Studies On Chemical Constituents Of Physalis Angulata And Their Anti-tumor And Anti-inflammatory Activities

Physalis angulata L.(Chinese name "Kuzhi")is an annual plant of Solanaceae family,which is mainly distributed in south and east of China.It has been used as a traditional folk medicine to treat various illnesses in China,such as dermatitis,diuretic,trachitis,impaludism,rheumatism,and hepatitis,especially pharyngitis.The genus Physalis is a rich source of withanolides with a C28 steroidal ?-or ?-lactone that possess remarkable anti-tumor and antiinflamatory activities.Various bioactive withanolides have been isolated from this genus,and some of them showed antiproliferative and antimicrobial activities,as well as inhibition of NO production.Therefore,Physalis angulata has been investigated in order to discovery anti-tumor and anti-inflamatory withanolides.The investigation of the 75%EtOH extracts of the stems and leaves of P.angulata has led to the isolation of 38 new compounds,and identified as physangulatins A-N(1-14),withaphysalin Y(15),withaphysalin Z(16),physalin ?(29),physalin ?(30),physalin D1(31),physalin ?(32),physalin ?(33),physalin ?(34),physalin ?(35),aromaphysalin A(36),aromaphysalin B(37),and phyangulatosides A-L(48-59)together with the known physagulide J(1 7),physagulin J(18),withaminimin(19),physagulin A(20),physagulin B(21).physagulin N(22),withaminimin acetonide(23),physagulin H(24),physagulin I(25),physagulin F(26),physagulide I(27),physagulin K(28),physalin D(38),physalin B(39),physalin F(40),physalin G(41),physalin P(42),physalin I(43),physalin H(44),physalin R(45),isophysalin B(46),25?-hydroxyphysalin D(47),trans-phytol(60),blumenol A(61),corchoinoside C(62),loliolide(63),dehydrovomifoliol(64),7-epi-loliolide(65),(3S,5R,6S,7E)-3,5,6-trihydroxy-7-megastigmen-9-one(66),(6R,9R)-9-hydroxy-4megastigmen-3-one(67),(6R,9S,7E)-9-hydroxy-4,7-megastigmadien-3-one(68),physanguloside A(69),benzyl ?-D-arabinopyranosyl-(1?6)-?-D-glucopyranoside(70),gaultherin(71),phenethanol ?-vicianoside(72),guaiacyl ?-primeveroside(73),methyl 4hydroxy-3-methoxycinnamate(74),tyrosol(75),oxylipin(76),methyl(9S,10S,11R,12Z)9,10,11-trihydroxyoctadeca-12-enoate(77),methyl(9S,10R,11E,13R,15Z)-9,10,13trihydroxyoctadeca-11,15-dienoate(78),methyl(9S,10R,11E,13S,15Z)-9,10,13?trihydroxyoctadeca-1 1,15-dienoate(79),methyl(9S,1OR,11E,13R)-9,10?13trihydroxyoctadec-11-enoate(80),methyl(9S,1OR,11E,13S)-9,10,13-trihydroxyoctadec-11enoate(81),(9S,10S,11R,12Z)-9,10,11-trihydroxyoctadeca-12,15-dienoic acid(82),liquiritigen-7-O-?-D-glucoside(83),liquiritigen(84),isorhamnetin-3-O-rutinoside(85),liquiritigen-4'-?-D-glucoside(86),quercetin(87),quercetin-3-O-rutinoside(88),quercetin-3O-?-D-glucoside(89),isoliquiritin(90),isorhamnethin-3-O-?-D-glucoside(91),1,6-hexano lactam(92),N-trans-feruloyloctopamine(93),N-p-coumaroyltyramine(94),iscariside E5(95).Among them,there are eighteen physalins.one neophysalin,two withaphysalins,twenty-six other withanolides,thirteen diterpenoids,seven phenolic acids,seven oxylipins,nine flavonoids,and four others.Compounds 66-68,70-73,76-82,and 92-95 were first isolated from the genus Physalis.The structural elucidation of the isolated compounds was conducted using UV,IR,1D-and 2D-NMR,MS,ECD,and X-ray crystallographic analyses,as well as theoretical calculations.A plausible biosynthetic pathway for compounds 29,34,36,37,and 48-59 was proposed based on isolated compounds and literatures.The isolated compounds were assayed for anti-proliferative activities against human prostate cancer cells(C4-2B and 22Rvl),human renal carcinoma cells(786-0,A-498,and ACHN),and human melanoma cells(A375-S2),as well as inhibitory effects on NO production induced by LPS in macrophages.Compounds 9,17,20-22,25,27,39,and 40 showed potent anti-proliferative activities against all tested human cancer cells with IC50 values of 0.18-7.43?M.Compounds 9,17,20-22,24,25,27,39,40,44,and 46 showed significant inhibitory activities against NO production with IC50 values of 0.32-5.56?M,respectively,and compounds 1-6,13,15,16,31,32,37,43,53,and 55-57 showed moderate inhibitory activities with IC50 values of 11.15?38.23?M.According to the above results,a series of compounds with anti-tumor and antiinflamatory activities were discoveried,which indicated the material foundation of efficacy of Phvsalis angulata.This study provides basises to develop and utilize Physalis angulata.