{Reference Type}: Journal Article
{Title}: Quantitative and network pharmacology: A case study of rhein alleviating pathological progress of renal interstitial fibrosis.
{Author}: Shen Y;Feng F;Sun H;Li G;Xiang Z;
{Journal}: J Ethnopharmacol
{Volume}: 261
{Issue}: 0
{Year}: Oct 2020 28
{Factor}: 5.195
{DOI}: 10.1016/j.jep.2020.113106
{Abstract}: <B>BACKGROUND: </B>The current network pharmacology model focuses mainly on static and qualitative characterisation between drugs and targets or molecular pathway networks, but it does not reflect the multi-scale, dynamic and quantitative process of drug action.<BR><B>OBJECTIVE: </B>In this study, we developed a new model known as quantitative and network pharmacology (QNP) to characterise the dynamic and quantitative interventions of drugs within a multi-scale biological network.<BR><B>METHODS: </B>Firstly, we used a systems biology method to construct a molecule-cell dynamic network model to simulate the pathological processes of diseases. Secondly, according to the principles of enzymatic kinetics, we generated a multi-scale drug intervention model to simulate the intervention of drugs in multi-scale networks at different concentrations and pathological stages. Finally, we took rhein treatment of renal interstitial fibrosis (RIF) as an example to illustrate the QNP model.<BR><B>RESULTS: </B>We successfully constructed the a QNP model that includes both a multi-scale dynamic network disease model and drug intervention model. The QNP model accurately simulated the pathological process of RIF, and the simulation results were validated by a series of cell and animal experiments. Meanwhile, the QNP model demonstrated that rhein can delay the pathological process at the studied concentrations of 5 nM, 10 nM, and 20 nM, and can also exert a better therapeutic effect on fibrosis before the proliferation stage of RIF. Furthermore, through uncertainty and sensitivity analysis, we identified that FAK and Smad3 may be potential targets for RIF.<BR><B>CONCLUSIONS: </B>Our QNP model provides a molecular-cellular understanding of the pathological mechanisms of RIF, serving as a new approach and strategy for the construction of dynamic multi-scale network model of diseases and drug intervention.