Nguyen Phuong Thao

Anti-inflammatory components of Euphorbia humifusa Willd.

Two new compounds, euphorbinoside (1) and dehydropicrorhiza acid methyl diester (2), along with 24 known compounds (3-26) were isolated from Euphorbia humifusa Willd. The effects of these compounds on soluble epoxide hydrolase (sEH) inhibitory activity were evaluated. Flavonoid compounds (10-21) exhibited high sEH inhibitory activity. Among them, compounds 12, 13, and 19 greatly inhibited sEH enzymatic activity, with IC50 values as low as 18.05±1.17, 18.64±1.83, and 17.23±0.84 μM, respectively. In addition, the effects of these compounds on lipopolysaccharide (LPS)-induced nitric oxide (NO) and tumor necrosis factor alpha (TNF-α) production by RAW 264.7 cells were investigated. Compounds 3-6, 8, 18, 20-23, and 25-26 inhibited the production of both NO and TNF-α, with IC50 values ranging from 11.1±0.9 to 45.3±1.6 μM and 14.4±0.5 to 44.5±1.2 μM, respectively.

Anti-inflammatory and PPAR transactivational effects of secondary metabolites from the roots of Asarum sieboldii

Phytochemical study on the roots of Asarum sieboldii resulted in the isolation of one new compound, (1R,2S,5R,6R)-5-O-methylpluviatilol (1) and 12 known compounds (2-13). Their structures were determined by extensive spectroscopic methods, including 1D and 2D NMR, and MS spectra. The absolute configuration of compound 1 was established using CD spectrum. Compounds 4, 5, and 12/13 significantly inhibited TNFα-induced NF-κB transcriptional activity in HepG2 cells in a dose-dependent manner, with IC(50) values ranging from 6.4 to 9.4 μM. Furthermore, the transcriptional inhibitory function of these compounds was confirmed based on decreases in COX-2 and iNOS gene expression in HepG2 cells. Compounds 1-3, 6,7, 10, and 11 significantly activated the transcriptional activity of PPARs in a dose-dependent manner, with EC(50) values ranging from 1.7 to 20.9 μM. Compounds 7, 10, and 11 exhibited significant dose-dependent PPARα transactivational activity, with EC(50) values of 19.5, 15.7, and 4.0 μM, respectively. Compounds 1, 6, 7, 10, and 11 activated PPARγ transcriptional activity, with EC(50) values ranging from 3.6 to 22.6 μM, whereas compounds 10 and 11 significantly increased PPARβ(δ) transactivational activity, with EC(50) values of 22.6 and 4.9 μM, respectively. These results provide a scientific support for the use of the roots of A. sieboldii and warrant further studies to develop new agents for the prevention and treatment of the inflammatory and metabolic diseases.

Anti-inflammatory components of Chrysanthemum indicum flowers

One new octulosonic acid derivative, chrysannol A (1), along with 17 known compounds (2-18), were isolated from Chrysanthemum indicum flowers. Their structures were determined from 1D NMR, 2D NMR, HR-ESI-MS spectral data, and comparisons with previous reports. The effects of these compounds on lipopolysaccharide (LPS)-induced nitric oxide (NO) and tumor necrosis factor alpha (TNF-α) production by RAW 264.7 cells were investigated. Compound 8 showed the highest inhibition of NO production of 46.09% at a concentration of 10.0μM. Compounds 7, 10, 11, and 16 inhibited TNF-α secretion at all concentration tested (0.4, 2.0, and 10.0μM), with inhibition values ranging from 22.27% to 33.13%. In addition, compound 8 and 9 decrease COX-2 and iNOS protein on Western blot analysis in dose dependent manner.

Anti-inflammatory norditerpenoids from the soft coral Sinularia maxima

Chemical investigation of the soft coral Sinularia maxima resulted in the isolation of seven norditerpenoids, including two new compounds, 12-hydroxy-scabrolide A (2) and 13-epi-scabrolide C (6). The structures of the isolated compounds were elucidated based on extensive spectroscopic evidence including Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) and both one- and two-dimensional nuclear magnetic resonance (1D and 2D NMR, respectively), in comparison with reported data. Compound 6 potently inhibited IL-12 and IL-6 production in LPS-stimulated bone marrow derived dendritic (BMDCs) with IC(50) values of 5.30 ± 0.21 and 13.12 ± 0.64 μM, respectively. Compound 1 exhibited moderate inhibitory activity against IL-12 and IL-6 production with IC(50) values of 23.52 ± 1.37 and 69.85 ± 4.11 μM, respectively.

Identification, characterization, kinetics, and molecular docking of flavonoid constituents from Archidendron clypearia (Jack.) Nielsen leaves and twigs.

In our search for natural soluble epoxide hydrolase (sEH) inhibitors from plants, we found that the methanolic extract of the leaves and twigs of Archidendron clypearia (Jack.) Nielsen (Fabaceae) significantly inhibits sEH in vitro. In a phytochemical investigation of the water layer of A. clypearia, we isolated two new chalcones, clypesides A-B (1-2), 13 flavonoid derivatives (3-15) and established their structures based on an extensive 1D and 2D NMR, CD data, and MS analysis. All of the flavonoid derivatives inhibited sEH enzymatic activity in a dose-dependent manner, with IC50 values ranging from 10.0±0.4 to 30.1±2.1μM. A kinetic analysis of compounds 4, 8-10, 12, 13, and 15 revealed that the compounds 8-10 were non-competitive, 4, 13, and 15 were mixed-type, and 12 was competitive inhibitors. Additionally, molecular docking increased our understanding of their receptor-ligand binding. These results demonstrated that flavonoid derivatives from A. clypearia are potential sEH inhibitors.

Rat intestinal sucrase inhibition of constituents from the roots of Rosa rugosa Thunb.

A new octanordammarane triterpene, 3β,15α-dihydroxymansumbinol (1) and a novel A-ring contracted oleanane triterpenoid, 2-formyl-(A)1-19α-hydroxy-1-norolean-2,12-dien-28-oic acid (2) were isolated from the roots extract of Rosa rugosa along with fifteen known compounds (3-17). Their structures were elucidated by extensive spectroscopic analysis, including 1D and 2D NMR, and FTICRMS. The MeOH extract, as well as CH2Cl2 and EtOAc fractions at a concentration of 0.5mg/mL showed potent sucrase inhibitory activity, with inhibition percentage values of 84.67±5.37%, 87.50±2.78%, and 81.91±2.90%, respectively. In addition, compounds 7-13 (1.0 mM) showed potent sucrase inhibitory activity (61.88±3.19% to 84.70±3.07% inhibition), which was comparable to that of the positive control, acarbose, with an inhibition percentage value of 50.96±2.97%. Compounds 1, 2, 4, and 14-17 showed moderate and/or weak inhibitory activities at the same concentration. The α-glucosidase inhibitory activities of the extracts and purified compounds may provide a novel opportunity to develop a new class of antidiabetic agents.

Pyrrole and furan oligoglycosides from the starfish Asterina batheri and their inhibitory effect on the production of pro-inflammatory cytokines in lipopolysaccharide-stimulated bone marrow-derived dendritic cells.

Three new pyrrole oligoglycosides, astebatheriosides A-C (1-3), and a new furan oligoglycoside, astebatherioside D (4), were isolated from the starfish Asterina batheri by various chromatographic methods. Their structures were elucidated by spectroscopic and chemical methods. Compounds 2, 3, and 4 moderately inhibited IL-12 p40 production in lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells (BMDCs) with IC50 values of 36.4, 31.6, and 22.8μM, respectively.

A New Phenolic Component from Triticum aestivum Sprouts and its Effects on LPS‐Stimulated Production of Nitric oxide and TNF‐α in RAW 264.7 Cells

An unusual new phenolic component, triticumoside (1), and eight known compounds, isoorientin (2), isoscoparin (3), (2R)‐2‐O‐β‐D‐glucopyranosyloxy‐4,7‐dimethoxy‐2H‐1,4‐benzoxazin‐3(4H)‐one (4), adenosine (5), β‐sitosterol (6), daucosterol (7), 6′‐O‐linolenoyl daucosterol (8), α‐tocopherol (9), were isolated from Triticum aestivum sprouts. The hybrid structure of 1, which is a hybrid between a flavone and a polyoxygenated benzene, is rarely found in natural sources. In addition, the effects of these compounds on LPS‐induced NO and TNF‐α production in RAW 264.7 cells were evaluated. At a concentration of 2.0u2009μM, compounds 2–4 significantly inhibited the production of both NO and TNF‐α. Compound 1 exhibited inhibitory activity on the secretion of TNF‐α at concentrations as low as 2.0u2009μM, but it did not reduce NO levels at any of the tested concentrations. Copyright

Anti‐Inflammatory and PPAR Transactivational Properties of Flavonoids from the Roots of Sophora flavescens

Anti‐inflammatory and peroxisome proliferator‐activated receptors (PPARs) transactivational effects of nine compounds (1u2009−u20099) from the roots of Sophora flavescens were evaluated using NF‐κB‐luciferase, reverse transcriptase polymerase chain reaction, peroxisome proliferator response element (PPRE)‐luciferase, and GAL‐4‐PPAR chimera assays. Compounds 4 and 8 significantly inhibited TNFα‐induced NF‐κB transcriptional activity in HepG2 cells in a dose‐dependent manner, with IC50 values of 4.0 and 4.4u2009μM, respectively. Furthermore, the transcriptional inhibitory function of these compounds was confirmed by a decrease in cyclooxgenase 2 and inducible nitric oxide synthase gene expression levels in HepG2 cells. Compounds 1, 3, 5, 6, 8, and 9 significantly activated the transcription of PPARs in a dose‐dependent manner, with EC50 values ranging from 1.1 to 13.0u2009μM. Compounds 1, 3, 5, 6, 8, and 9 exhibited dose‐dependent PPARα transactivational activity, with EC50 values in a range of 0.9u2009−u200916.0u2009μM. Compounds 1, 3, 8, and 9 also significantly upregulated PPARγ activity in a dose‐dependent manner, with EC50 values of 10.5, 6.6, 15.7, and 1.6u2009μM, whereas compounds 1, 8, and 9 demonstrated transactivational PPARβ(δ) effects with EC50 values of 11.4, 10.3, and 1.5u2009μM, respectively. These results provide a scientific rationale for the use of the roots of S. flavescens and warrant further studies to develop new agents for the prevention and treatment of inflammatory and metabolic diseases. Copyright

Effect of triterpenes and triterpene saponins from the stem bark of Kalopanax pictus on the transactivational activities of three PPAR subtypes.

Kalopanax pictus (Araliaceae) is a deciduous tree that grows in East Asian countries. Its stem bark and leaves have been used in traditional medicine to treat rheumatic arthritis, neurotic pain, and diabetes mellitus. A phytochemical study on a methanol extract of the stem bark of K. pictus resulted in the isolation of three new compounds, 6β,16α-dihydroxy-hederagenin 3-O-β-D-glucuronopyranoside (1), 3-O-β-D-glucuronopyranosyl-28-O-β-D-glucopyranosyl-6β,16α-dihydroxy-oleanolic acid (2), and 3-O-β-D-galactopyranosyl(1→3)-α-L-arabinopyranosyl hederagenin 28-O-β-D-glucopyranosyl-(1→6)-β-D-glucopyranosyl ester (3), along with eight known compounds (4-11). Their structures were established on the basis of chemical and spectroscopic methods (IR, 1D and 2D NMR, and HRESITOFMS). Compounds 1-6 and 8-10 upregulated PPARs transcriptional activity in a dose-dependent manner in HepG2 cells, with EC(50) values in the range 0.20-15.5 μM. Moreover, the specific PPAR transactivational effects of compounds 1-6 and 8-10 on separate PPAR subtypes, PPARα, -γ, and -β(δ) were further investigated. Compounds 4, 5, 8, and 10 showed significant PPARα transactivational activity, with EC(50) values of 7.8, 8.0, 10.3, and 17.3 μM, respectively. Compounds 2, 4, 6, and 8-10 exhibited PPARγ dose-dependent transactivational activity, with EC(50) values of 14.7, 15.5, 14.8, 10.9, 17.1, and 16.3 μM, whereas compounds 8 and 10 significantly upregulated PPARβ(δ) transcriptional activity, with EC(50) values of 15.7 and 17.7 μM, respectively.