Identification And Characterization Of CFTR Chloride Channel Activators From Antihypertensive Traditional Chinese Medicine

China's traditional Chinese medicine is able to prevent and control the disease, there is a material basis, and its role in prevention and treatment of the material that is the active ingredient of Chinese medicine. Chinese medicine active ingredients extracted from traditional Chinese medicine separated is confirmed by pharmacology experiments the efficacy of the chemical composition, and is the material basis of traditional Chinese medicine treatment of disease in China for thousands of years. However, hundreds of Chinese medicine formulations of active ingredients, the vast majority of the existence shortcomings is that drug structure, active ingredient and drug target are not clear which limited the development of the modernization and internationalization. In this study, a new strategy was proposed based on HTS and traditional Chinese medicine chemistry research platform, to discovery a new approach to have the active natural medicine component from the Chinese traditional medicine, a higher purity of the monomer active compounds can be achieved by applicating of this methed. Aim at screening the biological activity natural medicine component from TCM fraction library, thereby fast and high efficiently obtains the natural monomer compound from the natural medicine which has an effect in the specific medicine target. This study is for the purpose of finding new drug targets for the discovery of new drugs and revealing the material basis of traditional Chinese medicine effective in the molecular mechanism of pharmacological action providing a new solution.Cystic fibrosis transmembrane conductance regulator(CFTR) protein, a cAMP-activated Cl– channel, is expressed in airway, intestinal, pancreatic, and other secretory and absorptive epithelia, which is the only Cl- channel from ATP binding cassette(ABC) family. Recent study manifested that CFTR is also expressed in smooth muscle of blood vessel and played a key role in blood pressure regulation. Many attentions have been paid to the potential drug target role of CFTR.In this study, the material basis of traditional Chinese medicine in the step-down flavonoids rutin and quercetin indicators for the study. Modern pharmacological experiments confirmed that the traditional Chinese medicine rutin, quercetin can regulate blood pressure of diastolic arterial, and both of which are the CFTR chloride channel activators, revealed one of a clear role that flavonoids played by effective antihypertensive drug target is cystic fibrosis transmembrane regulator(CFTR). Further research of its physiological function and pathological, will be essential to the mechanism of disease brought new breakthroughs, and then developed as a drug target. CFTR as an innovation-based antihypertensive drug targets , enhancing of research of CFTR target will develop more specific therapeutic effect and non-side effects new antihypertensive drugs, the field of Chinese medicine treatment for high blood pressure brought about new diseases breakthrough. To further investigate the molecular pharmacology of traditional Chinese medicine research laid the foundation for the mechanism, and also the material basis of traditional Chinese medicine for the study of the molecular mechanism of pharmacological action provide new ideas, new strategies and new techniques.In the screening process, the widespread existence flavonoids were carried on active screening from the Chinese native medicine, and which active screening result was superior to other kinds of nature compounds. Rutin and Quercetin as a representative of flavonoids, because the activity of test results are positive,it plays an vital role in studying the content of both the natural componds.Rutin, Quercet in flavonoids which are widely present in natural substances, with a wide range of physiological activity and medicinal affects, receive the domestic and foreign scholar's attention. Objective:To compare the contents of Rutin and Quercetin in five anti-hypertention herbal plants. Methods:To establish a RP-HPLC method for quantification of Rutin and Quercetin contents in five Chinese herbs (Forsythia suspensa (Thunb.) vahl., Sophora japonica L., Saussurea involucrate, Lonicera japonica, Thunb, Eucommia ulmoides oliv). Regression analyses with the peak area (A) and the concentration of reference substance (C) were carried out under the same HPLC condition. Linear regression equations of Rutin and Quercetin reference substance can be found respectively. Results:The linear range of these flavonoids were 10～5000 ng. The average recovery range was 97%～102%. The RSD of the two compounds in sensitivity and reproducibility are both less than 7%, the least quantity (S/N=10) is 5.0 ng. Conclusion:The method is simple, sensitive, reproducible, accurate and applicable for quantification of flavonoids in various Chinese herbs. It can be used for establishing quality standards of Chinese herbs.