Potent Hydroxyl Radical Scavenger Research Articles

Dietary plant flavonoid supplementation for poultry as a potent scavenger of hydroxyl radicals and antioxidants: a review

The poultry industry is paying more attention to plant-based feed additives. Flavonoids are plant secondary metabolites derived from fruits, grains, vegetables, herbs, and medicinal plants. One of the most significant environmental stressors affecting the poultry industry worldwide is heat stress, which lowers the quality and safety of production. An imbalance between the production of free radicals and the body’s natural antioxidant defenses leads to oxidative stress in cells. These reactive species can damage proteins, lipids, DNA, and cellular structures. Improving the antioxidant status of poultry bodies by feeding them antioxidant-supplemented feed can increase productivity and health. Plant flavonoid compounds have drawn attention from researchers as possible natural antioxidant sources because of their potential for use as feed additives in poultry production. Numerous studies have demonstrated that dietary flavonoids have strong antioxidant effects and can be utilized as a tonic in poultry to improve health and productivity. Overall, research on the antioxidant capacity of plant flavonoids has generally shown promising results; however, there are still significant issues regarding the detrimental effects of flavonoids to be resolved, and measuring oxidative damage in vivo is challenging. This review summarizes the current understanding of dietary plant flavonoid supplementation for poultry as a potent scavenger of hydroxyl radicals and antioxidants.

Nicaraven protects against endotoxemia-induced inflammation and organ injury through modulation of AMPK/Sirt1 signaling in macrophages

Endotoxemia is a disease characterized by systemic inflammatory responses and organ injury caused by lipopolysaccharide (LPS) infection, with high mortality. Nicaraven (AVS), a potent hydroxyl radical scavenger, has been proven to regulate the inflammatory response in tumors. To investigate the protective effects and mechanisms of AVS in endotoxemia, mice were injected intraperitoneally with LPS to induce endotoxemia. AVS treatment significantly decreased the levels of pro-inflammatory cytokines in the serum, reduced neutrophil infiltration, attenuated multiple organ injury, and increased the survival rate in LPS-challenged mice. In the LPS-induced inflammatory model of macrophages, AVS inhibited macrophage activation, suppressed nitric oxide (NO) production, and inhibited the expression and secretion of pro-inflammatory cytokines. Mechanistically, AVS treatment up-regulated silence information regulator transcript-1 (Sirt1) expression in a time- and dose-dependent manner. AVS treatment activated the AMP-dependent protein kinase (AMPK)/Sirt1 signaling pathway and suppressed the activation of nuclear factor kappa B (NF-κB) in macrophages exposed to LPS. However, the anti-inflammatory effects of AVS could be reversed by the AMPK, the Sirt1 inhibitor, or the histone deacetylase inhibitor. We confirmed that the AMPK inhibitor inhibited AVS-mediated AMPK/Sirt1 activation and NF-κB p65 acetylation. These results suggested that AVS alleviated endotoxemia by activating the AMPK/Sirt1 signaling pathway in macrophages.

Green synthesis of Ceriumoxide Nanoparticles using Bacopa monnieri Leaf Extract - In vitro A ntioxidant Activity

Objectives: Cerium oxide nanoparticles were synthesized by a rapid green method using an aqueous leaf extract of Bacopa monnieri to investigate its antioxidant activity. Methods: Cerium oxide nanoparticles (CeO2 NPs) were synthesized using Bacopa monnieri leaf extract as a stabilizing agent by solution combustion method. Characterization techniques like FTIR, PXRD,SEMEDAX, HR-TEM, UV-visible, and Raman spectroscopy confirmed the synthesized NPs. The antioxidant capacity was assessed by in vitro Hydroxyl radical scavenging assay. Findings: The biosynthesized CeO2 NPs possess tiny spherical shapes and sizes ranging from 5-50nm, and the average particle size is 27 nm as measured by HR-TEM. XRD and Raman confirm the nanoparticle’s polycrystalline nature and face-centered cubic fluorite structure with maximum UV-visible absorbance at l max 301.2nm. The biosynthesized CeO2 NPs exhibited better scavenging activity than Vitamin C. However, further in vitro and in vivo studies must be warranted to explore its mechanism and therapeutic potential. Novelty: To the best of our knowledge, this is the first report involving the green synthesis of cerium oxide nanoparticles using Bacopa monnieri leaf extract, which exhibited potent hydroxyl radical scavenging activity which can be a promising therapeutic candidate in oxidative stress-related disorders. Keywords: CeO2 NPs; Green synthesis; Bacopa monnieri; HR-TEM; Hydroxyl radical

Structural Characterization, Antioxidant and Antitumor Activities of the Two Novel Exopolysaccharides Produced by Debaryomyces hansenii DH-1.

Exopolysaccharides produced by edible microorganisms exhibit excellent constructive physicochemical and significant biological activity, which provide advantages for the food or pharmaceutical industries. Two novel exopolysaccharides produced by Debaryomyces hansenii DH-1 were characterized, named S1 and S2, respectively. S1, with a molecular weight of 34.594 kDa, primarily consisted of mannose and glucose in a molar ratio of 12.19:1.00, which contained a backbone fragment of α-D-Manp-(1→4)-α-D-Manp-(1→2)-α-D-Glcp-(1→3)-α-D-Manp-(1→3)-β-D-Glcp-(1→4)-β-D-Manp-(1→. S2, with a molecular weight of 24.657 kDa, was mainly composed of mannose and galactose in a molar ratio of 4.00:1.00, which had a backbone fragment of α-D-Manp-(1→6)-β-D-Manp-(1→2)-α-D-Manp-(1→4)-α-D-Galp-(1→3)-β-D-Manp-(1→6)-α-D-Manp-(1→. Both S1 and S2 exhibited good thermal stability and potent hydroxyl radical scavenging activity, with ~98%. Moreover, S1 possessed an additional strong iron-reducing capacity. In vitro antitumor assays showed that S1 and S2 significantly inhibited the proliferation of Hela, HepG2, and PC-9 cancer cells. Moreover, PC-9 was more sensitive to S1 compared with S2. The above results indicate that S1 and S2 have great potential to be utilized as natural antioxidants and candidates for cancer treatment in the food and pharmaceutical industries.

Synthesis and Antioxidant Properties of Novel 1,2,3-Triazole-Containing Nitrones.

Herein, we report the synthesis and antioxidant capacity of twelve novel 1,2,3-triazole-containing nitrones such as N-(2-(4-aryl-1H-1,2,3-triazol-1-yl)ethylidene)methanamine oxides 8a-f and N-(2-(4-aryl)-1H-1,2,3-triazol-1-yl)ethylidene)-2-methylpropan-2-amine oxides 9a-f, bearing an N-methyl, and an N-t-butyl substituent, respectively, at the nitrogen of the nitrone motif. Nitrones 8 and 9 were studied with regard to their antioxidant ability, as well as their ability to inhibit soybean lypoxygenase (LOX), and their in vitro antioxidant activity. For this, we used three different antioxidant assays, such as that featuring the interaction with the water-soluble azo compound AAPH for the inhibition of lipid peroxidation (LP), the competition with the DMSO for scavenging hydroxyl radicals, and the ABTS•+-decolorization assay. t-Butyl nitrone 9e, bearing the 2,4-difluorophenyl motif, showed a strong LP inhibitory effect (100%), close to the reference compound Trolox (93%), being the most potent LP inhibitor (LPi) of the whole series of tested nitrones. Nitrones 9d, 9e and 9f, bearing the 4-fluorophenyl, 2,4-difluorophenyl, and 4-fluoro-3-methylphenyl motif, respectively, were almost equipotent, and the most potent hydroxyl radical scavengers (~100%), more potent than Trolox (88%), were used as a reference compound. Regarding the LOX inhibition, the most potent inhibitor was the t-butyl substituted nitrone 9f (27 μM), bearing the 4-fluoro-3-methylphenyl motif, being 60-fold less potent than NDGA (0.45 μM), which was used as the standard in this test. The results from the antioxidant determination in the ABTS radical cation (ABTS•+) decolorization assay were not significant. N-Methyl nitrone 8f, bearing the 4-fluoro-3-methylphenyl motif, was the only promising representative, with a value of 34.3%, followed by nitrone 9f (16%). From the antioxidant analyses, we have identified N-(2-(4-(4-fluoro-3-methylphenyl)-1H-1,2,3-triazol-1-yl)ethylidene)-2-methylpropan-2-amine oxide (9f), bearing t-butyl and 4-fluoro-3-methylphenyl motifs in its structure, as the most balanced and potent antioxidant agent among the tested nitrones, as it was the most potent LOX inhibitor (27 μM), an extremely efficient and potent hydroxyl radical scavenger (99.9%), as well as one of the most potent LPi (87%) and ABTS•+ scavengers (16%).

Novel Peptide Sequences with ACE-Inhibitory and Antioxidant Activities Derived from the Heads and Bones of Hybrid Groupers (Epinephelus lanceolatus × Epinephelus fuscoguttatus).

The heads and bones of hybrid groupers are potential precursors for angiotensin-converting enzyme (ACE)-inhibitory and antioxidant peptides. The aim of this study was to isolate the dual-action peptides from the Alcalase-treated head and bone hydrolysate of hybrid groupers followed by identification of the novel peptides. The stability of these peptides against stimulated in vitro gastrointestinal digestion (SGID) was also determined. Fraction HB-IV (less than 1 kDa) obtained from ultrafiltration showed the strongest ACE-inhibition ability (IC50: 0.28 mg/mL), which was comparable to the potency of the commercial supplement, PeptACE (IC50: 0.22 mg/mL). This fraction also demonstrated the highest hydroxyl radical scavenging and metal-chelating activities. However, further fractionation of HB-IV by a series of chromatography resulted in peptide fractions of reduced ACE-inhibitory and antioxidant activities. The hydroxyl radical scavenging and reduction potential of HB-IV were enhanced, whereas ACE-inhibitory and metal-chelating activities were reduced following SGID. A total of 145 peptide sequences were identified from HB-IV, of which 137 peptides were novel to the BIOPEP database. The results suggested that the bioactive peptides isolated from the heads and bones of hybrid groupers could be used as functional foods/ingredients with potential ACE-inhibitory and antioxidant effects.

Antioxidant potentials of the pod extract of Caesalpinia pulcherrima Swartz (Fabeace) and the theoretical evaluation of the antioxidant property of the isolated compounds

Various diseases associated with oxidative stress have necessitated the need to investigate plants for antioxidant agents. This study aims to investigate the antioxidant potential of the extract and fractions of C. pulcherrima and estimate the quantum chemical properties of polyphenolic compounds isolated from its most active antioxidant fraction. Methanolic extract and partition fractions of the pods of the plant were assayed for their antioxidant activity using four models: 1,1-diphenyl-2-dipicrylhydrazyl radical scavenging, ferric reducing antioxidant power, total antioxidant capacity and hydroxyl radical scavenging activity. Total phenolic and flavonoid contents of the extract and fractions were also investigated. Furthermore, the quantum chemical properties of two polyphenolic compounds were calculated to predict the antioxidant potential. The extract exhibited good antioxidant activity with IC50 = 45.63 µg/ml comparable to ascorbic acid of IC50 = 37.94 µg/ml, high reducing power with value at 376.74 ± 6.78, total antioxidant capacity obtained at ascorbic acid equivalence of 383 ± 8.16 mgAAE/g and potent hydroxyl radical scavenging activity with value at 580.97 µg/ml with ascorbic acid at 30.7 µg/ml. The total phenol and flavonoid contents values at 540.53 ± 3.71 and 347.87 ± 7.13 respectively. Furthermore, the results obtained from the quantum chemical calculations reveals polyphenolic compounds; 5(4-hydroxyphenyl)-3-hydroxy-2-methoxyphenol and 3(4-methanetriiol-2,6-dihydroxyphenoxy)-3’, 4’, 5’, 5, 7-pentahydroxy flavonol as promising antioxidant agents. The study concluded that C. pulcherrima pods have good antioxidant activity. Also, the polyphenolic compounds are among the chemical constituents responsible for the antioxidant activity obtained for the extract and ethyl acetate fraction.

Pharmacological studies of Azadirachta indica leaves extracts

The present study was undertaken to explore the anticarcinogenic, anti-bacterial and anti-oxidant screening of the hydro-methanolic leaves extract of Azardirchta indica using mouse skin papilloma model, disc diffusion and DPPH methods. In phytochemical screening, Azardirchta indica extract showed presence of secondary metabolites such as carbohydrate, tannins etc. In anticarcinogenic studies, the Tumour incidence was 100% in control group which was reduced in treated group and remains 60.0%. in Control group the papilloma appeared early i.e on 5th week which was increased week wise and finally reaches upto 26 in numbers, whereas it was 9 on treated group by the same time. Results denote the anticarcinogenic, antibacterial and antioxidant activities of the Azardirchta indica leaves extracts. The Azardirchta indica leaves extracts possessed potent hydroxyl radical scavenging activity against the positive control Ascorbic acid. The antibacterial activities were also observed against the test organisms.

Antimicrobial Potential of Zinc Oxide Nanoparticles from Marine Macroalgae

Abstract: The current study evaluates the free antimicrobial and radical scavenging properties of zinc oxide nanoparticles(ZnONP’s) synthesized from an aqueous extract of Sargassum polycystum brown algae. The free radical scavenging potential of ZnO nanoparticles was evaluated through DPPH, Nitric oxide, Hydroxyl radical and Hydrogen peroxide scavenging assays. In addition to that, the antibacterial and antifungal activity of synthesized ZnO nanoparticles was examined against different species. The free radical scavenging and antimicrobial potential of these Sargassum polycystum ZnO nanoparticles were associated with their phenolic compounds. ZnO- NP’s DPPH radical reducing potential was found to be 12.45 ± 0.19μg/mL, Nitric oxide at 0.68±0.04 μg/ml, Hydrogen peroxide to be 0.39±0.01 μg/ml and Hydroxyl radical scavenging potential with 0.63±0.04 μg/ml. Furthermore, ZnO- NP’s antimicrobial efficacy showed significant results against Staphylococcus aureus, Escherichia coli, Salmonella typhi, Klebsiella pneumonia and fungal strains of A. niger Candida albicans. Further research is on purifying the selected phenolic compounds and developing their acuteness for specificity for ultimate pharmaceutical use. Keywords: Marine algae, ZnO nanoparticles, antioxidant and antimicrobial activity, Gulf of Mannar.

Nucleobase-Derived Nitrones: Synthesis and Antioxidant and Neuroprotective Activities in an In Vitro Model of Ischemia-Reperfusion.

Herein, we report the synthesis, antioxidant, and neuroprotective properties of some nucleobase-derived nitrones named 9a–i. The neuroprotective properties of nitrones, 9a–i, were measured against an oxygen-glucose-deprivation in vitro ischemia model using human neuroblastoma SH-SY5Y cells. Our results indicate that nitrones, 9a–i, have better neuroprotective and antioxidant properties than α-phenyl-N-tert-butylnitrone (PBN) and are similar to N-acetyl-L-cysteine (NAC), a well-known antioxidant and neuroprotective agent. The nitrones with the highest neuroprotective capacity were those containing purine nucleobases (nitrones 9f, g, B = adenine, theophylline), followed by nitrones with pyrimidine nucleobases with H or F substituents at the C5 position (nitrones 9a, c). All of these possess EC50 values in the range of 1–6 μM and maximal activities higher than 100%. However, the introduction of a methyl substituent (nitrone 9b, B = thymine) or hard halogen substituents such as Br and Cl (nitrones 9d, e, B = 5-Br and 5-Cl uracil, respectively) worsens the neuroprotective activity of the nitrone with uracil as the nucleobase (9a). The effects on overall metabolic cell capacity were confirmed by results on the high anti-necrotic (EC50′s ≈ 2–4 μM) and antioxidant (EC50′s ≈ 0.4–3.5 μM) activities of these compounds on superoxide radical production. In general, all tested nitrones were excellent inhibitors of superoxide radical production in cultured neuroblastoma cells, as well as potent hydroxyl radical scavengers that inhibit in vitro lipid peroxidation, particularly, 9c, f, g, presenting the highest lipoxygenase inhibitory activity among the tested nitrones. Finally, the introduction of two nitrone groups at 9a and 9d (bis-nitronas 9g, i) did not show better neuroprotective effects than their precursor mono-nitrones. These results led us to propose nitrones containing purine (9f, g) and pyrimidine (9a, c) nucleobases as potential therapeutic agents for the treatment of cerebral ischemia and/or neurodegenerative diseases, leading us to further investigate their effects using in vivo models of these pathologies.

In vitro Antioxidant and Free Radical Scavenging Activity of the Bark of Dillenia indica L.

The aim of the study was to explore the antioxidant and free radical scavenging activity of bark of Dillenia indica L. The methanolic extract (CME) of coarse powder of the dried bark was fractionated with pet-ether (PETF), chloroform (CHF), and water (AQF) and each fraction was investigated for antioxidant and free radical potentials. The phenolic contents of CME, CHF, PETF and AQF were found to be 90.2, 171.1, 52.1 and 158.1 and flavonoid contents 182.6, 340.2, 285.9, and 362.6 mg of GAE/g of dried extract, respectively. The total antioxidant activity of CME, PETF, CHF, AQF and standard catechin in terms of absorbance were 0.373, 0.707, 0.88, 1.051 and 0.804, respectively at 160 μg/ml concentration indicating AQF possessing the highest total antioxidant activity. In DPPH radical scavenging activity, the AQF and CHF showed potential radical scavenging activity followed by CME and PETF with IC50 values of 1.5, 2.5, 23 and 61 μg/ml, respectively, whereas standard ascorbic acid showed IC50 at 8 μg/ml. Among the extractives, AQF and CHF exhibited potent hydroxyl radical scavenging activity with IC50 values of 49.0 and 42 μg/ml followed by CME and PETF with IC50 of 86 and 168 μg/ml, respectively. In ferric-reducing antioxidant assay, AQF, CHF and CME (absorbance 2.262, 2.418 and 2.157, respectively) showed higher activity than that of standard (1.793) followed by PETF (absorbance 0.593). Since polyphenols like flavonoids play a vital role in controlling antioxidants, polyphenol rich extracts are potent source of antioxidants. Our data showed that the chloroform fraction of the bark of D. indica provided highest polyphenols and antioxidant activities, hence, can be used further as a source of natural antioxidants. Bangladesh Pharmaceutical Journal 25(1): 38-43, 2022 (January)

Hydroxyl radical scavenging potential of the late embryogenesis abundant proteins (LEA) proteins from Ramonda serbica – in silico approach

Hydroxyl radical scavenging potential of the late embryogenesis abundant proteins (LEA) proteins from Ramonda serbica – in silico approach

Antioxidant and anti-inflammatory activities of methanol and aqueous extracts of Sargassum wightii

Introduction: Antioxidants of natural sources for the treatment of many ailments have taken priority since the last decades. Recently, researches have been focused on marine algae as they are the largest reservoir of bioactive compounds. Hence, the objective of this study was to explore the in-vitro antioxidant and anti-inflammatory activities of methanolic and aqueous extracts of Sargassum wightii. Methods: The total phenolics, flavonoids, and ascorbic acid (AA) contents were evaluated informs of gallic acid equivalent (GAE), rutin equivalent (RUE), and AA equivalent, respectively. The aqueous and methanolic extracts were isolated. The antioxidant activities were explored using2,2-diphenyl-1-picrylhydrazil (DPPH), superoxide dismutase (SOD), hydroxyl radical scavenging, and ferric reducing power assays. The in vitro anti-inflammatory activity was assayed using nitric oxide radical scavenging, inhibition of protein denaturation, and antiproteinase activities. Results: We observed significant changes in DPPH scavenging activity with both methanolicSargassum extract (MSE) and aqueous Sargassum extract (ASE) [IC50: 511.15 µg/mL and 927.05µg/mL, respectively]. Methanolic extract showed a greater SOD scavenging activity [IC50: 369.56µg/mL] and hydroxyl radical scavenging potential [IC50: 668.93 µg/mL] than that of ASE [SOD,IC50: 923.94 µg/mL; hydroxyl ion, IC50: 953.57 µg/mL]. In the Ferric reducing antioxidant power assay, MSE and ASE exhibited absorbance of 0.93±0.12 and 0.59±0.08, respectively, at 1200 µg/mL each. Both methanol and ASEs showed NO– scavenging activity having IC50 in order, AA(96.46 µg/mL) <MSE (963.50 µg/mL) <ASE (1974.88 µg/mL). However, the protein denaturation inhibition and antiproteinase activity of both these extracts at 1000 µg/mL were similar. Conclusion: Sargassum wightii has promising antioxidant and anti-inflammatory activities and could be a potential candidate for drug development targeting oxidative stress-mediated inflammatory diseases.

Effect of Freeze-Thaw Treatment on<i> </i>Free Radical Scavenging and Linoleic Acid Reducing Potential of <i>Nelumbo nucifera </i>Rhizome Starch: Response-surface Optimization

Background/Objective: Repeated freezing and thawing results in the structural, compositional, and functional modifications in food materials. The present study was designed to optimize the effect of Freeze-thaw treatment (FTT) on free radical scavenging and linoleic acid reduction potentials of Nelumbo nucifera rhizome starch (NNRS). Methodology: A 4-factorial response-surface central composite design (CCD) based on three levels of each of the four input factors including freezing temperature (FT: -40, -20, and 0°C), freezing time (Ft: 24, 48, and 72 h), thawing time (Tt: 2, 4, and 6 h), and number of freeze-thaw cycles (FTC: 2, 4, and 6) was constructed. The NNRS was treated at different combinations of input variables as selected by CCD. The Freeze-thaw-treated N. nucifera rhizome starch (FTT-NNRS) was analyzed for antioxidant potential. Principle Findings: A statistically significant main effect (p=0.0017-0.0029) of FTT was observed on free radical scavenging and linoleic acid reducing potential (LARP) of NNRS. The 2, 2-diphenylpicrylhydrazyl (DPPH) radical scavenging potential was found to be a linear positive function of FT and Ft while hydroxyl radical scavenging potential showed a linear linear negative response towards FT and linear positive response towards FTC. The LARP also showed a linear positive response towards FT and Tt and quadratic positive response towards FT. Conclusion: FTT significantly affected the free radical scavenging potential and LARP of NNRS that may be attributed to the time-dependent variation in the structure of starch and exposure of some antioxidant residues after repeated freezing and thawing treatments.

Pharmacological studies of Mangifera indica leaf extract

The present study was undertaken to explore the phytochemical screening, anti-bacterial and anti-oxidant activities of the hydro-methanolic leaves extract of Mangifera indica using standard screening methods such as disc diffusion and DPPH methods. In phytochemical screening, Mangifera indicaextract showed presence of secondary metabolites such as carbohydrate, phenols, tanins and proteins whereas Saponins were absent. It also showed antibacterial activities against almost all the test organisms. The extracts possessed potent hydroxyl radical scavenging activity against the positive control standard Ascorbic acid. Results denote the presence of hydroxyl radical scavenging principles in the extracts.

Self-Organized Amphiphiles Are Poor Hydroxyl Radical Scavengers in Fast Photochemical Oxidation of Proteins Experiments.

Analysis of membrane protein topography using fast photochemical oxidation of proteins (FPOP) has been reported in recent years but is still underrepresented in literature. Based on the hydroxyl radical reactivity of lipids and other amphiphiles, it is believed that the membrane environment acts as a hydroxyl radical scavenger decreasing effective hydroxyl radical doses and resulting in less observed oxidation of proteins. We found no significant change in bulk solvent radical scavenging activity upon the addition of disrupted cellular membranes up to 25600 cells/μL using an inline radical dosimeter. We confirmed the nonscavenging nature of the membrane in bulk solution with the FPOP results of a soluble model protein in the presence of cell membranes, which showed no significant difference in oxidation with or without membranes. The use of detergents revealed that, while soluble detergent below the critical micelle concentration is a potent hydroxyl radical scavenger, additional detergent has little to no hydroxyl radical scavenging effect once the critical micelle concentration is reached. Examination of both an extracellular peptide of the integral membrane protein bacteriorhodopsin as well as a novel hydroxyl radical dosimeter tethered to a Triton X-series amphiphile indicate that proximity to the membrane surface greatly decreases reaction with hydroxyl radicals, even though the oxidation target is equally solvent accessible. These results suggest that the observed reduced oxidation of solvent-accessible surfaces of integral membrane proteins is due to the high local concentration of radical scavengers in the membrane or membrane mimetics competing for the local concentration of hydroxyl radicals.

Nicaraven inhibits TNFα-induced endothelial activation and inflammation through suppression of NF-κB signaling pathway.

Inflammation-induced activation and dysfunction of endothelial cells play an important role in the pathology of multiple vascular diseases. Nicaraven, a potent hydroxyl radical scavenger, has recently been found to have anti-inflammatory roles; however, the mechanism of its action is not fully understood. Here we investigated the effects of Nicaraven on tumor necrosis factor α (TNFα) - induced inflammatory response in human umbilical vein endothelial cells and we explore the underlying mechanisms related to the nuclear factor-κB (NF-κB) signaling pathway. Our results showed that Nicaraven significantly reduced the reactive oxygen species production after TNFα stimulation. Nicaraven suppressed TNFα-induced mRNA expression of multiple adhesion molecules and pro-inflammatory cytokines, including vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), E-selectin, MCP-1, TNFα, interleukin-1β (IL-1β), IL-6, and IL-8. In addition, Nicaraven inhibited monocyte adhesion and reduced the protein levels of VCAM-1 and ICAM-1. Mechanistically, Nicaraven prevented TNFα-induced activation of NF-κB signaling pathway by suppressing the phosphorylation of NF-κB p65, IκBα, and IκB kinase (IKK)α/β, stabilizing IκBα, and inhibiting the translocation of p65 from cytosol to nucleus. Finally, we showed that Nicaraven improved the functions of endothelial cells, seen as the upregulation of endothelial nitric oxide synthase and increased nitric oxide levels. Our findings indicated that Nicaraven effectively inhibits TNFα-induced endothelial activation and inflammatory response at least partly through inhibiting NF-κB signaling pathway.

Theoretical Study on the Antioxidant Activity of Natural Depsidones.

Depsidones are secondary metabolites in lichens with a range of potential health benefits. Among others, these compounds are believed to exhibit high hydroxyl radical and superoxide scavenging abilities, warranting a detailed investigation of their antioxidant properties. In this study, the radical scavenging activity of natural depsidones from Ramalina lichenized fungi was investigated in silico. Calculations of the thermodynamic parameters suggested that the main radical scavenging pathway follows the formal hydrogen transfer (FHT) mechanism; however, unexpectedly low rate constants were found in the CH3OO• scavenging reaction. Establishing that the depsidones are mostly ionized in an aqueous environment suggested that the single-electron transfer (SET) mechanism should not be ruled out. Consistently, depsidones were revealed to be excellent HO• and O2•– scavengers in aqueous solutions (k = 4.60 × 105 – 8.60 × 109 M–1 s–1 and k = 2.60 × 108 – 8.30 × 109 M–1 s–1, respectively) following the sequential proton loss electron transfer (SPLET) mechanism. These results suggest that natural fungal depsidones are potent hydroxyl and superoxide radical scavengers in aqueous solutions.

Synthesis and Biological Activities of Hydroxytyrosol Ester Derivatives

A series of hydroxytyrosol (HT) derivatives were synthesized by modification of alcohol hydroxyl group of HT, twenty-five target compounds were obtained and characterized by NMR and HRMS. The antioxidant activities of those compounds were evaluated in three different assays. Except 3e and 3y, all other compounds demonstrated significant 2,2and#39;-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) free radical cation scavenging activity ranging from IC50 3.4 to 24.4 μM, which were more potent than L-ascorbic acid (IC50=24.8 μM). Compounds 3b-3d, 3f-3k, 3m-3x were better than Trolox (18.3 M). Moreover, the ferric reducing antioxidant power (FRAP) of all compounds were discovered to be more potent than L-ascorbic acid (40.7 mmol/g), except 3e, all other compounds (141.5-202.1 mmol/g) were better than Trolox (94.7 mmol/g). Compounds 3a-3d, 3f-3j, 3l-3m, 3o, 3q, 3t, 3v-3y exhibited more potent hydroxyl radical scavenging activity (IC50=245.1-475.1 M) than L-ascorbic acid (554.4 M) and Trolox (500.4 M). Compounds 3q, 3t and 3y exhibited more potent -Glucosidase inhibition activity (39.1-52.4 M) than Acarbose (60.9 M). Compounds 3a, 3d, 3f-3m, 3s-3t, 3v-3y showed some acetylcholinesterase inhibition activities, compounds 3a, 3d, 3f-3j, 3l-3m, 3o-3p, 3s-3t, 3w showed some butyrylcholinesterase inhibition activities.

Synthesis and Biological Activities of Hydroxytyrosol Ester Derivatives

A series of hydroxytyrosol (HT) derivatives were synthesized by modification of alcohol hydroxyl group of HT, twenty-five target compounds were obtained and characterized by NMR and HRMS. The antioxidant activities of those compounds were evaluated in three different assays. Except 3e and 3y, all other compounds demonstrated significant 2,2and#39;-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) free radical cation scavenging activity ranging from IC50 3.4 to 24.4 μM, which were more potent than L-ascorbic acid (IC50=24.8 μM). Compounds 3b-3d, 3f-3k, 3m-3x were better than Trolox (18.3 M). Moreover, the ferric reducing antioxidant power (FRAP) of all compounds were discovered to be more potent than L-ascorbic acid (40.7 mmol/g), except 3e, all other compounds (141.5-202.1 mmol/g) were better than Trolox (94.7 mmol/g). Compounds 3a-3d, 3f-3j, 3l-3m, 3o, 3q, 3t, 3v-3y exhibited more potent hydroxyl radical scavenging activity (IC50=245.1-475.1 M) than L-ascorbic acid (554.4 M) and Trolox (500.4 M). Compounds 3q, 3t and 3y exhibited more potent -Glucosidase inhibition activity (39.1-52.4 M) than Acarbose (60.9 M). Compounds 3a, 3d, 3f-3m, 3s-3t, 3v-3y showed some acetylcholinesterase inhibition activities, compounds 3a, 3d, 3f-3j, 3l-3m, 3o-3p, 3s-3t, 3w showed some butyrylcholinesterase inhibition activities.