Humulene derivatives from Zingiber zerumbet with the inhibitory effects on lipopolysaccharide-induced nitric oxide production

A new humulene sesquiterpene, 5-hydroxyzerumbone (5-hydroxy-2E,6E,9E-humulatrien-8-one) (1) and a known compound, zerumboneoxide (2) were isolated from the rhizomes of Zingiber zerumbet (Zingiberaceae), and found to inhibit lipopolysaccharide-induced nitric oxide production in murine macrophage RAW 264.7 cells with IC50 values of 14.1 and 23.5 microM, respectively, by bioassay-guided fractionation (positive control: N(omega)-monomethyl-L-arginine, IC50=21.3 microM). The structure of 1 was determined by spectroscopic methods including 1D and 2D-NMR.     

A new triterpenoid saponin from Gleditisia sinensis and structure-activity relationships of inhibitory effects on lipopolysaccharide-induced nitric oxide production

A phytochemical investigation of the anomalous fruits of Gleditisia sinensis led to one new oleanane-type triterpenoid saponin acylated with one monoterpenic acid, 3-O-beta-D-glucopyranosyl oleanolic acid 28-O-beta-D-xylopyranosyl-(1 --> 3)-beta-D-xylopyranosyl-(1 --> 4)-alpha-L-rhamnopyranosyl-(1 --> 2)-[(6S,2E)-6-hydroxy-2,6-dimethyl-2,7-octadienoyl-(1 --> 6)]-beta-D-glucopyranosyl ester, named gleditsioside Z (1), together with nine known ones (2-10). Their structural details were mainly established on the basis of 1D, 2D NMR and HR-MS analysis as well as some chemical methods. Structure-activity relationships of the isolated saponins that affected nitric oxide production from cultured mouse macrophages (RAW 264.7 cell lines) induced by lipopolysaccharide were discussed.     

New seco-dibenzocyclooctadiene lignans with nitric oxide production inhibitory activity from the roots of Kadsura longipedunculata

Four new seco-dibenzocyclooctadiene lignans,kadlongilignans A-D(1-4),consisting of a rare 6,7-seco-(1),two 15,16-seco-(2 and 3) and a 9,10-seco-dibenzocyclooctadiene(4) lignans,were isolated from the roots of Kadsura longipedunculata.Their structures were elucidated by spectroscopic analysis,including extensive NM R,MS and ECD(electronic circular dichroism) spectra.Compounds 3 and 4 exhibited potent inhibitory activities against NO(nitric oxide) production of LPS(lipopolysaccharide)-induced murine macrophages with the inhibition rates of 36.3% and 26.9%,respectively.     

Melampolides from the leaves of Smallanthus sonchifolius and their inhibitory activity of lps-induced nitric oxide production

Two new melampolide-type sesquiterpene lactones, 8beta-epoxyangeloyloxy-9alpha-ethoxy-14-oxo-acanthospermolide (1) and 8beta-angeloyloxy-9alpha-ethoxy-14-oxo-acanthospermolide (2), were isolated from the leaves of yacon [Smallanthus sonchifolia (POEPP. et ENDL.) H. Robinson] along with eleven known melampolides, allo-schkuhriolide (3), enhydrin (4), polymatin A (5), fluctuanin (6), 8beta-angeloyloxy-9alpha-acetoxy-14-oxo-acanthospermolide (7), 8beta-angeloyloxy-14-oxo-acanthospermolide (8), 8beta-methacryloyloxymelampolid-14-oic acid methyl ester (9), uvedalin (10), polymatin B (11), 8beta-tigloyloxymelampolid-14-oic acid methyl ester (12), and sonchifolin (13). Their structures were established on the basis of spectroscopic evidence including 1D- and 2D-NMR experiments. All isolates were evaluated for inhibition of LPS-induced nitric oxide production in murine macrophage RAW 264.7 cells.     

Sesquiterpene coumarins from Ferula fukanensis and nitric oxide production inhibitory effects

Four new sesquiterpene coumarin derivatives, fukanemarin B (1), fukanefuromarin E (2), fukanefuromarin F (3) and fukanefuromarin G (5) were isolated from a 80% aqueous methanol extract of the roots of Ferula fukanensis. The structures were elucidated based on spectral evidence, especially heteronuclear multiple-bond connectivity (HMBC) and high-resolution MS. The 80% aqueous methanol extract of the roots of Ferula fukanensis (FFE) and the sesquiterpene coumarin derivatives inhibited nitric oxide (NO) production and inducible NO synthase (iNOS) gene expression by a murine macrophage-like cell line (RAW 264.7), which was activated by lipopolysaccharide (LPS) and recombinant mouse interferon-gamma (IFN-gamma).     

New Labdane diterpenes from Hedychium yunnanense with cytotoxicity and inhibitory effects on nitric oxide production

Two new labdane diterpenes, hedychenoids A (1) and B (2), were isolated from the rhizomes of Hedychium yunnanense, together with four known ones hedychenone (3), forrestin A (4), villosin (5) and calcaratarin C (6). Their structures were determined on the basis of NMR (1D and 2D) and mass spectroscopic analysis. Compounds 2, 3 and 5 exhibited cytotoxicity against SGC-7901 with IC₅₀ values of 14.88 ± 0.52, 7.08 ± 0.21 and 7.76 ± 0.21 μg/ml, 3 and 5 against HeLa with IC₅₀ values of 9.76 ± 0.48 and 13.24 ± 0.63 μg/ml, respectively. Compounds 2, 5 showed inhibitory effects against nitric oxide production in LPS and IFN-γ-induced RAW 264.7 murine macrophages with IC₅₀ values of 6.57 ± 0.88 and 5.99 ± 1.20 μg/ml, respectively.     

Polyphenols from Sophora yunnanensis, and their inhibitory effects on nitric oxide production

A new flavonoid, (2R,3R)-3,7,4'-trihydroxy-3',5'-dimethoxyflavanone, named sophorayunnanol (1), together with eight known polyphenols (2-9), were isolated from the roots of Sophora yunnanensis C.Y.MA (Leguminosae). The structure including absolute stereochemistry of 1 was determined by spectroscopic (high resolution (HR)-MS, 1D- and 2D-NMR, and circular dichroism (CD)) methods. The inhibitory activity of these compounds was examined against nitric oxide (NO) production by lipopolysaccharide (LPS) and interferon (IFN)-γ activated macrophages, RAW264.7 cells. 3,7,3',5'-Tetrahydroxy-4'-methoxyflavone (6) and piceatannol (9) showed potent inhibitory activity against the production of NO with IC(50) values of 14.4±2.5 and 12.9±1.8 μM, respectively. This article is the first report on phytochemical study of S. yunnanensis.     

New stilbenoids from Pholidota yunnanensis and their inhibitory effects on nitric oxide production

Six new stilbenoids, a (bibenzyldihydrophenanthrene) ether designated phoyunnanin D (1), a bis(dihydrophenanthrene) ether designated phoyunnanin E (2), and four stilbenes designated phoyunbene A-D (3-6), were isolated from the air-dried whole plant of Pholidota yunnanensis ROLFE. The new compounds were identified as 7-[2-(3-hydroxyphenethyl)-4-hydroxy-6-methoxyphenoxy]-4-hydroxy-2-methoxy-9,10-dihydrophenanthrene (1), 1-[(9,10-dihydro-4-hydroxy-2-methoxy-7-phenanthrenyl)oxy]-4,7-dihydroxy-2-methoxy-9,10-dihydrophenanthrene (2), trans-3,3'-dihydroxy-2',4',5-trimethoxystilbene (3), trans-3,4'-dihydroxy-2',3',5-trimethoxystilbene (4), trans-3,3'-dihydroxy-2',5-dimethoxystilbene (5), and trans-3-hydroxy-2',3',5-trimethoxystilbene (6) based on spectroscopic evidence. Furthermore, the inhibitory effects of compounds 1-6 on nitric oxide production in a murine macrophage-like cell line (RAW 264.7) activated by lipopolysaccharide and interferon-gamma were examined.     

Synthesis of new pyrimidine nucleoside derivatives with nitric oxide donors for antiviral activity

New pyrimidine nucleoside derivatives with nitric oxide(NO) donor were systematically synthesized.The antivirus activities of these nucleoside analogues against vesicular stomatitis virus(VSV) in Wish cell were evaluated.It was demonstrated that most of compounds had stronger antiviral acitivity than acyclovir,while their toxicities were similar or lower to acyclovir.     

Flavonoids from Daphne aurantiaca and their inhibitory activities against nitric oxide production

Chemical examination of the methanolic extract from the stem bark of Daphne aurantiaca led to the isolation of three new flavonoids (1-3), and 29 known flavonoids. All 32 compounds were isolated for the first time from Daphne aurantiaca. The isolates were tested for inhibitory activities against lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7 macrophages. Compounds 21 and 24 showed potent inhibitory activities against the production of NO with IC?? values of 0.006 and 0.076 μM, respectively.     

Electrochemical determination of nitric oxide and of its derivatives

Nitric oxide (NO) is one of the simplest odd electron species. Furthermore, it is relatively hydrophobic, which is consistent with its role as a diffusible intracellular messenger or as an immune effector. NO is generated in biological systems and plays important roles as a regulatory molecule. The main problem in NO analysis is its extreme reactivity; in aerated water solution it is transformed into nitrite and nitrate, inactive biological forms. Moreover, it may lose an electron forming the NO⁺ ion, involved in the synthesis of nitrosothiols (RSNOs). The main problems encountered in the analytical determination of free NO and of RSNOs in biological systems are the low stability and the very low concentration of these compounds. The determination of nitrates and nitrites may also be difficult when their concentration is in the nmolar range. We describe an electrochemical assay for the determination in the same sample of free NO and of its derivatives in nmolar range. Owing to its high sensitivity, the procedure could also be applied to environmental analyses     

Highly-oxygenated isopimarane-type diterpenes from Orthosiphon stamineus of Indonesia and their nitric oxide inhibitory activity

From the methanolic extract of Indonesian Orthosiphon stamineus, nine new highly-oxygenated isopimarane-type diterpenes [7-O-deacetylorthosiphol B (1), 6-hydroxyorthosiphol B (2), 3-O-deacetylorthosiphol I (3), 2-O-deacetylorthosiphol J (4), siphonols A-E (5-9)] have been isolated together with nine known diterpenes [orthosiphols H (10), K (11), M (12) and N (13); staminols A (14) and B (15); neoorthosiphols A (16) and B (17); norstaminol A (18)]. Their structures were determined based on the spectroscopic data. The isolated diterpenes inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-activated macrophage-like J774.1 cells. Compounds 4-7, 9, 10, 14, and 17 showed inhibitory activities more potent (IC(50), 10.8-25.5 microM) than a positive control N(G)-monomethyl-L-arginine (L-NMMA; IC(50), 26.0 microM).     

Chemical constituents from Curcuma longa L. and their inhibitory effects of nitric oxide production

A new bisabolane-type sesquiterpenoid, turmerone Q (1), along with six known compounds (2–7), were isolated from the rhizomes of Curcuma longa L. The structural elucidation of the new compound was conducted using ¹H NMR, ¹³C NMR, HSQC, HMBC and NOESY spectroscopic analyses. The absolute configuration of 1 was elucidated by comparison of the experimental and calculated ECD spectra. The anti-inflammatory effects of 1–7 were evaluated through lipopolysaccharide-induced nitric oxide (NO) production in RAW 264.7 macrophages assays, and compounds 6 and 7 showed potent inhibitory activity against NO production.     

An efficient synthesis of a potent anti-inflammatory agent, viscolin, and its inducible nitric oxide synthase inhibitory activity

A new and efficient synthetic pathway employed the aldol condensation between the acetophenone (3) and vanillin derivative (4) resulted in the precursor chalcone intermediate (14). The target compound viscolin (1) could be afforded through the hydrogenation of the chalcone and followed by deprotection. The present strategy described the development of a more efficient procedure that allowed large-scale production of viscolin for the further research of biological activity both in vitro and in vivo.     

Synthesis of novel methotrexate derivatives with inhibition activity of nitric oxide synthase

Seventeen 4-alkylamino/arylamino-substituted methotrexate(MTX)derivatives 6a-14a were designed and synthesized.Their inhibition activities against inducible nitric oxide synthase(iNOS)were evaluated in vitro.The pharmacological results showed that most of the prepared compounds displayed the potent inhibitory effects on iNOS.     

Measurement of nitric oxide production by the lesioned rat retina with a sensitive nitric oxide electrode

Nitric oxide (NO) plays multiple roles in the nervous system. It is produced as a result of damage or injury of the retina as a part of the central nervous system. Detailed knowledge of the extent and the time course of NO production is of great importance for the understanding of pathological processes and their appropriate medical treatment.Sections of rat retina were stained with antibodies against the three isoforms of NO synthase (NOS) at several time points after a lesion of the optic nerve. No significant changes of NOS expression could be seen at any of the checked time points.For the electrochemical detection of NO production, we modified small platinum electrodes with a NO-sensitive nickel porphyrin by electrochemical polymerisation. Compared to other substances, electrochemically polymerised eugenol was found to be most suitable for protection against interferences. For the measurements, differential pulse amperometry was used. The response to nitric oxide was linear.NO production of adult rat retinas was measured post axotomy after different time points with electrochemical electrodes ex vivo. With non-treated retinas, an NO concentration of approximately 15 M was measured. NO concentration is elevated after an axotomy reaching its highest value of up to 30 M 5 days after the lesion. The NO concentration is decreased below the initial value after 9–14 days post axotomy.     

Inhibition on HIV-1 integrase activity and nitric oxide production of compounds from Ficus glomerata

An ethanol Ficus glomerata wood extract and its purified components were investigated for their HIV-1 integrase (IN) and nitric oxide (NO) inhibitory activities. From bioassay-guided isolation, five compounds: beta-sitosterol-D-glucoside (1), aloe-emodin (2), genistein (3), 1,3,6-trihydroxy-8-methyl-anthraquinone (4) and 3-(1-C-beta-D-glucopyranosyl)-2,6-dihydroxy-5-methoxybenzoic acid (5) were isolated. Among the tested samples, at concentrations of 100 microM; compound 2 showed 31.9% inhibition of HIV-1 IN, followed by 4 (19.5%), whereas other compounds were inactive. With regard to the inhibitory effect on NO production, 3 possessed the highest activity with an IC50 value of 27.5 microM, followed by 4 (IC50 = 34.7 microM) and 2 (IC50 = 41.8 microM), respectively. This is the first time that compounds 2-5 have been isolated from Ficus glomerata.     

Synthesis, inhibitory effects on nitric oxide and structure-activity relationships of a glycosphingolipid from the marine sponge Aplysinella rhax and its analogues

The novel glycosphingolipid, β-D-GalNAcp(1-->4)[α-D-Fucp(1-->3)]-β-D-GlcNAcp(1-->)Cer (A), isolated from the marine sponge Aplysinella rhax has a unique structure, with D-fucose and N-acetyl-D-galactosamine moieties attached to a reducing-end N-acetyl-D-glucosamine through an α1-->3 and β1-->4 linkage, respectively. We synthesized glycolipid 1 and some non-natural di- and trisaccharide analogues 2-6 containing a D-fucose residue. Among these compounds, the natural type showed the most potent nitric oxide (NO) production inhibitory activity against LPS-induced J774.1 cells. Our results indicate that both the presence of a D-Fucα1-3GlcNAc-linkage and the ceramide aglycon portion are crucial for optimal NO inhibition.     

Ergosta-4,6,8(14),22-tetraen-3-one from Vietnamese Xylaria sp. possessing inhibitory activity of nitric oxide production

From the methanolic extract of Xylaria sp. collected in Vietnam, a fluorescent constituent, ergosta-4,6,8(14),22-tetraen-3-one (1) was isolated and elucidated by the combination of 2D NMR, high resolution MS, IR and UV spectroscopy. Its inhibitory activity of nitric oxide production in RAW 264.7 cells stimulated by lipopolysaccharide was examined and showed a potential activity with the IC(50) value of 28.96 microM.