RESUMO
Notoginsenoside R1(NGR1),a critical compound in traditional herb Panax notoginseng, is a kind of estrogen receptor agonist.It is reported to exhibit anti-apoptotic,anti-oxidative and anti-inflammatory properties activity, so it is widely used for treatment of various diseases.In order to investigate the potential neuroprotective effect of NGR1 in hypoxic-ischemic brain damage(HIBD), primary cortical neurons were used in this study to establish oxygen-glucose deprivation/reoxygenation(OGD/R) injury models. They were treated with NGR1 and estrogen receptor inhibitor ICI-182780 respectively, then the neuronal survival, cell membrane integrity and apoptosis were assessed by MTT assay,lactate dehydrogenase test(LDH) and Hoechst 33342 stain respectively, while the protein expression levels of ATF6α,p-Akt,Akt,Bax and Cleaved Caspase-3 were measured by Western blotting. Results indicated that as compared with the blank control group,OGD/R could induce cell injury and apoptosis(P<0.05), reduce relative integrity of cell membrane(P<0.05), decrease protein expression of ATF6α,p-Akt(P<0.05), and increase protein expression of Bax and Cleaved Caspase-3(P<0.05) in the primary cortical cells. After NGR1 treatment, the expression levels of ATF6α,p-Akt were obviously increased, and the expression levels of Bax and Cleaved Caspase-3 and the apoptosis of neuron were decreased(P<0.05). However, these neuroprotective properties of NGR1 against ODG/R-induced cell damage could be blocked by ICI-182780. This finding indicated that NGR1 may protect the primary cortical neurons against OGD/R induced injury,and the mechanism may be associated with accelerating the activation of the ATF6/Akt signaling pathway via estrogen receptors.
Assuntos
Fator 6 Ativador da Transcrição/metabolismo , Ginsenosídeos/farmacologia , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Animais , Apoptose , Hipóxia Celular , Sobrevivência Celular , Células Cultivadas , Glucose , Neurônios/citologia , Oxigênio , RatosRESUMO
KEY MESSAGE: Transcriptome analysis of barley embryogenic callus from isolated microspore culture under salt stress uncovered a role of translation inhibition and selective activation of stress-specific proteins in cellular defense. Soil salinity is one of the major abiotic stresses which constrains the plant growth and reduces the productivity of field crops. In this study, it was observed that the salt stress in barley isolated microspore culture impacted not only on the quantity of embryogenic callus but also on the quality for later differentiation. The barley microspore-derived embryogenic callus, a transient intermediate form linked cells and plants, was employed for a global transcriptome analysis by RNA sequencing to provide new insights into the cellular adaptation or acclimation to stress. A total of 596 differentially expressed genes (DEGs) were identified, in which 123 DEGs were up-regulated and 473 DEGs were down-regulated in the embryogenic callus produced from microspore culture under salt stress as compared to the control conditions. KEGG pathway analysis identified 'translation' (27 DEGs; 12.56 %) as the largest group and followed by 'folding, sorting and degradation' (25 DEGs; 11.63 %) in 215 mapped metabolic pathways. The results of RNA-Seq data and quantitative real-time polymerase chain reaction validation showed that the genes related to translation regulation (such as eIF1A, RPLP0, RPLP2, VARS) were down-regulated to control general protein synthesis, and the genes related to endoplasmic reticulum stress response (such as small heat shock protein genes) were selectively up-regulated against protein denaturing during microspore embryogenesis under continuous salt stress. These transcriptional remodeling might affect the essential protein synthesis for the cell development to fulfill totipotency under salt stress.
Assuntos
Perfilação da Expressão Gênica , Hordeum/embriologia , Hordeum/genética , Pólen/genética , Pólen/fisiologia , Biossíntese de Proteínas/genética , Cloreto de Sódio/farmacologia , Estresse Fisiológico/genética , Regulação da Expressão Gênica de Plantas , Hordeum/efeitos dos fármacos , Hordeum/fisiologia , Pólen/efeitos dos fármacos , Biossíntese de Proteínas/efeitos dos fármacos , Reação em Cadeia da Polimerase em Tempo Real , Sementes/efeitos dos fármacos , Sementes/embriologia , Sementes/genética , Sementes/fisiologia , Análise de Sequência de RNA , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Estresse Fisiológico/efeitos dos fármacosRESUMO
OBJECTIVE: To screen out main molecular target promoting human neural stem cells (NSCs) of ginsenoside Rg1 by using the gene chip technology. METHOD: First, MTT assay was adopted to screen out the optimal concentration of Rg1-promoted NSC proliferation (120 mg x L(-1)). Then, on the 7th day after the Rg1-promoted NSC proliferation, the expression of target genes was observed by the gene chip technology. The most important target gene and signal transduction pathways were screened out through the data calculations. RESULT: On the 7th day after the Rg1-promoted NSC proliferation, obtained 440 differential genes, 266 significantly upregulated genes and 174 significantly down-regulated genes. HES1 gene, CAMP (cyclic adenosine monophosphate)-PKA (protein kinase A) and PI3K (phosphatidylinositol 3 kinase)-AKT signal transduction pathways were closely related to the NSC proliferation. CONCLUSION: The differentially expressed genes screened out by gene chip may provide new clues for studies on molecular mechanism of ginsenoside Rg1-promoted NSCs proliferation.
Assuntos
Ginsenosídeos/farmacologia , Células-Tronco Neurais/efeitos dos fármacos , Análise de Sequência com Séries de Oligonucleotídeos , Proliferação de Células/efeitos dos fármacos , Humanos , Células-Tronco Neurais/citologia , Células-Tronco Neurais/metabolismo , RNA/genética , RNA/isolamento & purificaçãoRESUMO
Herbal plants are enriched with compounds with a wide range of biological activities. Furanodiene is a sesquiterpene isolated from Rhizoma Curcumae. Growing evidence shows furanodiene exhibits diversified activities of hepatoprotection, anti-inflammation, anti-angiogenesis, and anti-tumor. However, its biological activities against breast cancer have not been deeply understood, and its potential as an anti-breast cancer agent combined with tamoxifen (TAM) has not been evaluated so far. This study describes the combined effects of furanodiene and TAM in human breast cancer cells in vitro. The results showed that ERa-negative MDA-MB-231 cells were much more sensitive than ERa-positive MCF-7 cells to the growth inhibition due to furanodiene. Combined administration of furanodiene and TAM led to marked increase in growth inhibition, cell cycle arrest and pro-apoptotic activity in ERa-positive cells compared to individual agent, and enhanced the down-regulation of p-cyclin D1, cyclin D1, CDK2, CDK6, p-Rb, Rb and p-p44, and the up-regulation of p27, Bax and Bad, but did not show increased cytotoxicity in ERa-negative MCF-10A non-tumorigenic breast epithelial cells. Co-incubation induced the typical PARP cleavage or caspase 9 cleavages compared to individual agent. In addition, PPARγ activity inhibition by its antagonist T0070907 did not significantly reverse the enhanced effect of furanodiene and TAM suggesting that anti-cancer properties of combination were PPARγ independent. Our data indicated that furanodiene could enhance the growth inhibitory and pro-apoptotic activity of TAM by inducing cell cycle arrest and cell apoptosis via CDKs-cyclins and mitochondria-caspases-dependent, and PPARγ-independent signaling pathways in breast cancer cells, without contributions to the cytotoxicity of TAM.
Assuntos
Neoplasias da Mama/metabolismo , Furanos/farmacologia , Compostos Heterocíclicos com 2 Anéis/farmacologia , PPAR gama/metabolismo , Tamoxifeno/farmacologia , Apoptose/efeitos dos fármacos , Western Blotting , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Fragmentação do DNA/efeitos dos fármacos , Eletroforese em Gel de Ágar , Humanos , ImunoprecipitaçãoRESUMO
OBJECTIVE: To observe the effects of ginsenoside Rg1 on the functional expression of human neural stem cells (hNSCs). METHOD: The membrane electrophysiological properties and sodium and potassium ion channels in the hNSCs induced by Rg1 were analyzed using the whole-cell patch-clamp. RESULT: On the 7th day, the neuron-like cells derived from ginsenoside Rg1 (20 mg x L(-1))-induced NSCs show: (1) The resting membrane potential: (-45.70 +/- 2.63) mV, the membrane capacitance: (26.89 +/- 1.91) pF, the membrane input impedance: (877.51 +/- 20.44) MH (P < 0.05 compared with the control group, respectively); (2) The detection rate of inward sodium current which is rapidly activated and inactivated in voltage-dependence was 50%, and its average peak value was (711.48 +/- 158.03) pA (P < 0.05 compared with the control group); (3) The outward potassium currents were composed of rapidly activated and inactivated transient outward potassium current and delayed rectifier outward potassium current, and its average peak value was (1 070.42 +/- 177.18) pA (P < 0.05 compared with the control group). CONCLUSION: Ginsenoside Rg1 can promote the functional expression and maturity of hNSCs.
Assuntos
Ginsenosídeos/farmacologia , Células-Tronco Neurais/efeitos dos fármacos , Extratos Vegetais/farmacologia , Células Cultivadas , Expressão Gênica/efeitos dos fármacos , Humanos , Potenciais da Membrana/efeitos dos fármacos , Células-Tronco Neurais/citologia , Técnicas de Patch-Clamp , Canais de Potássio/genética , Canais de Potássio/metabolismo , Canais de Sódio/genética , Canais de Sódio/metabolismoRESUMO
Much correlative evidence indicates that the oxidative modification of protein by reactive oxygen species (ROS) is involved in normal aging as well as the pathogenesis of neurodegenerative diseases such as Alzheimer's disease. In this study, we explored the antioxidative and neuroprotective effects of a naphthoquinone, 2-methoxy-6-acetyl-7-methyljuglone (MAM), purified from the dried rhizome of POLYGONUM CUSPIDATUM (Chinese name Hu-Zhang). Pretreatments with MAM (24 h) were investigated for their protective effects against apoptosis induced by the oxidizing agent TERT-butyl hydroperoxide ( T-BHP) in PC12 cells. The results indicated that MAM pretreatments could effectively protect PC12 cells against cytotoxicity induced by T-BHP in a dose-dependent manner. Cell viability was determined by both MTT and LDH assays. Increasing concentrations of MAM enhanced cell viability significantly and completely prevented cell death induced by T-BHP at 2.5 µM. The corresponding extracellular lactate dehydrogenase (LDH) levels were also attenuated significantly by various concentrations of MAM. In addition, it was found that the antioxidative effect of MAM was stronger than those of resveratrol and lipoic acid. The antiapoptotic property of MAM was further investigated with Hoechst 33342 nuclear staining and TUNEL assay. Pretreatments of MAM were able to prevent the T-BHP-induced nucleus fragmentation and accumulation of apoptotic bodies (commonly accepted as markers of apoptosis) inside the cells in a dose-dependent manner. T-BHP induced the phosphorylation of ERK 1/2, JNK and p38 MAPK, which were all impeded by pretreatments with MAM, indicating that MAM may act as a potent antioxidant which significantly interferes with the MAPK apoptotic cascades, probably rescuing cells by inhibiting the death pathways.
Assuntos
Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Fallopia japonica/química , Naftoquinonas/farmacologia , Fármacos Neuroprotetores/farmacologia , Animais , Antioxidantes/isolamento & purificação , Núcleo Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/química , L-Lactato Desidrogenase/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Naftoquinonas/isolamento & purificação , Fármacos Neuroprotetores/isolamento & purificação , Células PC12 , Fosforilação , Ratos , Resveratrol , Rizoma , Estilbenos/farmacologia , Ácido Tióctico/farmacologia , terc-Butil HidroperóxidoRESUMO
OBJECTIVE: To explore the methods and efficacy of unilateral extra-pedicle precision puncture percutaneous vertebroplasty (PVP) or percutaneous kyphoplasty(PKP) by digital subtraction angiography (DSA) for the treatment of osteoporotic vertebral compression fractures (OVCFs). METHODS: The clinical data of 68 patients with osteoporotic vertebral compression fractures treated from August 2015 to December 2018 were retrospectively analyzed. There were 20 males and 48 females, aged 56 to 90(73.5±8.0) years, 40 cases of double segments, 28 cases of three segments, a total of 168 vertebrae. All the patients were performed PVP orPKP through unilateral extra pedicle precision puncture under the guidance of DSA. The vertebrae were distributed in T1-T6(29 vertebrae), T6-T12(89 vertebrae), and L1-L5(50 vertebrae). Whether the puncture needle tip reached the midline of vertebral body was observed during operation, the leakage rate of bone cement was recorded after operation. The height of anterior edge and middle of the fractured vertebral body were measured after operation. Visual analogue scale (VAS) and the Oswestry Disability Index (ODI) were used to assess pain and lumbar function before operation, 3 days after operation and final follow-up time. RESULTS: All the punctures were successful in 68 patients. All the puncture needles reached the midline of vertebral body, and the bone cement was well dispersed in the vertebral body with symmetrical distribution. The operation time was 35 to 60 (41.6±3.2) minutes, and there was no puncture complications. The injection volume of bone cement was 3 to 5 (3.6±0.5) ml in each vertebra. There were 8 cases of bone cement leakage, with a leakage rate of 11.76%. All 68 patients were followed up from 12 to 27 (14.3±3.5) months in the study. VAS score and ODI at 3 days after surgery and at final follow-up time were significantly improved (P<0.05). The height of the anterior edge and the middle of vertebral body at 3 days after operation and at final were significantly recovered (P<0.05). CONCLUSION: PVP or PKP under the guidance of DSA via a unilateral extrapedicular approach with precision puncture can effectively relieve pain, restore vertebral body height and spinal function, which is a safe, fast and effective method in the treatment of osteoporotic vertebral compression fractures.
Assuntos
Fraturas por Compressão , Cifoplastia , Fraturas por Osteoporose , Fraturas da Coluna Vertebral , Vertebroplastia , Angiografia Digital , Feminino , Fraturas por Compressão/diagnóstico por imagem , Fraturas por Compressão/cirurgia , Humanos , Masculino , Fraturas por Osteoporose/diagnóstico por imagem , Fraturas por Osteoporose/cirurgia , Estudos Retrospectivos , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/cirurgiaRESUMO
Static liquid culture of Ganoderma lucidum, a traditional Chinese medicinal mushroom, is a proven technology for producing ganoderic acids, which are secondary metabolites that possess antitumor properties. In this work, the addition of phenobarbital, a P450 inducer, was used to enhance the production of total and individual ganoderic acids in a two-stage cultivation involving a period of initial shake flask culture followed by static liquid culture of G. lucidum. The dosage and time of phenobarbital induction were critical for the enhanced production of ganoderic acids. The addition of 100 muM (final concentration) phenobarbital on day 5 after the shake flask culture was converted to the static liquid culture was found to be optimal, resulting in a maximal amount of total ganoderic acids of 41.4 +/- 0.6 mg/g cell dry weight and increases in the levels of ganoderic acid-Mk, -T, -S, and -Me in the treated cells by 47%, 28%, 36%, and 64%, respectively. Meanwhile, the accumulation of lanosterol, a key intermediate, was found to decrease and transcriptions of three key genes encoding 3-hydroxy-3-methylglutaryl coenzyme A reductase, squalene synthase, and lanosterol synthase in the triterpene biosynthetic pathway were up-regulated under phenobarbital induction. This work demonstrated a useful strategy for the enhanced production of ganoderic acids by G. lucidum.
Assuntos
Regulação Fúngica da Expressão Gênica/efeitos dos fármacos , Lanosterol/análogos & derivados , Fenobarbital/farmacologia , Reishi/genética , Medicamentos de Ervas Chinesas , Lanosterol/biossíntese , Lanosterol/metabolismo , Reishi/efeitos dos fármacos , Reishi/crescimento & desenvolvimentoRESUMO
A new ganoderic acid (GA), 7-O-ethyl ganoderic acid O (GA-O) (1), together with two known compounds, GA-T (2) and GA-Me (3), was isolated and purified from fermented mycelia of Ganoderma lucidum. The structure of the new triterpenoid was elucidated on the basis of the interpretation of extensive spectroscopic data (HR-MS, IR, UV, 1D and 2D NMR) as 3 alpha,15 alpha,22-triacetoxy-7 alpha-ethoxy-5 alpha-lanost-8,24E-dien-26-oic acid. The new compound was found to contain a rare ethoxyl group at C-7. In addition, its cytotoxicity against 95D and HeLa human cancer cell lines was also evaluated.
Assuntos
Lanosterol/análogos & derivados , Lanosterol/isolamento & purificação , Reishi/química , China , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Células HeLa , Humanos , Lanosterol/química , Lanosterol/farmacologia , Estrutura Molecular , Micélio/química , Ressonância Magnética Nuclear BiomolecularRESUMO
PURPOSE: It is well known that diet Eicosapentaenoic acid (EPA) is beneficial to colon cancer (CC). However, the underlying molecular mechanisms of EPA-relating miRNAs on genesis and development of this area is still unclear. MATERIALS AND METHODS: This study tries to find the function and specific role of EPA in CC through quantitative PCR (qPCR), Western blotting, immunofluorescence (IF), mass spectrometry, and immunohistochemistry (IHC) assays. By these methods, the enrichment of 15-LOX-1 metabolites of EPA, the expression of miR-101 and Cox2, and the relationship among them in CC are measured. RESULTS: The quantity of miR-101 was obviously suppressed in CC tissues and SW480 cells. After application of miR-101 mimics in CC cell lines, the Cox2 expression was inhibited too. Next, we confirmed that EPA could increase the expression of miR-101 induced by 15-LOX-1. Finally, we tested whether EPA functions as a regulator of miR-101 via the production of resolvin E3. CONCLUSION: Our data demonstrate that the EPA-15-LOX-1-miR-101-Cox2 signaling pathway owns a crucial position in the pathogenesis and development of diet-related CC. These findings exert exciting meanings for presenting new therapeutic angles in CC.
RESUMO
Synergy analysis of anticancer agents is an important approach to determining the ratio and/or dose of drugs for clinical combination therapy. However, this method is rarely used to evaluate the composition of traditional Chinese medicine formulation. 'Yanhusuo San' (YHSS), which consists of yanhusuo (Rhizoma Corydalis) and Ezhu (Rhizoma Curcumae), has been an archaic Chinese medicine prescription since the Song dynasty (960-1279 AD). We previously demonstrated that either yanhusuo or ezhu has strong anticancer effect. Herein, we sought to determine the possible synergic effect between these two Chinese herbs. We measured the IC50 of each herb extract and both extracts at different ratios of doses by MTT assay. Isobologram and combination index (CI) analyses were used to evaluate the synergistic effect of yanhusuo and ezhu in different fixed ratios. Our results indicated that a combination of two herbal extracts exhibits the strongest anticancer cell proliferation effect at the ratio of 3:2 (ezhu to yanhusuo; referred to as E3Y2). Using Boyden Chamber assay, flow cytometry, and fluorescence microscopy analysis, we found that E3Y2 could markedly reduce the cell invasion ability and induce cytochrome c release rather than single use, but E3Y2 could not influence the cell cycle distribution. When the levels of ERK1/2, p-ERK1/2 and p-Rb were determined by Western blot analysis, we found that the E3Y2 significantly suppresses the level of p-ERK. Thus, our studies provide a plausible molecular basis of the synergistic anti-tumor effect of ezhu and yanhusuo.
Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Corydalis/química , Medicamentos de Ervas Chinesas , Extratos Vegetais/uso terapêutico , Apoptose/efeitos dos fármacos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sinergismo Farmacológico , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Humanos , Plantas Medicinais , Células Tumorais CultivadasRESUMO
Curcumin is a major active component isolated from Curcuma longa. Previously, we have reported its significant antidepressant effect. However, the mechanisms underlying the antidepressant effects are still obscure. In the present study, we explored the effect of curcumin against glutamate excitotoxicity, mainly focusing on the neuroprotective effects of curcumin on the expression of Brain-Derived Neurotrophic Factor (BDNF), which is deeply involved in the etiology and treatment of depression. Exposure of rat cortical neurons to 10 microM glutamate for 24 h caused a significant decrease in BDNF level, accompanied with reduced cell viability and enhanced cell apoptosis. Pretreatment of neurons with curcumin reversed the BDNF expression and cell viability in a dose- and time-dependent manner. However, K252a, a Trk receptor inhibitor which is known to inhibit the activity of BDNF, could block the survival-promoting effect of curcumin. In addition, the up-regulation of BDNF levels by curcumin was also suppressed by K252a. Taken together, these results suggest that the neuroprotective effect of curcumin might be mediated via BDNF/TrkB signaling pathway.
Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , Córtex Cerebral/efeitos dos fármacos , Curcumina/farmacologia , Ácido Glutâmico/toxicidade , Neurônios/efeitos dos fármacos , Receptor trkB/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Carbazóis/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Células Cultivadas , Córtex Cerebral/metabolismo , Córtex Cerebral/fisiopatologia , Curcumina/uso terapêutico , Transtorno Depressivo/tratamento farmacológico , Transtorno Depressivo/metabolismo , Transtorno Depressivo/fisiopatologia , Relação Dose-Resposta a Droga , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/fisiologia , Inibidores Enzimáticos/farmacologia , Alcaloides Indólicos/farmacologia , Degeneração Neural/tratamento farmacológico , Degeneração Neural/metabolismo , Degeneração Neural/fisiopatologia , Neurônios/metabolismo , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Ratos , Ratos Sprague-Dawley , Receptor trkB/metabolismo , Regulação para Cima/efeitos dos fármacosRESUMO
Curcuma longa is a main constituent of many traditional Chinese medicines, such as Xiaoyao-san, used to manage mental disorders effectively. Curcumin is a major active component of C. longa and its antidepressant-like effect has been previously demonstrated in the forced swimming test. The purpose of this study was to explore the possible contribution of serotonin (5-HT) receptors in the behavioral effects induced by curcumin in this animal model of depression. 5-HT was depleted by the tryptophan hydroxylase inhibitor p-chlorophenylalanine (PCPA, 100 mg/kg, i.p.) prior to the administration of curcumin, and the consequent results showed that PCPA blocked the anti-immobility effect of curcumin in forced swimming test, suggesting the involvement of the serotonergic system. Moreover, pre-treatment of pindolol (10 mg/kg, i.p., a beta-adrenoceptors blocker/5-HT(1A/1B) receptor antagonist), 4-(2'-methoxy-phenyl)-1-[2'-(n-2''-pyridinyl)-p-iodobenzamino-]ethyl-piperazine (p-MPPI, 1 mg/kg, s.c., a selective 5-HT(1A) receptor antagonist), or 1-(2-(1-pyrrolyl)-phenoxy)-3-isopropylamino-2-propanol (isamoltane, 2.5 mg/kg, i.p., a 5-HT(1B) receptor antagonist) was found to prevent the effect of curcumin (10 mg/kg) in forced swimming test. On the other hand, a sub-effective dose of curcumin (2.5 mg/kg, p.o.) produced a synergistic effect when given jointly with (+)-8-hydroxy-2-(di-n-propylamino)tetralin, (8-OH-DPAT, 1 mg/kg, i.p., a 5-HT(1A) receptor agonist), anpirtoline (0.25 mg/kg, i.p., a 5-HT(1B) receptor agonist) or ritanserin (4 mg/kg, i.p., a 5-HT(2A/2C) receptor antagonist), but not with ketanserin (5 mg/kg, i.p., a 5-HT(2A/2C) receptor antagonist with higher affinity to 5-HT(2A) receptor) or R(-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI, 1 mg/kg, i.p., a 5-HT(2A) receptor agonist). Taken together, these results indicate that the antidepressant-like effect of curcumin in the forced swimming test is related to serotonergic system and may be mediated by, at least in part, an interaction with 5-HT(1A/1B) and 5-HT(2C) receptors.
Assuntos
Antidepressivos/farmacologia , Curcumina/farmacologia , Depressão/tratamento farmacológico , Animais , Antidepressivos/administração & dosagem , Curcuma/química , Curcumina/administração & dosagem , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Fluoxetina/administração & dosagem , Fluoxetina/farmacologia , Masculino , Medicina Tradicional Chinesa , Camundongos , Camundongos Endogâmicos ICR , Receptor 5-HT1A de Serotonina/efeitos dos fármacos , Receptor 5-HT1A de Serotonina/metabolismo , Receptor 5-HT1B de Serotonina/efeitos dos fármacos , Receptor 5-HT1B de Serotonina/metabolismo , Receptor 5-HT2C de Serotonina/efeitos dos fármacos , Receptor 5-HT2C de Serotonina/metabolismo , NataçãoRESUMO
Ganoderma ludicum polysaccharides (GlPS) are the major bioactive composition of Ganoderma lucidum, a well-recognized oriental medical fungus. The published data have shown a complementary effect of GlPS in cancer therapy. The present study was designed to determine the anti-tumor efficacy of GlPS and the possible mechanism covering this effect. Murine Sarcoma 180 (S180) model was established, and GlPS administered orally for 10 days. On the 10th day, tumors were weighed to assess the inhibitory effect of GlPS and sera were collected for proteomic analysis and in vitro study. The in vivo results demonstrated that 25, 50 and 100 mg/kg GlPS inhibited S180 growth by 32.67, 44.80 and 45.24%, respectively (P<0.01). Proteomic study revealed marked protein changes after the process of treatment. Three significantly changed proteins were identified by ESI-Q-TOF-MS and database search indicated that they were haptoblobin, apolipoprotein A-II and serum amyloid A (SAA), respectively. Additionally, the expression change of SAA was confirmed by both Western blot and RT-PCR. The adhesion assay showed that GlPS-treated sera dramatically inhibited the adhesion ability of human prostate carcinoma (PC-3M) cells to human umbilical cord vascular endothelial cells (HUVECs), and this effect partially recovered after immunodepletion by the antibody against SAA. Collectively, these results suggest that GlPS inhibited the tumor growth and tumor cell adhesion to HUVECs via up-regulation of SAA protein expression.
Assuntos
Adesão Celular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Polissacarídeos/uso terapêutico , Neoplasias da Próstata/metabolismo , Reishi/química , Sarcoma 180/tratamento farmacológico , Proteína Amiloide A Sérica/metabolismo , Sequência de Aminoácidos , Animais , Apoptose/efeitos dos fármacos , Células Cultivadas , Eletroforese em Gel Bidimensional , Endotélio Vascular/citologia , Endotélio Vascular/efeitos dos fármacos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Dados de Sequência Molecular , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Proteômica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sarcoma 180/metabolismo , Sarcoma 180/patologia , Proteína Amiloide A Sérica/antagonistas & inibidores , Proteína Amiloide A Sérica/imunologia , Espectrometria de Massas por Ionização por Electrospray , Veias Umbilicais/citologia , Veias Umbilicais/efeitos dos fármacos , Veias Umbilicais/metabolismoRESUMO
OBJECTIVE: To investigate the effects of total saponins of panax ginseng (TSPG) on proliferation and differentiation of human embryonic neural stem cell (NSC) into dopaminergic neuron. METHOD: Isolation, cultivation and identification of human embryonic NSC from cerebral cortex of 7-12 week abortus. By using flow cytometry and MTT assay, the effects of various concentration of TSPG and TSPG cooperating with cytokines( EGF, bFGF) in NSC culture media for 3 days on proliferation of human embryonic NSC has studied. By employing immunocytochemistry assay of the expression of tyrosine hydroxylase (TH), the effect of different dilution of TSPG and TSPG cooperating with IL-1 on induced differentiation of human embryonic NSC into dopaminergic neuron has researched. RESULT: TSPG can significantly promote the proliferation of NSC. When TSPG cooperating with EGF and bFGF, the proliferation of NSC is much stronger than that of only using FGF and bFGF. TSPG also induces NSC to differentiate into dopaminergic neuron, especially when TSPG is cooperating with IL-1. CONCLUSION: TSPG can not only obviously accelerate the proliferation of NSC, but also significantly induce differentiation of NSC into dopaminergic neuron.
Assuntos
Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Dopamina/metabolismo , Neurônios/efeitos dos fármacos , Panax/química , Saponinas/farmacologia , Células Cultivadas , Sinergismo Farmacológico , Células-Tronco Embrionárias/citologia , Células-Tronco Embrionárias/efeitos dos fármacos , Células-Tronco Embrionárias/metabolismo , Fator de Crescimento Epidérmico/farmacologia , Fator 2 de Crescimento de Fibroblastos/farmacologia , Humanos , Imuno-Histoquímica , Interleucina-1/farmacologia , Neurônios/citologia , Neurônios/metabolismo , Plantas Medicinais/química , Saponinas/isolamento & purificação , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
The present study aimed to investigate the expression status of miRNA199a3p in patients with diabetic neuropathy (DN) and the mechanism by which this miRNA is involved in the genesis of DN. The expression of miRNA199a3p in plasma of peripheral blood was compared between patients with diabetes and a family history of diabetes and control volunteers by reverse transcriptionquantitative polymerase chain reaction (RTqPCR); in 60 diabetes patients, 45 (75%) demosntrated upregulated miR199a3p expression compared with control volunteer plasma. RTqPCR was also used to detect miRNA199a3p expression in paired lower limb skin tissues from 30 patients with DN and 20 control volunteers; miR199a3p expression in patients with DN was significantly higher than in the control group. Next miR199a3p expression levels were evaluated with respect to the clinicpathological parameters of diabetes; increased expression of miR199a3p was significantly associated with increased disease duration (P=0.041), glycated hemoglobin (HbA1C) levels (P=0.033), and fibrinogen levels (P=0.003). Finally, the effects on downstream mRNA expression levels were investigated as a result of manipulating miR199a3p levels. miR199a3p overexpression inhibited the expression of the extracellular serine protease inhibitor E2 (SerpinE2). Therefore, it may be hypothesized that miR199a3p can induce DN via promoting coagulation in skin peripheral circulation, through the downregulation of SerpinE2. The present findings suggested that miR199a3p may have potential as a novel therapeutic target for the treatment of patients with DN.
Assuntos
Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/genética , Neuropatias Diabéticas/genética , MicroRNAs/genética , Serpina E2/genética , Adulto , Idoso , Coagulação Sanguínea , Linhagem Celular , Diabetes Mellitus Tipo 2/sangue , Neuropatias Diabéticas/sangue , Progressão da Doença , Regulação para Baixo , Feminino , Humanos , Masculino , MicroRNAs/sangue , Pessoa de Meia-Idade , Regulação para CimaRESUMO
A crude glycosidic fraction was prepared from fresh tea leaves and treated with the crude tea enzyme, fractions of cis-3-hexenol, linalool oxide I (cis-furanoid), linalool oxide II (trans-furanoid), linalool, methyl salicylate, geraniol, benzyl alcohol, and 2-phenylethanol were monitored to be the major aglycone moieties by analyzing the released volatiles. The amount of the released aglycone moieties is 5.8 times higher than those in free form. For investigation of the functions of the glycosidically bound form aroma constituents in tea leaves, their antifungal activities were determined by antifungal assay. Geraniol, linalool, methyl salicylate, benzyl alcohol, and 2-phenylethanol exhibited significant antifungal activities toward Colletorichum camelliae Massea, although cis-3-hexenol and linalool oxides showed weaker activities by comparison. Among them, geraniol was shown to be the most potential antifungal substance with a MIC value of 440 microg/mL. The crude glycosidic fraction prepared from tea leaves also exhibited significant antifungal activities in a wide range of concentrations from 2 to 25 mg/mL in a PDA medium. It was deduced that the glycosidically bound volatiles are formed and stored in the intact tissue of tea leaf and hydrolyzed by the actions of both the endogenous and the exogenous glycosidases to release volatiles as antifungal substances when exposed to Colletorichum camelliae Massea. The results suggested that the higher content of the bound form geraniol in tea leaves of var. sinensis might be responsible for their stronger antipathogen properties toward tea leaf blight, as opposed to those of var. assamica.
Assuntos
Camellia sinensis/química , Colletotrichum/efeitos dos fármacos , Fungicidas Industriais/farmacologia , Extratos Vegetais/farmacologia , Folhas de Planta/química , Glicosídeos/análise , Glicosídeos/farmacologia , Odorantes/análise , Folhas de Planta/enzimologia , Volatilização , beta-Glucosidase/metabolismoRESUMO
OBJECTIVE: To explore the clinical effects of surgical treatment with cable dragged reduction and cantilever beam internal fixation by posterior approach for odontoid fracture associated with atlantoaxial dislocation. METHODS: The clinical data of 12 patients with odontoid fracture associated with atlantoaxial dislocation from January 2008 to December 2013 were retrospectively analyzed. There were 8 males and 4 females, ranging in age from 21 to 53 years with an average of 37.2 years. Eleven cases were fresh fracture and 1 case was old fracture, all patients complicated with atlantoaxial anterior dislocation. According to Anderson-D' Alonzo typing method modified by Grauer, 3 cases were type IIA, 5 cases were type IIB, 3 cases were type IIC, and 1 case was type IIIA. All patients underwent surgical treatment with cable dragged reduction and cantilever beam internal fixation by posterior approach. JOA score and ADI method were respectively used to evaluate the nerve function and reductive condition of atlantoaxial dislocation. RESULTS: All patients were followed up from 6 months to 2 years with an average of 1 year and 3 months. At 1 week, 6 months after operation, and final follow up, JOA scores were 13.2±1.3, 13.5±1.4, 14.3±1.5, respectively, and these data were obviously better than that of preoperative 8.3±1.4(P<0.05). Postoperative X rays and CT showed satisfactory reduction of atlantoaxial dislocation. At 1 week, 6 months after operation, and final follow up, ADI were (2.2±0.4), (2.4±0.6), (2.3±0.5) mm, respectively, and these data were obviously better than that of preoperative.(5.8±1.2) mm(P<0.05). All screws and cables had good location without looseness and breakage, and bone graft got fusion. CONCLUSIONS: Surgical treatment with cable dragged reduction and cantilever beam internal fixation by posterior approach for odontoid fracture associated with atlantoaxial dislocation is a good method, with advantage of firm fixation and high safety. It could obtain good clinical effects.
Assuntos
Articulação Atlantoaxial/lesões , Fixação Interna de Fraturas/métodos , Luxações Articulares/complicações , Processo Odontoide/lesões , Traumatismos da Coluna Vertebral/cirurgia , Feminino , Humanos , Masculino , Traumatismos da Coluna Vertebral/complicações , Resultado do TratamentoRESUMO
A series of new analogs based on the structure of lead compound 10 were designed, synthesized and evaluated for their in vitro anti-cancer activities against four selected human cancer cell lines (HL-60, Bel-7402, SK-BR-3 and MDA-MB-468). Several synthesized compounds exhibited improved anti-cancer activities comparing with lead compound 10. Among them, 1,3,4-oxadiazole analogs 17o showed highest bioactivity with IC50 values of 1.23, 0.58 and 4.29 µM against Bel-7402, SK-BR-3 and MDA-MB-468 cells, respectively. It is noteworthy that 17o has potent anti-proliferation activity toward a panel of cancer cells with relatively less cytotoxicity to nonmalignant cells. The further mechanistic study showed that it induced apoptosis and cell cycle arrest through disrupting spindle assembly in mitotic progression, indicating these synthesized dithiocarbamates represented a novel series of anti-cancer compounds targeting mitosis.