Meso-Dihydroguaiaretic Acid Ameliorates Acute Respiratory Distress Syndrome through Inhibiting Neutrophilic Inflammation and Scavenging Free Radical

The pathogenesis of acute respiratory distress syndrome (ARDS) is very complex. Patients with ARDS still suffer high mortality rates. Infiltration and activation of neutrophils in lungs are critical pathogenic factors in ARDS. In this study, we demonstrate that meso-dihydroguaiaretic acid (MDGA), a natural lignan, inhibits inflammatory responses in human neutrophils and ameliorates ARDS in mice. MDGA inhibited superoxide anion generation and elastase release in various G-protein coupled receptor agonists-induced human neutrophils. However, MDGA did not alter superoxide anion generation and elastase activity in cell-free systems. These results suggest that the anti-inflammatory effects of MDGA are mediated by regulating cellular signals in human neutrophils. In consistent with this, MDGA suppressed phosphorylation of extracellular signal-regulated kinase and c-Jun N-terminal kinase in activated human neutrophils. Moreover, MDGA inhibited CD11b expression and adhesion in activated human neutrophils. Interestingly, MDGA reduced reactive oxygen species (ROS) generation but not superoxide anion generation in protein kinase C (PKC) activator-induced human neutrophils, suggesting that MDGA may also have ROS scavenging ability. Indeed, MDGA showed strong free radical scavenging activity in cell-free assays. Significantly, MDGA suppressed PKC-induced neutrophil extracellular trap formation. Additionally, treatment of MDGA attenuated neutrophil infiltration and lung damage on lipopolysaccharide-induced ARDS in mice. In conclusion, our results demonstrate that MDGA has anti-neutrophilic inflammatory effects and free-radical scavenging activity. We also suggest that MDGA has potential to serve as a lead for developing new therapeutics to treat ARDS.

Constituents from the Fruiting Bodies of Trametes cubensis and Trametes suaveolens in Vietnam and Their Anti-Inflammatory Bioactivity

It is reported that various fungi have been used for medicine and edible foods. The tropical Trametes genus is popular and well-known in Vietnam for its health effects and bioactivities. In this study, the fruiting bodies of the edible fungi T. cubensis and T. suaveolens were collected in Vietnam. The preliminary bioactivity screening data indicated that the methanol extracts of the fruiting bodies of T. cubensis and T. suaveolens displayed significant inhibition of superoxide anion generation and elastase release in human neutrophils. Therefore, the isolation and characterization were performed on these two species by a combination of chromatographic methods and spectrometric analysis. In total, twenty-four compounds were identified, and among these (1–3) were characterized by 1D-, 2D-NMR, and HRMS analytical data. In addition, the anti-inflammatory potentials of some purified compounds were examined by the cellular model for the inhibition of superoxide anion generation and elastase release in human neutrophils. Among the isolated compounds, (5,14), and (19) displayed significant anti-inflammatory potential. As the results suggest, the extracts and isolated compounds from T. cubensis and T. suaveolens are potential candidates for the further development of new anti-inflammatory lead drugs or natural healthy foods.

An Anti-Inflammatory 2,4-Cyclized-3,4-Secospongian Diterpenoid and Furanoterpene-Related Metabolites of a Marine Sponge Spongia sp. from the Red Sea

Chemical investigation of a Red Sea Spongia sp. led to the isolation of four new compounds, i.e., 17-dehydroxysponalactone (1), a carboxylic acid, spongiafuranic acid A (2), one hydroxamic acid, spongiafuranohydroxamic acid A (3), and a furanyl trinorsesterpenoid 16-epi-irciformonin G (4), along with three known metabolites (−)-sponalisolide B (5), 18-nor- 3,17-dihydroxy-spongia-3,13(16),14-trien-2-one (6), and cholesta-7-ene-3β,5α-diol-6-one (7). The biosynthetic pathway for the molecular skeleton of 1 and related compounds was postulated for the first time. Anti-inflammatory activity of these metabolites to inhibit superoxide anion generation and elastase release in N-formyl-methionyl-leucyl phenylalanine/cytochalasin B (fMLF/CB)-induced human neutrophil cells and cytotoxicity of these compounds toward three cancer cell lines and one human dermal fibroblast cell line were assayed. Compound 1 was found to significantly reduce the superoxide anion generation and elastase release at a concentration of 10 μM, and compound 5 was also found to display strong inhibitory activity against superoxide anion generation at the same concentration. Due to the noncytotoxic activity and the potent inhibitory effect toward the superoxide anion generation and elastase release, 1 and 5 can be considered to be promising anti-inflammatory agents.

Anti-Inflammatory Cembranoids from a Formosa Soft Coral Sarcophyton cherbonnieri

The present investigation on chemical constituents of the soft coral Sarcophyton cherbonnieri resulted in the isolation of seven new cembranoids, cherbonolides F–L (1–7). The chemical structures of 1–7 were determined by spectroscopic methods, including infrared, one- and two-dimensional (1D and 2D) NMR (COSY, HSQC, HMBC, and NOESY), MS experiments, and a chemical reduction of hydroperoxide by triphenylphosphine. The anti-inflammatory activities of 1–7 against neutrophil proinflammatory responses were evaluated by measuring their inhibitory ability toward N-formyl-methionyl-leucyl-phenylalanine/cytochalasin B (fMLF/CB)-induced superoxide anion generation and elastase release in primary human neutrophils. The results showed that all isolates exhibited moderate activities, while cherbonolide G (2) and cherbonolide H (3) displayed a more active effect than others on the inhibition of elastase release (48.2% ± 6.2%) and superoxide anion generation (44.5% ± 4.6%) at 30 µM, respectively.

The Molecular and Functional Characterization of the Durum Wheat Lipoxygenase TdLOX2 Suggests Its Role in Hyperosmotic Stress Response

In plants, lipoxygenases (LOXs) are involved in various processes, such as growth, development, and response to stress cues. In the present study, the expression pattern of six durum wheat LOX-encoding genes (TdLpx-B1.1, TdLpx-B1.2, TdLpx-A2, TdLpx-B2, TdLpx-A3 and TdLpx-B3) under hyperosmotic stress was investigated. With osmotic (0.42 M mannitol) and salt (0.21 M NaCl) stress imposed at the early stages of seedling growth, a strong induction of the TdLpx-A2 gene expression in the shoots paralleled an equally strong increase in the LOX activity. Enhanced levels of malondialdehyde (MDA) and increased rates of superoxide anion generation were also observed as a result of the stress imposition. Sequence analysis of the TdLOX2 encoded by the TdLpx-A2 gene revealed that it belonged to the type-1 9-LOX group. When overexpressed in E. coli, TdLOX2 exhibited normal enzyme activity, high sensitivity to specific LOX inhibitors, with 76% and 99% inhibition by salicylhydroxamic and propyl gallate, respectively, and a preference for linoleic acid as substrate, which was converted exclusively to its corresponding 13-hydroperoxide. This unexpected positional specificity could be related to the unusual TV/K motif that in TdLOX2 replaces the canonical TV/R motif of 9-LOXs. Treatment of seedlings with propyl gallate strongly suppressed the increase in LOX activity induced by the hyperosmotic stress; the MDA accumulation was also reduced but less markedly, whereas the rate of superoxide anion generation was even more increased. Overall, our findings suggest that the up-regulation of the TdLpx-A2 gene is a component of the durum wheat response to hyperosmotic stress and that TdLOX2 may act by counteracting the excessive generation of harmful reactive oxygen species responsible for the oxidative damages that occur in plants under stress.

Phytochemical Investigation and Anti-Inflammatory Activity of the Leaves of Machilus japonica var. kusanoi

In a series of anti-inflammatory screenings of lauraceous plants, the methanolic extract of the leaves of Machilus japonica var. kusanoi (Hayata) J.C. Liao showed potent inhibition on both superoxide anion generation and elastase release in human neutrophils. Bioassay-guided fractionation of the leaves of M. japonica var. kusanoi led to the isolation of twenty compounds, including six new butanolides, machinolides A–F (1–6), and fourteen known compounds (7–20). Their structures were characterized by 1D and 2D NMR, UV, IR, CD, and MS data. The absolute configuration of the new compounds were unambiguously confirmed by single-crystal X-ray diffraction analyses (1, 2, and 3) and Mosher’s method (4, 5, and 6). In addition, lignans, (+)-eudesmin (11), (+)-methylpiperitol (12), (+)-pinoresinol (13), and (+)-galbelgin (16) exhibited inhibitory effects on N-formyl-methionyl-leucyl-phenylalanine/cytochalasin B (fMLP/CB)-induced superoxide anion generation in human neutrophils with IC50 values of 8.71 ± 0.74 μM, 2.23 ± 0.92 μM, 6.81 ± 1.07 μM, and 7.15 ± 2.26 μM, respectively. The results revealed the anti-inflammatory potentials of Formosan Machilus japonica var. kusanoi.

THE EFFECT OF PROPARGYLGLYCINE ON THE ENDOTHELIUM-DEPENDENT RELAXATION AND ACTIVITY OF MAIN SOURCES OF SUPEROXIDE ANION GENERATION DURING AGING

The objective of the present study was to investigate the effect of propargylglycine (PAG), an inhibitor of the CSE-dependent pathway of hydrogensulfide synthesis, on the endotheliumdependent relaxation of aortic smooth muscle (SM) in old rats. It was found a violation of SM relaxation in this group of animals. The average value of its amplitude was 7.5 ± 1.4% compared with 64.9 ± 3.5% in healthy adult rats. PAG significantly improved endothelium-dependent relaxation in old rats, the average value of its amplitude increased from 7.5 ± 1.4% to 44,5 ± 3,2%. This effect was due to suppression of superoxide anion generation by inhibition of xanthineoxidase activity.

1H NMR-Based Isolation of Anti-Inflammatory 9,11-Secosteroids from the Octocoral Sinularia leptoclados

Octocoral Sinularia leptoclados has been identified as a source of bioactive 9,11-secosteroids. This study adopted a targeted isolation approach to the discovery and analysis of five 9,11-secosteroids, including two novel compounds named sinleptosterols A (1) and B (2) as well as five known analogues (8αH-3β,11-dihydroxy-24-methylene-9,11-secocholest-5-en-9-one (3), 8βH-3β,11-dihydroxy-24-methylene-9,11-secocholest-5-en-9-one (4), leptosterol A (5), (24S)-3β,11-dihydroxy-24-methyl-9,11-secocholest-5-en-9-one (6), and 3β,11-dihydroxy-9,11-secogorgost-5-en-9-one (7)) in terms of 1H-NMR patterns and potency against neutrophilic inflammation. The structure of secosteroids 1 and 2 was deduced from general spectroscopic analysis and an examination of NMR spectra. Among the above-mentioned isolates, compound 4 had the most pronounced effect in inhibiting elastase release and superoxide anion generation, with the IC50 values of 2.96 and 1.63 μM, respectively.