National Center of Mass Spectrometry in Changchun & Jilin Province Key Laboratory of Chinese Medicine Chemistry and Mass Spectrometry & Chemical Biology Laboratory, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China; University of Chinese Academy of Sciences, Beijing 100049, China.
National Center of Mass Spectrometry in Changchun & Jilin Province Key Laboratory of Chinese Medicine Chemistry and Mass Spectrometry & Chemical Biology Laboratory, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.
J Pharm Biomed Anal. 2018 Sep 10;159:179-185. doi: 10.1016/j.jpba.2018.06.067. Epub 2018 Jul 4.
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 cm s, 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.
影响肠道有效成分的吸收是中药的重要配伍机制之一。模拟药物在体外肠上皮细胞系中的吸收是研究药物配伍与药物生物利用度相互作用的重要方法。本研究采用体外 Caco-2 细胞单层模型研究定志小丸（DZXW）的配伍机制。首次使用将方剂分解为单味药和药对的方法来阐明配伍机制。选择 20 种主要生物活性化合物的转运特征，包括 8 种人参皂苷、6 种茯苓三萜、3 种远志皂苷、1 种远志寡糖和 2 种精油，作为主要评价指标，通过超高效液相色谱-三重四极杆质谱联用（UHPLC-QqQ-MS）检测这些化合物在单味药组、药对组和 DZXW 组中 Caco-2 细胞的吸收情况。结果表明，人参皂苷和多糖的吸收与糖基化程度有关，而茯苓三萜的吸收主要受脂溶性影响。远志在人参皂苷通透性中起关键作用，石菖蒲在茯苓三萜通透性中起主导作用。人参皂苷和茯苓三萜的表观渗透系数均大于 14.0×10cm/s，表明它们可以很好地被吸收，人参和茯苓可能在 DZXW 的功效中发挥了关键作用。草药组合可以显著提高 18 种化合物的吸收，证明了 DZXW 配方的科学合理性。
