RESUMO
The acupoint application of Euodiae Fructus at Yongquan(KI1) can significantly improve the sleep quality of patients with insomnia with berberine as the main effective component for the efficacy. Nineteen active compounds and 203 drug targets were screened out from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). After comparison with GeneCards and Online Mendelian Inheritance in Man(OMIM), 24 common genes of diseases and drugs were obtained. STRING 11.0 was used to construct a protein-protein interaction(PPI) network of the overlapping genes, and Matthews correlation coefficient(MCC) was employed to screen the core genes, which were then subjected to enrichment analysis with gene ontology(GO) and Kyoto encyclopedia of genes and genomes(KEGG). The results revealed that the main compounds of Euodiae Fructus, such as berberine and rutaecarpine, participated in the biological processes(such as neurotransmitter receptor activity) by regulating C-reactive protein(CRP), estrogen receptor 1(ESR1), 5-hydroxytryptamine(5-HT) receptor, and interleukin-6(IL-6) to exert sedative, anxiolytic, and antidepressant effects. Sixty 4-week-old SPF mice were randomly divided into a control group, a model group, a positive drug(diazepam tablets) group, and low-, medium-, and high-dose berberine groups. Medication with corresponding drugs was performed for one week. The results demonstrated that berberine was potent in reducing the activities and standing times of mice, down-regulating the levels of CRP and IL-6 mRNA in the hypothalamus, and up-regulating the expression of 5-HT(P<0.01); however, no significant effect on ESR1 was observed. The network of Euodiae Fructus in treating insomnia was constructed by network pharmacology and verified by tests. The findings indicated that the therapeutic efficacy of Euodiae Fructus in treating insomnia was achieved by participating in multiple biological processes, such as neurotransmitter receptor activity, which provided a scientific basis for its clinical application.
Assuntos
Medicamentos de Ervas Chinesas , Distúrbios do Início e da Manutenção do Sono , Animais , Bases de Dados Genéticas , Medicamentos de Ervas Chinesas/farmacologia , Ontologia Genética , Humanos , Medicina Tradicional Chinesa , Camundongos , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Distúrbios do Início e da Manutenção do Sono/genéticaRESUMO
Selenium (Se), as a nutritionally essential trace element, has been shown to decrease with age and is closely related to Alzheimer's disease (AD). To probe the effects of Se on AD pathology, two-dimensional fluorescence difference gel electrophoresis was applied to the serum samples collected from the wild-type (WT) mice and the triple transgenic (PS1M146V/AßPPSwe/TauP301L) AD mice (3xTg-AD), treated with or without sodium selenate in drinking water for 4 months beginning at 2 months of age. Proteomics results revealed 17 differentially expressed proteins between WT and 3xTg-AD mice. It was found that the administration of selenate reversed the alterations of the differentially expressed serum proteins by up-regulating 13 proteins and down-regulating 2 proteins which were reported to be involved in the key pathogenesis of AD, including regulation of Aß production, lipid metabolism regulation, and anti-inflammation. These results suggested that a dietary supplement with selenate is effective for prevention and treatment of AD, and the mechanism was maybe related to its role in Aß regulation, lipid metabolism, and anti-inflammation. Moreover, we also presented that α-2 macroglobulin, transthyretin, haptoglobin, alpha-2-HS-glycoprotein, and alpha-1-antitrypsin in the serum can be used to evaluate the effect of selenate on AD pathology.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Modelos Animais de Doenças , Proteômica , Ácido Selênico/farmacologia , Doença de Alzheimer/sangue , Doença de Alzheimer/patologia , Animais , Glicoproteínas/antagonistas & inibidores , Glicoproteínas/sangue , Haptoglobinas/análise , Haptoglobinas/antagonistas & inibidores , Camundongos , Camundongos Endogâmicos , Camundongos Transgênicos , Pré-Albumina/análise , Pré-Albumina/antagonistas & inibidores , alfa 2-Macroglobulinas Associadas à Gravidez/análise , alfa 2-Macroglobulinas Associadas à Gravidez/antagonistas & inibidores , alfa 1-Antitripsina/sangue , alfa 1-Antitripsina/metabolismoRESUMO
BACKGROUND: Retinal ischemia-related eye diseases result in visual dysfunction. This study investigates the protective effects and mechanisms of Xue-Fu-Zhu-Yu decoction (XFZYD) with respect to retinal ischemia. METHODS: Retinal ischemia (I) was induced in Wistar rats by a high intraocular pressure (HIOP) of 120 mmHg for 1 h, which was followed by reperfusion of the ischemic eye; the fellow untreated eye acted as a control. Electroretinogram (ERG), biochemistry and histopathology investigations were performed. RESULTS: Significant ischemic changes occurred after ischemia including decreased ERG b-wave ratios, less numerous retinal ganglion cells (RGCs), reduced inner retinal thickness, fewer choline acetyltransferase (ChAT) labeled amacrine cell bodies, increased glial fibrillary acidic protein (GFAP) immunoreactivity and increased vimentin Müller immunolabeling. These were accompanied by significant increases in the mRNA/protein concentrations of vascular endothelium growth factor, hypoxia-inducible factor-1α, pyruvate kinase M2 and retinoblastoma-binding protein 2. The ischemic changes were concentration-dependently and significantly altered when XFZYD was given for seven consecutive days before or after retina ischemia, compared to vehicle. These alterations included enhanced ERG b-wave amplitudes, more numerous RGCs, enhanced inner retinal thickness, a greater number of ChAT immunolabeled amacrine cell bodies and decreased GFAP/vimentin immunoreactivity. Furthermore, decreased mRNA levels of VEGF, HIF-1α, PKM2, and RBP2 were also found. Reduced protein concentrations of VEGF, HIF-1α, PKM2, and RBP2 were also demonstrated. Furthermore, there was an inhibition of the ischemia-associated increased ratios (target protein/ß-actin) in the protein levels of VEGF, HIF-1α, PKM2, and RBP2, which were induced by Shikonin, JIB-04 or Avastin. CONCLUSION: XFZYD would seem to protect against well-known retinal ischemic changes via a synergistic inhibition of RBP2 and PKM2, as well as down-regulation of HIF-1α and a reduction in VEGF secretion.
Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Isquemia/tratamento farmacológico , Fitoterapia , Retina/efeitos dos fármacos , Doenças Retinianas/metabolismo , Animais , Regulação para Baixo , Medicamentos de Ervas Chinesas/uso terapêutico , Eletrorretinografia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Isquemia/metabolismo , Masculino , Piruvato Quinase/metabolismo , Ratos Wistar , Retina/metabolismo , Retina/patologia , Doenças Retinianas/tratamento farmacológico , Proteína 2 de Ligação ao Retinoblastoma/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
BACKGROUND: Glutamate-gated chloride channels (GluCl) mediate fast inhibitory neurotransmission in invertebrate nervous systems. Although only one GluCl gene was presented in insects, it showed diverse alternative splicing that was speculated could affect channel function and pharmacology. RESULTS: In this study, we isolated GluCl cDNAs from adults of the small brown planthopper (SBPH) Laodelphax striatellus and showed that six L. striatellus GluCl variants (LsGluCl-AS, LsGluCl-BS, LsGluCl-CS, LsGluCl-AL, LsGluCl-BL, LsGluCl-CL) were present in the SBPH. The expression patterns of six variants differed among developmental stages (egg, first- to fifth-instar nymphs, male and female adults) and among the body parts (head, thorax, abdomen, leg) of the female adult SBPH. All the transcripts were abundant in the head of the adult. When expressed in African clawed frog, Xenopus laevis, oocytes, the two functional variants (LsGluCl-AS, LsGluCl-AL) had similar EC50 and IC50 values for L-glutamate and channel blockers picrotoxinin and fipronil. CONCLUSION: This study represents a comprehensive molecular, expression and pharmacological characterisation of GluCl in the SBPH. These findings should be useful in providing more opportunities to discover novel insect control chemicals. © 2016 Society of Chemical Industry.
Assuntos
Canais de Cloreto/genética , Antagonistas de Receptores de GABA-A/farmacologia , Hemípteros/efeitos dos fármacos , Hemípteros/genética , Proteínas de Insetos/genética , Inseticidas/farmacologia , Processamento Alternativo , Sequência de Aminoácidos , Animais , Sequência de Bases , Canais de Cloreto/química , Canais de Cloreto/metabolismo , Clonagem Molecular , DNA Complementar/genética , DNA Complementar/metabolismo , Feminino , Ácido Glutâmico/metabolismo , Hemípteros/crescimento & desenvolvimento , Hemípteros/metabolismo , Proteínas de Insetos/química , Proteínas de Insetos/metabolismo , Dose Letal Mediana , Masculino , Ninfa/efeitos dos fármacos , Ninfa/genética , Ninfa/crescimento & desenvolvimento , Ninfa/metabolismo , Picrotoxina/análogos & derivados , Picrotoxina/farmacologia , Pirazóis/farmacologia , Alinhamento de Sequência , SesterterpenosRESUMO
AIM: To study the protective effects of hydroxyethylpuerarin against the injury of astrocytes induced by hydrogen peroxide (H2O2). METHODS: Experiments were performed with cells from passage 4. Plasma membrane integrity was measured by lactate dehydrogenase (LDH) release. The occurrence of apoptosis was measured by flow cytometry. The glutamate uptake of astrocytes was studied with [3H]-glutamate incorporation. Intracellular superoxide dismutase (SOD) activity and malondialdehyde (MDA) level were assessed by automatic biochemistry analyzer. RESULTS: Compared with H2O2 injured group, the occurrence of apoptosis, levels of LDH release and intracellular MDA of astrocytes reduced in hydroxyethylpuerarin pre-treated groups, but the glutamate uptake and intracellular SOD activity of astrocytes increased. CONCLUSION: Hydroxyethylpuerarin could reduce the occurrence of apoptosis and improve neurotrophic function of astrocytes, which may be related with its antioxidant effects during oxidative stress.