Chemical Constituents From The EtOAc Fraction Of Lomatogonium Rotatum And Their Inhibitory Effect On Tumor Cell Proliferation

Lomatogonium rotatum(L.)Fries ex Nym.is mainly distributed in Inner Mongolia,Jilin,Heilongjiang,Qinghai and Xinjiang,which possess calm "xieri",refrigeration,stomachic and callus.Previous investigation suggested that the main constituents of this species were the xanthones,flavonoids,triterpenoids and henylpropanoids with anti-tumor,liver protection,antilipemic activities.In order to make rational use of and sufficiently exhibit the medicinal value of natural pharmaceutical resources,the chemical compositions from the EtOAc fraction of L.rotatum and their anti-tumor effects were studied.Thirty compounds were isolated from the EtOAc fraction of L.rotatum using silica gel column and preparative middle pressure liquid chromatography.The chemical structures were identified by nuclear magnetic resonance and other spectroscopic methods,including eleven lignans,(+)-pinoresinol(1),(+)-medioresinol(2),syringaresinol(3),pinoresinol-4-O-β-D-glucoside(4),(+)-syringaresinol-4-O-β-D-glucopyranoside(5),ficusal(6),(-)-jatrointelignan D(7),(7S,8R)-dehydrodiconiferyl alcohol-9’-β-D-glucopyranoside(8),9’-methoxydehydro diconiferyl alcohol-4-O-β-D-glucopyranoside(9),(7S,8S,7’E)-4,9-dihydroxy-3,7,3’,9’-tetramethoxy-8,4’-oxyneolign-7’-ene(10),(-)-7’R-O-methyl-7-epi-tanegool(11),seven flavonoids,apigenin(12),luteolin(13),5,7,4’-trihydroxy-8-methoxyflavone(14),swertisin(15),1-hydroxy-3,5,8-trimethoxyxanthone(16),1,3,5,8-tetrahydroxy-5,6,7,8-tetrahydroxanthone(17),5-O-β-D-glucopyranosyl-1,3,8-trihydroxy-5,6,7,8-tetrahydroxanthone(18),four triterpenoids,2α,3β,19α-trihydroxyurs-12-en-28-oic acid(19),asiatic acid(20),urs-12-ene-2α,3β,28-triol(21)28-O-β-D-glucopyranoside pomolic acid(22),four iridoides,2-(2-methoxy-5-vinyltetrahydro-2H-pyran-4-yl)ethan-l-ol(23),3-epi-s wertiaj aposide C(24),swertiajaposide C(25),swertiamarin(26),one coumarin,isoscopoletin(27),one sesquiterpenes,heterophyllol(28),one megastigmane,(6R,9R)-vomifoliol(29),one monoterpene,loliolide(30).Among them,compound 23 was a new natural product,compounds 4,6-11,21,22 and 28-30 were the first time to be reported in the family Gentianaceae,compounds 1-3,5,14,19,20,24,25 and 27 were firstly identified from the genus Lomatogonium,compound 18 was obtained from L.rotatum for the first time.Based on the above research results,the inhibition of tumor cell proliferation of the isolated compounds was measured by the MTT method.The results showed that compounds 7,15,19 and 20 exhibited cytotoxic inhibitory effects against A549,SK-Hepl and HeLa cell lines at 30 Mm.Triterpenoids 19 and 20 showed better cytotoxic activities against three human cancer cells than the other compounds.In the experiment of cytotoxic activity against A549 cells,compounds 19 and 20 exhibited effects with IC50 values of 20.37±2.06 and 29.26±2.35μM.In the experiment of cytotoxic activity against SK-Hepl cells,compounds 19 and 20 exhibited effects with IC50 values of 13.79±1.23 and 16.24±2.09μM.In the experiment of cytotoxic activity against HeLa cells,compounds 19 and 20 exhibited effects with IC50 values of 29.14±1.45 and 21.34±1.62μM.To sum up,the chemical constituents of L.rotatum were enriched,and the monomers with better inhibition of tumor cell proliferation were screened through this investigation,which provided a theoretical basis for the development and utilization of L.rotatum.