A new (E)-4-hydroxy-dodec-2-enedioic acid from the stem bark ofalbizzia julibrissin

A new unsaturated hydroxy acid was isolated from the stem bark extract of Albizzia julibrissin through repeated silica gel and Sephadex LH-20 column chromatography. The chemical structure of the new acid was determined as (E)-4-hydroxy-dodec-2-enedioic acid on the basis of several spectral data including 2D-NMR. The stereochemical feature of the double bond was determined to be E on the basis of the coupling pattern of related proton signals in the 1H-NMR and COSY experiments.     

北马兜铃的化学成分研究——Ⅱ、马兜铃酸E的化学结构

From the root of Aristolochia contorta Bunge six chemical constituents were isolated; one of them is a new phenanthrene compound containing nitro group for which the name aristolochic acid E is suggested. By means of spectral methods combined with chemical analysis the chemical structure of aristolochic acid E was determined to be 7-methoxy-8-hydroxy-aristolochic acid. The other components were identified as allantoin, aristolochic acid A, magnoflorine, β-sitosterol and daucosterol respectively.     

刺梨酸的分离与结构研究

从刺梨中分离出一种新的五环三萜酸,命名为刺梨酸。通过光谱分析和衍生物的制备,确定其化学结构为2β,3α,7β,19α-四羟基乌苏-12-烯-28-羧酸。     

Triacylglycerols of the lipid fraction from fruits of two <Emphasis Type="Italic">Echinacea</Emphasis> species

Fatty oils extracted from the fruits of Echinacea purpurea and E. pallida species have been analyzed. The extracts represent oily and readily mobile light yellow liquids. Fruits of E. purpurea contain 33.6% fatty oil; of E. pallida, 23.2%. NMR spectroscopy analyses of fatty oils from fruits of the two Echinacea species show that these substances belong to liquid plant oils such as linoleic acid, which is confirmed by the measured numerical indices. Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 43, No. 3, pp. 32 – 34, March, 2009.     

Tungtungmadic acid, a novel antioxidant, fromSalicornia herbacea

Tungtungmadic acid (3-caffeoyl-4-dihydrocaffeoyl quinic acid) is a new chlorogenic acid derivative that was isolated from the Salicornia herbacea. The structure of tungtungmadic acid was determined using chemical and spectral analysis. The antioxidant activity of tungtungmadic acid was evaluated using various antioxidant assays, including free radical scavenging, lipid peroxidation and hydroxyl radical-induced DNA strand breaks assays. Tungtungmadic acid (IC50 = 5.1 microM and 9.3 microM) was found to have higher antioxidant activity in the DPPH scavenging assay as well as in the iron-induced liver microsomal lipid peroxidation system. In addition, the tungtungmadic acid was also effective in protecting the plasmid DNA against strand breakage induced by hydroxyl radicals.     

Lactonase and lactonizing activities of human serum paraoxonase (PON1) and rabbit serum PON3

Human paraoxonase (PON1) was previously shown to hydrolyze over 30 different lactones (cyclic esters). In the present study purified human PON1 was found to catalyze the reverse reaction (lactonization) of a broad range of hydroxy acids. Hydroxy acid lactonization or lactone hydrolysis is catalyzed until equilibrium between the open and closed forms is reached. Lactonization by PON1 was calcium-dependent, had a pH optimum of 5.5-6 and could be stimulated with dilauroylphosphatidylcholine. Rabbit serum PON3 and a serine esterase in mouse plasma, presumably a carboxylesterase, also catalyzed hydroxy acid lactonization. Two endogenous oxidized unsaturated fatty acids, (+/-)4-hydroxy-5E,7Z,10Z,13Z,16Z,19Z-docosahexaenoic acid (4-HDoHE) and (+/-)5-hydroxy-6E,8Z,11Z,14Z-eicosatetraenoic acid (5-HETE) lactone, were very efficiently lactonized and hydrolyzed, respectively, by PON1. Human and mouse plasma samples also catalyzed 4-HDoHE lactonization and 5-HETE lactone hydrolysis. Studies with the PON1 inhibitor EDTA and the serine esterase inhibitor phenylmethylsulfonylfluoride suggest that about 80-95% of both activities can be attributed to PON1 in the human samples. In the mouse sample, PON1 accounted for about 30% of the 4-HDoHE lactonizing activity and 72% of the 5-HETE lactonase activity. Our results demonstrate that PON1 can lactonize the hydroxy acid form of its lactone substrates and that reversible hydrolysis of lactones may be a property of lactonases that is not generally considered. Also, the high activity of PON1 towards 4-HDoHE and 5-HETE lactone suggests that oxidized eicosanoids and docosanoids may be important physiological substrates for PON1.     

Cytotoxic constituents of the octocoralDendronephthya gigantea

A known monoalkyl glycerol ether, (+/-)-1-nonadecyloxy-2,3-propanediol (1) was isolated from the ethyl acetate extract of a soft coral Dendronephthya gigantea as a weakly cytotoxic constituent against four human cancer cell lines, A549, HT-29, HT-1080, and SNU-638. In addition, a known ceramide, (2S,3R,4E,8E)-N-hexadecanoyl-2-amino-4,8-octadecadiene-1,3-diol (2), was also isolated as an inactive constituent. This is the first report on the isolation of the compounds 1 and 2 from the octocoral, Dendronephthya species.     

A quinic acid ester from Strychnos lucida

A new quinic acid ester, 4-O-(3,5-dimethoxy-4-hydroxybenzoyl)quinic acid (1) was isolated, together with 22 known compounds, from the barks and woods of Strychnos lucida. The structure of the new compound was determined by spectroscopic (NMR, MS) and chemical means.     

Inhibition of inducible prostaglandin E(2) synthase by 15-deoxy-Delta(12,14)-prostaglandin J(2) and polyunsaturated fatty acids

Prostaglandin E(2) synthase (PGE synthase) is one of the membrane-associated proteins in the eicosanoid and glutathione metabolism (MAPEG) family of microsomal enzymes and constitutes a novel inducible enzyme involved in inflammation and pyretic responses. We report, using a reversed-phase HPLC assay for the production of tritiated prostaglandin E(2) (PGE(2)) by membranes from cells overexpressing human microsomal PGE synthase, that PGE synthase activity is inhibited effectively by 15-deoxy-Delta(12,14)-prostaglandin J(2) and arachidonic acid. The anti-inflammatory compound 15-deoxy-PGJ(2) was considerably more potent at inhibiting PGE synthase (IC(50)=0.3 microM) than the closely related PGJ(2) or Delta(12)-PGJ(2), or the reaction product PGE(2). Arachidonic acid, docosahexaenoic acid, and eicosapentaenoic acid inhibited PGE synthase with a similar potency (IC(50)=0.3 microM) and were more potent inhibitors than various fatty acid analogues. The present results on the inducible PGE synthase extend observations on the ability to bind arachidonic acid to another member of the MAPEG family, and also suggest a novel mechanism of action for the anti-inflammatory effects of DHA, EPA, and 15-deoxy-PGJ(2).     

香茶菜抗癌成分的研究

从香茶菜属植物香茶菜Rabdosia amethystoides(Benth) Hara中分得七种成分,其中之一香茶菜甲素为一新的四环二萜,有抗实验肿瘤及抑制金黄色葡萄球菌作用。用光谱法配合衍生物制备,确定甲素为7α,14β=羟基-20α羟甲基-16-贝壳杉烯-11,15=酮乙素为乌苏酸,丙素为β-谷甾醇,己素为硬脂酸,其余成分尚在研究中。     

Incorporation of sciadonic acid into cellular phospholipids reduces pro-inflammatory mediators in murine macrophages through NF-κB and MAPK signaling pathways

Sciadonic acid (SCA; Δ5,11,14–20:3), a non-methylene-interrupted polyunsaturated fatty acid (NMIFA), can substitute for arachidonic acid (AA) and reduce prostaglandin E₂ (PGE₂) synthesis in macrophages. However, little is known about how SCA exerts its anti-inflammatory effects. The objectives of this study were to purify SCA from seeds of Podocarpus nagi and investigate mechanisms underlying the modulatory effects of SCA on inflammatory responses in murine RAW264.7 macrophages. We describe how high-purity SCA (>98%) can be obtained using argentated column chromatography. SCA was dose-dependently incorporated into cellular phospholipids, and increasing SCA incorporation correlated with decreases in the proportions of AA, total monounsaturated fatty acids (MUFA) and total saturated fatty acids (SFA). SCA decreased production of PGE₂ (29%), nitric oxide (NO) (31%), interleukin-6 (IL-6) (34%) and tumor necrosis factor-α (TNF-α) (14%). The suppression of pro-inflammatory mediators was due, in part, to decreased expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). SCA incorporation suppressed nuclear factor-kappa B (NF-κB) translocation and phosphorylation of mitogen-activated protein kinases (MAPK), including extracellular signal-regulated kinase (ERK), p38 and c-Jun N-terminal kinase (JNK). These findings indicate that by altering the cellular fatty acid composition SCA can modulate the responsiveness of macrophages to LPS through inactivation of NF-κB and MAPK pathways.     

夏至草中两种黄酮苷类化合物的研究

目的研究夏至草的化学成分。方法用硅胶柱色谱和葡聚糖凝胶柱法对夏至草的黄酮部分进行分离,应用波谱学方法鉴定结构。结果分离出2种黄酮类成分,分别鉴定为7-O-(6″-反式-对-香豆酰基)-β-D-半乳糖-芹菜素苷(I),7-O-(3″,6″-二-反式-对-香豆酰基)-β-D-半乳糖-芹菜素苷(II)。结论I和II均为新化合物。     

Single-dose tolerance and pharmacokinetics of 2-n-propyl-2(E)-pentenoate (Δ2(E)-valproate) in healthy male volunteers

2-n-Propyl-2(E)-pentenoic acid (^2(E)-valproate) was administered to healthy volunteers in oral doses of 50–800 mg. The drug was tolerated well and no significant adverse effects were observed. Pharmacokinetic parameters were determined. Valproate and 3-keto-valproate were detected as metabolites.     

New polyunsaturated fatty acid amides isolated from the seeds of <Emphasis Type="Italic">Zanthoxylum piperitum</Emphasis>

Five linear fatty acid amides (1-5) of the sandshool class, including two new compounds, were isolated from Zanthoxylum piperitum seeds. Based on combined spectral analyses, the structures of new compounds 4 and 5 were determined to be 2',3'-dihydroxy-alpha-sanshool and 2',3'-dihydroxy-beta-sanshool, respectively. These compounds exhibited weak cytotoxicity in the A-549 (human lung cancer) cell line.     

Soraphen A, an inhibitor of acetyl CoA carboxylase activity, interferes with fatty acid elongation

Acetyl CoA carboxylase (ACC1 and ACC2) generates malonyl CoA, a substrate for de novo lipogenesis (DNL) and an inhibitor of mitochondrial fatty acid β-oxidation (FAO). Malonyl CoA is also a substrate for microsomal fatty acid elongation, an important pathway for saturated (SFA), mono- (MUFA) and polyunsaturated fatty acid (PUFA) synthesis. Despite the interest in ACC as a target for obesity and cancer therapy, little attention has been given to the role ACC plays in long chain fatty acid synthesis. This report examines the effect of pharmacological inhibition of ACC on DNL and palmitate (16:0) and linoleate (18:2, n − 6) metabolism in HepG2 and LnCap cells. The ACC inhibitor, soraphen A, lowers cellular malonyl CoA, attenuates DNL and the formation of fatty acid elongation products derived from exogenous fatty acids, i.e., 16:0 and 18:2, n − 6; IC₅₀ ∼ 5 nM. Elevated expression of fatty acid elongases (Elovl5, Elovl6) or desaturases (FADS1, FADS2) failed to override the soraphen A effect on SFA, MUFA or PUFA synthesis. Inhibition of fatty acid elongation leads to the accumulation of 16- and 18-carbon unsaturated fatty acids derived from 16:0 and 18:2, n − 6, respectively. Pharmacological inhibition of ACC activity will not only attenuate DNL and induce FAO, but will also attenuate the synthesis of very long chain saturated, mono- and polyunsaturated fatty acids.     

Screening for in vitro antioxidant properties and fatty acid profiles of five Centaurea L. species from Turkey flora

Centaurea species are used for the treatment of various ailments in the popular medicine in some countries. This study was designed to examine antioxidant potentials and fatty acid profiles of five Centaurea species from Turkey flora. Antioxidant properties of methanolic extracts from these species were evaluated by six different methods: phosphomolybdenum assay, free radical scavenging assay, β-carotene/linoleic acid test system, metal chelating activity, ferric and cupric reducing power. Total phenolic and flavonoid concentrations of each extract were also determined using the Folin–Ciocalteu reagent and aluminum chloride. The results of these assay showed a significant antioxidant capacity in all researched extracts. Centaurea cheirolopha extract, with the highest amount of total phenolic and flavonoids, showed the highest antioxidant activities in all assay, except for metal chelating. Fatty acid profiles of these species were examined by GC–FID and 30 fatty acids were identified. Palmitic, linoleic, oleic, and linolenic acid were detected as the main components. The results of the study indicated that the Centaurea species can be considered as a source of new natural antioxidants and unsaturated fatty acids for food, cosmetic and pharmaceutical industries.     

N2-芳基三嗪青霉素和N2-苯基-N4-烷基(芳基)三嗪青霉素的合成及其抗菌活性

设计合成了十个N²-芳基三嗪青霉素和六个N²-苯基-N⁴-烷基(芳基)三嗪青霉素,这十六个化合物均为未见文献报道的新化合物,元素分析数据和光谱数据证实了它们的结构。初步体外抑菌试验表明,十六个化合物对G(+)菌和G(-)菌均有一定的活性,其中的五个化合物具有一定程度的广谱特征。     

Isolation of fatty acids with anticancer activity from<Emphasis Type="Italic">Protaetia brevitarsis</Emphasis> Larva

In this study, biologically active compounds were isolated from Protaetia brevitarsis larva (PBL) by dichloromethane extraction. The dichloromethane extract from PBL was highly cytotoxic to various cancer cells. From a silica gel column chromatograpy of this extract, we obtained four fractions (F-2, F-4, F-5 and F-7) having apoptosis-inducing activity. These fractions induced DNA ladder and caspase-3 activation during apoptosis in colon 26 tumor cells. In 1H and 13C NMR and mass spectral analysis of the fraction F-2 showing the highest apoptosis-inducing activity, we found that the fraction was composed of three free fatty acids such as palmitic acid, (Z)-9-octadecenoic acid and octadecenoic acid. These results indicate that the dichloromethane extract of PBL includes anticancer components composed of at least three fatty acids, and apoptosis-inducing activity of the extract was mediated by caspase-3 activation in tumor cells.     

野蔷薇根化学成分的研究

野蔷薇根系蔷薇科植物多花蔷薇(Rosa multiflora Thunb.)的干燥根,民间用其除风湿、活气血和治疗乳糜尿。Takahashi等从野蔷薇根中分离出2α,19α-二羟基熊果酸(tomentic acid)。我们从野蔷薇根中分离出三个化合物,通过光谱和化学反应分别鉴定为β-谷甾醇,2α,19α-二羟基熊果酸,和2α,19α-二羟基熊果酸-(28-1)-β-D-     

Antioxidative effects ofCichorium intybus root extract on LDL (Low Density Lipoprotein) oxidation

The water extract of Cichorium intybus (WECI) showed a remarkable antioxidative effect on LDL, and inhibitory effects on the production of thiobarbituric acid reactive substance and the Degradation of fatty acids in LDL. Vitamin E and unsaturated fatty acids in LDL were protected by adding WECI from the effects of metal catalyzed LDL oxidation. From the results obtained, we conclude that LDL oxidation is inhibited in vitro by the addition of WECI, and that LDL is protected by WECI from oxidative attack, as shown by agarose gel electrophoresis.