Study on the compatibility interactions of formula Ding-Zhi-Xiao-Wan based on their main components transport characteristics across Caco-2 monolayers model

Abstract

Influencing the absorption of effective components in the intestines is one of the important compatibility mechanisms of the traditional Chinese medicine. Simulation of drug absorption through an in vitro intestinal epithelial cell line is an important method to study the interaction of drug compatibility and bioavailability of drugs. In this study, the compatibility mechanism of Ding-Zhi-Xiao-Wan (DZXW) was investigated by using the in vitro Caco-2 cell monolayers model. Decomposing the formula into single herb and drug-pair to clarify the compatibility mechanism was firstly used. The transport characteristics of 20 major bioactive compounds including 8 ginsenosides, 6 poria triterpenes, 3 onjisaponins, one polygala oligosaccharide and two essential oils were selected as the main evaluation factor, and the absorption of these compounds by Caco-2 cells in the single herb group, drug-pair group and DZXW group were detected by ultra-high performance liquid chromatography coupled with triple quadrupole mass spectrometry (UHPLC-QqQ-MS). The results showed that the absorption of ginsenosides and polysaponins were related to the numbers of glycosyl groups, and the uptaken of poria triterpenes was dominated by lipophilicity. Polygala radix played a critical role in the permeability of gensenosides, and acorus tatarinowii rhizome dominated permeability of poria triterpenes. The apparent permeability coefficients of ginsenosides and poria triterpenes were greater than 14.0 × 10−6 cm s−1, indicating they could be absorbed well, and the ginseng and poria cocos might played the crucial role in the efficacy of DZXW. Herbal combination could remarkable improve the absorption of 18 compounds and the scientific rationality compatibility of DZXW formula was proved.