Synergistic mechanism of traditional Chinese medicine based on target combination of PepT1 and PPARα / 中国中药杂志

Synergistic effect is main pharmacological mechanism of traditional Chinese medicine(TCM). The research method based on the key targets combination is an important method to explore the synergistic effect of TCM. Peptide transporter 1 (PepT1) is an essential target for drug uptake into the bloodstream, accounting for about 50% of the total transporter protein content from the small intestine. Peroxisome proliferator-activated receptor α(PPARα) is the lipid-lowering target of fibrates, which have a good hypolipidemic effect by activating PPARα. It has been reported that PPARα could activate the gene expression of PepT1s, and PPARα agonists can promote the uptake of PepT1 substrates, indicating their synergistic effect. In this paper, PepT1 substrates and PPARα agonists from TCM were discovered, and their synergistic mechanism was also been discussed based on the target combination of PepT1 and PPARα. The support vector machine(SVM) model of PepT1 substrates was first constructed and utilized to predict potential TCM components. Meanwhile, merged pharmacophore and docking model of PPARα agonists was used to screen the potential active ingredients from TCM. According to the analysis results of two groups, the TCM combination of Panax notoginseng and Ganoderma lucidum, as well as TCM combination of P. notoginseng and Salvia miltiorrhiza were identified to have the synergistic mechanism based on target combination of PepT1 and PPARα. In this study, synergistic mechanism of TCM was analyzed for absorption and hypolipidemic effect based on target combination, which provides a new way to explore the synergetic mechanism of TCM related to pharmacokinetics.

Interactions of intestinal H~+/oligopeptide cotransporter PEPT1 with drugs and regulation by affecting factors / 中国临床药理学与治疗学

H+/oligopeptide cotransporter PEPT1 mainly located at the brush border membrane of intestinal epithelium cell. transports dipeptide/tripeptide which is the degradation products of protein in digestive tract. Peptide-like drugs such as ?-lactam antibiotics,angiotensin-converting enzyme inhibitor (ACEI) and non-peptide drugs valaciclovir also can be transported and uptaked by PEPT1. PEPT1 is important for maintaining the homeostasis and the absorption of drugs in gastrointestinal tract. With the further research of PEPT1 gene, protein structure, and functional activity, we have known the factors about regulation of PEPT1 expression in membrane, their functional activities and substrate affinities. Some associated mechanism of regulation have been studied. As the wide substrate specificities of PEPT1, it becomes the target molecular on drug development and implication for drug delivery. Studies about interactions of PEPT1 with drugs are important for knowing the interactions of drugs, evaluating bioavailability of drug by intestinal absorption, researching the target treatment in anti-tumor drugs and individualization administration.