Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 5 de 5
Filtrar
Más filtros

Medicinas Complementárias
Métodos Terapéuticos y Terapias MTCI
Bases de datos
Tipo del documento
País de afiliación
Intervalo de año de publicación
1.
Phytomedicine ; 40: 1-9, 2018 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-29496161

RESUMEN

BACKGROUND: The nuclear factor erythroid 2-related factor 2 (Nrf2) is a potential molecular target for cancer chemoprevention. Si-Wu-Tang (SWT), a popular traditional Chinese medicine for women's health, was reported with a novel activity of cancer prevention. PURPOSE: The present study was aimed to identify the bioactive constituents in SWT responsible for the Nrf2 activating and cancer preventive activity and explore the pharmacological mechanisms. METHODS: Nine compounds detectable from various batches of SWT were ranked using in silico molecular docking based on their ability to interfere the forming of Nrf2-Keap1 complex. The predicted Nrf2 activating effect was validated using the antioxidant response element (ARE) luciferase reporter assay and quantitative RT-PCR analysis for select Nrf2 regulated genes Hmox1, Nqo1 and Slc7a11. The antimutagenic activity of the compounds were determined by the Ames test. The chemopreventive activity of these compounds were assessed on EGF-induced neoplastic transformation of JB6 P+ cells, an established non-cancerous murine epidermal model for studying tumor promotion and identifying cancer preventive agents. These compounds were further characterized using luciferase reporter assay on EGF-induced activation of AP-1, a known transcription factor mediating carcinogenesis. RESULTS: Three of the nine compounds predicted as Nrf2 activators by molecular docking, gallic acid (GA), Z-liguistilide (LIG), and senkyunolide A (SA), were confirmed with highest potency of increasing the Nrf2/ARE promoter activity and upregulating the expression of Hmox1, Nqo1 and Slc7a11. In addition, GA, LIG and SA exhibited an antimutagenic activity against the direct mutagen 2-nitrofluorene while no mutagenic effects were observed at the same time in Ames test. At nontoxic concentrations, GA, LIG, and SA inhibited EGF-induced neoplastic transformation of JB6 P+ cells. Combined treatment of GA, LIG and SA, in the same ratio as detected in SWT, showed enhanced effect against JB6 transformation compared with that of the single compound alone. GA, LIG and SA, alone or in combination, suppressed EGF-induced activation of AP-1. CONCLUSION: We identified three bioactive constituents in SWT responsible for the Nrf2 activating and cancer preventive activity. This study provides evidence supporting novel molecular basis of SWT in cancer prevention.


Asunto(s)
Anticarcinógenos/química , Anticarcinógenos/farmacología , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Factor 2 Relacionado con NF-E2/metabolismo , Animales , Elementos de Respuesta Antioxidante/efectos de los fármacos , Elementos de Respuesta Antioxidante/genética , Línea Celular , Transformación Celular Neoplásica/efectos de los fármacos , Transformación Celular Neoplásica/genética , Regulación de la Expresión Génica/efectos de los fármacos , Hemo-Oxigenasa 1 , Humanos , Medicina Tradicional China , Ratones , Simulación del Acoplamiento Molecular , NAD(P)H Deshidrogenasa (Quinona)/genética , NAD(P)H Deshidrogenasa (Quinona)/metabolismo , Transducción de Señal/efectos de los fármacos , Factor de Transcripción AP-1/genética , Factor de Transcripción AP-1/metabolismo
2.
Nutrients ; 9(3)2017 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-28335476

RESUMEN

Exploring traditional medicines may lead to the development of low-cost and non-toxic cancer preventive agents. Si-Wu-Tang (SWT), comprising the combination of four herbs, Rehmanniae, Angelica, Chuanxiong, and Paeoniae, is one of the most popular traditional Chinese medicines for women's diseases. In our previous studies, the antioxidant Nrf2 pathways were strongly induced by SWT in vitro and in vivo. Since Nrf2 activation has been associated with anticarcinogenic effects, the purpose of this study is to evaluate SWT's activity of cancer prevention. In the Ames test, SWT demonstrated an antimutagenic activity against mutagenicity induced by the chemical carcinogen 7,12-dimethylbenz(a)anthracene (DMBA). In JB6 P+ cells, a non-cancerous murine epidermal model for studying tumor promotion, SWT inhibited epidermal growth factor (EGF)-induced neoplastic transformation. The luciferase reporter gene assays demonstrated that SWT suppressed EGF-induced AP-1 and TNF-α-induced NF-κB activation, which are essential factors involved in skin carcinogenesis. In a DMBA-induced skin hyperplasia assay in 'Sensitivity to Carcinogenesis' (SENCAR) mice, both topical and oral SWT inhibited DMBA-induced epidermal hyperplasia, expression of the proliferation marker Proliferating cell nuclear antigen (PCNA), and H-ras mutations. These findings demonstrate, for the first time, that SWT prevents tumor promoter and chemical-induced carcinogenesis in vitro and in vivo, partly by inhibiting DNA damage and blocking the activation of AP-1 and NF-κB.


Asunto(s)
Anticarcinógenos/farmacología , Transformación Celular Neoplásica/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Hiperplasia/prevención & control , Piel/efectos de los fármacos , 9,10-Dimetil-1,2-benzantraceno/toxicidad , Animales , Proteínas Portadoras/genética , Proteínas Portadoras/metabolismo , Línea Celular Tumoral , Daño del ADN/efectos de los fármacos , Femenino , Regulación de la Expresión Génica , Genes Reporteros , Hiperplasia/etiología , Ratones , Ratones Endogámicos SENCAR , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , FN-kappa B/genética , FN-kappa B/metabolismo , Piel/patología , Factor de Transcripción AP-1/genética , Factor de Transcripción AP-1/metabolismo , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo
3.
Toxicol Sci ; 139(2): 338-49, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24595819

RESUMEN

Ginkgo biloba has been used for many thousand years as a traditional herbal remedy and its extract has been consumed for many decades as a dietary supplement. Ginkgo biloba leaf extract is a complex mixture with many constituents, including flavonol glycosides and terpene lactones. The National Toxicology Program 2-year cancer bioassay found that G. biloba leaf extract targets the liver, thyroid gland, and nose of rodents; however, the mechanism of G. biloba leaf extract-associated carcinogenicity remains unclear. In the current study, the in vitro genotoxicity of G. biloba leaf extract and its eight constituents was evaluated using the mouse lymphoma assay (MLA) and Comet assay. The underlying mechanisms of G. biloba leaf extract-associated genotoxicity were explored. Ginkgo biloba leaf extract, quercetin, and kaempferol resulted in a dose-dependent increase in the mutant frequency and DNA double-strand breaks (DSBs). Western blot analysis confirmed that G. biloba leaf extract, quercetin, and kaempferol activated the DNA damage signaling pathway with increased expression of γ-H2AX and phosphorylated Chk2 and Chk1. In addition, G. biloba leaf extract produced reactive oxygen species and decreased glutathione levels in L5178Y cells. Loss of heterozygosity analysis of mutants indicated that G. biloba leaf extract, quercetin, and kaempferol treatments resulted in extensive chromosomal damage. These results indicate that G. biloba leaf extract and its two constituents, quercetin and kaempferol, are mutagenic to the mouse L5178Y cells and induce DSBs. Quercetin and kaempferol likely are major contributors to G. biloba leaf extract-induced genotoxicity.


Asunto(s)
Daño del ADN , Ginkgo biloba/química , Mutágenos/toxicidad , Extractos Vegetales/toxicidad , Animales , Técnicas de Cultivo de Célula , Línea Celular , Supervivencia Celular/efectos de los fármacos , Ensayo Cometa , Relación Dosis-Respuesta a Droga , Glutatión/metabolismo , Quempferoles/toxicidad , Ratones , Hojas de la Planta/química , Quercetina/toxicidad , Especies Reactivas de Oxígeno/metabolismo
4.
Toxicol Sci ; 124(2): 388-99, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-21908763

RESUMEN

Kava is a plant traditionally used for making beverages in Pacific Basin countries and has been used for the treatment of nervous disorders in the United States. The pharmacological activity of kava is achieved through kavalactones in kava extract, which include kawain, 7,8-dihydrokawain, yangonin, 5,6-dehydrokawain, methysticin, and 7,8-dihydromethysticin. Recent studies have shown that kava extract induces hepatic CYP1A1 enzyme; however, the mechanisms of CYP1A1 induction have not been elucidated, and the kavalactones responsible for CYP1A1 induction have not yet been identified. Using a combination of biochemical assays and molecular docking tools, we determined the functions of kava extract and kavalactones and delineated the underlying mechanisms involved in CYP1A1 induction. The results showed that kava extract displayed a concentration-dependent effect on CYP1A1 induction. Among the six major kavalactones, methysticin triggered the most profound inducing effect on CYP1A1 followed by 7,8-dihydromethysticin. The other four kavalactones (yangonin, 5,6-dehydrokawain, kawain, and 7,8-dihydrokawain) did not show significant effects on CYP1A1. Consistent with the experimental results, in silico molecular docking studies based on the aryl hydrocarbon receptor (AhR)-ligand binding domain homology model also revealed favorable binding to AhR for methysticin and 7,8-dihydromethysticin compared with the remaining kavalactones. Additionally, results from a luciferase gene reporter assay suggested that kava extract, methysticin, and 7,8-dihydromethysticin were able to activate the AhR signaling pathway. Moreover, kava extract-, methysticin-, and 7,8-dihydromethysticin-mediated CYP1A1 induction was blocked by an AhR antagonist and abolished in AhR-deficient cells. These findings suggest that kava extract induces the expression of CYP1A1 via an AhR-dependent mechanism and that methysticin and 7,8-dihydromethysticin contribute to CYP1A1 induction. The induction of CYP1A1 indicates a potential interaction between kava or kavalactones and CYP1A1-mediated chemical carcinogenesis.


Asunto(s)
Citocromo P-450 CYP1A1/biosíntesis , Kava/química , Lactonas/farmacología , Extractos Vegetales/química , Piranos/farmacología , Pironas/farmacología , Animales , Sitios de Unión , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Citocromo P-450 CYP1A1/genética , Relación Dosis-Respuesta a Droga , Inducción Enzimática , Expresión Génica/efectos de los fármacos , Lactonas/aislamiento & purificación , Ligandos , Ratones , Modelos Moleculares , Estructura Molecular , Unión Proteica , Piranos/aislamiento & purificación , Pironas/aislamiento & purificación , Receptores de Hidrocarburo de Aril/agonistas , Receptores de Hidrocarburo de Aril/genética , Transfección
5.
Zhong Yao Cai ; 25(1): 29-31, 2002 Jan.
Artículo en Chino | MEDLINE | ID: mdl-12583239

RESUMEN

OBJECTIVE: To study the protective effect of tea pigments on mice skin photoaging induced by UV irradiation. METHOD: Total antioxidative ability and content of lipid peroxidation products malondialdehyde in the skin of mice were examined with colorimetry. RESULT: By ig or smearing, tea pigments could significantly improve total antioxidative ability and decline content of malondialdehyde in UV-irradiation-induced skin photoaging mice. CONCLUSION: The results suggested that tea pigments could prevent mice skin from free radicals injury resulting from UV irradiation and moderate skin photoaging.


Asunto(s)
Catequina/análogos & derivados , Pigmentos Biológicos/farmacología , Protectores contra Radiación/farmacología , Envejecimiento de la Piel/efectos de los fármacos , , Rayos Ultravioleta , Animales , Antioxidantes/aislamiento & purificación , Antioxidantes/farmacología , Biflavonoides/aislamiento & purificación , Biflavonoides/farmacología , Catequina/aislamiento & purificación , Catequina/farmacología , Femenino , Ratones , Fenoles/aislamiento & purificación , Fenoles/farmacología , Pigmentos Biológicos/aislamiento & purificación , Polifenoles , Protectores contra Radiación/aislamiento & purificación , Piel/efectos de los fármacos , Piel/efectos de la radiación , Envejecimiento de la Piel/efectos de la radiación , Té/química
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA