Study On The Chemical Constituents And Their Bioactivities From Macleaya Cordata

Macleaya cordata (Willd.) R. Br. is a plant of Papaveraceae family which is a source of bioactive isoquinoline alkaloids and widely distributed. So far, many papers with chemical and pharmacological research of M. cordata (Willd.) R. Br. have been reported, especially the main components:isoquinoline alkaloids and protopine alkaloids. It also contains sugar, polysaccharides and their glycosides, steroids, terpenoids, saponins, flavonoids and their glycosides, cardiac glycoside, coumarin lactone and their glycoside, volatile oil and other components. Modern pharma-cological studies show that the main active ingredients of Macleaya are alkaloids that have the functions of antimicrobial, anti-tumor and detumescence. It also has the properties of treating cough insecticidal and so on.In order to search the bioactive constituents from natural source, we began to study the chemical consitituents from M. cordata by repeated column chromato-graphy, including silica gel, toyopearl HW-40and preparative HPLC,18compounds were isolated from75%EtOH extract of M. cordata. By analysis of IR, MS,1D-NMR and2D-NMR spectra, the structures of isolated compounds were identified as follows:(S)6-((R)-1-hydroxyethyl) dihydrochelerythrine (1),(R)-6-((R)-1-hydro-xyethyl) dihydrosanguinarine (2),6a-(1-carboxymethyl) dihydrochelilutine (3), R-6-((R)-1-hydroxy ethyl) dihydrochelerythrine (4),6-methoxy dihydrochelerythrine (5), dihydrochelilutine (6),6-carboxymethyl dihydrochelerythrine (7), bocconline (8), dihydrosanguinarine (9),6-methoxy dihydrosanguinarine (10),6-carboxyme-thyl dihydrosanguinarine (11), dihydrochelirubine (12), norchelerythrine (13), norsanguinarine (14), allocryptopine (15), protopine (16),3a-hydorxy-olenana-12(13)-ene-30-oic acid (17), ferulic acid (18). Compounds1～3were new which didn’t be reported any more, compounds4,6,7and11were isolated from this genus for the first time, and compound18was isolated from this plant for the first time.MTT method was used to determine the non-cytotoxic concentrations for the isolated compounds. Then transwell chemotaxis experiment was used to evaluate the role of inhibiting tumor cell migration. Compounds1,4～6,12,16showed positive inhibiting effects on breast cancer cells migration. And compound1exhibited significant anti-metastasis activity (IC5o=0.12μM). PKCζ is involved in human breast cancer cell chemotaxis signal transduction pathway which is induced by EGF, and plays a very important role. This paper further detect the effect of compound1 PKCζ phosphorylation level in breast cancer cells by using Western blot method, results shows that compound1dose-dependent inhibited phosphorylation of PKCζ. It was suggested that alkaloid compounds might inhibit breast cancer cells migration through inhibiting phosphorylation of PKCζ.