| TCM is a complex multi-component system, the content and biological activity of the components are very different. When the components of traditional Chinese medicine and its preparation were evaluated not take into account each component. How to select the representative components to the overall properties of the components in a number of traditional Chinese medicine chemical composition, and thus reflect the overall characteristics of traditional Chinese medicine, which is the traditional Chinese medicine preparation urgent research. With the development of modern preparation technology, the research on Chinese medicine gradually down to the component level. To resolve the key issues faced during the modernization of traditional Chinese medicine, we use phenolic components as the model drug to explore the new research ideas of TCM:Chapter One:Progress in Chinese medicine ingredients Biopharmaceutics Classification System Construction and phenolic components chemical composition and pharmacological effects of prevention and treatment of cerebral ischemia made whole elaborate. Under the guidance of Chinese medicine theory, from the following four aspects:the material basis of Chinese medicine study course, limited representation of each component on the "N", to characterize the nature of traditional Chinese medicine ingredients overall data processing method, the components of biological medicine pharmacy the nature of the classification system construction, to explore new models to study traditional Chinese medicine group is divided into functional units of TCM preparations. Also, we do an in-depth summary and elaboration on the mechanism of action and chemical composition of Salvia militorrhiza Bunge treating cerebral disease progress.Chapter Two:Representative components were screened by in vitro drug efficacy tests. Established a potential tool for screening of blood-brain barrier(BBB) permeable drug candidates from plant-derived materials, the permeability parameters and TEER values showed that the co-cultured model was of integrity and vitality. The active compounds of phenolic components were screened with this in vitro BBB model. We found that 6 compounds at least from phenolic components could permeate across BBB model, in which Danshensu, Protocatechuic acid, Caffeic acid, Isoferulic acid, lithospermic acid, Rosmarinicacid were identified. Secondly, using human brain microvascular endothelial cells OGD model to optimal screening representative components of phenolic components. By morphological observation showed that phenolic components and various components of the active ingredient combination can effectively reduce the damage of hypoxia on cell morphology, Danshensu, Protocatechuic acid, Caffeic acid, Isoferulic acid, Rosmarinic acid group(main components group A) and Danshensu, Protocatechuic acid, Caffeic acid, Isoferulic acid, lithospermic acid, Rosmarinic acid group(main components group B) exhibit better cytoprotective action. The measurement results show that the relevant biochemical factors, phenolic components is capable of reducing oxidative damage (T-SOD, MDA, GSH-PX and CAT), relieve hypoxia cells, reducing inflammatory cytokines(TNF-α, IL-6, sICAM-1) expression in order to protect the HBMEC, the purpose of remission after ischemic injury in neurological function. Compared with phenolic components, main components group B hypoxia HBMEC antioxidant group compared with the group phenolic components the effect is obvious, and no significant difference(P>0.05). MMP-9, VEGF expression in cells and MMP-9, VEGF, mRNA expression results show that, B group compared with phenolic components, no significant difference(P>0.05).Chapter Three:This part adopts the middle cerebral artery occlusion(MCAO) model of rats to observe the main components group A, group B and phenolic components. The results showed that B group compared with phenolic components, no significant difference(P>0.05). They can significantly relieve neurologic impairment and reduce the cerebral infarction area of cerebral ischemia rats, at the same time, it can improve the oxidation index:elevated activities of SOD, CAT, GSH-PX, reduced content of MDA; improved the expression of VEGF, TIMP-1 and reduced the expression of p-p38MPAK, TLR-4, NFkBp65, Caspase-3, MMP-2 and MMP-9; improved the expression of bcl-2, reduced the expression of bax to inhibits apoptosis; reduced the expression of NMDAR1 mRNA and increased the expression of VEGF mRNA.Chapter Four:The structure of the representative components of the phenolic components was resolved by HPLC. Ultimately determine the content of Danshensu, Protocatechuic acid, Caffeic acid, Isoferulic acid, lithospermic acid, Rosmarinicacid in component is 12.47%,3.98%, 3.01%,6.05%,7.36% and 20.96% respectively. Its authentic constitutes is 4.14:1.32:1.00:2.01:6.93:2.45.Chapter Five:We determined the biopharmaceutical properties of phenolic components such as equilibrium solubility, apparent partition coefficient and Caco-2 cell permeability. Using Mathematical model of the nature of representative value similarity component analysis and integration of characterization. The results showed that the biopharmaceutical properties of these components are similar. The weight coefficient method was used to fit the value of each component. The maximum equilibrium solubility of phenolic components was 28.127 mg·mL-1, the minimum was 6.203 mg·mL-1. The maximum value of oil/water partition coefficient(LogP) is 1.387, and the minimum value is 0.037. The fitting value of the apparent permeability coefficient Papp of Caco-2 cells was 0.693×10-6 cm·s-1. The result showed that phenolic componentst water soluble, fat soluble, which belongs to the type of Ⅲ drug. |
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