Studies On The Cucurbitane Compounds Of Momordica Charantia L.and Their Biological Activities

Momordica charantia L.(Cucurbitaceae),an annual climber and bears oblong fruits,possesses multiple pharmacological activities in crude extract including hypoglycemic,hypolipidemic,antitumor,liver protective effect,antiviral,antibacterial and immunoregulatory activities,and the active components of M.charantia are saponins.Based on the previous studies,more in-depth and systematic studies on the chemical components and biological activities of M.charantia and its hydrolysates were conducted.46 compounds were isolated from 70%ethanol extract and their hydrolyzated products by using a variety of chromatographic separation methods,of which 12 are novel compounds.All compound structures were identified by physicochemical properties,spectral data analysis,and these compounds are furpyronecucurbitane A(1),charantoside Ⅸ(2),charantoside Ⅹ(3),goyaglycoside Ⅰ(4),charantagenin F(5),charantoside Ⅺ(6),charantoside Ⅻ(7),charantoside ⅩⅢ(8),charantoside ⅩⅣ(9),charantoside Ⅴ(10),charantoside Ⅵ(11),5β,19epoxy-23(S)-methoxycucurbita-6,24-dien-3β-ol(12),25-O-methylkaraviagein D(13),charantoside C(14),karaviloside Ⅰ(15),karaviloside Ⅱ(16),momordicoside K(17),momordicoside Ⅰ(18),momordicoside F1(19),momordicoside G(20),goyaglycoside b(21),goyaglycoside c(22),goyaglycoside d(23),charantoside Ⅰ(24),charantagenin E(25),(19R,23E)-5β,19-epoxy-19-methoxycucurbita-6,23-dien-3β,25-diol(26),23E-5β,19-epoxycucurbita-6,23-dien-3β,25-diol(27),(19S,23E)-5β,19-epoxy-19-methoxycucurbita-6,23diene-3β,25-diol(28),charantoside D(29),charantoside E(30),7β,25-dimethoxycucurbita5(6),23(E)-dien-19-al(31),7β,25-dimethoxycucurbita-5(6),23(E)-dien-19-al 3-O-β-Dallopyranoside(32),karaviloside Ⅲ(33),Karavilagenin B(34),19(R)-5β,19-epoxy-25methoxy-cucurbita-6,23-diene-3β,19-diol(35),19(S)-5β,19-epoxy-25-methoxy-cucurbita6,23-diene-3β,19-diol(36);19(R)-5β,19-epoxycucurbita-6,23,25-trien-3β,19-diol(37),19(S)-5β,19-epoxycucurbita-6,23,25-trien-3β,19-diol(38),19(R)-5β,19-epoxycucurbita6,23-diene-3β,19-25-triol(39),kuguacin R(40),5β,19-epoxy-25-methoxycucurbita-6,23Edien-3β-ol(41),Karavilagenin A(42),(23E)-5β,19-epoxycucurbita-6,23,25-triene-3β-ol(43),charantian A(44),charantian B(45)and charantian C(46).Among them,compounds 1-9,4446 are new compounds.The hypoglycemic activity of α-glucosidase and PTP1B were screened.The results showed that compounds 13,32,33,43 and 45 have higher inhibitory activity against α-glucosidase,the values of IC50 were 10.19 ± 1.59,2.32± 0.46,2.73 ± 0.87,3.22 ± 0.91,and 7.43 ± 1.78 μM,respectively.The structure-activity relationship showed that the S configuration at the C-23 position was superior to that of the R configuration at the C23 position,and the activity of C-3 position linked allose was superior to that of glucose,and the activity of sapogenins was superior to that of saccharified.The R configuration of C-19 position is superior to the S configuration when the C-19 position is connected to the methoxyl group,C-25-linked hydroxyl activity is better than connecting methoxyl.Compounds 13,43,44 and 45 have significant inhibitory activity against PTP1B,the values of IC50 were 51.80±3.91,14.03 ± 2.74,31.94 ± 4.16 and 47.49 ± 5.79 μM,respectively.The structure-activity relationship showed that the binding activity of methoxyl group was superior to that of hydroxyl group in the presence of oxygen at the C-25 position.With the same skeleton,the activity of sapogenins is superior to that of saccharified,and the structure of C-5 and C-19 formed furan ring(C-6 and C-7 formed double bonds)is superior to that of uncyclized ring(C-5 and C-6 form a double bond).Among them,compounds 13,43 and 45 have better inhibitory activity on these targets.The protective effect of some cucurbitane compounds on H2O2 induced pancreatic islet β cell damage was evaluated,the compounds tested showed a protective effect against H2O2 at 10 μM,among them,the protective effects of compounds 7,8 and 26 were as high as 95.03%,93.07%and 80.12%.The structure-activity relationship shows that the R configuration at C-23 position is superior to S configuration.The R configuration at C-19 position is superior to that at S configuration when oxygen is attached to C-19 position.By using human liver fibrosis cell t-HSC/Cl-6,hepatic fibrosis activity of cucurbitane compounds was studied.Most of these compounds tested have some anti-hepatic fibrosis effects.The results showed that compound 33 exhibited significant activity in anti-hepatic fibrosis,IC50 was 3.74 ± 0.13 μM.The structure-activity relationship showed that when C-5 and C-19 were formed to furan ring and C-19 position connected with oxygen,the activity of methoxyl at C-19 position was superior to that of hydroxyl group,and the S configuration was superior to the R configuration.The activity of C-3 position connecting to glucose is superior to that of allose.When C-5 and C-19 were uncyclized,the activity of the formyl group at the C-19 position is superior to that of the methoxyl group.The anticancer activity of cucurbitane type compounds was screened by human liver cancer cell line HepG2 and Hep3B,and compound 33 showed significant activity in anti-proliferation,the values of IC50 were 16.68± 2.07 and 4.12 ± 0.27 μM.