RESUMO
Cornus Officinalis (Cornus), the dried pulp of mature Cornus, is used to treat liver diseases. However, the pharmacological mechanism of Cornus in the treatment of hepatocellular carcinoma (HCC) has not been systematically studied. The chemical compounds and the bioactive chemical compounds of Cornus were screened through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Gene Cards database was used to explore the targets in liver cancer pathogenesis. The disease-drug Venn diagram was constructed using the VENN 2.1 and the STRING database was used to analyze protein-protein Interaction Network (PPI). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed using the R package. Molecular docking was performed using Discovery Studio were assessed using Pymol and Discovery Studio 2016. Cell survival of BEL-7404 cells treated by Hydroxygenkwanin (HGK) were valued through CCK-8 assay. Expressions of caspase-3 and cleaved PARP was detected through Western blot. Pharmacological network diagrams of the Cornus compound-target network and HCC-related target network were successfully constructed. A total of 20 active compounds, 1841 predicted biological targets of Cornus, and 7100 HCC-related targets were identified. 37 target genes between Cornus and HCC were screened trough the network pharmacology. Molecular docking studies suggested that HGK has the highest affinity with caspase-3. HGK could induce apoptosis of HCC cells and significantly activate the caspase-3 protease activity in BEL-7404. This study systematically elaborated the mechanism of Cornus in the treatment of HCC and provided a new perspective to exploit Antineoplastic from Cornus.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Cornus/química , Medicamentos de Ervas Chinesas/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Antineoplásicos Fitogênicos/uso terapêutico , Apoptose/efeitos dos fármacos , Apoptose/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Caspase 3/metabolismo , Linhagem Celular Tumoral , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Simulação de Acoplamento Molecular , Farmacologia em Rede , Mapas de Interação de Proteínas/efeitos dos fármacos , Mapas de Interação de Proteínas/genética , Transdução de Sinais/genéticaRESUMO
The paper mainly reported the changes in quality ingredients of Qi chrysanthemum flowers treated with elevated UV-B radiation at different growth stages. The experiment included two levels of UV-B radiation (ambient UV-B, a 10% increase in ambient UV-B). Elevated UV-B radiation was carried out for 10-days during seedling, vigorous growth, bud and flower stages of Qi chrysanthemum, respectively. Elevated UV-B treatments applied during four development stages did not significantly affect flower yield, the rate of superoxide radical production and malondialdehyde concentration in flowers, while increased free amino acid concentration. The amino acid concentration induced by elevated UV-B radiation applied during bud stage was higher than that during the other stages. Elevated UV-B radiation applied during vigorous growth (except for flavone), bud and flower stages of chrysanthemum significantly increased hydrogen peroxide concentration, phenylalanine ammonia lyase enzyme activity, vitamin C, chlorogenic acid and flavone concentrations in flowers. These results suggested that active and nutritional ingredients in flowers of chrysanthemum could be increased by elevated UV-B radiation applied during the later growth stages of chrysanthemum. The paper supplied a simple and environmental-friendly method to improve quality of medicinal plants.
Assuntos
Chrysanthemum/crescimento & desenvolvimento , Chrysanthemum/efeitos da radiação , Flores/efeitos da radiação , Aminoácidos/metabolismo , Ácido Ascórbico/metabolismo , Ácido Clorogênico/metabolismo , Chrysanthemum/metabolismo , Flavonas/metabolismo , Flores/metabolismo , Peróxido de Hidrogênio/metabolismo , Malondialdeído/metabolismo , Fenilalanina Amônia-Liase/metabolismo , Plantas Medicinais/efeitos da radiação , Qi , Superóxidos/metabolismo , Raios UltravioletaRESUMO
BACKGROUND: Homoharringtonine (HHT) is a kind of cephalotaxus alkaloid used in traditional Chinese medicine. Although HHT has been successfully used as a therapeutic agent for leukemia, the drug resistance and toxicity are major concerns. MicroRNAs (miRNAs) have been identified to modulate cellular sensitivity to anticancer drugs. We examined the synergistic action between miR-370 and HHT in vitro and in vivo. METHODS: The synergistic action between miR-370 and HHT was examined by flow cytometry. The effect of HHT on miR-370 expression was determined by quantitative RT-PCR (qRT-PCR). The expression of miR-370 and Forkhead box M1 (FoxM1) in 23 patients with newly diagnosed chronic-phase chronic myeloid leukemia (CML-CP) and 10 patients with blast-crisis CML (CML-BP) as well as miR-370-targeted FoxM1 was determined by qRT-PCR and western blot analysis. RESULTS: Ectopic expression of miR-370 sensitized the CML K562 cell line to HHT by targeting FoxM1, the major regulator in cell proliferation and apoptosis. miR-370 significantly promoted HHT-mediated cell apoptosis and miR-370 and HHT cooperated in affecting FoxM1 expression. As well, miR-370 was moderately upregulated after HHT treatment in K562 cells. In addition, the expression of miR-370 was significantly reduced in CML patients as compared with healthy controls. Furthermore, the expression of miR-370 was lower in CML-BP than CML-CP patients. CONCLUSIONS: MiR-370 sensitized K562 cells to HHT by inducing apoptosis in part by downregulation of FoxM1 expression. These findings may provide further information for CML treatment with HHT.