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OBJECTIVE: To investigate the anti-invasion efficacy of the ethanol extract of Oldenlandia diffusa Will. (EEOD) on a three-dimensional (3D) human malignant glioma (MG) cell invasion and perfusion model based on microfluidic chip culture and the possible mechanism of action of Oldenlandia diffusa Will. (OD). METHODS: The comprehensive pharmacodynamic analysis method in this study was based on microfluidic chip 3D cell perfusion culture technology, and the action mechanism of Chinese medicine (CM) on human MG cells was investigated through network pharmacology analysis. First, the components of EEOD were analyzed by ultraperformance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). Then, cell viability and apoptosis were assessed to determine the optimum concentration of EEOD for invasion experiments, and two-dimensional (2D) migration and invasion abilities of U87 and U251 MG cells were evaluated using scratch wound and Transwell assays. The possible mechanism underlying the effects of EEOD on glioma was analyzed through a network pharmacology approach. RESULTS: Thirty-five compounds of EEOD were detected by UPLC-Q-TOF/MS. EEOD suppressed the viability of MG cells, promoted their apoptosis, and inhibited their migratory and invasive potentials (all P<0.05). Network pharmacology analysis showed that OD inhibited the invasion of MG cells by directly regulating MAPK and Wnt pathways through MAPK, EGFR, MYC, GSK3B, and other targets. The anti-invasion effect of OD was also found to be related to the indirect regulation of microtubule cytoskeleton organization. CONCLUSIONS: ]EEOD could inhibit the invasion of human MG cells, and the anti-invasion mechanism of OD might be regulating MAPK and Wnt signaling pathways and microtubule cytoskeleton organization.
Assuntos
Medicamentos de Ervas Chinesas , Glioma , Oldenlandia , Humanos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Glioma/tratamento farmacológico , Microfluídica , Farmacologia em Rede , Oldenlandia/química , Extratos Vegetais/farmacologiaRESUMO
Ganoderma lucidum is a famous edible and medicinal fungus. Through a bioactive phytochemical investigation of the ethanolic extracts of the fruiting bodies of G. lucidum, twenty-nine triterpenoids, including eleven previously undescribed triterpenoids, were isolated and characterized based on spectroscopic data. The inhibitory effects of all the triterpenes against fatty acid amide hydrolase (FAAH) were found to be in the range of 30-60% at 100 µM. Methyl ganoderate A displayed the strongest inhibitory activity (61%) against FAAH. Furthermore, all compounds displayed no cytotoxicity against LOVO and MCF-7 human cancer cells. Hence, our present study provides information about G. lucidum as a functional food or pharmaceutical supplement for the treatment of neuroinflammation.
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Amidoidrolases , Reishi , Triterpenos , Amidoidrolases/antagonistas & inibidores , Carpóforos/química , Humanos , Estrutura Molecular , Reishi/química , Esteroides/análise , Triterpenos/químicaRESUMO
Following the publication of the above article, an interested reader to the authors' attention that there appeared to be several duplications of data panels featured within Figs. 13. After having consulted their original data, the authors have realized that a number of the data panels were inadvertently assembled incorrectly in these figures. The corrected versions of Fig. 1A (showing the correct data for the NC2W and NC4W experiments), Fig. 1B (including the correct data for the C4W, M2W, NC2W and NC4W experiments), Fig. 2 (showing the correct data for the YGD2W experiment), Fig. 3A (NC3W data panel corrected), Fig. 3B (HGF1W and NC3W data panels corrected) and Fig. 3C (C4W data panel corrected) are shown on the next four pages. All these corrections were approved by all authors. The authors regret that these errors were not resolved before the publication of the paper, thank the Editor of Molecular Medicine Reports for granting them the opportunity to publish this corrigendum, and apologize to the readership for any inconvenience caused. [the original article was published in Molecular Medicine Reports 15: 613626, 2017; DOI: 10.3892/mmr.2016.6083].
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Two novel quinolone alkaloids (1 and 2) and two novel indole alkaloids (5 and 8), together with eleven known analogues, were isolated from the nearly ripe fruits of Evodia rutaecarpa. Their structures were determined by extensive spectroscopic data, including NMR, HRESIMS, and ECD. Additionally, the anti-tumor, hypoglycemic, and anti-bacterial activities of the isolated alkaloids were evaluated in vitro. Compound 5 as a new alkaloid displayed moderate inhibitory effect against four human cancer cell lines (MCF-7 IC50 = 30.7 µM, Hepg-2 IC50 = 65.2 µM, A549 IC50 = 39.1 µM, and SHSY-5Y IC50 = 24.7 µM), α-glucosidase (IC50 = 23.9 µM) and PTP1B (IC50 = 75.8 µM). Compound 11 showed better inhibitory effect against PTP1B (IC50 = 16.2 µM) compared with that of the positive control. Compounds 5, 13, and 14 showed moderate inhibitory effects against Bacillus cereus with MIC values of 50, 25, and 10 µM, respectively.
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Antibacterianos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Evodia/química , Frutas/química , Alcaloides Indólicos/farmacologia , Quinolonas/farmacologia , Antibacterianos/isolamento & purificação , Antineoplásicos Fitogênicos/isolamento & purificação , Bacillus cereus/efeitos dos fármacos , Linhagem Celular Tumoral , China , Humanos , Alcaloides Indólicos/isolamento & purificação , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Quinolonas/isolamento & purificaçãoRESUMO
A previous study reported that Yi Guan Jian (YGJ) may increase the proliferation and differentiation of hepatic oval cells in a rat liver cirrhosis model. The aim of the present study was to investigate the effect and mechanism of action of YGJ on inducing hepatic differentiation in bone marrowderived mesenchymal stem cells (BMMSCs) via stromalcell derived factor1 (SDF1). Murine BMMSCs were isolated with whole bone marrow adherence, then identified by immunocytochemical staining and flow cytometry. Passage 2 cells were divided into 8 groups and their differentiation was induced by cell factors added to the medium, including hepatocyte growth factor (HGF), SDF1 and YGJ. Each of the cell factors was used alone and any two or three of them were combined to establish different cell microenvironments in the different treatment groups. Albumin (ALB) was selected as a hepatocellular marker and cytokeratin18 (CK18) as a cholangiocellular marker. The protein and mRNA expression levels of ALB and CK18 were used to determine the differentiation of BMMSCs using immunocytochemical staining, western blotting and reverse transcriptionquantitative polymerase chain reaction on days 7, 14, 21 and 28 during induction. The relative expression levels of ALB and CK18 resulted in timedependent increases in the groups supplemented only with HGF, SDF1 or YGJ. Combination treatment of any two HGF, SDF1 and YGJ led to a higher expression of ALB and CK18 compared with only one cell factor treatment. Additionally, when all three were used in a combined treatment the expression levels of ALB and CK18 occurred at an earlier time and was higher overall. Therefore, the present study suggested that YGJ had an effect on inducing hepatic differentiation in BMMSCs via SDF1 and may act in a synergistic manner with HGF and SDF1.
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Diferenciação Celular/efeitos dos fármacos , Quimiocina CXCL12/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Hepatócitos/citologia , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Albuminas/análise , Albuminas/genética , Animais , Células Cultivadas , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Fator de Crescimento de Hepatócito/farmacologia , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Queratina-18/análise , Queratina-18/genética , Masculino , Células-Tronco Mesenquimais/metabolismo , CamundongosRESUMO
Yi Guan Jian decoction (YGD) may induce the differentiation of bone marrow mesenchymal stem cells (BMSCs) into hepatocyte-like cells (HLCs); however, the underlying mechanisms remain to be elucidated. The present study aimed to investigate this process. To do this, a dimethylnitrosamine (DMN)-induced liver cirrhosis mouse model was established. The mice from the model group were randomly divided into three subgroups: i) Negative control, ii) hepatocyte growth factor and iii) YGD. The overall health, liver function and histological alterations were monitored. The expression of αsmooth muscle actin (αSMA), CXC chemokine receptor type 4 (CXCR4), extracellular signalregulated kinase (ERK1/2), nuclear factor κB p65 subunit (NFκB p65) and ßcatenin were measured by immunohistochemistry, western blotting and reverse transcriptionquantitative polymerase chain reaction. Following administration of DMN, the overall health of the mice significantly decreased, with an increase in pathological developments and liver damage resulting in a decrease in liver function. Immunohistochemistry revealed that the expression of αSMA, CXCR4, ERK1/2, NFκB p65 and ßcatenin was upregulated. Following treatment with YGD, the overall health, liver function and pathology improved. The mRNA and protein expression levels of CXCR4 and ERK1/2 were upregulated, where as αSMA, NFκB p65 and ßcatenin levels were downregulated. The results demonstrated that YGD may induce the differentiation of BMSCs into HLCs to reverse DMNinduced liver cirrhosis; this may be achieved via an upregulation of the SDF1/CXCR4 axis to activate the mitogen activated protein kinase/ERK1/2 signaling pathway.