Studies On The Chemical Constituents Of Rehmannia Glutinosa And The Activity Of Inhibiting α-Glucosidase

This thesis was consisted of four parts.The research progress ofα-glucosidase screening model was introduced in the first chapter.In the second chapter,the isolation and strctural elucidation of the chemical constituents from Rehmannia glutinosa was described.Theα-glucosidase inhibition activity of chemical constituents was presented in the third chapter.The summary and prospect of the thesis was discussed in the fourth chapter.Diabetes is a common chronic endocrine disease second only topped to cardiovascular disease and cancer.The blood glucose control of diabetic patients mainly depended on injecting insulin or oral hypoglycemic drugs.α-glucosidase inhibitors（AGI）are one of important hypoglycemic drugs.Three kinds of AGI drugs have been marketed,including voglibose,acarbose and miglitol.However,the preparation process of the three AGI drugs were complicated due to their monosaccharides or sugar-like skeleton.In addition,the three AGI drugs also can cause some side effects.Therefore,it was still greatly valuable to search and developt new AGI compounds towards the diabetes treatment.Rehmannia glutinosa Libosch is a plant of Rehmannia in Scrophulariaceae family.It was used in the treatment of Xiaoke symptom（known as diabetes in modern medicine）since ancient China.R.glutinosa is also widely used in modern hypoglycemic Chinese medicine.The roots of R.glutinosa was selected as the research materials in the current study.57 compounds were isolated and identified from R.glutinosa by various chromatographic and spectral techniques.Among of the 57 compounds,there are 3 new compounds rehmannias A-C（1,16 and 17）and 54 known compounds.The known compounds was consisted of 14 iridoids,7 ionones,12 phenylethanoid glycosides,5sugars,6 simple alkaloids,and 10 other types of compounds.The different polar segments（Fr.1-4）and the obtained compounds were screened forα-glucosidase inhibition activity in vitro.The results showed that Fr.1 and Fr.2 and compounds 10-11,20-21,23 and 28 demonstrated inhibitory effects on the production of p-nitrophenol-phenol（p NP）from 4-nitrophenol-α-D-glucopyranoside（p NPG）,showing significantα-glucosidase inhibitory activity with IC₅₀ values of 2.47,2.18,1.78,1.51,1.79,1.42,0.89,and 1.79 mg/m L,respectively.The molecular docking analysis of the six active compounds withα-glucosidase was carried out by Autodock technology.The results showed that the docking score of iridoid glycoside compound 11 was-7.7745,and hydrogen bonds were formed with Asp60,Arg197,His326 and Arg411 ofα-glucosidase.It was speculated that the glycoside moiety of 11 was the main binding site toα-glucosidase.The results of this paper enrich the research content of the chemical constituents of R.glutinosa.And also,it can provide some references for further exploring the hypoglycemic effect of R.glutinosa and developing new AGI.