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1.
J Ginseng Res ; 44(3): 475-482, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32372869

RESUMO

BACKGROUND: Active natural ingredients, especially small molecules, have recently received wide attention as modifiers used to treat neurodegenerative disease by promoting neurogenic regeneration of neural stem cell (NSC) in situ. 20(S)-protopanaxadiol (PPD), one of the bioactive ingredients in ginseng, possesses neuroprotective properties. However, the effect of PPD on NSC proliferation and differentiation and its mechanism of action are incompletely understood. METHODS: In this study, we investigated the impact of PPD on NSC proliferation and neuronal lineage differentiation through activation of the Wnt/glycogen synthase kinase (GSK)-3ß/ß-catenin pathway. NSC migration and proliferation were investigated by neurosphere assay, Cell Counting Kit-8 assay, and EdU assay. NSC differentiation was analyzed by Western blot and immunofluorescence staining. Involvement of the Wnt/GSK3ß/ß-catenin pathway was examined by molecular simulation and Western blot and verified using gene transfection. RESULTS: PPD significantly promoted neural migration and induced a significant increase in NSC proliferation in a time- and dose-dependent manner. Furthermore, a remarkable increase in antimicrotubule-associated protein 2 expression and decrease in nestin protein expression were induced by PPD. During the differentiation process, PPD targeted and stimulated the phosphorylation of GSK-3ß at Ser9 and the active forms of ß-catenin, resulting in activation of the Wnt/GSK-3ß/ß-catenin pathway. Transfection of NSCs with a constitutively active GSK-3ß mutant at S9A significantly hampered the proliferation and neural differentiation mediated by PPD. CONCLUSION: PPD promotes NSC proliferation and neural differentiation in vitro via activation of the Wnt/GSK-3ß/ß-catenin pathway by targeting GSK-3ß, potentially having great significance for the treatment of neurodegenerative diseases.

3.
Mol Pharm ; 12(6): 2112-25, 2015 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-25881668

RESUMO

Oleanolic acid (OA) is a natural triterpenoid with anticancer properties, but its hydrophobic nature and poor aqueous solubility pose challenges in pharmaceutical formulation development. The present study aimed at developing OA-loaded mPEG-PLGA or mPEG-PLA nanoparticles (NPs) to improve the delivery of OA. The NPs were prepared by nanoprecipitation, and their physicochemical properties were characterized. The OA encapsulation efficiency of the NPs was between 40 and 75%. The size of the OA-loaded NPs was around 200-250 nm, which fell within the range required for tumor targeting by means of the enhanced permeability and retention (EPR) effect, and the negatively charged NPs remained physically stable for over 20 weeks with no aggregation observed. The OA-loaded NPs produced significant cytotoxic effects through apoptosis in cancer cell lines. Overall, the OA-loaded mPEG-PLGA NPs and mPEG-PLA NPs shared similar physicochemical properties. The former, especially the OA-loaded mPEG-P(D,L)LGA NPs, were more cytotoxic to cancer cells and therefore were more efficient for OA delivery.


Assuntos
Ácido Láctico/química , Nanopartículas/química , Ácido Oleanólico/química , Ácido Poliglicólico/química , Apoptose/efeitos dos fármacos , Linhagem Celular , Portadores de Fármacos , Células Hep G2 , Humanos , Espectroscopia de Ressonância Magnética , Neoplasias , Ácido Oleanólico/farmacologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico
4.
Menopause ; 20(7): 767-76, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23793167

RESUMO

OBJECTIVE: The aim of this study is to investigate the effectiveness and safety of a Chinese herbal formula, Er-Xian decoction (EXD), in the treatment of menopausal symptoms among Hong Kong perimenopausal women. METHODS: A randomized, double-blind, controlled trial was conducted for 12 weeks among 108 Hong Kong perimenopausal women who reported Menopause Rating Scale (MRS) total scores of 28 or higher. Posttreatment follow-up was performed 3 months after the intervention. The primary outcome measure was the frequency and severity of hot flushes. The secondary outcome measures included the MRS, the Menopause-Specific Quality of Life questionnaire, and serum hormone levels. RESULTS: Among 108 participants, 101 participants finished the study. EXD significantly reduced the mean (SD) frequency of hot flushes from 5.8 (5.0) to 2.2 (3.0) in the treatment group and from 5.0 (3.8) to 2.4 (2.5) in the placebo group (P = 0.04). The mean (SD) hot flush score was also reduced from 19.6 (6.6) to 4.9 (7.8) in the treatment group and from 16.6 (5.4) to 7.0 (6.4) in the placebo group (P = 0.02). The superiority of EXD to placebo was also observed with greater improvement in the total scores for the MRS (P = 0.03) and the Menopause-Specific Quality of Life questionnaire (P < 0.01). There were no differences in serum hormone levels between the EXD group and the placebo group. There were no serious adverse events, and the safety indices of whole blood counts, renal function, and liver function were within the normal range before and after treatment. CONCLUSIONS: The Chinese herbal formula EXD is superior to placebo in reducing the frequency and severity of hot flushes and in improving menopausal symptoms in Hong Kong perimenopausal women. It is well tolerated, with no serious adverse events noted during the study period.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Perimenopausa , Método Duplo-Cego , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Hong Kong , Fogachos/tratamento farmacológico , Humanos , Hormônio Luteinizante/sangue , Pessoa de Meia-Idade , Placebos , Progesterona/sangue , Qualidade de Vida , Inquéritos e Questionários
5.
Integr Cancer Ther ; 12(4): 336-46, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23241639

RESUMO

OBJECTIVES: Erxian Decoction (EXD) is a well-documented Chinese medicinal formulation, which has been clinically applied for years for relieving menopausal syndromes by modulating hormonal levels indicating that EXD might also be effective in treating hormone-related tumors. This study aimed to differentially investigate the efficacy of EXD and its antimetastatic property on human ovarian cancer cells, OVCA429. METHODS: The efficacy and cell cycle progression of EXD on OVCA429 cells was determined by MTT assay and flow cytometry, respectively. The modulated expression of metastatic markers by EXD in OVCA429 cells and xenografts was evaluated at transcriptional and translational levels by Western blotting and real-time polymerase chain reaction, respectively. The migrating and invasive ability of the cancer cells were determined by wound healing and invasive assays. RESULTS: The IC50 value of EXD on OVCA429 cells was determined after 24 hours incubation with EXD at 1 mg/mL. EXD (1.5 mg/mL) mediated S-phase cell cycle arrest and apoptotic cell death at 24 hours posttreatment. EXD repressed the expression of several metastatic mediators, including EGFR, ErbB2, MMP2, MMP7, MMP9, and VEGF in OVCA429 cells and xenografts at transcriptional and/or translational levels. Furthermore, EXD functionally demonstrated significant inhibition of migrating and invasive ability of OVCA429 cells. EXD suppressed tumor size in xenografts without any adverse effects on body weight. CONCLUSIONS: This is the first study that illustrates the antimetastatic property of EXD on human ovarian cancer models. This decoction merits serious consideration for further delineation of its multiple pharmacological effects, especially on hormone-related cancers, and these would be valuable for future clinical applications of EXD as an alternative regime for cancers.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa , Neoplasias Ovarianas/tratamento farmacológico , Animais , Proliferação de Células/efeitos dos fármacos , Feminino , Humanos , Camundongos , Camundongos Nus , Metástase Neoplásica , Neoplasias Ovarianas/patologia , Fitoterapia , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
6.
Biol Pharm Bull ; 35(12): 2119-27, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23018578

RESUMO

Erxian Decoction (EXD), a traditional Chinese herbal formula, has been used to treat menopausal symptoms and other aging diseases for several decades. Recently, our laboratory found that EXD could inhibit the proliferation of breast cancer cells. This activity may be mediated by anti-angiogenic action. To investigate the anti-angiogenic activity of EXD, its inhibitory effect on blood vessel formation was evaluated using both wild type and transgenic zebrafish embryos with fluorescent vasculature in vivo. Both semi-quantitative and real-time quantitative polymerase chain reaction (qPCR) were carried out to evaluate the effect of EXD on the expression of several genes closely associated with angiogenesis in zebrafish. EXD was found to inhibit vessel formation in zebrafish embryos in a dose- and time-dependent manner. Furthermore, it reduced the mRNA expression of vascular endothelial growth factor A (VEGF-A) and the protein level of hypoxia inducible factor 1α (HIF-1α) in the embryos, suggesting the involvement of HIF-1 mediated VEGF-A signaling pathway in the anti-angiogenic action of EXD. The anti-angiogenic activity of EXD provides new insights to its clinical application and may in the future lead to the development of potential drugs for treating various cancers, especially in menopausal period.


Assuntos
Inibidores da Angiogênese/farmacologia , Vasos Sanguíneos/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Expressão Gênica/efeitos dos fármacos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neovascularização Patológica/prevenção & controle , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Antineoplásicos Fitogênicos/farmacologia , Vasos Sanguíneos/metabolismo , Neoplasias da Mama/tratamento farmacológico , Relação Dose-Resposta a Droga , Feminino , Fitoterapia , Reação em Cadeia da Polimerase , RNA Mensageiro/metabolismo , Transdução de Sinais , Fator A de Crescimento do Endotélio Vascular/genética , Peixe-Zebra
7.
Integr Cancer Ther ; 10(1): 58-69, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20702488

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Tian-Xian liquid (TXL), a commercially available Chinese medicine decoction, has been used as an anticancer dietary agent for more than 10 years without reported side effects. AIM OF THE STUDY: The safety and quality consistency of TXL and its mechanisms of action on antiproliferation, antimetastasis, and reversion of multidrug resistance (MDR) regimens were explored. MATERIALS AND METHODS: In this study, an atomic absorption spectrophotometer and reversed phase high performance liquid chromatography with photodiode array detection (HPLC-DAD) were used to evaluate the main toxic elements and the quality consistency among different batches of TXL extracts, respectively. HT29 human colon cancer cell line and tumor-bearing nude mice were used. TXL was provided by China-Japan Feida Union Company Limited. The effect of TXL on in vitro proliferation of HT29 human colon cancer cell line was examined. The percentages of treated cells distributed in different phases of the cell cycles were analyzed by flow cytometry. Antiproliferative effect after treatment with TXL was assessed by determination of the protein levels of p21, cyclinD1, PCNA, and cdk-2, which are the key regulators for cell cycle progression. Meanwhile, the protein levels of MMP-1 and MDR-1 (multidrug resistance protein-1) were also determined to assess the effect of TXL on antimetastasis and reversion of MDR regimen, respectively. RESULTS: The contents of main toxic elements were lower in TXL extract compared with the standard set by the Department of Health of the Government of Hong Kong Special Administrative Region (SAR). Our HPLC results showed that the relative standard deviations of the amount of the 5 standards were less than 5% in different batches of TXL. Immunoblotting analysis revealed a dramatic induction of cyclin kinase inhibitor p21 as well as an inhibition of cyclinD1, PCNA, and cdk-2 in the TXL-treated in vitro models, thereby, impeding cell progression from G1/S phase. Results obtained from the in vivo study also demonstrated that TXL upregulated the protein level of p21 and downregulated the protein levels of MMP-1 and MDR-1. CONCLUSIONS: Results obtained from the present investigation not only demonstrate the safety and quality of TXL extract but also demonstrate that TXL possesses antiproliferative and antimetastatic activities and brings about reversion of MDR on HT29 cell and on xenografted tissue in tumor-implanted nude mice.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/biossíntese , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/biossíntese , Medicamentos de Ervas Chinesas/farmacologia , Metaloproteinase 1 da Matriz/biossíntese , Subfamília B de Transportador de Cassetes de Ligação de ATP , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Animais , Proteína Quinase CDC2/biossíntese , Proteína Quinase CDC2/genética , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Inibidor de Quinase Dependente de Ciclina p21/genética , Medicamentos de Ervas Chinesas/efeitos adversos , Medicamentos de Ervas Chinesas/química , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células HT29 , Humanos , Metaloproteinase 1 da Matriz/genética , Camundongos , Camundongos Nus , Antígeno Nuclear de Célula em Proliferação/biossíntese , Antígeno Nuclear de Célula em Proliferação/genética
8.
Protein Pept Lett ; 17(1): 38-43, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20214629

RESUMO

An agglutinin with a molecular mass of 130 kDa has been isolated from the seeds of Alpinia zerumbet cv.'Variegata'. The isolation procedure involved anion exchange chromatography on DEAE-cellulose, affinity chromatography on Affi-gel blue gel, and gel filtration by fast protein liquid chromatography on Superdex 75. The agglutinin exhibited hemagglutinating activity toward rabbit erythrocytes which could not be inhibited by simple sugars. It was composed of four identical 32-kDa subunits with substantial N-terminal sequence similarity to chitinase and yieldin. The hemagglutinating activity of A. zerumbet agglutinin was stable up to 80(o)C and not affected by presence of a variety of salts. The agglutinin stimulated [methyl-(3)H]-thymidine uptake by mouse splenocytes. It did not exhibit antifungal activity.


Assuntos
Aglutininas/química , Alpinia/química , Cromatografia por Troca Iônica/métodos , Aglutininas/genética , Aglutininas/metabolismo , Aglutininas/farmacologia , Animais , Processos de Crescimento Celular/efeitos dos fármacos , Células Cultivadas , Camundongos , Micélio/efeitos dos fármacos , Micélio/crescimento & desenvolvimento , Estabilidade Proteica , Sementes/química
9.
Biomed Chromatogr ; 24(5): 479-89, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-19688819

RESUMO

A simple and specific LC-DAD-ESI-MS/MS method has been developed and applied for the primary investigation of the chemical constituents absorbed or metabolized in vivo, after the rat oral administration of Erxian Decoction (EXD), a Chinese medicine prescription for menopausal syndromes. Through the online ESI-MS(n) analysis, a total of 35 compounds have been identified or tentatively characterized from the seven tested samples, and 13 of them were unambiguously identified through a direct comparison of the retention time, UV spectra and MS(n) fragmentation patterns with the authentic ones. The results showed that 21 compounds were detected from rat plasma, 20 compounds were detected from rat kidneys and adrenal glands, 19 compounds were detected from rat ovaries, 12 compounds were found in rat intestines, nine compounds were identified from rat livers and nine compounds were detected from rat brains at certain time points after oral administration of the effective EXD fraction.


Assuntos
Cromatografia Líquida/métodos , Medicamentos de Ervas Chinesas/análise , Medicamentos de Ervas Chinesas/farmacocinética , Espectrometria de Massas por Ionização por Electrospray/métodos , Administração Oral , Animais , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/metabolismo , Feminino , Ratos , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem/métodos
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