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.     

New sesquiterpenes from Inula japonica Thunb. with their inhibitory activities against LPS-induced NO production in RAW264.7 macrophages

Twenty-two new sesquiterpenes were isolated from the aerial parts of Inula japonica Thunb., together with fifteen known ones. Their structures were determined by detailed spectroscopic analysis, X-ray diffraction studies, and modified Mosher method. All 37 compounds were evaluated for the inhibition of LPS-induced nitric oxide (NO) production in RAW264.7 macrophages, and most of isolates significantly inhibited the NO production with IC₅₀ values in the range of 3.5-20 μM. Besides, results obtained in our studies provided a structure-activity relationship that would be used to design anti-inflammatory agents in the future.     

Chemical constituents from the bark of bauhinia purpurea and their NO inhibitory activities

Abstract

Phytochemical studies led to the isolation of a new phenylpropanoid glucoside, named purpuroside (1), along with eight known compounds (2–9) from the bark of Bauhinia purpurea. The structure of the new compound was elucidated on the basis of its spectroscopic data. The absolute configuration of compound 2 was verified by X-ray diffraction analysis. Compounds 1, 2, 7, 8, and 9 inhibited NO production in mouse peritoneal macrophages with IC₅₀ values from 35.5 to 63.0?μM.     

A new guaianolide from the roots of Pterocypsela elata

In order to find more biologically active substances,we have carefully investigated the chemical constituents of Pterocypsela elata.One new guaianolide,(4S)-11-methoxycarbonyl-guaiane- 1(10),5(6),7(11),8(9)-tetraen-6,l2-olide was isolated from the EtOAc extracts of the roots of P.elata. Its structure was elucidated by various spectroscopic methods and confirmed by X-ray crystallographic analysis.     

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.     

Chemical constituents from Gueldenstaedtia verna and their anti-inflammatory activity

A new triterpenoid glycoside (1) and 15 known compounds (2–16) were isolated from the whole plants of Gueldenstaedtia verna. The new compound (1) was identified as complogenin 22-O-β-d-glucopyranoside by extensive spectroscopic techniques including 1D (¹H and ¹³C) and 2D NMR experiments (HSQC, HMBC and NOESY), HR-DART-MS and chemical methods. Most of the isolates were evaluated for their inhibitory activities on LPS-induced NO production in RAW 264.7 cells. The inhibitory effects of the active compounds, sulphuretin (8) and (22E,24S)-5α,8α-epidioxy-24-methyl-cholesta-6,9(11),22-trien-3β-ol (13), on the production of pro-inflammatory mediators (including IL-6, IL1β and PGE₂) were further estimated in vitro by ELISA in RAW 264.7 macrophages.     

Synthesis and NO production inhibition of novel Mannich base derivatives of irisolidone

Five new C-8 Mannich base derivatives of irisolidone 2a-2e were synthesized and their nitric oxide（NO）production inhibitory activity was evaluated.Compounds 2a,2b,2c and 2e displayed stronger activities in vitro than the parent compound irisolidone.     

Sesquiterpenes from an Egyptian herbal medicine, Pulicaria undulate, with inhibitory effects on nitric oxide production in RAW264.7 macrophage cells

The methylene chloride-methanol (1?:?1) extract from the air-dried aerial parts of wild Pulicaria undulata collected in North Sinia, Egypt, showed inhibitory effects on lipopolysaccharide (LPS)-induced production of nitric oxide (NO) in RAW264.7 macrophages. From the extract, three new sesquiterpenes named 5α-hydroperoxyivalin, 8-epi-xanthanol, and 8-epi-isoxanthanol were isolated together with four known sesquiterpenes. The structure of each new sesquiterpenes was determined on the basis of physicochemical and chemical evidence. In addition, all the sesquiterpenoids significantly inhibited the production of NO. Ivalin (IC50=2.0?μM) and 2α-hydroxyalantolactone (1.8?μM) showed particularly strong inhibitory effects, but had strong cytotoxic effects as well. Furthermore, ivalin and 2α-hydroxyalantolactone concentration-dependently reduced inducible NO synthase (iNOS) protein levels in RAW264.7 cells.     

Panos-Fermented Extract-Mediated Nanoemulsion: Preparation,Characterization, and In Vitro Anti-Inflammatory Effects on RAW 264.7 Cells

This study focused on developing Panos nanoemulsion (P-NE) and enhancing the anti-inflammatory efficacy for the treatment of inflammation. The effects of P-NE were evaluated in terms of Nitric oxide (NO production) in Lipopolysaccharide (LPS), induced RAW 264.7 cells, Reactive oxygen species (ROS) generation using Human Keratinocyte cells (HaCaT), and quantitative polymerase chain reaction (qPCR) analysis. Sea buckthorn oil, Tween 80, and span 80 were used and optimize the process. Panos extract (P-Ext) was prepared using the fermentation process. Further high-energy ultra-sonication was used for the preparation of P-NE. The developed nanoemulsion (NE) was characterized using different analytical methods. Field emission transmission electron microscopy (FE-TEM) analyzed the spherical shape and morphology. In addition, stability was analyzed by Dynamic light scattering (DLS) analysis, where particle size was analyzed 83 nm, and Zeta potential −28.20 ± 2 (mV). Furthermore, 90 days of stability was tested using different temperatures conditions where excellent stability was observed. P-NE are non-toxic in (HaCaT), and RAW264.7 cells up to 100 µg/mL further showed effects on ROS and NO production of the cells at 50 µg/mL. The qPCR analysis demonstrated the suppression of pro-inflammatory mediators for (Cox 2, IL-6, IL-1β, and TNF-α, NF-κB, Ikkα, and iNOS) gene expression. The prepared NE exhibited anti-inflammatory effects, demonstrating its potential as a safe and non-toxic nanomedicine.     

A new diarylheptanoid and a new diarylheptanoid glycoside isolated from the roots of Juglans mandshurica and their anti-inflammatory activities

A new diarylheptanoid, (2S,3S,5S)-2,3,5-trihydroxy-1,7-bis(4-hydroxy- 3-methoxyphenyl)heptane (1), and a new diarylheptanoid glycoside, (2S,3S,5S)-2,3-dihydroxy-5-O-β-d-xylopyranosyl-7-(4-hydroxy-3-methoxyphenyl)-1-(4-hydroxyphenyl)heptane (2), together with three known compounds, rhoiptelol C (3), rhoiptelol B (4) and 3′,4″-epoxy-2-O-β-d-glucopyanosyl-1-(4-hydroxyphenyl)- 7-(3-methoxyphenyl)heptan-3-one (5) were isolated from the roots of Juglans mandshurica (Juglandaceae). The structures of compounds 1 and 2 were identified based on HR-ESI-MS, 1D and 2D NMR spectroscopic methods. Compounds 1–5 were assayed for their inhibitory effects on the production of NO, TNF-α and IL-6 in LPS-stimulated RAW264.7 cells.     

Chemical constituents from the rhizomes of Polygonatum sibiricum Red. and anti-inflammatory activity in RAW264.7 macrophage cells

Chemical investigation of the rhizomes of Polygonatum sibiricum Red. led to the identification of 27 constituents. Among them, a total of 16 compounds were obtained from Polygonatum for the first time, in which, 3 and 4 were also firstly isolated as natural products. Anti-inflammatory activity studies on 13 isolated compounds showed that β-carboline constituents, especially compounds 1 and 2, significantly inhibited the expression of NO, TNF-α, IL-6 and IL-1β in lipopolysaccharide (LPS)-treated RAW264.7 macrophage cells. Moreover, western blotting analysis demonstrated that compound 1 significantly inhibited the expression of COX-2, iNOS and the activation of NF-κB, suggesting that β-carboline structures may play an important role in inhibition of NF-κB signaling pathway, which thereby inhibits the production of inflammatory factors. The present research may not only help further elucidation of the anti-inflammatory mechanism of P. sibiricum Red., but also provide the potential bioactive molecules for inflammatory diseases research.     

Inhibitory effects of constituents from Euphorbia lunulata on differentiation of 3T3-L1 cells and nitric oxide production in RAW264.7 cells

A new flavonol galactopyranoside, myricetin 3-O-(2',3'-digalloyl)-β-D-galactopyranoide (1), and 23 known constituents, including myricetin 3-O-(2'-galloyl)-β-D-galactopyranoide (2), myricitrin (3), myricetin (4), quercetin 3-O-(2', 3'-digalloyl)-β-D-galactopyranoide (5), quercetin 3-O-(2'-galloyl)-β-D-galactopyranoide (6), hyperin (7), isoquercetrin (8), quercetin (9), kaempferol (10), apigenin (11), luteolin (12), 3-O-methylquercetin (13), 5,7,2',5'-tetrahydroxyflavone (14), 1,3,4,6-tetra-O-galloyl-β-D-glucose (15), 1,2,6-tri-O-galloyl-β-D-glucose (16), 1,3,6-tri-O-galloyl-β-D-glucose (17), gallic acid (18), protocatechuic acid (19), 3,4,5-trimethoxybenzoic acid (20), 2,6-dihydroxyacetophenone (21), 3,3'-di-O-methylellagic acid (22), ellagic acid (23) and esculetin (24) were isolated from Euphorbia lunulata Bge. Their structures were determined by spectroscopic analysis. Isolated hydrolysable tannins, flavonoids, and flavonol galactopyranoside gallates showed significant inhibition of the differentiation of 3T3-L1 preadipocytes and triglyceride accumulation in maturing adipocytes, and nitric oxide production in RAW 264.7 cells.     

New Benzil and Isoflavone Derivatives with Cytotoxic and NO Production Inhibitory Activities from Placolobium vietnamense

The phytochemical investigation of Placolobium vietnamense stems led to the isolation of a new isoflavone derivative (1) and three new benzil derivatives (2–4), together with four known pyranoisoflavones (5–8). The structures of all isolated compounds were determined on the basis of extensive spectroscopic analyses, including NMR and HRMS spectral data, as well as comparison of their spectroscopic data with those reported in the literature. The cytotoxicity of all isolated compounds was assessed against the human liver hepatocellular carcinoma (Hep G2) cell line, and compound 1 displayed the most significant cytotoxicity with an IC₅₀ value of 8.0 μM. Furthermore, all isolated compounds were also tested for their inhibitory activity against NO production in RAW 264.7 macrophages. Of these, compound 1 exhibited the strongest inhibitory efficacy against the LPS-induced NO production with the IC₅₀ value of 13.7 μM.     

Neolignans from the Fruits of Magnolia obovata Inhibit NO Production and Have Neuroprotective Effects

One new sesquineolignan, obovatalignan A ( 1 ), and one new neolignan, obovatalignan B ( 2 ), were isolated from the Magnolia obovata fruits. Their chemical structure, including absolute configuration, was determined based on various spectroscopic methods, such as HR‐EI‐MS, 1D‐NMR (¹H, ¹³C, DEPT), 2D‐NMR (gCOSY, gHSQC, gHMBC, NOESY), and CD spectroscopy. The compounds were evaluated for protective effects against glutamate‐induced oxidative stress in HT22‐immortalized hippocampal cells and inhibitory activity against NO production in LPS‐induced RAW 264.7 cells. Compounds 1 and 2 exhibited protective effects against glutamate‐induced oxidative stress with EC₅₀ values of 18.1 ± 1.23 and 7.10 ± 0.78 μm , respectively, as well as inhibitory effects on NO production with IC₅₀ values of > 30.0 and 8.22 ± 2.01 μm , respectively.     

Inhibitory effects of constituents from Morus alba var. multicaulis on differentiation of 3T3-L1 cells and nitric oxide production in RAW264.7 cells

A new arylbenzofuran, 3',5'-dihydroxy-6-methoxy-7-prenyl-2-arylbenzofuran (1), and 25 known compounds, including moracin R (2), moracin C (3), moracin O (4), moracin P (5), artoindonesianin O (6), moracin D (7), alabafuran A (8), mulberrofuran L (9), mulberrofuran Y (10), kuwanon A (11), kuwanon C (12), kuwanon T (13), morusin (14), kuwanon E (15), sanggenon F (16), betulinic acid (17), uvaol (18), ursolic acid (19), β-sitosterol (20), oxyresveratrol 2-O-β-D-glucopyranoside (21), mulberroside A (22), mulberroside B (23), 5,7-dihydroxycoumarin 7-O-β-D-glucopyranoside (24), 5,7-dihydroxycoumarin 7-O-β-D-apiofuranosyl-(1→6)-O-β-D-glucopyranoside (25) and adenosine (26), were isolated from Morus alba var. multicaulis Perro. (Moraceae). Their structures were determined by spectroscopic methods. The prenyl-flavonoids 11-14, 16, triterpenoids 17,18 and 20 showed significant inhibitory activity towards the differentiation of 3T3-L1 adipocytes. The arylbenzofurans 1-10 and prenyl-flavonoids 11-16 also showed significant nitric oxide (NO) production inhibitory effects in RAW264.7 cells.     

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.     

Triterpene saponins with XOD inhibitory activity from the roots of Ilex pubescens

A new triterpene saponin with 28-nor-urs-12(13),18(17)-dien-3β-ol as aglycone,named ilexsaponin C(1) was isolated from the roots of Ilex pubescens,together with three known saponins 2,3 and 4.The structure of 1 was elucidated on the basis of spectral analysis including 1D and 2D NMR and HR-ESI-MS.Saponins 1 and 4 exhibited significant XOD inhibitory activity in the test.     

Investigation on the effects of diamide on NO production in vascular endothelial cells (VEC)

Nitric oxide (NO) controls several physiological functions of the cardiovascular system. The study on the effect of diamide (N₂H₄·H₂O) on NO production in vascular endothelial cells (VEC) may provide significant reference for VEC’s modeling in studying cardiovascular diseases. The objective of this study was to elucidate how high concentration diamide (V_diamide/V_{culture miedium}=5 ml/l) and low concentration diamide (V_diamide/V_{culture miedium}=0.5 ml/l) affect NO production in a human endothelial cell line (ECV304). After cells were incubated with diamide (5 or 0.5 ml/l) for 4, 6, 8 or 10 h, respectively, the amounts of NO metabolites released by the cells were quantitated and the degree of damage of VEC was observed using microscope. The results showed that NO production in VEC tended to decrease with the lapse of time in the 0.5 ml/l diamide group. In the 5 ml/l diamide group, on the contrary, NO production in VEC tended to increase with the lapse of time. At the same time, from the morphologic observation, the VEC were damaged severely after treated with 5ml/l diamide. So it could be concluded that the severe damage induced by high concentration diamide would have triggered the express of inducible nitric oxide synthases (iNOS). Just for the expresssion of iNOS, NO production in VEC treated with high concentration diamide occurred abnormally in contrast to the 0.5 ml/l group.     

一氧化氮对ACC 氧化酶活性的抑制动力学研究

NO可以通过其辅因子氧化灭活作用抑制ACC氧化酶(ACO)活性,从而降低乙烯释放速率。本文主要研究了NO对ACO抑制作用的化学动力学,揭示了NO对ACO活性的抑制机理。NO溶液与ACC氧化酶的最佳反应时间是30min,底物ACC的最佳浓度为2mmol/L,作为酶促反应的辅因子,抗坏血酸钠和Fe2+的最适浓度分别为60mmol/L和60μmol/L,碳酸氢钠的最适浓度为60mmol/L。Lineweaver-Burk图显示NO是一种非竞争性抑制剂。NO与ACO反应的米氏常数Km为2.54mmol/L,抑制常数Ki为3.22μmol/L。