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1.
Int J Mol Sci ; 24(5)2023 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-36902464

RESUMEN

A convenient and practical method for the synthesis of bioactive ester-containing chroman-4-ones through the cascade radical cyclization of 2-(allyloxy)arylaldehydes and oxalates is described. The preliminary studies suggest that an alkoxycarbonyl radical might be involved in the current transformation, which was generated via the decarboxylation of oxalates in the presence of (NH4)2S2O8.


Asunto(s)
Ésteres , Oxalatos , Metales , Ciclización , Cromanos
2.
Phytomedicine ; 61: 152848, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31035048

RESUMEN

BACKGROUND: 2-hydroxy-3-methylanthraquinone (HMA), an anthraquinone monomer in traditional Chinese medicine Hedyotis diffusa, has been reported to inhibit the growth of several types of cancer, but its effect on lung cancer has not been adequately investigated. HYPOTHESIS/PURPOSE: This study aimed to test the hypothesis that HMA inhibit the growth, migration, and invasion of lung cancer cells in part via downregulation of interleukin (IL)-6-induced JAK2/STAT3 pathway. METHODS: Growth and apoptosis of lung cancer cells were quantitated by CCK-8 assay and Annexin V-FITC/PI flow cytometric analysis, respectively. Migration and invasion of A549 cells were determined by wound-healing assay and transwell invasion assay, respectively. The effect of HMA on cytokines expression in A549 cells was evaluated by the cytokine antibody array assay. Gene expression and protein levels of related molecular markers were quantitated by real time-PCR and Western blot analysis, respectively. RESULTS: HMA significantly inhibited IL-6-stimulated growth and colony formation of A549 cells, increased the number of apoptotic cells, and inhibited invasion associated with downregulation of expression of IL-6-induced MMP-1, MMP-2, and MMP-9 genes. IL-6 increased the levels of tyrosine phosphorylation of JAK2 and STAT3 in A549 cells, which was reversed by HMA treatment. In addition, HMA reduced the expression of a series of inflammation-related cytokines in A549 cells supernatant, including IL-6, G-CSF, IL-6R, IL-8, MCP-1, RANTES, TNF-α. CONCLUSION: These results suggest that HMA may inhibit the growth and invasion of lung cancer cells in part via downregulation of IL-6-induced JAK2/STAT3 pathway.


Asunto(s)
Antraquinonas/farmacología , Antineoplásicos Fitogénicos/farmacología , Janus Quinasa 2/metabolismo , Neoplasias Pulmonares/tratamiento farmacológico , Factor de Transcripción STAT3/metabolismo , Células A549 , Animales , Apoptosis/efectos de los fármacos , Carcinoma Pulmonar de Lewis/tratamiento farmacológico , Citocinas/metabolismo , Regulación hacia Abajo/efectos de los fármacos , Regulación hacia Abajo/genética , Medicamentos Herbarios Chinos/farmacología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Interleucina-6/metabolismo , Interleucina-6/farmacología , Neoplasias Pulmonares/patología , Metaloendopeptidasas/genética , Metaloendopeptidasas/metabolismo , Ratones , Fosforilación/efectos de los fármacos , Fosforilación/genética , Transducción de Señal/efectos de los fármacos
3.
Int J Mol Sci ; 19(2)2018 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-29393891

RESUMEN

Luteolin (LTL) exerts remarkable tumor suppressive activity on various types of cancers, including non-small cell lung cancer (NSCLC). However, it is not completely understood whether the mechanism of its action against NSCLC is related to microRNAs (miRNAs). In the present study, we investigated the anti-tumor effects of LTL on NSCLC in vitro and in vivo. The results revealed that LTL could inhibit cell proliferation and induce apoptosis in both A549 and H460 cells. In a H460 xenograft tumor model of nude mice, LTL significantly suppressed tumor growth, inhibited cell proliferation, and induced apoptosis. miRNA microarray and quantitative PCR (qPCR) analysis indicated that miR-34a-5p was dramatically upregulated upon LTL treatment in tumor tissues. Furthermore, MDM4 was proved to be a direct target of miR-34a-5p by luciferase reporter gene assay. LTL treatment was associated with increased p53 and p21 protein expressions and decreased MDM4 protein expression in both NSCLC cells and tumor tissues. When miR-34a-5p was inhibited in vitro, the protein expressions of Bcl-2 and MDM4 were recovered, while that of p53, p21, and Bax were attenuated. Moreover, caspase-3 and caspase-9 activation induced by LHL treatment in vitro were also suppressed by miR-34a-5p inhibition. Overall, LTL could inhibit tumorigenesis and induce apoptosis of NSCLC cells by upregulation of miR-34a-5p via targeting MDM4. These findings provide novel insight into the molecular functions of LTL that suggest its potential as a therapeutic agent for human NSCLC.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares/tratamiento farmacológico , Luteolina/farmacología , MicroARNs/genética , Proteínas Nucleares/genética , Proteínas Proto-Oncogénicas/genética , Animales , Apoptosis/efectos de los fármacos , Carcinogénesis/efectos de los fármacos , Carcinogénesis/genética , Carcinogénesis/metabolismo , Carcinogénesis/patología , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Caspasas/genética , Caspasas/metabolismo , Proteínas de Ciclo Celular , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Perfilación de la Expresión Génica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Masculino , Ratones , Ratones Desnudos , MicroARNs/metabolismo , Análisis por Micromatrices , Proteínas Nucleares/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Carga Tumoral/efectos de los fármacos , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto , Proteína X Asociada a bcl-2/genética , Proteína X Asociada a bcl-2/metabolismo
4.
Mol Med Rep ; 16(5): 6262-6268, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28901520

RESUMEN

Puerarin has attracted increasing attention because of its beneficial effects on anti­osteoporosis, but the molecular mechanisms underlying its actions on osteoblasts are not fully understood. The current study aimed to investigate the effect of puerarin on the cell viability and differentiation of mouse MC3T3­E1 osteoblast­like cells in vitro and its underlying mechanisms. The results indicated that 0.01, 0.1 and 1 mg/ml puerarin significantly promoted the viability of osteoblasts, enhanced alkaline phosphatase (ALP) activity and increased the expression of transforming growth factor­ß1, Smad2, Smad3 and Runt­related transcription factor (Runx)2. Micro (mi)RNA target prediction programs predicted that miR­204 may directly target Runx2. Following treatment with 0.1 mg/ml puerarin for 48 h, the expression level of miR­204 was downregulated. Besides, miR­204 dramatically repressed the luciferase activity of wildtype Runx2 3'­UTR transfected cells, but not that of the mutant ones. Overexpression of miR­204 in osteoblasts significantly decreased the protein expression of Runx2, while inhibition of miR­204 enhanced Runx2's expression. In addition, overexpression of miR­204 inhibited the cell viability and ALP activity of osteoblasts, while inhibition of miR­204 had the opposite effect. The results suggested that puerarin may promote MC3T3­E1 osteoblast­like cell viability and differentiation, which may be related to the downregulation of miR­204 and the following activation of Runx2.


Asunto(s)
Diferenciación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Subunidad alfa 1 del Factor de Unión al Sitio Principal/genética , Isoflavonas/farmacología , MicroARNs/genética , Regulación hacia Arriba/efectos de los fármacos , Regiones no Traducidas 3'/efectos de los fármacos , Fosfatasa Alcalina/genética , Animales , Células Cultivadas , Regulación hacia Abajo/efectos de los fármacos , Ratones , Osteoblastos/efectos de los fármacos , Proteína smad3/genética , Activación Transcripcional/efectos de los fármacos
5.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 36(9): 1112-1118, 2016 Sep.
Artículo en Chino | MEDLINE | ID: mdl-30645853

RESUMEN

Objective To observe the mechanism of Xiaoai Jiedu Recipe (XJR) for fighting a- gainst hepatoma by detecting tumor miRNAs expression profiles in H22tumor-bearing mice. Methods To- tally 50 H22tumor-bearing mice were randomly divided into the model group, the low dose XJR group, the medium dose XJR group, the high dose XJR group, the Cisplatin group, 10 in each group. Different expressions of tumor tissues in H22 tumor-bearing mice under light microscope were detected using histopathological technique. Differentially expressed miRNAs of tumor tissue in H22tumor-bearing mice were detected by using miRNA chip technique. Differentially expressed miRNAs associated with antitumor mechanism of XJR were found out by statistical analysis. Results Histopathological results showed that reduced pathologic mitosis, smaller cancer cells, and obviously enhanced anti-cancer effect along with increased XJP dose. Results of miRNA chip analyses indicated XJP could significantly up-regulate the ex- pressions of miRNAs, such as miR-1298-5p, miR-874-3p, miR-721, miR-298-5p, miR-551b-5p, miR-346- 5p, miR-105, and so on. It could also down-regulate the expressions of miR-24-3p, miR-3963, miR-127- 3p, miR-434-5p, miR-1187, miR-468-3p, miR-221-5p, and miR-6695-5p. Conclusion XJP could fight a- gainst tumor possibly by regulating expressions of multiple miRNAs.


Asunto(s)
Medicamentos Herbarios Chinos , MicroARNs , Análisis de Secuencia por Matrices de Oligonucleótidos , Animales , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/metabolismo , Medicamentos Herbarios Chinos/farmacología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/metabolismo , Ratones , MicroARNs/metabolismo
6.
Chin J Nat Med ; 13(12): 896-905, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26721708

RESUMEN

5-Hydroxymethylfurfural (5-HMF), a water-soluble compound extracted from wine-processed Fructus corni, is a novel hepatic protectant for treating acute liver injury. The present study was designed to investigate the protective effect of 5-HMF in human L02 hepatocytes injured by D-galactosamine (GalN) and tumor necrosis factor-α (TNF-α) in vitro and to explore the underlying mechanisms of action. Our results showed that 5-HMF caused significant increase in the viability of L02 cells injured by GalN/TNF-α, in accordance with a dose-dependent decrease in apoptotic cell death confirmed by morphological and flow cytometric analyses. Based on immunofluorescence and Western blot assays, we found that GalN/TNF-α induced ER stress in the cells, as indicated by the disturbance of intracellular Ca(2+) concentration, the activation of protein kinase RNA (PKR)-like ER kinase (PERK), phosphorylation of eukaryotic initiation factor 2 alpha (eIF2α), and expression of ATF4 and CHOP proteins, which was reversed by 5-HMF pre-treatment in a dose-dependent manner. The anti-apoptotic effect of 5-HMF was further evidenced by balancing the expression of Bcl-2 family members. In addition, the knockdown of PERK suppressed the expression of phospho-PERK, phospho-eIF2α, ATF4, and CHOP, resulting in a significant decrease in cell apoptosis after the treatment with GalN/TNF-α. 5-HMF could enhance the effects of PERK knockdown, protecting the cells against the GalN/TNF-α insult. In conclusion, these findings demonstrate that 5-HMF can effectively protect GalN/TNF-α-injured L02 hepatocytes against ER stress-induced apoptosis through the regulation of the PERK-eIF2α signaling pathway, suggesting that it is a possible candidate for liver disease therapy.


Asunto(s)
Cornus/química , Estrés del Retículo Endoplásmico/efectos de los fármacos , Factor 2 Eucariótico de Iniciación/metabolismo , Furaldehído/análogos & derivados , Hepatocitos/efectos de los fármacos , Extractos Vegetales/farmacología , Factor de Necrosis Tumoral alfa/metabolismo , eIF-2 Quinasa/metabolismo , Apoptosis/efectos de los fármacos , Factor 2 Eucariótico de Iniciación/genética , Furaldehído/farmacología , Galactosamina/metabolismo , Hepatocitos/citología , Hepatocitos/metabolismo , Humanos , Hígado/citología , Hígado/efectos de los fármacos , Hígado/metabolismo , Sustancias Protectoras/farmacología , Transducción de Señal/efectos de los fármacos , Factor de Necrosis Tumoral alfa/genética , eIF-2 Quinasa/genética
7.
Zhong Yao Cai ; 36(1): 85-9, 2013 Jan.
Artículo en Chino | MEDLINE | ID: mdl-23750415

RESUMEN

OBJECTIVE: To study the hepatoprotective effects of extracts from processed Corni Fructus against D-galactose-induced liver injury in mice. METHODS: Acute liver injury model was established by D-galactose. The activity of alanine aminotransferase (ALT), aspartate aminotransferase (AST), superoxide dismutase (SOD) and level of liver malondialdehyde (MDA) of serum was measured. Hematoxylin and Eosin (HE) staining of pathological section and transmission electron microscopic observation were used to measure the apoptosis of liver cells. RESULTS: Compared with the normal control group, SOD activity was decreased, MDA level and ALT, AST activity was increased in the model group, and the differences were significant (P < 0.05); While three kinds of cornel active sites showed significant improvement with increasing SOD activity and decreasing ALT, AST activity and MDA levels (P < 0.05). Furthermore, model group appeared obvious necrosis inflammation, and apoptosis characteristics; While liver structural damage were improved significantly in cornel active site groups. CONCLUSION: Cornel polysaccharide extract, n-butanol extraction site and petroleum ether extraction sites all have hepatoprotective effects, suggesting that they are the active material of cornel product, and the mechanism may be related to the inhibition of oxidative stress and inflammatory response.


Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Cornus/química , Medicamentos Herbarios Chinos/farmacología , Hígado/efectos de los fármacos , Sustancias Protectoras/farmacología , 1-Butanol , Alanina Transaminasa/sangre , Animales , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Relación Dosis-Respuesta a Droga , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/aislamiento & purificación , Femenino , Frutas/química , Galactosa/efectos adversos , Hígado/metabolismo , Hígado/patología , Masculino , Malondialdehído/metabolismo , Ratones , Ratones Endogámicos ICR , Sustancias Protectoras/administración & dosificación , Distribución Aleatoria , Superóxido Dismutasa/metabolismo
8.
J Ethnopharmacol ; 148(3): 851-60, 2013 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-23711831

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Liangxue Huayu Recipe (LHR) as a classical prescription is clinically employed to treat liver diseases in traditional Chinese medicine. AIM OF STUDY: In this study, we attempt to show that LHR attenuates hepatocyte apoptosis and hepatic injury induced by lipopolysaccharide (LPS) and D-galactosamine (GalN) in rats. The present study was also designed to examine whether LHR had the protective effects on d-GalN and tumor necrosis factor-α (TNF-α)-treated human L02 hepatocytes and its possible association with the mitochondrial pathway. MATERIALS AND METHODS: LHR is composed of three traditional Chinese medicines: Herba Rehmannia, Rhubarb and Radix Paeoniae Rubra. LHR at 541, 1082 and 2164 mg/kg was orally administered to model and normal rats for 7 days. The effects of LHR on serum levels of liver enzymes, including alanine aminotransferase (ALT) and aspartate aminotransferase (AST), were measured. Hepatocyte apoptosis in vivo was assessed by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL) method. Apoptosis in vitro and related morphological changes of human L02 hepatocytes were determined by high content screening (HCS) assay. The expression levels of Bcl-2, Bax and cytochrome c were detected by Western-blot analysis in L02 cells. In addition, the activities of caspase-3 and caspase-9 were tested by enzyme-linked immunosorbent detector. RESULTS: It revealed that LHR pretreatment effectively ameliorated the GalN/LPS-induced elevation of serum ALT and AST levels, and attenuated hepatocyte apoptosis in the rat model characterized by the addition of GalN/LPS. In subsequent experiments in vitro, LHR also attenuated GalN/TNF-α-induced apoptosis in human L02 hepatocytes. Furthermore, LHR improved the mitochondrial function, inhibited the upregulation of Bax/Bcl-2 protein ratio, decreased the release of cytochrome c from the mitochondria into the cytosol, as well as inhibited caspase-3 and caspase-9 activation in this cell model. CONCLUSIONS: These results indicate that LHR is effective in attenuating hepatocyte apoptosis both in vivo and in vitro, and this effect is partly mediated through the activation of the mitochondrial pathway and subsequent regulation of particular pro-apoptotic gene expression.


Asunto(s)
Medicamentos Herbarios Chinos/farmacología , Hígado/efectos de los fármacos , Sustancias Protectoras/farmacología , Animales , Apoptosis/efectos de los fármacos , Caspasa 3/metabolismo , Caspasa 9/metabolismo , Línea Celular , Citocromos c/metabolismo , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Humanos , Hígado/metabolismo , Masculino , Mitocondrias Hepáticas/efectos de los fármacos , Mitocondrias Hepáticas/fisiología , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Ratas , Ratas Sprague-Dawley , Proteína X Asociada a bcl-2/metabolismo
9.
Zhongguo Zhong Yao Za Zhi ; 38(20): 3544-8, 2013 Oct.
Artículo en Chino | MEDLINE | ID: mdl-24490570

RESUMEN

Endoplasmic reticulum stress (ERS) is a new pathway inducing cell apoptosis that has been discovered in recent years. This study focused on the protective effect of Liangxue Huayu recipe (LHR) on tumor necrosis factor-alpha (TNF-alpha) and D-GalN-induced hepatocyte apoptosis. It found that TNF-alpha and D-GalN could obviously inhibit hepatocyte proliferation, induce cell apoptosis, and significantly increase free calcium ions in cytoplasms, as well as protein expressions of ERS apoptosis-related signal molecules phosphorylated PERK, phosphorylated elF2alpha, cleaved Caspase-12, GRP78 and CHOP. After the administration of LHR of different concentrations, compared with the TNF-alpha/GalN injury group, LHR could significantly alleviated L02 hepatocyte proliferation, decreased cell apoptosis, inhibited growth of intracytoplasmic free calcium content, and gradually reduced the protein expressions of phosphorylated PERK, phosphorylated elF2alpha, cleaved Caspase-12, GRP78 and CHOP. These findings indicated that LHR has the inhibitory effect on TNF-alpha and D-GalN-induced hepatocyte apoptosis. Its mechanism may be related to down-regulation of ERS apoptosis-related signal molecules phosphorylated PERK, phosphorylated elF2alpha, cleaved Caspase-12, GRP78 and CHOP that maintain calcium homeostasis in endoplasmic reticulum.


Asunto(s)
Apoptosis/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Estrés del Retículo Endoplásmico/efectos de los fármacos , Hepatocitos/efectos de los fármacos , Línea Celular , Proliferación Celular/efectos de los fármacos , Chaperón BiP del Retículo Endoplásmico , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Hepatocitos/citología , Humanos , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo II/metabolismo , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo
10.
Artículo en Inglés | MEDLINE | ID: mdl-24391673

RESUMEN

Neural stem cells (NSCs) are self-regenerating cells, but their regenerative capacity is limited. The present study was conducted to investigate the effect of ß -sitosterol-D-glucoside (BSSG) on the proliferation of hippocampal NSCs and to determine the corresponding molecular mechanism. Results of CCK-8 assay showed that BSSG significantly increased NSC proliferation and the effectiveness of BSSG was similar to that of basic fibroblast growth factor and epidermal growth factor. mRNA expression profiling showed that 960 genes were differentially expressed after NSCs were treated with BSSG. Among the 960 genes, IGF1 is considered as a key regulatory gene that functionally promotes NSC proliferation. MicroRNA (miRNA) expression profiling indicated that 30 and 84 miRNAs were upregulated and downregulated, respectively. miRNA-mRNA relevance analysis revealed that numerous mRNAs including IGF1 mRNA were negatively regulated by miRNAs with decreased expression, thereby increasing the corresponding mRNA expression. The increased expression of IGF1 protein was validated by ELISA. Picropodophyllin (PPP, an inhibitor of IGF-1R) inhibition test confirmed that the proliferation-enhancing effect depended on IGF1. This study provided information about BSSG as an efficient and inexpensive growth factor alternative, of which the effect is closely involved in IGF1.

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