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1.
Oncol Rep ; 38(3): 1597-1604, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28714027

RESUMO

Worldwide, colorectal cancer is the third most common cancer in men and the second most common in women. As conventional colorectal cancer therapies result in various side effects, there is a need for adjuvant therapy that can enhance the conventional therapies without complications. In this study, we investigated the anticancer effects of combined mixture of the several medicinal mushrooms and Panax ginseng root extracts (also called Amex7) as an adjuvant compound in the treatment of human colorectal cancer. We observed the in vivo inhibitory effect of Amex7 (1.25, 6.25, and 12.5 ml/kg, oral administration, twice daily) on tumor growth in a mouse model xenografted with HT-29 human colorectal cancer cells. In vitro, at 6, 12, and 24 h after 4% Amex7 treatment, we analyzed cell cycle by flow cytometry and the expression levels of cell cycle progression, apoptosis, and DNA damage repair-related proteins using immunoblotting and immunofluorescence staining in HT-29 cell line. As a result, Amex7 significantly suppressed tumor growth in HT-29 human colorectal cancer cells and xenografts. In vitro, Amex7 induced G2/M arrest through the regulation of cell cycle proteins and cell death by apoptosis and autophagy. Additionally, Amex7 consistently induced DNA damage and delayed the repair of Amex7-induced DNA damage by reducing the level of HR repair proteins. In conclusion, Amex7 enhanced anticancer effects through the induction of G2/M arrest and cell death, including apoptosis and autophagy. Furthermore, Amex7 impaired DNA damage repair. The present study provides a scientific rationale for the clinical use of a combined mixture of medicinal mushrooms and P. ginseng root extracts as an adjuvant treatment in human colorectal cancer.


Assuntos
Agaricales/química , Neoplasias Colorretais/tratamento farmacológico , Panax/química , Extratos Vegetais/farmacologia , Raízes de Plantas/química , Animais , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Reparo do DNA/efeitos dos fármacos , Sinergismo Farmacológico , Células HT29 , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus
2.
J Med Food ; 18(12): 1317-26, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26291170

RESUMO

Ilex latifolia Thunb. (Aquifoliaceae), a Chinese bitter tea called "kudingcha," has been widely consumed as a health beverage and found to possess antioxidant, antidiabetic, antihypertensive, anti-inflammatory, and anti-ischemic activities. The aim of the present study was to investigate the neuroprotective effects of an ethanol extract of I. latifolia against amyloid ß protein (Aß)-induced memory impairment in mice and neurotoxicity in cultured rat cortical neurons. Memory impairment in mice was induced by intracerebroventricular injection of 15 nmol Aß (25-35) and measured by the passive avoidance test and Morris water maze test. Chronic administration of I. latifolia (25-100 mg/kg, p.o.) significantly prevented Aß (25-35)-induced memory loss. I. latifolia also prevented the decrease of glutathione concentrations, increased lipid peroxidation, expression of phosphorylated tau (p-tau), and changes in apoptosis-associated proteins in the memory-impaired mouse brain. Exposure of cultured cortical neurons to 10 µM Aß (25-35) for 36 h induced neuronal apoptotic death. The neuronal cell death, elevation of intracellular Ca(2+) concentration, generation of reactive oxygen species, and expression of proapoptotic proteins caused by Aß (25-35) in the cultured neurons were inhibited by treatment with I. latifolia (1-50 µg/mL). These results suggest that I. latifolia may have a possible therapeutic role in managing cognitive impairment associated with Alzheimer's disease. The underlying mechanism might involve the antiapoptotic effects mediated by antioxidant activity and inhibition of p-tau formation.


Assuntos
Doença de Alzheimer/metabolismo , Proteínas Reguladoras de Apoptose/metabolismo , Encéfalo/efeitos dos fármacos , Transtornos Cognitivos/metabolismo , Ilex , Transtornos da Memória/metabolismo , Proteínas tau/metabolismo , Doença de Alzheimer/complicações , Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/efeitos adversos , Peptídeos beta-Amiloides/metabolismo , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Apoptose , Encéfalo/citologia , Encéfalo/metabolismo , Cálcio/metabolismo , Células Cultivadas , Transtornos Cognitivos/tratamento farmacológico , Glutationa/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Memória/efeitos dos fármacos , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/etiologia , Camundongos Endogâmicos ICR , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Fosforilação , Fitoterapia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo
3.
Arch Pharm Res ; 35(6): 1115-22, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22870822

RESUMO

Ilex latifolia (Aquifoliaceae), one of the primary components of "Ku-ding-cha", has been used in Chinese folk medicine to treat headaches and various inflammatory diseases. A previous study demonstrated that the ethanol extract of I. latifolia could protect against ischemic apoptotic brain damage in rats. The present study investigated the protective activity of I. latifolia against glutamate-induced neurotoxicity using cultured rat cortical neurons in order to explain a possible mechanism related to its inhibitory effect on ischemic brain damage and identified potentially active compounds from it. Exposure of cultured cortical neurons to 500 µM glutamate for 12 h triggered neuronal cell death. I. latifolia (10-100 µg/mL) inhibited glutamate-induced neuronal death, elevation of intracellular calcium ([Ca(2+)](i)), generation of reactive oxygen species (ROS), the increase of a pro-apoptotic protein, BAX, and the decrease of an anti-apoptotic protein, BcL-2. Hypoxia-induced neuronal cell death was also inhibited by I. latifolia. 3,4-Dicaffeoylquinic acid (diCQA), 3,5-diCQA, and 3,5-diCQA methyl ester isolated from I. latifolia also inhibited the glutamate-induced increase in [Ca(2+)](i), generation of ROS, the change of apoptosis-related proteins, and neuronal cell death; and hypoxia-induced neuronal cell death. These results suggest that I. latifolia and its active compounds prevented glutamate-induced neuronal cell damage by inhibiting increase of [Ca(2+)](i), generation of ROS, and resultantly apoptotic pathway. In addition, the neuroprotective effects of I. latifolia on ischemia-induced brain damage might be associated with the anti-excitatory and anti-oxidative actions and could be attributable to these active compounds, CQAs.


Assuntos
Córtex Cerebral/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Agonistas de Aminoácidos Excitatórios/toxicidade , Ácido Glutâmico/toxicidade , Ilex , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Extratos Vegetais/farmacologia , Ácido Quínico/análogos & derivados , Animais , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/metabolismo , Cálcio/metabolismo , Hipóxia Celular , Células Cultivadas , Córtex Cerebral/embriologia , Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/isolamento & purificação , Ilex/química , Neurônios/metabolismo , Neurônios/patologia , Fármacos Neuroprotetores/isolamento & purificação , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/isolamento & purificação , Folhas de Planta , Plantas Medicinais , Ácido Quínico/isolamento & purificação , Ácido Quínico/farmacologia , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Fatores de Tempo
4.
BMC Cancer ; 11: 307, 2011 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-21781302

RESUMO

BACKGROUND: Polysaccharides extracted from the Phellinus linteus (PL) mushroom are known to possess anti-tumor effects. However, the molecular mechanisms responsible for the anti-tumor properties of PL remain to be explored. Experiments were carried out to unravel the anticancer effects of PL. METHODS: The anti-cancer effects of PL were examined in SW480 colon cancer cells by evaluating cell proliferation, invasion and matrix metallo-proteinase (MMP) activity. The anti-angiogenic effects of PL were examined by assessing human umbilical vein endothelial cell (HUVEC) proliferation and capillary tube formation. The in vivo effect of PL was evaluated in an athymic nude mouse SW480 tumor engraft model. RESULTS: PL (125-1000 µg/mL) significantly inhibited cell proliferation and decreased ß-catenin expression in SW480 cells. Expression of cyclin D1, one of the downstream-regulated genes of ß-catenin, and T-cell factor/lymphocyte enhancer binding factor (TCF/LEF) transcription activity were also significantly reduced by PL treatment. PL inhibited in vitro invasion and motility as well as the activity of MMP-9. In addition, PL treatment inhibited HUVEC proliferation and capillary tube formation. Tumor growth of SW480 cells implanted into nude mice was significantly decreased as a consequence of PL treatment, and tumor tissues from treated animals showed an increase in the apoptotic index and a decrease in ß-catenin expression. Moreover, the proliferation index and microvessel density were significantly decreased. CONCLUSIONS: These data suggest that PL suppresses tumor growth, invasion, and angiogenesis through the inhibition of Wnt/ß-catenin signaling in certain colon cancer cells.


Assuntos
Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Polissacarídeos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Carga Tumoral/efeitos dos fármacos , Agaricales/química , Animais , Western Blotting , Linhagem Celular , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Ciclina D1/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica , Neovascularização Patológica/prevenção & controle , Phellinus , Extratos Vegetais , Polissacarídeos/metabolismo , Ligação Proteica , Fatores de Transcrição TCF/metabolismo , Proteínas Wnt/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , beta Catenina/metabolismo
5.
J Ethnopharmacol ; 133(2): 558-64, 2011 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-21029769

RESUMO

AIMS OF THE STUDY: Ilex latifolia (Aquifoliaceae), a primary component of "kudingcha", has been used in Chinese folk medicine to treat various kinds of diseases including headaches, inflammatory diseases, and cardiac ischemic injury. The present study investigated the protective effect of the ethanol extract of Ilex latifolia against transient, focal, ischemia-induced neuronal damage. MATERIALS AND METHODS: Transient focal ischemia was induced by 2 h middle cerebral artery occlusion followed by 24 h reperfusion (MCAO/reperfusion) in rats. After MCAO/reperfusion, brain infarction and neuronal death were measured by triphenyltetrazolium chloride and hematoxylin and eosin staining, respectively. Glutathione concentration and lipid peroxidation rate were measured. The expression levels of phosphorylated mitogen activated proteins kinases (MAPKs), cyclooxygenase 2 (COX-2), and anti-apoptotic and pro-apoptotic proteins were detected by Western blot. RESULTS: Ilex latifolia (50-200 mg/kg) significantly reduced MCAO/reperfusion-induced infarction and edema formation, neurological deficits, and brain cell death. Depletion of glutathione level and lipid peroxidation induced by MCAO/reperfusion were inhibited by administration of Ilex latifolia. The increase of phosphorylated MAPKs, COX-2, and proapoptotic proteins and the decrease of antiapoptotic protein in MCAO/reperfusion rats were significantly inhibited by treatment with Ilex latifolia. CONCLUSION: Ilex latifolia ameliorated ischemic injury induced by MCAO/reperfusion in rats, and this neuroprotective effect might be associated with its anti-apoptotic effect, resulting from anti-oxidative and anti-inflammatory actions.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Ilex , Fármacos Neuroprotetores/farmacologia , Fitoterapia , Animais , Comportamento Animal/efeitos dos fármacos , Isquemia Encefálica/patologia , Isquemia Encefálica/fisiopatologia , Ciclo-Oxigenase 2/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Etnofarmacologia , Glutationa/metabolismo , Humanos , Ilex/química , Peroxidação de Lipídeos/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Medicina Tradicional Chinesa , Neurônios/efeitos dos fármacos , Neurônios/patologia , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia
6.
Planta Med ; 74(7): 726-9, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18484520

RESUMO

To provide a better understanding of the anti-complement activity of triterpenoids, seven unusual pentacyclic triterpenoids bearing a carboxyl group at C-27 were evaluated for their anticomplement activities against the classical pathway of the complement system. The triterpenoids were isolated from the whole plant of Aceriphyllum rossii of the family Saxifragaceae and were determined to be 3alpha,23-isopropylidenedioxyolean-12-en-27-oic acid (1), 3-oxoolean-12-en-27-oic acid (2), 3alpha-hydroxyolean-12-en-27-oic acid (3), beta-peltoboykinolic acid (4), 3alpha,23-diacetoxyolean-12-en-27-oic acid (5), 23-hydroxy-3-oxoolean-12-en-27-oic acid (6) and aceriphyllic acid A ( 7). Among them, compounds 2, 3, and 5 showed significant anticomplement activity on the classical pathway with IC (50) values of 71.4, 98.5, and 180.7 microM, respectively, whereas compounds 1, 4, 6, and 7 were inactive. Our findings suggest that both the ketone at C-3 and the methyl at C-23 in the oleanane triterpenoids with a carboxyl group at C-27 are important for the anticomplement activity against the classical pathway.


Assuntos
Via Clássica do Complemento/efeitos dos fármacos , Ácido Oleanólico/análogos & derivados , Triterpenos Pentacíclicos/farmacologia , Saxifragaceae/química , Proteínas do Sistema Complemento/metabolismo , Humanos , Masculino , Triterpenos Pentacíclicos/isolamento & purificação
7.
Chem Pharm Bull (Tokyo) ; 56(1): 115-7, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18175990

RESUMO

Two new lignans, 4-methoxymagnaldehyde B (1) and coumanolignan (2), were isolated from the stem bark of Magnolia obovata, together with 11 known compounds (3-13). The structures of compounds 1 and 2 were determined to be 5'-allyl-2'-hydroxyphenyl-4-methoxy-3-cinnamic aldehyde (1) and 6-allyl-8-(5'-allyl-2'-hydroxyphenyl)coumarin (2) on the basis of spectroscopic and physicochemical analyses including 2D NMR and high-resolution EI-MS. Compounds 1-8, 11, 12, and 13 were tested in vitro for their cytotoxic activities against the HeLa, A549, and HCT116 cancer cell lines. Among the compounds tested, compound 1 showed the strongest cytotoxic activity against the HCT116 cancer cell line, with an IC(50) value of 1.3 microg/ml.


Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Lignanas/isolamento & purificação , Lignanas/farmacologia , Magnolia/química , Plantas Medicinais/química , Antineoplásicos Fitogênicos/química , Cinamatos , Cumarínicos , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Humanos , Japão , Lignanas/química , Estrutura Molecular , Casca de Planta/química
8.
Chem Pharm Bull (Tokyo) ; 55(9): 1376-8, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17827765

RESUMO

Bioassay-guided fractionation of a MeOH extract of the whole plant of Aceriphyllum rossii (Saxifragaceae) led to the isolation of two new triterpenes, 3alpha,23-isopropylidenedioxyolean-12-en-27-oic acid (1) and 23-hydroxy-3-oxoolean-12-en-27-oic acid (2), together with six known triterpenes, 3-oxoolean-12-en-27-oic acid (3), 3alpha-hydroxyolean-12-en-27-oic acid (4), beta-peltoboykinolic acid (5), aceriphyllic acid A (6), oleanolic acid (7), and gypsogenic acid (8). The structures of these compounds were elucidated on the basis of physicochemical and spectroscopic analyses. These compounds were evaluated for in vitro cytotoxicity against the K562 and HL-60 cell lines. Olean-12-en-27-oic acid derivatives (1-6) exhibited considerable cytotoxicity against K562 and HL-60 cell lines with IC(50) values ranging from 12.2 to 28.7 microM and from 12.1 to 25.8 microM, respectively.


Assuntos
Antineoplásicos Fitogênicos/toxicidade , Saxifragaceae/química , Triterpenos/toxicidade , Antineoplásicos Fitogênicos/isolamento & purificação , Células HL-60 , Humanos , Células K562 , Espectroscopia de Ressonância Magnética , Extratos Vegetais/química , Solventes , Espectrofotometria Infravermelho , Espectrofotometria Ultravioleta , Sais de Tetrazólio , Tiazóis , Triterpenos/isolamento & purificação
9.
Phytother Res ; 18(9): 737-41, 2004 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15478203

RESUMO

The ethanol extract from the fruit of Terminalia chebula (Combretaceae) exhibited significant inhibitory activity on oxidative stress and the age-dependent shortening of the telomeric DNA length. In the peroxidation model using t-BuOOH, the T. chebula extract showed a notable cytoprotective effect on the HEK-N/F cells with 60.5 +/- 3.8% at a concentration of 50 microg/ml. In addition, the T. chebula extract exhibited a significant cytoprotective effect against UVB-induced oxidative damage. The life-span of the HEK-N/F cells was elongated by 40% as a result of the continuous administration of 3 microg/ml of the T. chebula extract compared to that of the control. These observations were attributed to the inhibitory effect of the T. chebula extract on the age-dependent shortening of the telomere, length as shown by the Southern blots of the terminal restriction fragments (TRFs) of DNA extracted from subculture passages.


Assuntos
Fitoterapia , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Envelhecimento da Pele/efeitos dos fármacos , Terminalia , DNA/efeitos dos fármacos , Frutas , Humanos , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Extratos Vegetais/uso terapêutico , Substâncias Protetoras/administração & dosagem , Substâncias Protetoras/uso terapêutico , Envelhecimento da Pele/efeitos da radiação , Telômero/efeitos dos fármacos , Raios Ultravioleta
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