Abstract
Because of the complex etiology, the treatment of gastric cancer is a formidable challenge for contemporary medical. The current treatment method focuses on traditional surgical procedures, supplemented by other treatments. Among these other treatments, Traditional Chinese Medicine (TCM) plays an important role. Here, we used the systems pharmacology approach to reveal the potential molecular mechanism of PRGRC on gastric cancer which composes of Pinellia ternata(Thunb.) Breit., Rheum palmatumL., Gentiana scabraBunge, Radix Aucklandiae and Citrus aurantium L. This approach combines pharmacokinetics analysis with pharmacodynamics evaluation for the active compounds screening, targets prediction and pathways assessing. Firstly, through pharmacokinetic evaluation and target prediction models, 83 potential compounds and 184 gastric cancer-related targets were screened out. Then, the results of network analysis suggested that the targets of PRGRC were mainly involved two aspects: apoptosis and inflammation. Finally, we verified the reliability of the above analysis at the cellular level by using naringenin and luteolin with good pharmacokinetic activity as representative compounds. Overall, we found that PRGRC could influence the development of gastric cancer from a multi-scale perspective. This study provided a new direction for analyzing the mechanism of TCM.
Highlights
Because of the complex etiology, the treatment of gastric cancer is a formidable challenge for contemporary medical
In order to screen for potential bioactive compounds of PRGRC, we evaluated the ADME (Absorption, Distribution, Metabolism, Excretion) properties of these compounds, including oral bioavailability (OB) and DL
We selected PRGRC commonly used in clinical practice as an example, and proposed the systems pharmacology approach to interpret the synergistic pharmacological mechanism of the Traditional Chinese Medicine (TCM) formula in the treatment of gastric cancer
Summary
Because of the complex etiology, the treatment of gastric cancer is a formidable challenge for contemporary medical. We used the systems pharmacology approach to reveal the potential molecular mechanism of PRGRC on gastric cancer which composes of Pinellia ternata (Thunb.) Breit., Rheum palmatum L., Gentiana scabra Bunge, Radix Aucklandiae and Citrus aurantium L. This approach combines pharmacokinetics analysis with pharmacodynamics evaluation for the active compounds screening, targets prediction and pathways assessing. We have successfully constructed a new systems pharmacology approach that includes ADME characterization of drugs evaluation, target prediction and network analysis, which facilitated the identification of multiple mechanisms of d rugs[11] Through this platform, a variety of herbs including Radix Salviae miltiorrhiza, Sophora flavescens, Sedum rosea and Glycyrrhiza uralensis Fisch. A variety of herbs including Radix Salviae miltiorrhiza, Sophora flavescens, Sedum rosea and Glycyrrhiza uralensis Fisch. have been verified to have potential mechanisms in the treatment of cancer, depression and cardiovascular diseases
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