Evaluating the Pharmacological Mechanism of Chinese Medicine Si-Wu-Tang through Multi-Level Data Integration

Abstract

Si-Wu-Tang (SWT) is a Traditional Chinese Medicine (TCM) formula widely used for the treatments of gynecological diseases. To explore the pharmacological mechanism of SWT, we incorporated microarray data of SWT with our herbal target database TCMID to analyze the potential activity mechanism of SWT's herbal ingredients and targets. We detected 2,405 differentially expressed genes in the microarray data, 20 of 102 proteins targeted by SWT were encoded by these DEGs and can be targeted by 2 FDA-approved drugs and 39 experimental drugs. The results of pathway enrichment analysis of the 20 predicted targets were consistent with that of 2,405 differentially expressed genes, elaborating the potential pharmacological mechanisms of SWT. Further study from a perspective of protein-protein interaction (PPI) network showed that the predicted targets of SWT function cooperatively to perform their multi-target effects. We also constructed a network to combine herbs, ingredients, targets and drugs together which bridges the gap between SWT and conventional medicine, and used it to infer the potential mechanisms of herbal ingredients. Moreover, based on the hypothesis that the same or similar effects between different TCM formulae may result from targeting the same proteins, we analyzed 27 other TCM formulae which can also treat the gynecological diseases, the subsequent result provides additional insight to understand the potential mechanisms of SWT in treating amenorrhea. Our bioinformatics approach to detect the pharmacology of SWT may shed light on drug discovery for gynecological diseases and could be utilized to investigate other TCM formulae as well.

Network Pharmacology: A Rosetta Stone for Traditional Chinese Medicine

“…Si‐Wu (meaning four herbs) Tang (SWT) is a TCM formula (Fu Fang) widely used for gynecological diseases (Table ). Microarray data of SWT and TCMID were combined to analyze the mode of action (MOA) of SWT ingredients and targets [Fang et al., ]. TCM Database@Taiwan is the second largest TCM database [Chen, ], which contains more than 20,000 pure compounds isolated from 453 TCM herbs.…”

“…Shaofu Zhuyu decoction has more effects on lipid metabolism, Xiangfu SWT on amino acid metabolism, THSWD on carbohydrate metabolism, and Qinlian SWT on ErbB and VEGF (vascular endothelial growth factor) signal transduction pathways. Microarray data for SWT were combined with the TCMID database (Table ) to analyze the potential activity mechanism of SWT and targets [Fang et al., ]. In total, 2405 DEGs were detected in the microarray data, 20 of which encode SWT targets.…”

Identifying the molecular targets of Salvia miltiorrhiza (SM) in ox-LDL induced macrophage-derived foam cells based on the integration of metabolomics and network pharmacology

“…[13][14][15] The development of analytical techniques has broadened the application of metabolomics; a typical research area is identifying drug(s)-affected pathways. 16,17 However, the proteins in the drug(s)-affected pathways obtained by metabolomics are mainly downstream disease-related proteins. Network pharmacology has been proven successful in target identication, however, it lacks the detailed representation of the regulation processes on specic metabolic pathways or molecular networks, resulting in the weak disease specicity of the target networks.…”

Integrating System Biology Tools to Decipher the Mechanisms of Action of Herbal Medicine

“…This increased the antioxidant effect of heme oxygenase-1 protein expression (alias HMOX1) responsible to protect against psychiatric diseases. Thus, incorporating microarray data with herbal target database would infer signaling pathway enrichment of the predicted target of TCM as well constructing an intelligent network of herbal ingredients-targets-drugs actions would provide insights about the mechanistic of the herbal formula [8]. On the other hands, to elaborate the potential pharmacological mechanisms of Si Wu Tang formula, 20 predicted targets were identified by interconnecting known targets in TCM database and differentially expressed genes.…”