| ObjectiveShanlvchaJiangya Capsule,a prescribed preparations of Traditional Chinese medicine,is made of llexhainanensis Merr.through a series process of extraction and purification,suitabling for vertigo,tinnitus,irritability,headache stretching,insomnia and high blood pressure,high cholesterol and other diseases.In order to control the quality of the ShanlvchaJiangya Capsule,it lays a foudation for further research.Based on the study on extraction and pharmacodynamic of the components of llexhainanensis Merr.in the laboratory.This study on the quality control of raw material of llexhainanensis Merr.in ShanlvchaJiangya Capsule as the research object to ensure the quality of the preparation.Through the ShanlvchaJiangya Capsule in pharmacokinetics study,preliminary inference the changing process of effective components in rat.From metabolomics,related genes to do the preliminary study of the mechanism of the ShanlvchaJiangya Capsule.The aim of this study to provide the basis for the clinical application and futher development of the ShanlvchaJiangya Capsule from the point of view of the characteristics of multi-component,multi-target,multi-pathway.Materials and Methods1.Using UPLC-Q-TOF-MS technology,then compared,integrated and analysed the obtained molecular mass information with standards,revelant literatures and related databases information,to carry out the chemical analysis study of llexhainanensis Merr.components.Using HPLC and the full-time multi-wavelength fusion technology to obtain the fingerprints which can reflect fully information of llexhainanensis Merr.,determine the multi-component contents of llexhainanensis Merr.By ICP-MS technique to determine the content of the inorganic elements in llexhainanensis Merr.Through the grey relational analysis software to correlation analysis the organic and inorganic constituents in llexhainanensis Merr.,more comprehensive study on the quality control of the llexhainanensis Merr..2.Using HPLC method to determine the levels of the effective components of ShanlvchaJiangya Capsule in rat plasma at different time points.Using DAS 3.0 software calculate the pharmacokinetic parameters.3.To establish the model of hypertension induced by L-NNA in rats,with systolic pressure,diastolic pressure and organ index as index,to study the effect ofShanlvchaJi angya Capsule on rats with hypertension.4.By using UPLC-Q-TOF-MS technology,Agilent MassHunter Profinder,Agile nt Mass Profiler Professional 12.0 software and HMDB,KEGG databases,The Shanlv chaJiangya Capsule intervention in serum samples of rats as the research object,obser ving the changes of endogenous metabolites,to carry out potential biological markers and metabolic pathways,based on metabonomics to studyon the mechanism in the trea tment of hypertension.5.UsingRT-PCR technique,detecting the related gene expression in rats tissue after ShanlvchaJiangya Capsule treatment,the mechanism of its treatment was investigated from the view of gene.Results1.The constituents were analysis by LC-MS method,deduce the 27 kinds of chemical components.Estabilished the full-time multi-wavelength fusion fingerprint of ten different picking time of Ilex hainanensis Merr.,the similarity analysis showed that compared with thereference fingerprint the similarity is up to 0.9,the results show that chemical composition consistency.To establish a method for simultaneous determination of six components of flavonoids and phenolic acids,and 22 inorganic elements were simultaneously determined in Ilex hainanensis Merr..The correlation analysis showed that the six components have high correlation with Na,Mg,Al,Mn,Fe,Zn,Ba.2.We received three components in rat plasma,i.e.,chlorogenic acid,isoquercitrin,isochlorogenic acid A after oral administration of ShanlvchaJiangya Capsule.The standard curves were linear over the range of0.1080-3.455 ?g/mL,0.2516-8.050 ?g/mL,0.0800-2.5600 ?g/mL(r=0.9990,0.9992,0.9953),the recovery of extraction,precision and accuracy,stability of the method met the requirements.It can be used for pharmacokinetics research of chlorogenic acid,isoquercitrin,isochlorogenic acid A after oral administration of ShanlvchaJiangya Capsule.3.The effect tests in vivo showed that compared with the model group,the ShanlvchaJiangya Capsule could reduce the blood pressure,and decreased the cardiac index.Have protective effect on heart.4.By studying changes of metabolites of the migraine model of rat which induce d by hypertension plasma samples,which intervent by effective constituents in Shanlvc haJiangya Capsule,totally find 18 potential biomarkers,the mechanism could be throu gh the energy matabolism,amino acid metabolism and sphingolipid metabolism in the body.5.TheShanlvchaJiangya Capsulecan make the eNOS,PKG mRNA expressionincreased in the heart tissue of rats.Conclusion1.The chemical constituents of llexhainanensis Merr.were identified to provided a rapid and effective means for the material basic research.Estabilished the fingerprint of llexhainanensis Merr.which based on the full-time multi-wavelength fusion technology,effective fusion of Chinese herbal medicine index components of the spectrum information.Based on the full-time multi-wavelength fusion technology to determine multi-composition in llexhainanensis Merr.at the same time.Then reflect the intrinsic quality of Chinese medicine hebal.Through the determination of the content of inorganic elements in llexhainanensis Merr..From the aspects of inorganic and organic,provided a powerful supplement to the evaluation of the quality of traditional Chinese medicine and preparation.To improve the quality control method and to study the pharmacokinetics and pharmacodynamics mechanism of the capsule.2.Using HPLC method to determine the levels of the effective components of ShanlvchaJiangya Capsule in plasma,to preliminarily describe the pharmacokineticscharacteristics.3.ShanlvchaJiangya Capsule have effective effect on L-NNA induced hypertension model,and lay foundation for the further study on the anti-hypertensive mechanism.4.Form metabonomics to study the changes of serum endogenous metabolites in hypertensive rats on the ShanlvchaJiangya Capsule,involved in amino acid metabolism pathways,sphingolipid metabolism pathway and energy metabolism,NO/cGMP/PKG signaling pathway.Form genes to study the changes of the expressions of eNOS,PKG mRNA,from many angles and aspects to explained the mechanism of anti-hypertensive treatment of ShanlvchaJiangya Capsule. |
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