P450 enzymes, HPLC: High performance liquid chromatography, LC-MS/MS : liquid chromatography-tandem mass spectrometry, MRM: multiple-reaction monitoring.
RESUMEN
This study assessed the inhibitory effects of Garcinia cambogia extract on the cytochrome P450 enzymes in vitro. G. cambogia extract was incubated with cytochrome P450 isozyme-specific substrates in human liver microsomes and recombinant CYP2B6 isozyme, and the formation of the marker metabolites was measured to investigate the inhibitory potential on cytochrome P450 enzyme activities. The results showed that G. cambogia extract has significant inhibitory effects on CYP2B6 activity in a concentration-dependent manner. Furthermore, the inhibition was potentiated following preincubation with NADPH, indicating that G. cambogia extract is a time-dependent inhibitor of CYP2B6. Meanwhile, hydroxycitric acid, the major bioactive ingredient of G. cambogia extract, did not exhibit significant inhibition effects on cytochrome P450 enzyme activities. G. cambogia extract could modulate the pharmacokinetics of CYP2B6 substrate drugs and lead to interactions with those drugs. Therefore, caution may be required with respect to concomitant intake of dietary supplements containing G. cambogia extract with CYP2B6 substrates.
Asunto(s)
Inhibidores del Citocromo P-450 CYP2B6/aislamiento & purificación , Garcinia cambogia/química , Microsomas Hepáticos/efectos de los fármacos , Extractos Vegetales/farmacología , Citocromo P-450 CYP2B6/metabolismo , Inhibidores del Citocromo P-450 CYP2B6/farmacología , Humanos , Técnicas In Vitro , Microsomas Hepáticos/enzimología , Plantas Medicinales/químicaRESUMEN
In this study, we investigated carotenoid profiles and contents from 27 types of paprika with different colors (red, orange, and yellow), shapes (blocky and conical), and cultivation methods (soil and soilless). We simultaneously analyzed 12 kinds of carotenoids using UPLC equipped with an HSS T3 column for 30 min, and we identified six kinds of carotenoids in red paprika and nine types in orange and yellow paprika. Zeaxanthin concentrations in orange paprika were in the range of 85.06±23.37-151.39±5.94 mg/100 g dry weight (dw), which shows that orange paprika is a great source of zeaxanthin. Generally, red paprika is a great source of capsanthin. However, a new cultivar, 'Mini Goggal Red', contained large amounts of zeaxanthin (121.41±30.10 mg/100 g dw) even though its visible color is red. This is very meaningful considering that consumers have a preference for red color and the potent functional value of zeaxanthin. Carotenoid profiles and concentrations in blocky and conical type paprika were not significantly different in red paprika except the 'Mini Goggal Red' cultivar and yellow paprika. Blocky type orange paprika contains plenty of zeaxanthin, unlike conical type orange paprika. Three new cultivars of the conical type were cultivated in both soil culture and soilless culture in the same province, and carotenoid profiles and concentrations were similar, showing that both cultivations methods can be used.
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Capsicum/química , Carotenoides/química , Extractos Vegetales/química , Capsicum/clasificación , Capsicum/crecimiento & desarrollo , Color , Frutas/química , Frutas/clasificación , Frutas/crecimiento & desarrolloRESUMEN
A simple, accurate and reproducible reversed-phase liquid chromatographic method was developed for qualitative and quantitative determination of four bioactive flavonoids (ampelopsin, taxifolin, myricetin and quercetin) from the fruit-stalk extract of Hovenia dulcis Thunb. Chromatographic separation was performed on a C18 column (4.6 × 150 mm, 3.5 µm) with mobile phase consisting of 0.1% acetic acid and 100% acetonitrile at a flow rate of 1.0 mL/min. The analysis was performed using a diode array detector at 365 nm. The method was validated in terms of selectivity, linearity, accuracy, precision and recovery. Good linearity was observed over the investigated concentration range (10-500 µg/mL), with correlation coefficient values greater than 0.99. The intra- and inter-day precisions over the concentration range were <3.91% (relative standard deviation), and the accuracy was between 91.57 and 106.66%. The mean recovery for all the analytes was 100.87%. This method was successfully applied in the quality assessment of bioactive flavonoids in the fruit-stalk extract of H. dulcis.
Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Flavonoides/análisis , Extractos Vegetales/análisis , Rosales/química , Frutas/químicaRESUMEN
Rhus verniciflua (Toxicodendron vernicifluum) is a medicinal tree popularly used in Asian countries such as China, Japan, and Korea as a food additive or herbal medicine because of its beneficial effects. R. verniciflua extract (RVE) contains diverse phenolic compounds, such as flavonoids, as its major biological active constituents. In this study, the pharmacokinetic profiles of eight phenolic compounds were investigated following oral administration of RVE to rats. The eight phenolic compounds were 2,4-dihydroxybenzoic acid, 3,4-dihydroxybenzoic acid, fisetin, fustin, butin, sulfuretin, taxifolin, and garbanzol. The plasma concentrations of the eight compounds were determined by using a liquid chromatography-triple-quadrupole mass spectrometer before and after treatment with ß-glucuronidase. When 1.5 g/kg RVE was administered, the eight compounds were all detected in plasma, mainly as conjugated forms. These pharmacokinetic data would be useful for understanding the pharmacological effects of RVE.
Asunto(s)
Fenoles/farmacocinética , Extractos Vegetales/farmacocinética , Rhus/química , Administración Oral , Animales , Masculino , Estructura Molecular , Fenoles/administración & dosificación , Fenoles/sangre , Corteza de la Planta/química , Extractos Vegetales/administración & dosificación , Extractos Vegetales/sangre , Ratas , Ratas Sprague-Dawley , República de CoreaRESUMEN
Saturated fatty acids (SFA) and monounsaturated fatty acids (MUFA) show different effects on the development of insulin resistance. In this study, we compared the effect of dietary SFA and MUFA on the insulin signaling pathway in the skeletal muscle of a type 2 diabetic animal model. Twenty-nine-week-old male Otsuka Long-Evans Tokushima fatty (OLETF) rats were randomly divided into three groups and fed one of the following diets for 3 weeks; a normal chow diet, an SFA (lard oil) enriched or a MUFA (olive oil) enriched high-fat diet. The vastus lateralis muscle was used for analyses. Insulin tolerance test showed improved insulin sensitivity in rats fed the MUFA diet, as compared to those fed the SFA diet (p < 0.001). The SFA diet reduced IRS-1 expression and phosphorylated PI3K levels in skeletal muscle, as compared with a chow diet (p < 0.001, respectively). On the contrary, muscle IRS-2 expression and phosphorylated ERK1/2 was significantly increased in rats fed the SFA diet (p < 0.001, respectively). Membrane translocation of glucose transporter type 4 decreased in the skeletal muscle of rats fed the SFA diet, as compared to those fed a chow diet (p < 0.001). These changes in insulin signaling pathway in skeletal muscle were not observed in rats fed the MUFA diet. In conclusion, the beneficial effect of dietary MUFA on insulin sensitivity is associated with a conserved IRS-1/PI3K insulin signaling pathway which was altered by dietary SFA.