| Paeonia Suffruticosa Andrews(Moutan Cortex)is an important ornamental and medicinal plant in China.The root cortex of Paeonia Suffruticosa Andrews is widely used for the treatment of anti-inflammation,immunity adjustment,anti-hypertension,hypoglycemia,anti-thrombus,et al.In this thesis,the chemical constituents from the root cortex of P.Suffruticosa Andrews were studied,and 64 compounds were obtained.The structures of new compounds were eludicated by the physico-chemical evidences and NMR spectroscopic data,and they are paeoniflorin B(1),oxypaeoniflorin sulfonate(2),4-O-methyloxypaeoniflorin(3),oxypaeonidanin(4),9-O-butyloxypaeonidanin(5),9-O-butylpaeonidanin(6),4-O-butyloxypaeoniflorin(7),9-epi-oxypaeonidanin(8),4-O-methylgalloyloxypaeoniflorin(9),paeoniflorin A(10),mudanoside C(11),(E)-icosyl 3-(2,4,5-trihydroxyphenyl)acrylate(12),The known compounds were determined as paeoniflorin(13),paeonidanin(14),4-O-methylpaeoniflorin(15),benzoylpaeoniflorin(16),mudanpioside E(17),oxypaeoniflorin(18),benzoyloxypaeoniflorin(19),mudanpioside D(20),moudanpioside C(21),8-O-debenzoylpaeoniflorin(22),galloyloxypaeoniflorin(23),galloylpaeoniflorin(24),moudanpioside B(25),moudanpioside F(26),4-O-butylpaeoniflorin(27),paeoniflorigenone(28),paeonidanin A(29),4-O-methylbenzoylpaeoniflorin(30),paeonolide(31),paeonoside(32),mudanoside B(33),suffruticoside D(34),suffruticoside A(35),suffruticoside B(36),3-O-?-D-glucopyranosy 1-4-methoxyacetophenone.(37),paeonol(38),1-(3-hydroxy-4-methoxyphenyl)ethanone(39),2,3-dihydroxy-4-methoxyacetophenone(40),apiopaeonoside(41),iriflophenone 2-O-?-D-glucopyranoside(42),cadina-4,11-dien-14-oic acid(43),1,2,3,4,6-penta-galloylglucose(44),1,3,4-trigalloylglucose(45),1,2,3,4-tetragalloylglucose(46),(-)-catechin(47),oleanolic acid(48),uridine(49),a-L-arabinopyranoside ethyl(50),?-sitosterol(51),mono-ethyl fumarate(52),dibutyl fumarate(53),vanillic acide(54),mono-methyl maleate(55),phthalic acid dibutyl ester(56),gallic acid(57),methyl gallate(58),ethyl gallate(59),butyl gallate(60),methyl palmitate(61),pentadecanoic acid(62),p-hydroxybenzoic acid(63),benzoic acid(64).Among them,twelve compounds(1-12)are new compounds,nine compounds(37,42,43,47,49,50,52,53 and 55)are isolated from Paenoina genus for the first time.The investigation enriched the constituent-types of Paenoina Suffruticosa Andrews and could provide material basis for further activity screening.The inorganic free radical NO has been implicated in physiological and pathological processes,such as vasodilation,nonspecific host defense,ischemia reperfusion injury,and chronic or acute inflammation.NO is produced by the oxidation of L-arginine by NO synthase(NOS).In the NOS family,inducible NOS in particular is involved in a pathological aspect with overproduction of NO,and can be expressed in response to pro-inflammatory agents such as interleukin-1?,tumor necrosis factor-a,and LPS in various cells including macrophages,endothelial cells,and smooth muscle cells.In this thesis,we evaluated the inhibitory effects of the 58 compounds on NO production in LPS-activated macrophages by Griess method.Among the tested compounds,13 of them(1,10,19,21,24,26,28,30,35,55,58,59 and 60)displayed more potent inhibitory effects than hydrocortisone,11 of them(4,22,32,33,36,37,39,43,51,53,62)showed weak activities.And other compounds showed no activity.Paeonol is one of the major bioactive components of Paenoina Suffruticosa Andrews,which exhibits a wide variety of bioactivities including anti-inflammatory,antibacterial,antioxidative and antitumor effects.Pharmacokinetic studies have indicated that paeonol has poor oral bioavailability and,so far,there are only a few reports on its metabolism in rats and no published study on the metabolism of paeonol in humans.Therefore,the metabolism of paeonol in human had been investigated in our lab,and five metabolites were isolated from human urine,and identified as resacetophenone(M1),resacetophenone-2-O-sulfate(M2),2-hydroxy-4-methoxyacetophenone-5-0-sulfate(M3),2-hydroxy-4-methoxyacetophenone-5-O-glucopyranuronoside(M4),2-hydroxyacetophenone-4-0-glucopyranuronoside(M5).In addition,a UPLC/Q-TOF-MS/MS method was developed for analyses of paeonol metabolites in human and rat urine,rat plasma,and rat bile by direct comparison of their retention times and mass spectra with those of authentic samples.In our continuing research on the metabolism of paeonol in vivo,M6(2,5-dihydroxy-4-methoxyacetophenone)was isolated from human urine and M10(2,4,5-trihydroxyacetophenone)was synthesized,meanwhile,we get more information from mass spectra to have a conclusion that the metabolites of paeonol in human and rat urine are not the same which is different from previous study.In addition,the in vitro anti-inflammatory and antioxidative activity of paeonol and its metabolites M1-M6 and M10 were evaluated,and it was found that M6 and M10 exhibited higher activity than the parent drug and other metabolites.And paeonol,Ml,M3,M5 and M6 exhibited significant scavenging activity against hydroxyl radicals.The preliminary research of paeonol's pharmacokinetics was also studied.The linearity of paeonol and its metabolites obtained in the range of 50?4000 ng/mL,12.5-1000 ng/mL were excellent,respectively.The concentration and excretion-rate of paeonol and its metabolites are different,respectively.At the same time,the concentration of metabolites in plasma seems to depend on the administration dosage.These results are important for understanding the metabolic pathway of paeonol in vivo,and would lay the foundation for its clinical applications and its further pharmacokinetic study. |
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