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1.
Int J Mol Med ; 43(3): 1497-1504, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30628642

RESUMO

Stachys riederi is one of the largest genera in the flowering plant family Lamiaceae. The aqueous extract of Stachys riederi var. japonica is known for its anti­allergic effect. In the present study, the antioxidant and cytoprotective effects of Stachys riederi var. japonica ethanol extract (SREE) on ultraviolet A (UVA)­irradiated human dermal fibroblasts (HDFs) were evaluated. At 100 µg/ml, SREE significantly inhibited production of reactive oxygen species (ROS) in UVA­irradiated HDFs. SREE at 100 µg/ml additionally markedly interfered with the loss of mitochondrial membrane potential (ΔΨm) in these cells. In addition, SREE at 100 µg/ml attenuated UVA­induced DNA fragmentation and caspase­3 activation in HDFs. SREE at 100 µg/ml additionally increased mRNA and protein expressions of Bcl­2 and decreased those of Bax and cytochrome c in UVA­irradiated HDFs. In summary, to the best of our knowledge, these results demonstrate for the first time that SREE exhibited antioxidant and cytoprotective effects on UVA­irradiated HDFs, which may be mediated through suppression of ROS generation, inhibition of the loss of ΔΨm and inhibition of apoptosis.


Assuntos
Antioxidantes/farmacologia , Citoproteção/efeitos dos fármacos , Derme/citologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Extratos Vegetais/farmacologia , Stachys/química , Antioxidantes/química , Apoptose/efeitos dos fármacos , Biomarcadores , Caspase 3/metabolismo , Células Cultivadas , Fragmentação do DNA/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Extratos Vegetais/química , Espécies Reativas de Oxigênio/metabolismo , Raios Ultravioleta
2.
Arch Toxicol ; 91(12): 4009-4015, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28634823

RESUMO

Discrepant incidence has been reported regarding the incidence of herb-induced liver injury (HILI). To address the growing worldwide concern of HILI, we evaluated the risk of HILI in a nationwide prospective study. Between April 2013 and January 2016, 1001 inpatients (360 males and 641 females) from 10 tertiary hospitals throughout South Korea were treated with herbal drugs and had their liver enzymes periodically measured. A total of six patients met the criteria for HILI with RUCAM scores ranging from 4 to 7. All these participants were women and developed the hepatocellular type of HILI. One HILI participant met the criteria for Hy's law; however, none of six cases presented clinical symptoms related to liver injury. This is the first nationwide prospective study that estimated the extent of the incidence of HILI [total: 0.60%, 95% confidence interval (CI) 0.12-1.08; women: 0.95%, 95% CI 0.19-1.68] and described its features in hospitalized participants.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Medicamentos de Ervas Chinesas/efeitos adversos , Fígado/enzimologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença Hepática Induzida por Substâncias e Drogas/enzimologia , Feminino , Humanos , Incidência , Fígado/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , República da Coreia/epidemiologia
3.
J Nanosci Nanotechnol ; 16(2): 1855-8, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27433687

RESUMO

In this work, hydrogen production from glycerol by steam reforming was studied using Ni-metal oxide catalysts. Ni-based catalyst becomes deactivated during steam reforming reactions because of coke deposits and sintering. Therefore, the aim of this study was to reduce carbon deposits and sintering on the catalyst surface by adding a promoter. Ni-metal oxide catalysts supported on Al2O3 were prepared via impregnation method, and the calcined catalyst was reduced under H2 flow for 2 h prior to the reaction. The characteristics of the catalysts were examined by XRD, TPR, TGA, and SEM. The Ni-Fe-Ce/Al2O3 catalyst, which contained less than 2 wt% Ce, showed the highest hydrogen selectivity and glycerol conversion. Further analysis of the catalysts revealed that the Ni-Fe-Ce/Al2O3 catalyst required a lower reduction temperature and produced minimum carbon deposit.


Assuntos
Óxido de Alumínio/química , Cério/química , Glicerol/química , Ferro/química , Níquel/química , Vapor , Catálise , Hidrogênio/química
4.
Biochem Biophys Res Commun ; 477(3): 440-7, 2016 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-27320863

RESUMO

We investigated the anti-lipogenic effect of betaine in rats fed methionine and choline-deficient diet (MCD). Intake of MCD for 3 wk resulted in a significant accumulation of hepatic lipids, which was prevented by betaine supplementation in drinking water (1%). Phosphorylation of AMP-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACC), sterol regulatory element-binding protein-1c (SREBP-1c), and liver kinase B1 (LKB1) was inhibited by MCD intake, and these changes were all inhibited by betaine feeding. Meanwhile, betaine supplementation reversed the reduction of methionine and S-adenosylmethionine (SAM), and the elevation of homocysteine levels in the liver, which could be attributable to the induction of betaine-homocysteine methyltransferase (BHMT) and methionine adenosyltransferase (MAT). Different cell lines were used to clarify the role of homocysteine on activation of the AMPK pathway. Homocysteine treatment decreased pAMPK, pACC, pSREBP-1c and pLKB1 in HepG2 cells. Metformin-induced activation of AMPK was also inhibited by homocysteine. Treatment with hydroxylamine, a cystathionine ß-synthase inhibitor, resulted in a reduction of pAMPK, pACC and pSREBP-1c, accompanied by an elevation of intracellular homocysteine. Betaine treatment prevented the homocysteine-induced reduction of pAMPK, pACC, pSREBP-1c and pLKB1 in H4IIE cells, but not in HepG2 cells. Also the elevation of cellular homocysteine and inhibition of protein expression of BHMT were prevented by betaine only in H4IIE cells which express BHMT. The results suggest that the beneficial effect of betaine against hepatic lipid accumulation may be attributed, at least in part, to the depletion of homocysteine via up-regulation of BHMT in hepatocytes.


Assuntos
Betaína-Homocisteína S-Metiltransferase/metabolismo , Betaína/metabolismo , Gorduras na Dieta/metabolismo , Homocisteína/metabolismo , Fígado/metabolismo , Regulação para Cima , Animais , Humanos , Masculino , Ratos , Ratos Sprague-Dawley
5.
Ann Thorac Cardiovasc Surg ; 22(1): 20-6, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26639937

RESUMO

PURPOSE: Malignant pleural effusion (MPE) is common in patients with advanced cancer. Chemical pleurodesis can be considered for MPE that do not respond to chemotherapy, radiotherapy, or therapeutic thoracentesis. However, it is not yet clear which agent is more effective and safer in chemical pleurodesis. METHODS: This study was designed as a single arm, multicenter, and open-label phase III clinical trial to evaluate efficacy and safety of chemical pleurodesis using mistletoe extraction (ABNOVAviscum(®) Injection). References of other agents in chemical pleurodesis were investigated to compare efficacy and safety. Efficacy was evaluated by followed up chest X-ray and changes of clinical symptoms and Karnofsky performance scale. Safety was evaluated by serious adverse event (SAE) and changes of laboratory findings. A follow-up period was 4 weeks after last pleurodesis. RESULTS: Of 62 patients, 49 (79.0%) had complete response, 11 (17.7%) had partial response, and two had no response. Mean response rate was significantly different in this study comparing with reference response rate which was 64% (p <0.0001). There were two SAEs, but all were recovered without sequelas. CONCLUSION: The results of this study suggest that mistletoe extraction (ABNOVAviscum(®) Injection) could be an effective and safe agent of chemical pleurodesis in patients with MPE.


Assuntos
Extratos Vegetais/administração & dosagem , Derrame Pleural Maligno/terapia , Pleurodese/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Avaliação de Estado de Karnofsky , Masculino , Pessoa de Meia-Idade , Erva-de-Passarinho/química , Fitoterapia , Extratos Vegetais/efeitos adversos , Extratos Vegetais/isolamento & purificação , Plantas Medicinais , Derrame Pleural Maligno/diagnóstico , Pleurodese/efeitos adversos , Indução de Remissão , República da Coreia , Fatores de Tempo , Resultado do Tratamento
6.
J Nanosci Nanotechnol ; 15(1): 522-6, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26328394

RESUMO

In this work, hydrogen production from glycerol by Steam Reforming (SR) was studied by Ni-Ce catalysts supported on LaAlO3 perovskite in order to effect of the cerium loading amount and the reaction conditions. Nano size Ni-Ce/LaAlO3 catalysts were prepared by precipitation method. The structure of the catalysts was characterized by XRD analysis. The morphology, dispersion and the reduction properties of catalysts was examined by SEM, TEM, H2-chemisorption and TPR, respectively. It was found that 15 wt% Ni-5 wt% Ce/LaAlO3 catalyst showed the highest glycerol conversion and hydrogen selectivity. In addition, the catalyst also showed the high carbon dioxide selectivity and the lowest methane selectivity. The results indicate that the catalyst promotes methane reforming reaction. The highest activity in the 15 wt% Ni-5 wt% Ce/LaAlO3 was attributed to the proper cerium loading amount. Moreover, the lowest metal crystal size and rise in active site were found to have an effect on catalytic activity and hydrogen selectivity. The 15 wt% Ni-5 wt% Ce/LaAlO3 catalyst exhibited excellent performance with respect to hydrogen production at reaction temperature of 450 degrees C, at atmospheric pressure, 20 wt% glycerol solution and GHSV = 6,000 mL/g-cat x hr.


Assuntos
Cério/química , Glicerol/química , Nanopartículas Metálicas/química , Níquel/química , Óxido de Alumínio/química , Hidrogênio/química , Lantânio/química , Nanotecnologia , Vapor
7.
Toxicol Res ; 31(2): 165-72, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26191383

RESUMO

Cornus officinalis is widely distributed in Korea, and its fruit has been used to make as herbal drug for traditional medicine in Korea, Japan, and China because of its tonic, analgesic, and diuretic properties. However, the effects of C. officinalis methanol extract (COME) on melanogenesis remain poorly understood. We evaluated the melanogenic capability of COME in melan-a cells, which are immortalized mouse melanocytes. COME increased melanin synthesis in a dose-dependent manner. Treatment with 12.5 µg/mL of COME significantly increased melanin content by 36.1% (p < 0.001) to a level even higher than that (31.6%) of 3-isobutyl-1-methyl-xanthine, a well-known pigmentation agent. COME also upregulated tyrosinase activity and its messenger RNA and protein expression. In addition, COME upregulated the expression of tyrosinase-related proteins 1 and 2 and microphthalmia-associated transcription factor-M messenger RNA expression. These results imply that COME may be appropriate for development as a natural product to treat hair graying.

8.
Complement Ther Med ; 23(3): 381-7, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26051573

RESUMO

OBJECTIVE: To investigate the effect of combining conventional treatment with regional hyperthermia on cancer pain in lung cancer patients. DESIGN: Case-control study. SETTING: One Korean university hospital and three complementary cancer clinics. MAIN OUTCOMES AND MEASURES: Main outcome was effective analgesic score (EAS, PI[1+(M/10)], 1: anti-inflammatory drug consumption at a regular dosage, M: weekly dose (mg) of oral morphine equivalent and PI: pain intensity) at four time points (baseline (days -30 to 0), time 1 (days 1-60), time 2 (days 61-120), and time 3 (days 121-180)). Propensity score matching between the hyperthermia and control groups was performed using a 1:5 ratio. A linear mixed effects model was employed to measure EAS changes over time in the two groups. RESULTS: At baseline, there were 83 subjects in the control group and 32 subjects in the hyperthermia group. At time 3, there were 49 subjects in the control group and 16 subjects in the hyperthermia group. Analyses showed rate of change of EAS, treatment×time was significant (p=0.038). This significant difference was mainly observed for time 1 (mean difference: 101.76 points, 95% confidence interval: 10.20-193.32 points, p=0.030). CONCLUSIONS: Our results indicate an increase in cancer pain in lung cancer patients administered regional hyperthermia, particularly during the early stage of hyperthermia treatment.


Assuntos
Hipertermia Induzida/métodos , Neoplasias Pulmonares/complicações , Manejo da Dor/métodos , Dor , Idoso , Analgésicos Opioides/uso terapêutico , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Morfina/uso terapêutico , Dor/etiologia , Dor/fisiopatologia , Resultado do Tratamento
9.
Phytother Res ; 29(7): 1026-31, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25892665

RESUMO

This study was designed to investigate the antitumor mechanism of Phytol in hepatocellular carcinomas including Huh7 and HepG2 cells in association with caspase dependent apoptosis and epithelial mesenchymal transition (EMT) signaling. Phytol significantly suppressed the viability of Huh7 and HepG2 cells. Also, Phytol significantly increased the sub G1 population and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling (TUNEL) positive cells in a concentration dependent manner in Huh7 and HepG2 cells. Consistently, Phytol cleaved poly (adenosine diphosphate-ribose) polymerase (PARP), activated caspase-9/3, and Bax attenuated the expression of survival genes such as Bcl-2, Mcl-1, and c-Myc in Huh7 and HepG2 cells. Of note, Phytol also suppressed typical morphology change of EMT such as loss of cell adhesion and formation of fibroblast like mesenchymal cells in HepG2 cells. Furthermore, Phytol also reversed the loss of E-cadherin and overexpression of p-smad2/3, alpha-smooth muscle actin, and Snail induced by EMT promoter transforming growth factor beta1 in HepG2 cells. Overall, our findings suggest that Phytol exerts antitumor activity via apoptosis induction through activation of caspas-9/3 and inhibition of EMT in hepatocellular carcinoma cells as a potent anticancer candidate for liver cancer treatment.


Assuntos
Antineoplásicos/farmacologia , Proteínas Reguladoras de Apoptose/metabolismo , Carcinoma Hepatocelular/patologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Neoplasias Hepáticas/patologia , Fitol/farmacologia , Apoptose/efeitos dos fármacos , Caderinas/metabolismo , Caspase 3/metabolismo , Caspase 9/metabolismo , Linhagem Celular Tumoral , Células Hep G2 , Humanos , Marcação In Situ das Extremidades Cortadas , Poli(ADP-Ribose) Polimerases/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Crescimento Transformador beta1/metabolismo
10.
J Vet Sci ; 16(2): 135-43, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25643794

RESUMO

Tea contains polyphenols and is one of the most popular beverages consumed worldwide. Because most tyrosinase inhibitors that regulate melanogenesis are phenol/catechol derivatives, this study investigated the inhibitory effects of Camellia sinensis water extracts (CSWEs), including black tea, green tea, and white tea extracts, on melanogenesis using immortalized melanocytes. CSWEs inhibited melanin accumulation and melanin synthesis along with tyrosinase activity in a concentration-dependent manner. These inhibitory effects were superior to those of arbutin, a well-known depigmenting agent. The anti-melanogenic activity of black (fermented) tea was higher than that of a predominant tea catecholamine, epigallocatechin gallate. CSWEs, especially black tea extract, decreased tyrosinase protein levels in a concentration-dependent manner. These results suggest that the anti-melanogenic effect of CSWEs is mediated by a decrease in both tyrosinase activity and protein expression, and may be augmented by fermentation. Thus, CSWEs could be useful skin-whitening agents in the cosmetic industry.


Assuntos
Melaninas/metabolismo , Melanócitos/metabolismo , Monofenol Mono-Oxigenase/metabolismo , Extratos Vegetais/farmacologia , Chá/química , Animais , Catequina/análogos & derivados , Catequina/metabolismo , Linhagem Celular , Melanócitos/enzimologia , Camundongos , Folhas de Planta/química
11.
BMC Complement Altern Med ; 14: 363, 2014 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-25262005

RESUMO

BACKGROUND: ß-sitosterol is a cholesterol-like phytosterol, which widely distributed in the plant kingdom. Here, anti-fibrotic effect of the ß-sitosterol was studied using the activated human hepatic stellate cell (HSC) model and dimethylnitrosamine (DMN)-induced mouse hepatic fibrosis model. METHOD: HSCs were activated by transforming growth factor-ß (TGF-ß) and the collagen-1 and α-smooth muscle actin (α-SMA) expressions were measured at the mRNA and protein level. We also studied the effect ß-sitosterol using DMN-induced mouse hepatic fibrosis model. We then measured the collagen-1 and α-SMA expression levels in vivo to investigate anti-hepatofibrotic effect of ß-sitosterol, at both of the mRNA and protein level. RESULTS: ß-sitosterol down regulated the mRNA and protein expression levels of collagen-1 and α-SMA in activated HSC. Oral administration of the ß-sitosterol successfully alleviated the DMN-induced mouse liver damage and prevented collagen accumulation. The mRNA and protein expression levels of collagen-1 and α-SMA were also down regulated in ß-sitosterol treated mouse group. CONCLUSIONS: This study shows the effect of ß-sitosterol on the TGF-ß -or DMN-induced hepatofibrosis. Hence, we demonstrate the ß-sitosterol as a potential therapeutic agent for the hepatofibrosis.


Assuntos
Artemisia/química , Células Estreladas do Fígado/efeitos dos fármacos , Cirrose Hepática/metabolismo , Extratos Vegetais/farmacologia , Sitosteroides/farmacologia , Actinas/análise , Actinas/genética , Actinas/metabolismo , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Colágeno Tipo I/análise , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Dimetilnitrosamina/efeitos adversos , Expressão Gênica/efeitos dos fármacos , Humanos , Cirrose Hepática/induzido quimicamente , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Extratos Vegetais/química , Sitosteroides/química
12.
Food Chem Toxicol ; 62: 292-8, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23994088

RESUMO

Previous studies suggested that the hepatoprotective activity of betaine is associated with its effects on sulfur amino acid metabolism. We examined the mechanism by which betaine prevents the progression of alcoholic liver injury and its therapeutic potential. Rats received a liquid ethanol diet for 6 wk. Ethanol consumption elevated serum triglyceride and TNFα levels, alanine aminotransferase and aspartate aminotransferase activities, and lipid accumulation in liver. The oxyradical scavenging capacity of liver was reduced, and expression of CD14, TNFα, COX-2, and iNOS mRNAs was induced markedly. These ethanol-induced changes were all inhibited effectively by betaine supplementation. Hepatic S-adenosylmethionine, cysteine, and glutathione levels, reduced in the ethanol-fed rats, were increased by betaine supplementation. Methionine adenosyltransferase and cystathionine γ-lyase were induced, but cysteine dioxygenase was down-regulated, which appeared to account for the increment in cysteine availability for glutathione synthesis in the rats supplemented with betaine. Betaine supplementation for the final 2 wk of ethanol intake resulted in a similar degree of hepatoprotection, revealing its potential therapeutic value in alcoholic liver. It is concluded that the protective effects of betaine against alcoholic liver injury may be attributed to the fortification of antioxidant defense via improvement of impaired sulfur amino acid metabolism.


Assuntos
Aminoácidos Sulfúricos/metabolismo , Antioxidantes/metabolismo , Betaína/farmacologia , Hepatopatias Alcoólicas/tratamento farmacológico , Animais , Peso Corporal/efeitos dos fármacos , Ciclo-Oxigenase 2/genética , Cisteína/metabolismo , Citosol/efeitos dos fármacos , Citosol/metabolismo , Suplementos Nutricionais , Enzimas/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Glutationa/metabolismo , Receptores de Lipopolissacarídeos/genética , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Hepatopatias Alcoólicas/genética , Hepatopatias Alcoólicas/metabolismo , Masculino , Óxido Nítrico Sintase Tipo II/genética , Tamanho do Órgão/efeitos dos fármacos , Ratos Wistar , Fator de Necrose Tumoral alfa/genética
13.
Planta Med ; 79(12): 997-1002, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23807810

RESUMO

It has been known that silymarin exhibits protective activity against oxidative liver injury induced by various hepatotoxicants, but the underlying mechanism of its beneficial action remains unclear. We determined the alterations in sulfur-containing amino acid metabolism induced by silymarin in association with its effects on the antioxidant capacity of liver. Male mice were treated with silymarin (100 or 200 mg/kg, p. o.) every 12 h for a total of 3 doses, and sacrificed 6 h after the final dosing. The hepatic methionine level was increased, but the activity and protein expression of methionine adenosyltransferase were decreased by silymarin in a dose-dependent manner. S-Adenosylmethionine or homocysteine concentration was not changed, whereas the sulfur-containing metabolites generated from homocysteine in the transsulfuration pathway including cystathionine, cysteine, and glutathione were increased significantly. Cystathionine ß-synthase was induced, but cysteine dioxygenase was downregulated, both of which would contribute to the elevation of cysteine and its product, glutathione, in liver. Oxygen radical scavenging capacity of liver cytosol against peroxyl radical and peroxynitrite was increased, and also hepatic lipid peroxidation was diminished in the silymarin-treated mice. Taken together, the results demonstrate that silymarin enhances hepatic glutathione generation by elevating cysteine availability via an increment in cysteine synthesis and an inhibition of its catabolism to taurine, which may subsequently contribute to the antioxidant defense of liver.


Assuntos
Aminoácidos Sulfúricos/metabolismo , Antioxidantes/metabolismo , Metionina Adenosiltransferase/metabolismo , Silybum marianum/química , Silimarina/farmacologia , Enxofre/metabolismo , Aminoácidos Sulfúricos/análise , Aminoácidos Sulfúricos/efeitos dos fármacos , Animais , Antioxidantes/análise , Glutationa/análise , Glutationa/efeitos dos fármacos , Glutationa/metabolismo , Peroxidação de Lipídeos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Taurina/análise , Taurina/metabolismo
14.
J Nanosci Nanotechnol ; 13(1): 653-6, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23646792

RESUMO

The experiment was carried out to produce hydrogen through steam reforming of glycerol over nano-sized Ni catalysts supported on alumina (Al2O3). The catalysts were characterized by BET surface area, metal dispersion, XRD, TPR, NH3-TPD and SEM. 15 wt% Ni/Al2O3 catalysts presented carbon nano fiber after the catalyst was used. However, when the Ni loading was higher than that of 15 wt%, the catalytic activity reduced, and the increase of the Ni particle size and the formation of graphitic carbon occurred. The Ni/SiO2(70)-Al2O3 with the high surface area and the small Ni particle size promoted the catalytic activity and could easily reduce from NiO to Ni, inhibiting the formation of NiAl2O4.


Assuntos
Óxido de Alumínio/química , Hidrogênio/química , Nanopartículas Metálicas/química , Níquel/química , Vapor , Catálise , Glicerol , Hidrogênio/isolamento & purificação , Teste de Materiais , Propriedades de Superfície
15.
Phytother Res ; 27(11): 1714-22, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23325562

RESUMO

Despite the antitumour effect of ursolic acid observed in several cancers, the underlying mechanism remains unclear. Thus, in the present study, the roles of AMP-activated protein kinase (AMPK) and glycogen synthase kinase 3 beta (GSK3ß) were examined in ursolic acid induced apoptosis in HepG2 hepatocellular carcinoma cells. Ursolic acid significantly exerted cytotoxicity, increased the sub-G1 population and the number of ethidium homodimer and terminal deoxynucleotidyl transferase(TdT) mediated dUTP nick end labeling positive cells in HepG2 cells. Also, ursolic acid enhanced the cleavages of poly-ADP-ribose polymerase (PARP) and caspase3, attenuated the expression of astrocyte elevated gene (AEG1) and survivin in HepG2 cells. Interestingly, ursolic acid increased the phosphorylation of AMPK and coenzyme A carboxylase and also enhanced phosphorylation of GSK3ß at inactive form serine 9, whereas ursolic acid attenuated the phosphorylation of AKT and mTOR in HepG2 cells. Conversely, AMPK inhibitor compound C or GSK3ß inhibitor SB216763 blocked the cleavages of PARP and caspase 3 induced by ursolic acid in HepG2 cells. Furthermore, proteosomal inhibitor MG132 suppressed AMPK activation, GSK3ß phosphorylation, cleaved PARP and deceased AEG-1 induced by ursolic acid in HepG2 cells. Overall, our findings suggest that ursolic acid induced apoptosis in HepG2 cells via AMPK activation and GSK3ß phosphorylation as a potent chemopreventive agent.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Apoptose/efeitos dos fármacos , Quinase 3 da Glicogênio Sintase/metabolismo , Triterpenos/farmacologia , Carcinoma Hepatocelular/patologia , Caspase 3/metabolismo , Moléculas de Adesão Celular/metabolismo , Glicogênio Sintase Quinase 3 beta , Células Hep G2 , Humanos , Indóis/farmacologia , Leupeptinas/farmacologia , Neoplasias Hepáticas/patologia , Maleimidas/farmacologia , Proteínas de Membrana , Fosforilação , Poli(ADP-Ribose) Polimerases/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas de Ligação a RNA , Serina-Treonina Quinases TOR/metabolismo , Ubiquitinação , Ácido Ursólico
16.
Neurotoxicology ; 34: 42-50, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23164932

RESUMO

3-Nitropropionic acid (3-NP), a mitochondrial toxin, has been reported to induce an acute cochlear damage. Korean red ginseng (KRG) is known to have protective effects from some types of hearing loss. This study aimed to observe the protective effect of KRG in an ototoxic animal model using 3-NP intratympanic injection. BALB/c mice were classified into 5 groups (n=15) and dose-dependent toxic effects after intratympanic injection with 3-NP (300-5000 mM) on the left ear were investigated to determine the appropriate toxicity level of 3-NP. For observation of the protective effects of KRG, 23 mice were grouped into 3-NP (500 mM, n=12) and KRG+3-NP groups (300 mg/kg KRG for 7 days before 500 mM 3-NP administration, n=11). Auditory brain response (ABR) and cochlear morphological evaluations were performed before and after drug administration. The ABR thresholds in the 800-5000 mM groups exceeded the maximum recording limit at 16 and 32 kHz 1 day after 3-NP administration. The ABR threshold in the 500 mM 3-NP+KRG group was significantly lower than that in the 500 mM 3-NP group from post 1 week to 1 month. The mean type II fibrocyte counts significantly differed between the control and 3-NP groups and between the 3-NP and 3-NP+KRG groups. Spiral ganglion cell degeneration in the 3-NP group was more severe than that in the 3-NP+KRG group. This animal model exhibited a dose-dependent hearing loss with histological changes. KRG administration ameliorated the deterioration of hearing by 3-NP.


Assuntos
Cóclea/efeitos dos fármacos , Doenças Cocleares/prevenção & controle , Perda Auditiva/prevenção & controle , Nitrocompostos , Panax , Extratos Vegetais/farmacologia , Propionatos , Animais , Limiar Auditivo/efeitos dos fármacos , Cóclea/patologia , Cóclea/fisiopatologia , Doenças Cocleares/induzido quimicamente , Doenças Cocleares/patologia , Doenças Cocleares/fisiopatologia , Citoproteção , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Potenciais Evocados Auditivos do Tronco Encefálico/efeitos dos fármacos , Células Ciliadas Auditivas Externas/efeitos dos fármacos , Células Ciliadas Auditivas Externas/patologia , Audição/efeitos dos fármacos , Perda Auditiva/induzido quimicamente , Perda Auditiva/patologia , Perda Auditiva/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Panax/química , Extratos Vegetais/isolamento & purificação , Raízes de Plantas , Plantas Medicinais , Gânglio Espiral da Cóclea/efeitos dos fármacos , Gânglio Espiral da Cóclea/patologia , Fatores de Tempo
17.
Bioorg Med Chem Lett ; 21(19): 5726-9, 2011 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-21873054

RESUMO

Compounds having α,ß-unsaturated lactones display a variety of biological activities. Many research groups have tested both natural and unnatural α,ß-unsaturated lactones for as-yet undiscovered biological properties. We synthesized α,ß-unsaturated lactones with various substituents at the δ-position and studied their immunosuppressive effects, that is, the inhibition of Interleukin-2 (IL-2) production. Among the compounds synthesized, the benzofuran-substituted α,ß-unsaturated lactone 4h showed the best inhibitory activity toward IL-2 production in Jurkat e6-1 T lymphocytes (IC(50)=66.9 nM) without cytotoxicity at 10 µM. The results indicated that 4h may be useful as a potent immunosuppressive agent, as well as in IL-2-related studies.


Assuntos
Imunossupressores/síntese química , Lactonas/síntese química , Testes Imunológicos de Citotoxicidade , Avaliação Pré-Clínica de Medicamentos , Humanos , Imunossupressores/metabolismo , Imunossupressores/farmacologia , Inflamação/tratamento farmacológico , Concentração Inibidora 50 , Interleucina-2/biossíntese , Células Jurkat , Lactonas/metabolismo , Lactonas/farmacologia , Estrutura Molecular , Relação Estrutura-Atividade , Linfócitos T/metabolismo
18.
Mol Cells ; 32(2): 123-32, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21614488

RESUMO

1,2,3,4,6-penta-O-galloyl-beta-D-glucose (PGG), a polyphenolic compound isolated from Rhus chinensis Mill. PGG has been known to have anti-tumor, anti-angiogenic and anti-diabetic activities. The present study revealed another underlying molecular target of PGG in MDA-MB-231 breast cancer cells by using Illumina Human Ref-8 expression BeadChip assay. Through the Beadstudio v3 micro assay program to compare the identified genes expressed in PGG-treated MDA-MB-231 cells with untreated control, we found several unique genes that are closely associated with pyruvate metabolism, glycolysis/gluconeogenesis and tyrosine metabolism, including PC, ACSS2, ACACA, ACYP2, ALDH3B1, FBP1, PRMT2 and COMT. Consistent with microarray data, real-time RT-PCR confirmed the significant down-regulation of these genes at mRNA level in PGG-treated MDA-MB-231 cells. Our findings suggest the potential of PGG as anticancer agent for breast cancer cells by targeting cancer metabolism genes.


Assuntos
Inibidores da Angiogênese/farmacologia , Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Taninos Hidrolisáveis/farmacologia , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Feminino , Estudo de Associação Genômica Ampla , Glicólise/genética , Humanos , Análise em Microsséries , Terapia de Alvo Molecular , Ácido Pirúvico/metabolismo , Rhus , Tirosina/metabolismo
19.
Immunopharmacol Immunotoxicol ; 33(4): 682-90, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21395405

RESUMO

Ka-mi-kae-kyuk-tang (KMKKT) is an Oriental herbal medicinal cocktail and has been shown to have potent antiangiogenic, anticancer, and antimetastatic activities in preclinical animal models without observable side effects. We previously found that in prostate cancer xenograft experiments, treating tumor-bearing mice with KMKKT alleviated the body weight loss toward the end of the study, suggesting a general health-promoting activity. We investigated whether KMKKT alleviated cancer chemotherapy drug-induced leukopenia and other hematotoxicity in vivo using a mouse model. KMKKT was given once daily orally for 10 days to the mice before they were given cyclophosphamide (CPA) daily injection for 4 days. KMKKT blunted CPA-induced decrease in red blood cells, hemoglobin content, and the total white blood cell/leukocyte counts. Examination of the multiple organ sites involved in hematopoiesis, and lymphocyte differentiation and maturation showed the attenuated changes induced by CPA in each and every type of cells examined. Particularly, some of the cell types are fully restored in the bone marrow and even overstimulated in the Sca-1(+), CD117(+), or Sca1(+)/CD117(+) and CD34(+)/CD117(+) stem cells, supporting a role of KMKKT to stimulate hematopoietic stem cell (HSC) signaling to compensate for CPA-induced destruction of leukocytes and other cell types. Taken together, KMKKT might be a safe and effective herbal complementary and alternative medicine (CAM) modality to alleviate cancer drug-induced hematological side effects in addition to its anticancer activities. Preclinical investigations with other chemo- and radiation modalities are warranted to support planning translation consideration for human patients.


Assuntos
Ciclofosfamida/efeitos adversos , Medicamentos de Ervas Chinesas/farmacologia , Leucopenia/tratamento farmacológico , Medicina Tradicional Coreana , Animais , Antígenos de Diferenciação/sangue , Antígenos de Diferenciação/imunologia , Ciclofosfamida/farmacologia , Células-Tronco Hematopoéticas/imunologia , Células-Tronco Hematopoéticas/metabolismo , Humanos , Contagem de Leucócitos , Leucopenia/sangue , Leucopenia/induzido quimicamente , Leucopenia/imunologia , Masculino , Camundongos , Agonistas Mieloablativos/farmacologia
20.
Arch Pharm Res ; 33(6): 867-73, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20607491

RESUMO

We determined the ability of extracts and active components isolated from nine medicinal plants, Poncirus trifoliata, Astragalus membranaceus, Magnolia obovata, Salvia miltiorrhiza, Angelica dahurica, Cornus officinalis, Cnidium officinale, Pueraria lobata and Ostericum koreanum, to neutralize peroxyl radicals using the total oxyradical scavenging capacity (TOSC) assay. Peroxyl radicals were generated from thermal homolysis of 2,2'-azobis(2-methylpropionamidine) dihydrochloride, which oxidize alpha-keto-gamma-methiolbutyric acid to yield ethylene, and the TOSC of the substances tested is quantified from their ability to inhibit ethylene formation. Extracts from S. miltiorrhiza, M. obovata and P. lobata were determined to be potent peroxyl radical scavenging agents with a specific TOSC (sTOSC) being at least threefold greater than that of glutathione. Major constituents of the three plants, tanshinone, cryptotanshinone, 15,16-dihydrotanshinone, syringin, honokiol, magnolol, daidzein, puerarin and genistein, were examined for the antioxidant potential toward peroxyl radical. Puerarin and genistein were shown to have microM sTOSCs at least ten-fold greater than sTOSC of glutathione. Daidzein, syringin and honokiol demonstrated the peroxyl radical scavenging capacity comparable to that of glutathione. The implication of peroxyl radical in lipid peroxidation and other cellular damage suggests a possible protective role for the extracts and isolated components in oxidative stress caused by this reactive oxygen species.


Assuntos
Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/isolamento & purificação , Peróxidos/química , Extratos Vegetais/química , Plantas Medicinais/química , Amidinas/química , Descoberta de Drogas , Etilenos/química , Genisteína/química , Genisteína/isolamento & purificação , Isoflavonas/química , Isoflavonas/isolamento & purificação , Cinética , Magnolia/química , Medicina Tradicional do Leste Asiático , Metionina/análogos & derivados , Metionina/química , Oxidantes/química , Estresse Oxidativo/efeitos dos fármacos , Pueraria/química , Salvia miltiorrhiza/química
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