Studies On The Chemical Constituents And Bioactivities Of The Caragana Sinica(Buc’hoz)Rehder

Caragana sinica(Buc ’hoz)Rehder is a shrub belonging to the genus Caragana of Fabaceae,which distributes naturally in arid and semi-arid regions of Eurasia.In China,C.sinica plants distributed mainly in northeast,north,northwest,southwest and other places.The root of Caragana,also known as "jinquegen" is recorded in the Compendium ofMateria Medica,which said it can be used to treat traumatic injury and cough and make effect on warming bones,treating gout,dredging blood vessels and eliminating toxin.In this thesis,the chemical constituents and biological activities of 80%ethanol extracts from the stems of C.sinica were studied,including the extraction of crude extracts,the isolation and identification of compounds,and the pharmacological activities of crude and monomeric compounds.Also,we did a review of the chemical constituents and pharmacological activities of the genus Caragana.In our research,the chemical constituents of 80%ethanol extract of the stems of C.sinica were investigated.The constituents were separated and purified by comprehensive application of liquid-liquid extraction,polyamide column chromatography,silica gel column chromatography,medium pressure liquid chromatography and preparative high performance liquid chromatography.Thus,42 compounds were obtained.Then by NMR,HRESIMS,UV,IR,and ECD spectrum,the structures of the 42 compounds were analyzed and identified,including 19 oligomer stilbenes(tetramers 1*-7*,trimers 8*,10*～13*,dimers 9*,14*,15*,19*,20*and a monomer 16*),4 alkaloids(21-24),3 coumarins(25-28),and 16 other type compounds(17*,18*,28,29-40).Among them,19 compounds were unreported,including 3 oligostilbenes with novel skeletons.And the absolute configurations of the new compounds were determined by ECD calculation.In this thesis,a variety of pharmacological model activity screening tests were carried out on the crude extracts and isolated compounds.In the research of the crude extract bioactivity,the total extract of the stems of C.sinica(CS)had significant inhibitory effects on PTP1B and α-glucosidase with IC50 values of 8.51 μg/mL and 2.62μg/mL,respectively.In the study of antioxidant activity,all extraction parts of the stems of C.sinica showed a significant inhibitory effect on malondialdehyde(MDA)production,with an inhibition rate of 71.30%～96.47%.In the activity test of monomeric compounds,compounds 6*,7*,9*,12*and 13*showed obvious inhibition on a-glucosidase with IC50 values of 0.36,0.11,0.14,0.24 and 0.25μM,respectively.The mode of action of some compounds with α-glucosidase was evaluated by computer simulation molecular docking.Besides,compound 6*showed a obvious inhibition on PTP1B with IC50 value of 1.18 μM.In terms of antiviral activity,compounds 2*,6*,9*,13*and 19 showed weak inhibitory effects on coxsackievirus B3(CVB3)infection in Vero cells(African green monkey kidney cells),with IC50 values ranging from 6.41 to 33.33 μM.Compounds 2*,3*,4*,6*,9*,13*,19,20,24 and 39 showed weak inhibitory effects on RSV infection in Hep2 cells(human laryngeal carcinoma epithelial cells)with IC50 values ranging from 11.11 to 33.33 μM.In this research,the stereochemistry of stilbene oligomers isolated from the stems of C.sinica was studied,which provided a reference for the determination of stilbene oligomers.At the same time,pharmacological activity tests found that some stilbene oligomers possessed remarkable hypoglycemic activity,which meant that stilbene oligomers could be a new source for the development of hypoglycemic medicine.