Abstract
Yuanhu Zhitong Tablet (YZT) is an example of a typical and relatively simple clinical herb formula that is widely used in clinics. It is generally believed that YZT play a therapeutical effect in vivo by the synergism of multiple constituents. Thus, it is necessary to build the relationship between the absorbed fingerprints and bioactivity so as to ensure the quality, safety and efficacy. In this study, a new combinative method, an intestinal absorption test coupled with a vasorelaxation bioactivity experiment in vitro, was a simple, sensitive, and feasible technique to study on the absorbed fingerprint-efficacy of YZT based on chemical analysis, vasorelaxation evaluation and data mining. As part of this method, an everted intestinal sac method was performed to determine the intestinal absorption of YZT solutions. YZT were dissolved in solution (n = 12), and the portion of the solution that was absorbed into intestinal sacs was analyzed using rapid-resolution liquid chromatography coupled with quadruple time-of-flight mass spectrometry (RRLC-Q-TOF/MS). Semi-quantitative analysis indicated the presence of 34 compounds. The effect of the intestinally absorbed solution on vasorelaxation of rat aortic rings with endothelium attached was then evaluated in vitro. The results showed that samples grouped by HCA from chemical profiles have similar bioactivity while samples in different groups displayed very different. Moreover, it established a relationship between the absorbed fingerprints and their bioactivity to identify important components by grey relational analysis, which could predict bioactive values based on chemical profiles and provide an evidence for the quantification of multi-constituents.
Highlights
The Chinese materia medica (CMM) is a unique healthcare system that has been successfully applied for thousands of years in East Asian countries, such as China, Japan, and Korea
Among them, bridging relationship between constituents and biactivity (RCB) and identifying key components (KC) were one (s) of the critical problems, which could increase the level of the quality control, improve the efficacy and reduce the toxicity of CMMs
The combinative bioassay in vitro, intestinal absorption test coupled with the bioactivity experiment, was developed to probe active constituents and their synergistic mechanism of Yuanhu Zhitong Tablet (YZT) in vasorelaxation
Summary
The Chinese materia medica (CMM) is a unique healthcare system that has been successfully applied for thousands of years in East Asian countries, such as China, Japan, and Korea. Absorption solutions of YZT obtained via using the everted sac method were full of vasorelaxant substances that produced a dose–response relationship. The activity of intestinally absorbed YZT solution was much higher than that of one or a few dominant chemical components [5] It was unclear whether the innovative combinative method of bioassay could be applied to appraise the quality of the different YZT samples and bridge the relationship between constituents and biactivity (RCB) and identified key components (KC) by data mining that relate to vasorelaxation activity. In order to better conduct the quality control of YZT products, we used the combinative method that involved an intestinal absorption test coupled with a vasorelaxation evaluation. Ligustrazine was purchased from Nanjing Qingze Pharmaceutical Technology Co., Ltd (Nanjing, China)
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