Bui Thi Thuy Luyen

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 asterosaponins from the starfish Astropecten monacanthus.

Four new asterosaponins, astrosteriosides A-D (1-3 and 5), and two known compounds, psilasteroside (4) and marthasteroside B (6), were isolated from the MeOH extract of the edible Vietnamese starfish Astropecten monacanthus. Their structures were elucidated by chemical and spectroscopic methods including FTICRMS and 1D and 2D NMR experiments. The effects of the extracts and isolated compounds on pro-inflammatory cytokines were evaluated by measuring the production of IL-12 p40, IL-6, and TNF-α in LPS-stimulated bone marrow-derived dendritic cells. Compounds 1, 5, and 6 exhibited potent anti-inflammatory activity comparable to that of the positive control. Further studies are required to confirm efficacy in vivo and the mechanism of effects. Such potent anti-inflammatory activities render compounds 1, 5, and 6 important materials for further applications including complementary inflammation remedies and/or functional foods and nutraceuticals.

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.

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.

Anti-Inflammatory Components of the Starfish Astropecten polyacanthus

Inflammation is important in biomedical research, because it plays a key role in inflammatory diseases including rheumatoid arthritis and other forms of arthritis, diabetes, heart disease, irritable bowel syndrome, Alzheimer’s disease, Parkinson’s disease, allergies, asthma, and even cancer. In the present study, we describe the inhibitory effect of crude extracts and steroids isolated from the starfish Astropecten polyacanthus on pro-inflammatory cytokine (Interleukin-12 (IL-12) p40, interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α)) production in lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells (BMDCs). Among those tested, compounds 5 and 7 showed potent inhibitory effects on the production of all three pro-inflammatory cytokines with IC50 values ranging from 1.82 ± 0.11 to 7.00 ± 0.16 μM. Potent inhibitory activities were also observed for compound 1 on the production of IL-12 p40 and IL-6 with values of 3.96 ± 0.12 and 4.07 ± 0.13 μM, respectively, and for compounds 3 and 4 on the production of IL-12 p40 with values of 6.55 ± 0.18 and 5.06 ± 0.16 μM, respectively. Moreover, compounds 2 (IC50 = 34.86 ± 0.31 μM) and 6 (IC50 = 79.05 ± 2.05 μM) exhibited moderate inhibitory effects on the production of IL-12 p40, whereas compounds 3 (IC50 = 22.80 ± 0.21 μM) and 4 (IC50 = 16.73 ± 0.25 μM) moderately inhibited the production of TNF-α and IL-6, respectively.

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.

Anti-Protozoal Activities of Cembrane-Type Diterpenes from Vietnamese Soft Corals

Based on our previous finding that certain cembranoid diterpenes possess selective toxicity against protozoan pathogens of tropical diseases such as Trypanosoma and Plasmodium, we have subjected a series of 34 cembranes isolated from soft corals living in the Vietnamese sea to an in vitro screening for anti-protozoal activity against Trypanosoma brucei rhodesiense (Tbr), T. cruzi (Tc), Leishmania donovani (Ld), and Plasmodium falciparum (Pf). Twelve of the tested compounds displayed significant activity against at least one of the parasites. Specifically, 7S,8S-epoxy-1,3,11-cembratriene-16-oic methyl ester (1), (1R,4R,2E,7E,11E)-cembra-2,7,11-trien-4-ol (2), crassumol D (12), crassumol E (13), and (1S,2E,4S,6E,8S,11S)-2,6,12(20)-cembrantriene-4,8,11-triol (16) from Lobophytum crassum, L. laevigatum, and Sinularia maxima showed the highest level of inhibitory activity against T. b. rhodesiense, with IC50 values of about 1 µM or less. Lobocrasol A (6) and lobocrasol C (8) from L. crassum and L. laevigatum exhibited particularly significant inhibitory effects on L. donovani with IC50 values < 0.2 µM. The best antiplasmodial effect was exerted by laevigatol A (10), with an IC50 value of about 3.0 µM. The cytotoxicity of the active compounds on L6 rat skeletal myoblast cell was also assessed and found to be insignificant in all cases. This is the first report on anti-protozoal activity of these compounds, and points out the potential of the soft corals in discovery of new anti-protozoal lead compounds.

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 2.0 μM, 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 2.0 μM, 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 (1 − 9) 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 4.4 μM, 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 13.0 μM. Compounds 1, 3, 5, 6, 8, and 9 exhibited dose‐dependent PPARα transactivational activity, with EC50 values in a range of 0.9 − 16.0 μM. 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 1.6 μM, whereas compounds 1, 8, and 9 demonstrated transactivational PPARβ(δ) effects with EC50 values of 11.4, 10.3, and 1.5 μM, 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

Secondary metabolites from Vietnamese marine invertebrates with activity against Trypanosoma brucei and T. cruzi.

Marine-derived natural products from invertebrates comprise an extremely diverse and promising source of the compounds from a wide variety of structural classes. This study describes the discovery of five marine natural products with activity against Trypanosoma species by natural product library screening using whole cell in vitro assays. We investigated the anti-trypanosomal activity of the extracts from the soft corals and echinoderms living in Vietnamese seas. Of the samples screened, the methanolic extracts of several marine organisms exhibited potent activities against cultures of Trypanosoma brucei and T. cruzi (EC50 < 5.0 μg/mL). Among the compounds isolated from these extracts, laevigatol B (1) from Lobophytum crassum and L. laevigatum, (24S)-ergost-4-ene-3-one (2) from Sinularia dissecta, astropectenol A (3) from Astropecten polyacanthus, and cholest-8-ene-3β,5α,6β,7α-tetraol (4) from Diadema savignyi showed inhibitory activity against T. brucei with EC50 values ranging from 1.57 ± 0.14 to 14.6 ± 1.36 μM, relative to the positive control, pentamidine (EC50 = 0.015 ± 0.003 μM). Laevigatol B (1) and 5α-cholest-8(14)-ene-3β,7α-diol (5) exhibited also significant inhibitory effects on T. cruzi. The cytotoxic activity of the pure compounds on mammalian cells was also assessed and found to be insignificant in all cases. This is the first report on the inhibitory effects of marine organisms collected in Vietnamese seas against Trypanosoma species responsible for neglected tropical diseases.