Study On The Chemical Constituents Of The Strongly Polar Parts Of Corydalis And Their Insulin Secretion-stimulating Activity

Corydalis edulis Maxim.is a grey-green herb of Corydalis genus(Papaveraceae),which is commonly found in gullies,hills or rocky areas at elevations of 400-1200 m in most of provinces of China.The whole plant of Corydalis edulis(CE)is traditionally used to clear heat and remove toxicity,stop itching and induce astringency,moisten lung for relieving cough.Recently,it is prepared as beverages for treating type 2 diabetes mellitus(T2DM)in the folk.In our prvious study,the extract of C.edulis was found to decrease the blood glucose level of high-fat and high-glucose diet induced ApoE-/-mice,and increase insulin secretion of HIT-T15 cells in vitro.Further study showed that n-butanol extract and water extract could significantly increase insulin secretion in HIT-T15 cells.In order to clarify the effective substance of CE,the chemical constituents of n-butanol extract and water extract and their effect on insulin secretion in HIT-T15 cells were investigated.The following results are achieved:1.The research progress of chemical constituents of Corydalis genus and hypoglycemic activity of alkaloids has been reviewed.The chemical components include alkaloids,flavonoids,triterpenes,chromones,coumarins,etc.Alkaloids are the main chemical constituents in the plants of Corydalis genus.Furthermore,it's reported that many types of alkaloids had hypoglycemic activity,including indole,berberine,amides,and quinolizidine alkaloids.2.The chemical constituents of CE were isolated and purified by various chromatographic methods,and the structures of pure compounds were elucidated on the basis of spectroscopic analysis and physiochemical properties.As a result,forty-two compounds were isolated from the n-butanol extract and water extract,including(±)-edulisine G(1/2),(±)-edulisine H(3/4),(±)-edulisine I(5/6),edulisine J(7),edulisine K(8),edulisine L(9),edulisine M(10),edulisine N(11),N-trans-sinapoyl-3-methoxytyramine-4'-O-?-glucoside(12),6'-?-D-xylosylicariside B2(13),cis-protopinium(14),trans-protopinium(15),tetrahydrocolumbamine(16),cheilanthifoline(17),hendersine B(18),6,7-dimethoyisoquinolin-1(2H)-one(19),6,7-methylenedioxy-1(2H)-isoquinolinone(20),adlumidiceine(21),N-methylnarceimicine(22),bicucullinine(23),N-trans-feruloyl 3'-O-methyldopamine(24),N-trans-feruloyloctopamine(25),N-trans-feruloyltyramine(26),N-trans-sinapoyloctopamine(27),flavifloramide B(28),melongenamide A(29),5-hydroxy-2-hydroxymethypyridine(30),uridine(31),cytidine(32),adenosine(33),icariside F2(34),icariside B2(35),?-daucosterol(36),5,5 '-dimethoxy biphenyl-2,2 '-diol(37),isosalicine(38),salicin(39),p-hydroxy-phenethyl-O-?-D-glucopyranoside(40),icariside D2(41)and pyrocatechol(42).Among them,compounds 1-13 are new compounds.Compounds 19,27-30,35 and 37-41 are obtained from the plants of Papaveraceae for the first time.Compounds 34 and 42 are firstly isolated from Corydalis genus,and compounds 14-18,20-26,31-33 and 36 are found from C.edulis for the first time.3.The insulin secretion improving effects of all the isolated compounds in the HIT-T15 cells were evaluated in vitro.The result showed that compounds(±)-edulisine G(1/2)and 6,7-dimethoyisoquinolin-1(2H)-one(19)showed significant insulinotropic effect.In conclusion,phytochemical investigation of C.edulis is performed in this study,and three compounds were found to be able to increase insulin secretion.This study could be helpful for clinical application and further development and utilization of C.edulis.