Chemical Constituents Of Lobelia Chinensis And Their Biological Activities

Systematical study on the chemical constituents of traditional medical herbs is one of important routes to discover bioactive compounds. There are more than380species belong to the genus Lobelia, family Campanulaceae. These plants distribute in tropical and subtropical regions of all cotinents, especially in Africa and America. The Lobelia Plants grow mostly in wet or pond, with a small number of species extended to temperate region, only two kinds distributed in Europe. There are about20species in China, except for Lobelia sessilifolia, most species are produced in the provinces located to the south of Changjiang River. Several species belong to the genus Lobelia are used as folk medicine for the treatment of cancer and snake bite. In this research, chemical constituents of Lobelia chinensis were studied systematically. Total alkaloids of L. chenesis and one of the pure compounds were selected for the testing of ET-1inhibition activity. Furthermore, the anti-tumor activities and the combination effects with cisplatin were investigated for some alkaloids.L. chinensis is an annual plant, one species of genus Lobelia, family Cam panulaceae. The whole plant is commonly used for promoting diuresis and detu mecscence, clearing away heat and detoxifying, also is used in clinic for the tr eatment of carbuncles boils, herpes zoster, acute nephritis, snake bites, ascites i nduced by late blood-sucking insects disease, cancer and andatherosclerosis. By using HP-20macroporous resin chromatography, silica gel chromatography, Se phadex LH-20chromatography, RP-18chromatography, semi-preparative HPLC, chiral high performance liquid column chromatography (Chiral-HPLC),22com pounds were isolated from the ethanol extract of this plant. The structures wer e elucidated by spectroscopic methods as follows:N-methyl-2,6-bis(2-hydroxybu tyl)-△3-piperideine (1), N-methyl-2-(2-oxybutyl)-6-(2-hydroxybutyl)-A3-piperideine (2), N-methyl-4-hydroxyl-2-(2-butanone)-6-(2-hydroxybutyl)-piperidine (3), N-met hyl-4-hydroxyl-2-(2-butanone)-6-(2-hydroxyamyl)-piperidine (4),2-(2-butanone)-6-(2-hydroxybutyl)-piperidine (5),2-(2-hydroxybutyl)-6-(2-hydroxybutyl)-piperidine (6) N-methyl-2-(2-hydroxypropyl)-6-(2-hydroxybutyl)-△3-piperideine (7), N-methy1-2-(2-hydroxypropyl)-6-(2-hydroxybutyl)-piperideine (8), lobetyol (9),(2Z,10E)-te tradecadien-4,6-diyne-8,9,14-triol (10),(7S,8R)-4,9,9’-trihydroxy-3,4’-dimethoxy-8-O-3’-neolignan (11a),(7R,8S)-4,9,9’-trihydroxy-3,4’-dimethoxy-8-O-3’-neolignan (11b),(7S,8R)-4,9,9’-trihydroxy-3,3’-dimethoxy-8-O-4’-neolignan (12a),(1R,8S)-4,9,9’-trihydroxy-3,3’-dimethoxy-8-O-4’-neolignan (12b), lobechinenoid A-D (13-16), β-sitosterol (17), β-daucosterol (18),3-methoxy-4-hydroxy-benzoic acid (19); lactone acid4-ethyl-2-hydroxy-succinate (20). Among them,11compounds inc luding compound3,4,6,8,10,11a,11b and13-16are new compounds.Compounds11and12were characterized as isomers, with the same planar structure by using HPLC-CD coupling technique,11and12were determined as mixtures of a pair of enantiomers respectively. The absolute configuration of the four stereoisomers was determined by measuring the on-line CD spectra. Compounds13-16are two diastereomeric pairs of enantiomers, by using the HPLC-CD technique, the on-line CD spectra of13-16were obtained. By substracting their respective CD contributions, the stereos tructures of compounds13-16were assigned.The total alkaloids of L. chinensis and one of the pure alkaloids were tested for the ET-1inhibition activity. The cytotoxity on A549lung cancer cells was also tested by MTT assay. The results showed that the inhibitory effect on tumor cells of compounds1and3was weak, but compound1showed moderate synergestic effects with cisplatin on tumor cells.