Study On The Chemical Components From Sibiraea Angustata And Their Hypolipidemic Activity

Sibiraea angustata(Rchd.)Hand-Mazz.is a plant of the Sibiraea in the Rosaceae family.Commonly known as "Liu Cha".Sibiraea angustata are widely distributed in central and western China(Qinghai,Gansu,Yunnan,Sichuan and Tibet).Its leaves and twigs are commonly used in folk medicine to treat indigestion and abdominal discomfort,According to the local Tibetans,the cattle or sheep will lose weight if this plant is mixed into feed.“Zhong Hua Ben Cao” records that it has the effect of aiding digestion and regulating vital energy.Modern pharmacological studies have shown that the extract of Sibiraea angustata can significantly reduce the contents of total cholesterol(TC),triglyceride(TG),low-density lipoprotein(LDL)and malondialdehyde(MDA),regulate lipid metabolism and inhibit weight gain in high-fat animal models.Sibiraea angustata also has immune regulation,digestion,antioxidant and other pharmacological effects.Therefore,our research group conducted a systematic study on the chemical composition of Sibiraea angustata.In previous studies,48 compounds such as monoterpenoids,flavonoids and phenylpropanoids were successfully isolated and identified by using modern chromatographic methods and spectral techniques.The content of monoterpenes were high in Sibiraea angustata,and pharmacological experiments showed that the monoterpenes could significantly reduce the body weight,blood triglycerides and blood glucose levels of the high-fat diet mice.However,the mechanism the of monoterpenes reducing blood lipid and weight is unclear.In order to find the effective lipid-lowering components in Sibiraea angustata,in this paper,a series of separation techniques and methods including silica gel column chromatography,ODS reversed-phase chromatography,semi preparative liquid chromatography,Sephadex LH-20 column chromatography and recrystallization were used to study the chemical components of Sibiraea angustata.48 compounds were isolated from 95% ethanol extract from the acrial part of Sibiraea angustata.47 compounds were identified by using 1D,2D NMR,HR-ESI-MS,infrared spectrum,ultraviolet spectrum and other spectral methods.including 23 monoterpenes: Sibiraglycoside O(1*),Sibiraglycoside P(2*),Sibiraglycoside Q(3*),Sibiraglycoside R(4*),Sibiraglycoside S(5*),Sibiraglycoside T(6*),Aglycone(19),Sibiskoside(20),Aruncide A(21),3-[(2E)-4-hydroxyl-4-methyl-2-pentenyl)] furan-5H-2-one(22),Ibiscolacton(23),Vomifoliol(24),Grasshopper ketone(25),3,7-dimethyl-3(E),6-octadien-5-one-1-O-?-D-glucoside(26),3,7-dimethyl-3(Z),6-octadien-5-one-1-O-?-D-glucoside(27),Sibiraglycoside K(28),3,7-dimethyl-3(Z)-octene-5-one-1-O-?-D-glucopyranoside(29),Sibiraglycoside G(30),Sibiraglycoside H(31),Sibiraglycoside E(32),Sibiraglycoside F(33),Sibiraglycoside C(34),Sibiraglycoside D(35).12 simple phenylpropanoid compounds: Sibiraphencoside A(7*),(E)-3,4-Dimethoxycinnamic acid methyl ester(8),Methyl veratrate(9),(E)-3,4-Dimethoxycinnamic acid methyl ester(10),(E)-methyl 3-(3-hydroxy-4-methoxyphenyl)acrylate(11),3,4-Dimethoxycinnamic acid(12),Veratric acid(13),trans-3,4,5-Trimethoxycinnamic alcohol(14),Linocinnamarin(15),Tecomin(16),3,4-dimethoxycinnamyl-?-D-glucopyranoside(17),Icariside H1(18).6 lignans compounds:(+)-Cycloolivil(36),(2R,3S,4S)-4-(4-hydroxy-3-methoxybenzyl)-2-(5-hydroxy-3-methoxyphenyl)-3-(hydr oxymethyl)-tetrahydrofuran-3-ol(37),1,2-bis(4-hydroxy-3-methoxyphenyl)-1,3-propanediol(38),Salicifoneoliganol(39),(7S,8R)-dihydrodehydrodiconiferyl alcohol(40),Herpetriol(41).3 triterpenoids compounds: Dammarenediol-II(42),Methyl maslinat(43),Alphitolic acid(44).One flavonoid: Quercetin-3-O-galactoside(45)and 2 long chain fatty acids.1*-7* are seven new compounds.Compounds 8-11,13-18,24,25,37-44,46 and 47 were isolated from Sibiraea plants for the first time.In this paper,the hypolipidemic activity of the compounds isolated from the acrial part of Sibiraea angustata were screened.Among them,monoterpenoid compounds 1,2,3,4,6,19,20,21,26,32,33 and triterpenoids 42,43 all have lipid lowering activities,The data results were significantly different from the model group.Compounds 2,6,32 and 42 showed the best hypolipidemic effects among these compounds.,It was speculated that the 3-hydroxyl-4-methoxycinnamic acid fragment bound to sugar had a decreasing effect on the lipid lowering activity of monoterpene glycosides through the structure-activity relationship comparison.Monoterpene aglycones are the main chemical fragments that play the role of hypolipidemic effect.Triterpenoids and monoterpene glycosides provide the material basis for the lipid-lowering function of Sibiraea angustata.Meanwhile,the hypolipidemic effect of compound 32(Sibiraglycoside E)in the in vitro were further studied.RT-PCR and lipidomics analysis showed that compound 32 may exert its hypolipidemic biological activity by inhibiting the synthesis of long-chain fatty acids,reducing the content of DG and TG in Hep G2 cells.