Study On The Chemical Constituents And Biological Activities Of Chinese Herbal Medicine Hawthorn

Cornus offcinalis Sieb.et Zucc.,a species of the Comaceae family,mainly distributed in Shaanxi,Shanxi,Henan and other province.Fructus Corni,the pulp of the dried ripe fruit of Cornus officinalis Sieb.et Zucc.,is the valuable traditional Chnese medicine originally contained in Shen-Nung's Pen-Ts'ao used for nourishing liver and kidney for about two thousand years.It can attemper chills and fever of the subjacent evil of heart,warm the middle warmer and eliminate cold,wet and pain or numbness,remove the three words,a long time usage can make you feel suitable.It has the properties of acid,astringent,a part of warm,attributing to liver and kidney.Moreover,Fructus Corni is the main constituents of some classic traditional Chinese ingredients such as the "pills of Liuweidihuang","pills of Jinkuishenqi","pills of Zuogui".Up to now,phytochemical studies on Fructus Corni indicated the presence of iridoids,tannins,flavonoids,triterpenoids and several other constituents.Pharmacological studies revealed that C.officinalis possessed a variety of bioactivities,such as anti-inflammatory,hypoglycemic effect,hypolipidemic effect,anti-diabetic,neuroprotective,anti-cancer,anti-oxidant,anti-aging,cardiovascular system activities.Although a lot of pharmacological activities about the crude extract have been reported,the research about monomeric compounds is very few.It is very important to further study the chemical compounds of Fructus Corni in order to better illuminate the material basis of it.This paper reported systematically the isolation and identification of water extract of C.officinalis and evaluate monomeric compounds isolated for the anti-inflammatory and neuroprotective effects,which provided scientific basis of better research of Fructus Corni.According to the maximal UV absorption of iridoid compounds,80 compounds have been isolated by Silica gel,ODS,Sephadex LH-20 column chromatograph and pre-HPLC and so on,and 72 of which were determined by extensive spectroscopic analysis including UV,IR,MS,HRESIMS,1D NMR,2D NMR,CD,ECD.These compounds included 41 iridoid glucosides,3 monoterpenoids,5 flavonoids,13 lignans and 10 other compounds.They are named as follows:cornuside A(1*),cornuside B(2*),cornuside C(3*),cornuside D(4*),cornuside E(5*),cornuside F(6*),cornuside G(7*),comuside H(8*),comuside ?(9*),cornuside J(10*),cornuside K(11*),comuside L(12*),cornuside M(13*),cornuside N(14*),cornuside O(15*),comuside P(16*),comuside Q(17*),cornusfuroside A(18*),corbusfuroside B(19*),cornusfuroside C(20*),cornusfuroside D(21*),6'-O-acetyl-7?-O-ethyl(22*),6'-O-acetyl-7?-O-ethyl(23*),comusglucoside A(24*),cornusglucoside B(25*),cornusglucoside C(26*),cornusglucoside D(27*),cornusglucoside E(28*),cornusglucoside F(29*),comusglucoside G(30*),cornusglucoside H(31*),williamsoside D(32),loganin(33),8-epiloganin(34),7?-O-morroniside(35),7?-O-morroniside(36),7?-0-methyl morroniside(37),7?-0-methyl morroniside(38),7?-O-ethyl morroniside(39),7a-0-ethyl morroniside(40),sweroside(41),sarracenin(42),sachalinoide B(43),(4a)-3-(5,5-dimethyltetrahydrofuranyl)-1-buten-3-ol 3-O-?-D-glucopyranoside(44),apigenin(45),chrysoderol(46),luteolin(47),quercetin(48),dihydroapigenin(49)3,4,3',4'-tetrahydroxy-?-truxinate(50),(-)-isolariciresinol 3a-O-?-D-glucopyranoside(51),(+)-isolariciresinol 3a-O-?-D-glucopyranoside(52),(+)-pinoresinol(53),(+)-epipinoresinol(54),syringaresinol(55),(-)-episyringaresinol(56),(-)-medioresinol(57),(7S,8R)-urolignoside(58),glochidioboside(59),(7R,8S)-dihydrodehydrodiconiferyl alcohol 9-O-?-D-glucopyranoside(60),(-)-secoisolariciresinol-9'-O-?-D-glucopyranoside(61),4-0-(6'-O-galloyl-?-D-glucopyranosyl)-cis-pcoumaric acid(62),5-(1'-hydroxyethyl ethylenediamine)-methyl nicotinate(63),cirsiumaldehyde(64),5-hydroxymethylfurfural(65),p-Hydroxybenzoic acid(66),ethyl gallate(67),syringate(68),p-coumaric acid(69),caffeic acid(70),caffeic acid methyl ester(71),p-methoxy cinnamic acid(72).Among them,1-31 were new iridoid glucosides,42?47,49-64 and 72 were obtained from the Cornus genus for the first time.Besides,Bioactivities of compounds from Cornus officinalis were screened by various pharmaceutical models:Compounds 1-15 and 32-41 were tested for their inhibitory activities based on the luciferase report gene technology.The result showed that all compounds had no cytotoxicity and compounds 3,12,33,35,and 36 had potent inhibitory effects,with IC50 values of 11.9,12.2,14.0,7.0,and 6.9 ?M,respectively.Examination of inhibition of IL-6 production by the tested iridoid glucoside dimmers suggested that two partial structures responsible for the bioactivity:the configuration of C-7",and the connection position of two monomers.In morroniside-type secoiridoid dimers(1-11,32),compound 3 with ?-orientation at C-7," and C-3'-O-C-7," linkage exhibited potent bioactivity(11.9 ?M).In 12-15,compound 12 with a-oriented at C-7" and C-6'-O-C-7" linkage exhibited potent bioactivity(12.2 ?M).In the monomers(32-41),loganin(33)7a-morroniside(35),and 7?-morroniside(36)showed potent bioactivities(14.0,7.0 and 6.9 ?M).Compounds 32-41 were evaluated for the viability of anti-inflammatory for Raw264.7 cells stimulated by LPS.The result showed that all compounds except compound 25 had no anti-inflammatory effect,and the inhibitory effects of compound 25 to the secretion of TNF-a exceeded 50%.Compounds 1-15 and 32-41 were evaluated for the viability of PC12 cells when exposed in conditions of oxygen and glucose deprivation.The MTT results showed that compound 1 and 3 increased cell viability moderately in OGD/R treated PC 12 cells.