RESUMO
This study analyzed the molecular mechanism of Huangjing Qianshi Decoction(HQD) in the treatment of prediabetes based on network pharmacology and molecular docking. The active components of HQD were identified and screened based on Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP, http://Lsp.nwu.edu.cn/tcmsp.php) and then the targets of the components and the genes related to prediabetes were retrieved, followed by identifying the common targets of the decoction and the disease. The medicinal component-target network was constructed by Cytoscape to screen key components. The protein-protein interaction(PPI) network was established by STRING and hub genes were identified by Cytoscape-CytoNCA, followed by Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) of the hub genes with R-clusterProfi-ler. Thereby, the possible signaling pathways were predicted and the molecular mechanism was deduced. A total of 79 active components of HQD and 785 diabetes-related targets of the components were screened out. The hub genes mainly involved the GO terms of tricarboxylic acid cycle, peptide binding, amide binding, hydrolase activity, and kinase activity regulation, and the KEGG pathways of AGE-RAGE signaling pathway, TNF signaling pathway, AMPK signaling pathway, IL-17 signaling pathway, and insulin signaling pathway. Western blot result showed that HQD-containing serum significantly reduced the expression of AKT1, AGE, and RAGE proteins in insulin resistance model cells. HQD's treatment of prediabetes is characterized by multiple pathways, multiple targets, and multiple levels. The main mechanism is that the components zhonghualiaoine, baicalein, kaempferol, and luteolin act on AKT1 and inhibit the AGE-RAGE axis.
Assuntos
Humanos , Medicamentos de Ervas Chinesas/farmacologia , Medicina Tradicional Chinesa , Simulação de Acoplamento Molecular , Farmacologia em Rede , Estado Pré-Diabético/genéticaRESUMO
Type 2 diabetes is the main health problem in Mexico. The growing number of cases, the high percentage of individuals with chronic complications and the treatment's cost are among the explanations for the inability in the control of this disease. Diabetes prevention is most likely to reduce the rate of growth of this diabetes burden on our health system. At- risk individuals can be identified and several interventions have proved to be effective in decreasing diabetes incidence. Diabetes prevention related interventions can become a reality with the active participation of the government and society. Thus, a joint collaboration between the medical community, the government and society is needed to phase out the diabetes epidemic. Published diabetes prevention programs were reviewed and interventions feasible for Mexico were summarized in a document called "Declaración de Acapulco". This paper was reviewed and approved by the Sociedad Mexicana de Nutrición y Endocrinología; additional endorsement was obtained from several Mexican and international societies and institutions. The manuscript describes several initiatives, which can be applied in schools, work places, primary health services and by the government. Some of these are focused on the general population; others are applicable to at-risk individuals. The "Declaración de Acapulco" is a-call-for-action position directed towards the whole society and designed to achieve effective diabetes prevention.
La diabetes es el principal problema de salud en México. El número creciente de casos, el elevado porcentaje que desarrollan complicaciones tardías y el costo del tratamiento hacen insuficientes los esfuerzos para confrontarla. La prevención de la diabetes es la forma más plausible para modificar el crecimiento de la epidemia. Los sujetos que desarrollarán la enfermedad pueden ser detectados y existen intervenciones que disminuyen la incidencia de la enfermedad. Las estrategias para la prevención de la diabetes sólo pueden ser llevadas a la práctica con la intervención de entidades gubernamentales y con el consenso de la sociedad. Por ello, se requiere un esfuerzo conjunto de la comunidad médica, del gobierno y de la sociedad para confrontar la epidemia de diabetes. Se revisaron los programas de prevención reportados en la literatura y se generó un documento, llamado "Declaración de Acapulco" que resume las maniobras que se consideraron factibles en nuestro país. El documento fue avalado por la Sociedad Mexicana de Nutrición y Endocrinología; también, recibió el aval de diversas sociedades e instituciones de México y otros países. El manuscrito describe iniciativas a realizar en escuelas, sitios de trabajo, servicios de salud y en el gobierno. Algunas acciones están dirigidas para la población general; otras son aplicables para sujetos en riesgo. La "Declaración de Acapulco" es un exhorto a la sociedad a tomar una actitud proactiva en la prevención de la diabetes.