Studies On The Chemical Constituents Of Corydalis Saxicola Bunting And Their Antitumor Activity

Corydalis saxicola Bunting is a member of Corydalis,Papaveraceae family.It is distributed in Guizhou,Yunnan,and Sichuan provinces,mainly in North and Northwest of Guangxi,such as Donglan,Bama,Du’an,Jingxi and Debao.The aerial parts of C.saxicola have been used for the treatment of acute jaundice hepatitis,cirrhosis,and liver cancer,et al,in traditional chinese medicine.In this study,chemical studies on C.saxicola were conducted by using various chromatographic techniques for the isolation of their chemical constituents and spectroscopic methods for the structural elucidation.The results showed that 38 compounds were isolated and identified from C.Saxicola.Including 9 lignanamides(1-9),19 isoquinoline alkaloids(10-28),and 10 other compounds(29-38).Their structures were elucidated as Corydalisin A(1),Corydalisin B(2),Corydalisin C(3),Cannabisin(4),Cannabisin E(5),Cannabisin D(6),1,2-dihydro-6,8-dimethoxy-7-hydroxyl-1-(3,5-dimethoxy-4-hydroxyphenyl)-N1,N2bis[2-(4-hydroxyphenyl)ethyl]-2,3-naphthalene dicarboxamide(7),Grossamide(8),N-trans-Feruloyl Tyramine(9),Corydalisine A(10),Ophiocarpine(11),Tetrahydrocolumbamine(12),(-)-Cavidine(13),Tetrahydrocoptisine(14),Tetrahydroberberine(15),Thalictrifoline(16),Tetrahydropalmatine(17),Neooxyberberine acetone(18),Palmatine(19),Dehydroscoulerine(20),Dehydrocorydaline(21),Columbamine(22),Corydalisine B(23),8-oxocoptisine(24),Protopine(25),8-Methoxyldihydrosanguinarine(26),Dihydrosanguinarine(27),Dihydrochelerythrine(28),p-hydroxyphenylacetic acid(29),Methyl p-hydroxybenzeneacetate(30),p-hydroxybenzoic acid(31),Protocatechuic acid(32),Caffeic acid(33),4-methoxy-4-oxo-2-butenoic acid(34),Dihydrophaseic acid(35),Esculetin(36),2-(3’,4’-dihydroxyphenyl)-1,3-benzodioxole-5-aldehyde(37),Kaempferol(38).Compounds 1,2,3,10,23 were new,4-9,11,14,18,20,21,24,26,29-38 were isolated from C.Saxicola for the first time.The ethyl acetate fraction was purified by activity-guided method,and the antitumor activity of the eight lignanamides were tested.The results showed that compound 3 showed good activity against MGC-803 and T24 cell lines(IC50=8.81 and 9.62 μM,respectively).At the same time,we investigated the molecular mechanism of MGC-803 cells induced by compound 3 in MGC-803 cells.The effect of compound 3 on the apoptosis of tumor cells was detected by Annexin V/PI co-staining,Hoechst 33258 fluorescence staining,AO/EB staining,JC-1 and flow cytometry.Moreover,the apoptosis induction mechanism of compound 3 was investigated by ROS assay.The results showed that compound 3,which have good antitumor activity,killed the tumor cells by inducing apoptosis of MGC-803 cells.