ABSTRACT
Objective::To predict the action targets of anti-lung cancer active ingredients of Xiao Chaihutang, in order to explore the " multi-components, multi-targets and multi-pathways" mechanism using network pharmacology. Method::The active ingredients of Xiao Chaihutang that obtained through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), traditional Chinese medicine integrative database for herb molecular mechanism analysis(TCMID) and literature were used to predict the targets by the reversed pharmacophore matching method.To screen out optimization targets, we chose elbow point analysis by using self-developed software TCMKD1.0, and screened out lung cancer-related targets by searching databases, such as Therapeutic Target Database (TTD), Online Mendelian Inheritance in Man(OMIM) and GeneCards, and reviewing literatures.Then components-target network, protein-protein interaction network and targets-pathways network were constructed.The pathway information was acquired with STRING.The Cytoscape 3.6 software was used to construct the ingredients-targets-pathways network of Xiao Chaihutang. Result::The 162 active components in Xiao Chaihutang were obtained, involving 71 anti-lung cancer targets and 11 related pathways.Through topological network analysis, 96 important components, such as quercetin, ginsenosideRh2, formononetin and β-sitosterol were obtained, 28 key targets, such as epidermal growth factor receptor (EGFR), vascular endothelial growth factor (KDR), cysteine protease-3 (Caspase-3), mitogen-activated protein kinase1(MAPK1), hepatocyte growth factor (MET) were received, and 61 core pathways, such as non-small cell lung cancer, small cell lung cancer, ErbB signaling pathway, VEGF signaling pathway were acquired. Conclusion::The result suggests that the active components of Xiao Chaihutang against lung cancer may include quercetin, ginsenoside Rh2, 6-shogaol, formononetin, β-sitosterol.And the mechanism may be related to ErbB signaling pathway, MAPK signaling pathway and VEGF signaling pathway.This research provides a scientific basis for further elucidation of the anti-lung cancer pharmacological mechanism of Xiao Chaihutang.
ABSTRACT
Objective: To set a criterion for determining whether herbs distribute to kidney meridian from the perspective of tissue expression of protein receptors, so as to provide new ideas and a new method for the quantitative study of meridian tropism. Method: The 9 Yang-tonifying herbs were selected as the training set, and 2 Yang-tonifying herbs were used as the verification set. The TCMSP2.3,PubChem,Uniprot and other database were used to collect the active compounds and targets of traditional Chinese medicine(TCM). The core target proteins of Yang-tonifying herbs were obtained by using the Maximum Similarity Algorithm for TCM in the training set. The THPA database was used to collect expressions of tissues and target proteins. The empirical regression equation was constructed to explore the tissue distribution of the receptors in the training set, and the criterion for determining whether herbs distribute to kidney meridian was established. The criteria model was tested through validation set data. Result: The herb-active ingredient-protein receptor-tissue expression data library was constructed. A total of 39 core target proteins of Yang-tonifying herbs were acquired. The equations in the training set were highly consistent, with no statistical difference (P=0.999 7). The data of the combined training set was finally fitted to a judgment equation. The model was successfully tested with herbs in the validation set. The accuracy of the model was 100%. Conclusion: This study explored a new method for judging whether TCM distributes to kidney meridian, established an effective criterion model and verified the reliability of the new method. It provides a theoretical basis for the modernization of meridian tropism of traditional Chinese medicine, and is of great significance for the rapid development of traditional Chinese medicine.