RESUMEN
To predict the targets of active ingredients of Kuihua Hugan Tablets by network pharmacology, and explore the "multi-component-multi-target-multi-pathway" hepatoprotective mechanism of action. First, through traditional Chinese medicine systems pharmacology(TCMSP) and TCM Database@Taiwan Database, main active ingredients of Kuihua Hugan Tablets were screened out based on oral bioavailability(OB), drug-likeness(DL) and effective half-lives(HL). The targets of active ingredients of Kuihua Hugan Tablets were predicted based on the PharmMapper method. Then, the prediction was conducted by screening the target genes associated with chronic hepatitis and early cirrhosis through CooLGeN and GeneCards databases. Target gene functions and signal pathways were analyzed by bioinformatics annotation database Metascape. Cytoscape software was used to construct the Kuihua Hugan Tablets ingredient-target and ingredient-target-pathway network. String database combined with Cytoscape software was used to construct the networks of component-target and component-target-pathway. STRING database was combined with Cytoscape software to draw protein-protein interaction(PPI) network and conduct network topology analysis. Finally, Systems Dock Web Site software was applied in verifying the molecular docking between active ingredients and potential protein targets. A total of 26 compounds and 509 potential targets were screened out from Kuihua Hugan Tablets in the experiment. The results of PPI network analysis indicated that albumin(ALB), insulin-like growth factor 1(IGF1), matrix metalloproteinase-9(MMP9), matrix metalloproteinase-2(MMP2), non-receptor tyrosine kinase proto-oncogene(SRC), estrogen receptor 1(ESR1) and cancer-signal transduction-inflammation-drugs metabolism-related biological processes and metabolic pathways were closely associated with the active ingredients in Kuihua Hugan Tablets. The effects of Kuihua Hugan Tablets in alleviating chronic hepatitis and early cirrhosis indicated the multi-component, multi-target, and multi-pathway characteristics of traditional Chinese medicines, providing new ideas for further research and development of Kuihua Hugan Tablets.
Asunto(s)
Medicamentos Herbarios Chinos/farmacología , Redes y Vías Metabólicas , Mapeo de Interacción de Proteínas , Medicina Tradicional China , Simulación del Acoplamiento Molecular , ComprimidosRESUMEN
OBJECTIVE: To explore interleukin-1 beta (IL-1 beta) and IL-6 gene polymorphism, and investigate the relationship between their gene polymorphism and the morbid state of patients with acute pancreatitis (AP). METHODS: The polymorphism of IL-1 beta gene 511C/T and IL-6 gene 634C/G site was analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in patients (74 patients) with AP, including mild acute pancreatitis (MAP, 36 patients) and severe acute pancreatitis (SAP, 38 patients), and also a group of normal control (78 patients). The plasma concentrations of IL-1 beta and IL-6 were measured by enzyme linked immunosorbent assay (ELISA). The patients with SAP were divided into groups on the basis of different genotypes, and the clinical data were compared among different groups. RESULTS: The plasma levels of IL-1 beta and IL-6 in patients with AP were significantly higher than normal control group [IL-1 beta: (13.16+/-2.82) ng/L vs. (6.21+/-1.57) ng/L; IL-6: (84.86+/-32.92) ng/L vs. (9.95+/-2.49) ng/L, both P<0.05]. There was no statistical significance between IL-1 beta gene 511 site and IL-6 gene 634 site genotype or allele frequency between the patients with AP and the normal control. In patients with SAP, IL-1 beta gene 511 site T/T genotype and T allele frequency were significantly higher than that of MAP group (both P<0.05). There was no statistically significant difference in plasma levels of IL-1 beta between C/C group and C/T+T/T group, and the plasma levels of IL-6 in patients with IL-6 gene 634 site C/G were significantly higher than C/C group [(97.23+/-35.49) ng/L vs. (72.14+/-24.55) ng/L, P<0.05]. In patients with SAP, the scores of clinical evaluation in IL-1 beta gene 511 site C/T+T/T group and IL-6 gene 634 site C/G group were significantly higher than that in IL-1 beta gene 511 site C/C group and IL-6 gene 634 site C/C group (all P<0.05). CONCLUSION: IL-1 beta gene 511 site C/T and IL-6 gene 634 site C/G polymorphism may be genetic susceptibility factors for exacerbation of AP.