| The theory of prescription compatibility is an important part of the theory of traditional Chinese medicine (TCM). But, for the complex composition and clinical application with philosophic thoughts, it's very difficult to express the mechanism of prescription compatibility by modern science and technology. Therefore, how to express the principle of prescription compatibility according to modern science and technology is a hotspot and a tough problem all the time. Monarch-guide compatible herbal medicine is the core of TCM. An important approach to enrich the theories of Traditional Chinese Medicine and develop highly effective new drugs is to find the key compatibility relationship through the studies of efficacious prescriptions and find their bioactive substances. Under the guidance of the theories of Traditional Chinese Medicine, the present research chose "Guangzao - Dalbergia" to systematically study the mechanism of monarch-guide herbal medicine in the body through metabolomics. The influence of guide herb (Dalbergia,JX) was revealed through investigating the pharmacokinetical (PK) changes of bioactive substances in monarch herb(Guangzao,GZ); The main contents are as follows:1. A new high performance liquid chromatography (HPLC) method for analysis of the gallic acid (GA) and protocatechuic acid (PA) of Guangzao in plasma and tissue is established. The results showed that the linear range of GA and PA is 0.04～2.0 mg·L-1. The relative recovery and absolute recovery of low, medium and high concentration, relative standard deviations (RSD) of precision and stability experiments are consistent with the requirements of biological sample analysis according to FDA.2. After intragastric administration of GZ and GZ-JX, the PK parameters of GA and PA in plasma and tissue of normal rabbits. The results indicated that dalbergia could change the pharmacokinetics of GA, also could increase the biological availability of PA. Further, it might indicate that the the dalbergia enhance curative effect of GZ in the cardiovascular diseases, which will provide evidences of dalbergia's synergism and explaination of the theory of prescription compatibility by modem science and technology.3. Tissue distribution of GA and PA is investigated to study the influence of synergism between SM and BC. The results show that the concentration sequence of GA in SM group is kidney >brain>spleen>heart>liver>lung. However, it convert to kidney> brain >liver> heart>spleen>lung under the influence of BC. The results show that the concentration sequence of PA in SM group is kidney >heart >spleen >liver>lung>brain, and it convert to kidney>spleen >liver> heart >lung > brain under the influence of BC, verifying the TCM theory on meridian distribution of SM and guidance distribution of BC.4. The mass data of HPLC is statistically processed by metabonomic ,with SPSS method and considering the change of concentration-time curves, 4 unkown substances were ascertained to be the bioactive substances of GZ-JX. An initial qualitative analysis on them was carried out by HPLC -MS, then the fragment ions corresponded with 2 unknown bioactive substances were supposed to be: m/z179.2 and m/z318.5. A new mode to investigate the bioactive substances of monarch-guide compatible herb was established, which could provide new pathway to develop highly effective new drugs. |
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