Drug Oral Bioavailability Prediction And Application In The Meridian Tropism Theory Of Traditional Chinese Medicine

Drug oral bioavailability(OB) is a key parameter to evaluate the pharmacokinetics process and druggability for drugs. However, experimental determination of drug OB on a large scale is costly, and even some monomeric compounds are not available. Therefore, predicting OB in silico is always a hot topic in the field of international drug research. In this study, utilizing computers, modern statistics, chemoinformatics and other technologies, we have respectively applied multiple linear regression(MLR), partial least squares regression(PLS) and support-vector machine regression(SVR) to predict oral bioavailability. The performance of SVR is slightly better than that of MLR and PLS. On this basis, we developed an update OB prediction system, which integrates the pharmacokinetics properties(absorption, metabolism, distribution and excretion, ADME) of the compounds that access the final decision-making system to improve the forecast accuracy of this model.Then, by integrating the OB prediction model with the systems pharmacology technologies, such as target prediction and network analysis, we have conducted the study of material basis and mechanism of action for the meridian tropism theory of Traditional Chinese Medicine. Focusing on the Heart Meridian, we firstly attempt to clarify the relationships between Heart Meridian and its related diseases in both traditional and modern medical system by text mining approach. Subsequently, an integrated systems pharmacology framework was constructed to further explore the molecular mechanism by combining Meridian-related ingredients screening, target identification, classification diseases and compound-target-disease network analysis. This strategy provides an efficient way to decipher why selected herbs contained different pharmacological properties and related to different clinical prescriptions maintain the similar specific affinity of the Heart Meridian systematically. Our work provides a novel systemic method to elucidate the complexity of herbs and the molecular mechanism of Meridian Tropism theory, as well as a rational way to illuminate the underlying mechanism of traditional Chinese medicine conceptions.