ABSTRACT
The aim of this paper was to explore the potential molecular mechanism of Banxia Xiexin Decoction in the treatment of colon cancer through pharmacology network and molecular docking methods. The chemical constituents and action targets of 7 herbs from Banxia Xiexin Decoction were collected by using TCMSP database,Chinese Pharmacopoeia and literatures consultation. GeneCards database was used to predict the potential targets of colon cancer. GO biological process analysis and KEGG pathway enrichment analysis of the disease and drug intersection targets were carried out through DAVID database. "Component-target-pathway" network and protein-protein interaction(PPI) network were construction by using Cytoscape and STRING database,and then the core components and targets of Banxia Xiexin Decoction in the treatment of colon cancer were selected according to the topological parameters. Finally, Autodock Vina was used to realize the molecular docking of core components and key targets. The prediction results showed that there were 190 active compounds and 324 corresponding targets for Banxia Xiexin Decoction,involving 74 potential targets for colon cancer. Cytoscape topology analysis revealed 11 key targets such as STAT3,TP53,AKT1,TNF,IL6 and SRC, as well as 10 core components such as quercetin,β-sitosterol,baicalein,berberine,and 6-gingerol.In bioinformatics enrichment analysis, 679 GO terms and 106 KEGG pathways were obtained, mainly involving PI3 K-AKT signaling pathway,TNF signaling pathway and TP53 signaling pathway. The results of molecular docking showed that baicalein,berberine,licochalcone A and 6-gingerol had a high affinity with SRC,STAT3,TNF and IL6. The results suggested that Banxia Xiexin Decoction could play an anti-colon cancer effect by inhibiting cell proliferation, regulating cell cycle, inducing apoptosis and anti-inflammatory function. The study revealed the multi-components,multi-targets and multi-pathways molecular mechanism of Banxia Xiexin Decoction,which could provide scientific basis and research ideas for the clinical application of Banxia Xiexin Decoction and the treatment of colon cancer with compound Chinese medicines.
Subject(s)
Humans , Colonic Neoplasms , Drugs, Chinese Herbal , Molecular Docking Simulation , TechnologyABSTRACT
Raw materials' quality variation could affect the quality consistency of product and the clinical efficacy. In this paper, the high shear wet granulation (HSWG) process of the ginkgo leaf tablet was taken as the research object. Ginkgo biloba extracts and excipients microcrystalline cellulose collected from various sources and batches were used to simulate raw materials' quality variation. Real-time torque was recorded to analyze the viscosity of the wetting mass, and then by combining with physical fingerprint, the impact of physical quality variation of powders on granule properties could be investigated. Based on regime map thesis, whether the granules' nucleation mode was in mechanical dispersion regime was determined by calculating dimensionless parameters, which would lead to the unstable output in considerations of granule yield ratio and particle size distribution (PSD) curve. The orthogonal partial least square (OPLS) model was adopted to build the relationship between the micromeritic properties and the mediangranule size (D50) of Ginkgo biloba granules and then the critical material attributes (CMAs) were screened by variable importance in the projection (VIP) indexes. The results demonstrated that the properties of powders including hygroscopicity, angle of repose, Hausner ratio, Carr index, D10 and loss on drying affected the granule size. Besides, Ginkgo biloba granules were compressed into tablets. In view of tensile strength analysis, the raw materials' quality variation did not result in decrease of tensile strength of the ginkgo leaf tablets. The design space of critical quality attributes (CQAs) and the process design space which could cope with raw materials' quality variation were proved to be robust..