Inhibition Of Peroxidation Research Articles

Visible light-promoted, catalyst-free synthesis of isoniazid azomethines: In vitro antioxidant activity, molecular docking, ADME and toxicity prediction

Green synthesis of biologically active molecules is essential for environmental sustainability, resource efficiency, reduced environmental impact, and compliance with regulations. It ensures a safer working environment, and fosters innovation in sustainable chemistry practices. In this context, we introduce an electron donor-acceptor (EDA)-mediated visible light-promoted, catalyst-free (VLCF) scalable synthesis of isoniazid azomethines. This synthesis encompasses the drug salizide and its analogues, which were subsequently evaluated for their antioxidant activities. Isoniazid azomethines 3e demonstrated superior activity compared to salizide and ascorbic acid, with an IC50 of 0.078 mg/mL in the hydrogen peroxide antioxidant assay. Specifically, 3e exhibited greater antioxidant properties (79.02 %) than isoniazid azomethine 3b (75.82 %), isoniazid azomethine 3d (62.2 %), isoniazid azomethine 3c (59.86 %), and isoniazid azomethine 3a (54.62 %). In the superoxide dismutase antioxidant assay, 3e was also identified as the most active, with a SOD activity level of 650 U/mg of protein, surpassing other compounds (3a-d) with SOD activity levels of 330, 560, 350, and 420 U/mg of protein, respectively. Molecular docking against horseradish peroxidase (1W4Y) showed compound 3e with the best binding energy (-6.561 kcal/mol), forming key hydrogen bonds (Asn135, Pro139) and a π-cation interaction with Arg38. These interactions suggest 3e may effectively inhibit hydrogen peroxide catalysis. The in silico assessment of the physicochemical properties, pharmacokinetics, and toxicology of synthesized compounds suggests that these compounds exhibit promising ADMET characteristics, with no identified toxicological concerns.

Deep eutectic solvent strategy for green extraction of chlorogenic acid from sea buckthorn: optimization and sustainability

BackgroundSea buckthorn (Hippophae rhamnoides), a deciduous species plant, is widely distributed around the globe, and native to the cold-temperate regions of Europe and Asia. This medicinal herb contains several bioactive constituents including chlorogenic acid. The conventional methods used for the extraction of phenolic antioxidants from natural herbs often result in low yields, high toxicity, and pose environmental hazards limiting their effectiveness and scalability. Therefore, green extraction techniques using deep eutectic solvents, composed of natural, non-toxic, and biodegradable components were applied for extraction of chlorogenic acid from sea buckthorn weed. Fourteen deep eutectic solvent mixtures were prepared and evaluated for extraction yield of chlorogenic acid. Parameters such as hydrogen bond donor-to-hydrogen bond acceptor ratio, liquid-to-solid ratio, shaking speed, and shaking time were optimized for the best mixture.ResultsThe combination of lactic acid and maltose (1:1) was found to give best extraction yield using response surface methodology. The deep eutectic solvent system under optimum conditions produced 12.2 g/100 g of crude extract sea buckthorn containing 174.7 mg gallic acid equivalents (mg GA)/g) of extract. Moreover, the optimized extract exhibited appreciable radical scavenging capacity (91%), trolox equivalent antioxidant capacity (11.2% of extract), and inhibition of peroxide in linoleic acid (80.6%). High-performance liquid chromatography-based characterization revealed the extracts contained chlorogenic acid (20.1 mg/g of extract) as the major constituent.ConclusionsIn summary, the adoption of DES for the extraction of bioactive phenolic constituents from sea buckthorn offers multiple benefits, including economic efficiency, enhanced extraction performance, and environmental sustainability. The findings of this study not only advance the understanding of DES in phytochemical extraction but also pave the way for broader application of green solvents in the natural products industry. Future research should focus on further optimizing DES formulations and scaling up the extraction process to fully realize the potential of this innovative extraction method in commercial applications.

Silencing of cysteine and serine rich nuclear protein 1 inhibits apoptosis, senescence and collagen degradation in human-derived vaginal fibroblasts in response to oxidative stress or DNA damage

Pelvic organ prolapse (POP) is a group of diseases caused by extracellular matrix (ECM) degradation in pelvic supportive tissues. Cysteine and serine rich nuclear protein 1 (CSRNP1) is involved in cell proliferation and survival regulation, and reportedly facilitates collagen breakdown in human chondrocytes. The present study aimed to probe the effect of CSRNP1 on collagen metabolism in human-derived vaginal fibroblasts. High expression of CSRNP1 was found in POP patient-derived vaginal fibroblasts in comparison to normal-derived vaginal fibroblasts. Following functional experiments revealed that CSRNP1 overexpression led to proliferation inhibition, apoptosis and collagen degradation in normal vaginal fibroblasts. In line with this, silencing of CSRNP1 inhibited hydrogen peroxide (H2O2)-triggered apoptosis, ROS generation and collagen loss in normal vaginal fibroblasts. Silencing of CSRNP1 also reduced the expression of cell senescence markers p21 and γ-H2Ax (the histone H2Ax phosphorylated at Ser139), as well as curbed collagen breakdown in normal vaginal fibroblasts caused by a DNA damage agent etoposide. Transcriptomic analysis of vaginal fibroblasts showed that differentially expressed genes affected by CSRNP1 overexpression were mainly enriched in the Wnt signaling pathway. Treatment with a Wnt pathway inhibitor DKK1 blocked CSRNP1 knockdown-caused collagen deposition. Mechanistically, CSRNP1 was identified to be a target of Snail family transcriptional repressor 2 (SNAI2). Forced expression of CSRNP1 reversed the anti-apoptotic, anti-senescent and anti-collagen loss effects of SNAI2 in normal vaginal fibroblasts exposed to H2O2 or etoposide. Our study indicates that the SNAI2/CSRNP1 axis may be a key driver in POP progression, which provides a potential therapeutic strategy for POP.

Monoclinic α-Bi2O3 nanorods by microwave-assisted synthesis: Photocatalytic and antioxidant properties

Nanotechnology has emerged as a new route for addressing most environmental and medical challenges, hence this field of research continues to generate research interest. Herein, Bi2O3 was synthesized by a microwave-assisted thermal process. X-ray diffraction (XRD) result confirmed that a nanocrystalline monoclinic crystal structure of the α-phase was formed, and both the Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM) analysis confirmed that the synthesized α-Bi2O3 were rod-like in shape. The length of the nanorods was in the range of 60–160 nm, with an average dimension of 101.5 nm, while the width has an average value of 23 nm. A band gap energy value of 2.75 eV was obtained from the absorption spectroscopy, and they absorbed light in the UV to visible range, with an absorption maximum of around 345 nm. Photocatalytic activity of the nanorods under UV irradiation was investigated by assessing the degradation of Bromocresol green (BG) as a model pollutant. The degradation process of the dye molecules was studied at different concentrations (20–80 mg/L), varied photocatalyst dosage (0.025, 0.05, 0.075, and 1.0 g), and a range of solution pH (3, 6, 9, and 12). About 75 % optimum photocatalytic efficiency was achieved at pH 6 after 3 h. In addition, the results showed that an increase in catalyst dosage and concentration of dye molecules contributed to promoting the degradation effect. Moreover, the photocatalyst was found to be stable after 4 consecutive cycles, with negligible loss of efficiency. The antioxidant potency of the nanorods was assessed by evaluating their free radical scavenging capabilities across 4 different assays: 1,1-diphenyl-2-picrylhydrazyle (DPPH), Nitric oxide (NO), Hydrogen peroxide (HP) radical inhibition, and Reducing power (RP). The results from the IC50 values indicated the sample exhibited better inhibition of HP (25.22 µg/mL), followed by RP (28.22 µg/mL), NO (29.37 µg/mL), and DPPH (32.72 µg/mL) respectively. However, the standard Ascorbic acid exhibited IC50 values of 16.25, 24.50, 25.07, and 28.40 µg/mL for DPPH, RP, HP, and NO, respectively. These unique properties of the nanorods showed that they have good antioxidant potential that is comparable with that of Ascorbic acid used as the standard.

Antioxidant and antimicrobial activities of mango peel and radish peel-a comparative investigation

The present study investigated the antioxidant and antimicrobial activities of Bao mango and daikon radish peel (Thai variety) ethanolic extracts. The percentage extraction yield of radish peel was higher compared to the mango peel (p < 0.05). However, Mango peel extract (MPE) contained higher total phenolic content (TPC) than radish peel extract (RPE) (p < 0.05). Similar to the TPC value, antioxidant activities including DPPH radical scavenging activity, reducing power, and peroxidation inhibition were higher in the MPE, compared to the RPE, except for metal chelating activity. The antimicrobial analyses suggested that the MPE showed lower minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values compared to the RPE (p < 0.05) against Gram-positive and Gram-negative bacteria. High-performance liquid chromatography (HPLC) revealed that mangiferin was the major phenolic compound present in MPE, followed by 3, 4 dihydroxybenzoic acid. Therefore, MP could be used as a promising natural antioxidant and antimicrobial agent for food applications.

Exploring the multifaceted effects of Ammi visnaga: subchronic toxicity, antioxidant capacity, immunomodulatory, and anti-inflammatory activities

ABSTRACT Ammi visnaga (A. visnaga) is an annual herb that has been used in traditional medicine to treat various ailments attributed to the presence of its bioactive compounds. The purpose of this study was to identify and examine the phytochemical properties of the hydroalcoholic extract of A. visnaga using in vitro and in vivo models. Our findings demonstrated that the extract contained a variety of beneficial components, including phenols, flavonoids, tannins, coumarins, saponins, khellin, and visnagin. The total polyphenolic content and total flavonoid content were 23.26 mg/GAE/g dry weight and 13.26 mg/GAE/g dry weight, respectively. In vitro tests demonstrated that the extract possessed antioxidant properties as evidenced by the ability to scavenge free radicals, including DPPH, ABTS, nitric oxide (NO), phosphomolybdate, and ferric-reducing antioxidant power (FRAP). Further, the extract was found to inhibit hydrogen peroxide (H2O2)-induced hemolysis. In a 90-d in vivo study, female Wistar rats were administered 1 g/kg of A. visnaga extract orally resulting in a significant increase in total white blood cell count. Although morphological changes were observed in the liver, no marked alterations were noted in kidneys and spleen. In a female Swiss albino mice model of acetic acid-induced vascular permeability, A. visnaga significantly inhibited extravasations of Evans blue at doses of 0.5 or 1 g/kg with inhibition percentages of 51 and 65%, respectively, blocking tissue necrosis. The extract also demonstrated potential immunomodulatory properties in mice by enhancing antibody production in response to antigens. In silico molecular docking studies demonstrated a strong affinity between khellin or visnagin and immunomodulatory proteins, NF-κB, p52, and TNF-α. These findings suggest that A. visnaga may be considered a beneficial antioxidant with immunomodulatory properties and might serve as a therapeutic agent to combat certain diseases.

Anthocyanins Inhibits Oxidative Injury in Human Retinal Pigment Epithelial ARPE-19 Cells via Activating Heme Oxygenase-1.

Anthocyanins belong to phenolic pigments and are known to have various pharmacological activities. This study aimed to investigate whether anthocyanins could inhibit hydrogen peroxide (H2O2)-induced oxidative damage in human retinal pigment epithelial ARPE-19 cells. Our results indicated that anthocyanins suppressed H2O2-induced genotoxicity, while inhibiting reactive oxygen species (ROS) production and preserving diminished glutathione. Anthocyanins also suppressed H2O2-induced apoptosis by reversing the Bcl-2/Bax ratio and inhibiting caspase-3 activation. Additionally, anthocyanins attenuated the release of cytochrome c into the cytosol, which was achieved by interfering with mitochondrial membrane disruption. Moreover, anthocyanins increased the expression of heme oxygenase-1 (HO-1) as well as its activity, which was correlated with the phosphorylation and nuclear translocation of nuclear factor-erythroid-2 related factor 2 (Nrf2). However, the cytoprotective and anti-apoptotic effects of anthocyanins were significantly attenuated by the HO-1 inhibitor, demonstrating that anthocyanins promoted Nrf2-induced HO-1 activity to prevent ARPE-19 cells from oxidative stress. Therefore, our findings suggest that anthocyanins, as Nrf2 activators, have potent ROS scavenging activity and may have the potential to protect ocular injury caused by oxidative stress.

Hydrogen sulfide delays postharvest ripening of white fleshed strawberry by regulating phytohormone accumulation and ROS generation

The white fleshed strawberry cultivar ‘Snow Princess’ of Fragaria ananassa, known for its unique flavor and visual appeal, is highly regarded worldwide. However, the inherent presence of endogenous phytohormones and reactive oxygen species accelerate the postharvest ripening process, leading to a shorter shelf life. Despite extensive research on the ability of hydrogen sulfide (H2S) to delay fruit ripening and senescence, its potential application to white fleshed strawberries remains unexplored. In this study, the effects of sodium hydrosulfide (NaHS) and hypotaurine on regulating postharvest ripening in white-fleshed strawberries (cv. ‘Snow Princess’) were evaluated. The findings revealed that NaHS treatment delayed weight loss, preserved sensory characteristics, and decreased the decay index, with an optimal NaHS concentration of 1.5 mM. Further research indicated that H2S synthesis gene expression was enhanced, and H2S synthesis enzyme activity was increased in the NaHS treatment group, leading to endogenous H2S accumulation. Furthermore, NaHS treatment repressed ethylene production and reduced respiratory rate. Concurrently, NaHS treatment increased alternative oxidase activity and decreased abscisic acid level, resulting in inhibited hydrogen peroxide and malondialdehyde generation. Ultimately, NaHS treatment delayed postharvest ripening of ‘Snow Princess’ strawberries, resulting in increased levels of total soluble solids, titratable acid, and total flavonoid. These findings underscore the potential of NaHS for prolonging the shelf life of white fleshed strawberries and offer insight into the role of H2S in postharvest strawberries.

S-nitroso-glutathione (GSNO) inhibits hydrogen peroxide production by alpha-ketoglutarate dehydrogenase: An investigation into sex and diet effects.

Pyruvate dehydrogenase (PDH) and α-ketoglutarate dehydrogenase (KGDH) are vital sources of hydrogen peroxide (H2O2) and key sites for redox regulation. Here, we report KGDH is more sensitive to inhibition by S-nitroso-glutathione (GSNO) when compared to PDH and deactivation of both enzymes by nitro modification is affected by sex and diet. Liver mitochondria from male C57BL/6N mice displayed a robust inhibition of H2O2 production after exposure to 500-2000μM GSNO. H2O2 genesis by PDH was not significantly affected by GSNO. Purified KGDH of porcine heart origin displayed a ∼82% decrease in H2O2 generating activity at 500μM GSNO, which was mirrored by a decrease in NADH production. By contrast, H2O2- and NADH-producing activity of purified PDH was only minimally affected by an incubation in 500μM GSNO. Incubations in GSNO had no significant effect on the H2O2-generating activity of KGDH and PDH in female liver mitochondria when compared to samples collected from males, which was attributed to higher GSNO reductase (GSNOR) activity. High fat feeding augmented the GSNO-mediated inhibition of KGDH in liver mitochondria from male mice. Exposure of male mice to a HFD also resulted in a significant decrease in the GSNO-mediated inhibition of H2O2 genesis by PDH, an effect not observed in mice fed a control-matched diet (CD). Female mice displayed higher resistance to the GSNO-induced inhibition of H2O2 production, regardless of being fed a CD or HFD. However, exposure to a HFD did result in a small but significant decrease in H2O2 production by KGDH and PDH when female liver mitochondria were treated with GSNO. Although, the effect was less when compared to their male counterparts. Collectively, we show for the first time GSNO deactivates H2O2 production by α-keto acid dehydrogenases and we demonstrate that sex and diet are determinants for the nitro-inhibition of both KGDH and PDH.

Selenium nanoparticles reduce oxidative stress-induced cardiomyocyte apoptosis in ascites syndrome in broiler chickens via the ATF6-DR5 signaling pathway

Broiler ascites syndrome (AS) is one of the main diseases threatening the health of broilers. It is well documented that myocardial hypertrophy and failure is one of the key mechanisms of broiler ascites syndrome. Therefore, prevention of cardiac hypertrophy and failure would be one goal to reduce broiler ascites syndrome incidence. Myocardial hypertrophy and failure are closely related to endoplasmic reticulum stress (ERS) in cardiac myocytes, and the endoplasmic reticulum stress signaling system (ATF6-DR5) is one of the important pathways of myocardial apoptosis. Excessive hypertrophy will affect the heart muscle’s normal contraction and diastole function, and the heart will turn from compensated to decompensate thus causing myocardial injury. Myocardial apoptosis is a core component of the pathological changes of this myocardial injury. Nano-selenium is a kind of red elemental selenium nanoparticle. Due to its excellent physical, chemical and biological properties, it has attracted extensive academic attention in recent years. It has been proven to have excellent antioxidant, antibacterial, antitumor, antihypertrophic, and antiapoptotic abilities. Herein, nano-selenium (1 µmol/L) can inhibit hydrogen peroxide (H2O2)-induced oxidative stress in broiler primary cardiomyocytes, and at the same time reduce cardiomyocyte apoptosis. In vivo, nano-selenium can reduce broiler myocardial injury-related enzyme indicators (AST, CK and LDH), and alleviate myocardial injury. It can also activate the antioxidant enzyme system (SOD, GSH-Px and CAT) and reduce MDA, and make the recovery of T-AOC ability in the organization. Meanwhile, nano-selenium can down-regulate the genes and proteins expression of ATF-6, GRP-78, CHOP and caspase 12 in the ERS-related signaling pathway, and inhibit that of downstream-related caspase 3, Bax and caspase 9, and increase that of the downstream anti-apoptotic Bcl-2, thereby maintaining the homeostasis of the endoplasmic reticulum and alleviating cardiomyocyte apoptosis. It can be seen that nano-selenium can protect the damaged myocardium in the broiler ascites caused by high-salt drinking by regulating the ATF6-DR5 signaling pathway. This study was performed in chickens and cardiomyocyte cells and attempted to demonstrate that selenium nanoparticles can protect the damaged myocardium in broiler ascites. This paper provides a new idea for preventing and treating broiler ascites syndrome.

Antioxidant Activities of Plant Extracts (Ammannia multiflora, Ammannia coccinea, and Salix gracilistyla) Activate the Nrf2/HO-1 Signaling Pathway

To identify potent plant extracts with strong antioxidant activity, we evaluated the free radical scavenging activity of 184 plant extracts obtained from the Freshwater Bioresources Culture Collection (FBCC) of Nakdonggang National Institute of Biological Resources (Republic of Korea), as various plant extracts have been used therapeutically to prevent chronic diseases associated with oxidative stress. From them, three plant extracts (FBCC-EP858 from Ammannia multiflora, FBCC-EP920 from Ammannia coccinea, and FBCC-EP1014 from Salix gracilistyla) were selected based on their abilities to scavenge the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical with more than 80% efficiency. We found that these extracts had in vitro half maximal inhibitory concentration (IC50) values ranging from 11.89 to 14.26 μg/mL and strong total antioxidant activity (corresponding to approximately 0.18, 0.22, and 0.23 mM Trolox, respectively). We also studied the effect of these extracts on RAW 264.7 macrophages and found that FBCC-EP920 significantly downregulated relative cell viability at a concentration of 100 μg/mL. However, the other two extracts, FBCC-EP858 and FBCC-EP1014, did not affect cell viability at the same concentration. Additionally, all three extracts inhibited hydrogen peroxide (H2O2)-induced reactive oxygen species (ROS) production and depolarization of mitochondrial membrane potential in RAW 264.7 macrophages. An additional experiment in zebrafish larvae showed that the three extracts reduced 2′,7′-dichlorodihydrofluorescein diacetate (DCFDA) fluorescent intensity induced by H2O2. The extracts also upregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression, and an HO-1 inhibitor, zinc protoporphyrin (ZnPP), attenuated the extract-induced antioxidant activity both in vivo and in vitro. Taken together, these findings suggest that the extracts from A. multiflora, A. coccinea, and S. gracilistyla have potential free radical scavenging and antioxidant capacities both in vivo and in vitro by activating the Nrf2/HO-1 signaling pathway. These results could be useful for the prevention and treatment of various oxidative stress-mediated human diseases.

Actividad biológica de los aceites de semillas de Annona muricata y A. cherimola

Vegetable extracts have become important raw materials for food, pharmaceutical and cosmetic industries because of their biological potential. The objective of this study was toassess the biological activity of vegetable oils (VOs) extracted from Annona muricata and A. cherimola. Antibacterial activity was determined by plaque microdilution. The assessment of hemolytic inhibition and morphological alterations was performed in erythrocyte cultures by spectrophotometry and microscopy, respectively. Neutrophils were used to analyze both cytotoxicity by the trypan blue exclusion method and the effect on gelatinase granule release (MMP9) via zymography. Whereas VOs showed a mild antibacterial activity (900 μL/mL) on five ATCC bacterial strains, they had no effect on multi-resistant bacteria. In addition, VOs inhibited hydrogen peroxide induced hemolysis and did not cause erythrocyte cell abnormalities. Cytotoxicity was not detected in neutrophils and VOs were able to stimulate MMP9 release. These results support their potential use by the food and cosmetic industries due to their antioxidant, non-cytotoxic, and slight antibacterial capacities

In Vitro Modulation of Genotoxicity and Oxidative Stress by Polyphenol-Rich Fraction of Chinese Ladder Brake (Pteris vittata L.).

Pteris vittata L. is a terrestrial genus growing in moist, shady forests and on hillsides. The plant has considerable ethnomedicinal importance. Investigations have been carried out on chemical profiling and antioxidant compounds from some genera of pteridophytes but studies on the biological properties of P. vittata are lacking. Therefore, the present study investigates antioxidant, antigenotoxic, and antiproliferative potential of the aqueous fraction of P. vittata (PWE). A battery of assays were carried out to assess the antioxidant potential of the PWE. SOS chromotest and DNA nicking assay were used to evaluate the antigenotoxicity of the fraction. The cytotoxic effect of PWE was analyzed using MTT and Neutral Single Cell Gel Electrophoresis comet assay. EC50 of 90.188µg/ml, 80.13µg/ml, 142.836µg/ml, and 12.274µg/ml was obtained in DPPH, superoxide anion scavenging, reducing power and lipid peroxidation assays, respectively. PWE was potent in inhibiting Fenton's reagent-induced nicking of pBR322 plasmid. The fraction significantly inhibited hydrogen peroxide (H2O2) and 4-nitroquinoline-N-oxide (4NQO) induced mutagenicity and a reduction in induction factor was found with increased PWE concentration. GI50 of 147.16µg/ml was obtained in MTT assay in human MCF-7 breast cancer cell line. PWE induced apoptosis as confirmed from confocal microscopy studies. The protective effects can be attributed to the presence of the phytochemicals in PWE. These results will be helpful in the development of functional food characteristics, as well as unravel the benefits of pteridophytes as promoters of health.

Biochemical Profile and In Vitro Therapeutic Properties of Two Euhalophytes, Halocnemum strobilaceum Pall. and Suaeda fruticosa (L.) Forske., Grown in the Sabkha Ecosystem in the Algerian Sahara.

This study reports the biochemical profile and in vitro biological activities of the aerial part of two shrubs: Halocnemum strobilaceum and Suaeda fruticosa, a halophytes species native to saline habitats. The biomass was evaluated by determining its physiological properties and approximate composition. Hydro-methanolic extracts from Halocnemum strobilaceum and Suaeda fruticosa have been investigated for the inhibition of bacterial growth, the protection of proteins (albumin) from denaturation, and cytotoxicity to hepatocellular carcinomas (Huh-7 and HepG2). Their antioxidant activity was evaluated by five tests, including one that examined their ability to inhibit hydrogen peroxide (H2O2)-induced hemolysis. The profile of their phenolic compounds was also determined. These two euhalophytes had a high moisture content, high levels of photosynthetic pigments, elevated levels of ash and protein, low oxidative damage indices, MDA (Malondialdehyde) and proline, and low lipids levels. Their content was also characterized by a moderate acidity with good electrical conductivity. They contained abundant levels of phytochemicals and varied phenolic contents. Reverse phase high performance liquid chromatography (RP-HPLC) analysis revealed the presence of caffeic acid, p-coumaric acid, rutin, and quercetin in both plant extracts. On the pharmaceutical level, the two euhalophytes had anti-inflammatory, antibacterial, antioxidant, and cytotoxic properties, and therefore it was recommended to isolate and identify biologically active compounds from these plants and evaluate them in vivo.

Effect of silymarin on oxidative damage in chicken liver cell membranes

In living beings, antioxidants are of vital importance for protection against oxidative damage caused by reactive oxygen species. Silymarin (SM), a plant-derived flavonoid present in the fruits and seeds of milk thistle Silybum marianum (L.) Gaertn., has a recognized hepatoprotective effect. In this work, the in vitro silymarin antioxidant effect on non-enzymatic peroxidation (NEP) in chicken liver mitochondria and microsomes was studied. Oxidative stress in the organelles was induced by subjecting the samples (1 mg of protein) to an ascorbate-Fe++-dependent prooxidant system at 37 °C. Oxidative damage was quantified by chemiluminescence (CL) using a Packard1900 TR liquid scintillation counter (Meriden CT, USA). CL expressed as cpm (counts per minute) was read every 10 minutes to establish the course of peroxidation as a function of time. Likewise, the total cpm value (sum of the readings) was used to compare the inhibitory effect of SM using different concentrations corresponding to 6.25; 12.5, and 25 μg of the active ingredient (silymarin phosphatide) per mg of mitochondrial and microsomal protein. Controls were run simultaneously without the addition of ascorbate. Peroxidation inhibition was dependent on the concentration of SM in the incubation mixture. The results show that a protective effect on induced oxidative damage was found for all concentrations tested.

Optimization of Polyphenol Extraction with Potential Application as Natural Food Preservatives from Brazilian Amazonian Species Dalbergia monetaria and Croton cajucara

Scientific interest has currently focused on natural products as a feasible approach for new food additives to replace synthetic preservatives. Thereby, the objective of this work was to optimize the polyphenol extraction from native Amazonian plant species Dalbergia monetaria L.f. and Croton cajucara Benth., and they were determined by the total content of these compounds. Accordingly, the hydroalcoholic extract’s phytocomposition was analyzed by ultra-high-performance liquid chromatography–diode array detector (UPLC-DAD) and various assays to determine the antioxidant capacity (e.g., 2,2-Diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging, ferric reduction power, peroxidation inhibition). In addition, response surface methodology applying a central composite design was used to optimize the antioxidant compound extraction conditions. Extract phytochemical profiles identified polyphenols such as (-)-epigallocatechin gallate, rutin, and hyperoside in both species. Furthermore, D. monetaria and C. cajucara extracts displayed significant antioxidant capacity, exhibiting similar values compared to the standard synthetic antioxidant butylated hydroxytoluene. Nevertheless, C. cajucara showed more antioxidant efficiency compared to D. monetaria. These results were consistent with the distribution matrix obtained by a Central Composite Design since the C. cajucara extracts exhibited the best response to the adopted optimization model. Therefore, data are promising for obtaining potential options for natural additives for the food industry.

Effect of slow-release amylase on extraction of peach peel phenolics and their antioxidant activities

AbstractThe present manuscript demonstrates the work undertaken to optimise and validate a slow-release amylase-assisted extraction of polyphenols from peach fruit peel. A careful investigation and optimisation revealed that peach peel when hydrolysed with 1.50% (w/w) of SRA containing enzyme formulation at 40 °C and 6.1 pH, for 35 min significantly (P < 0.05) increased the extraction yield, levels of polyphenol contents (242.89 ± 1.56 mg gallic acid equivalents – GAE), and coumaric, chlorogenic, ferulic acids or their conjugate esters in extracts. Moreover, the extracts produced through SRA-assisted extraction exhibited ample level of free radical scavenging capacity (DPPH IC50 2.67 ± 0.03 μg mL−1), Trolox equivalent (TE) antioxidant capacity (450.52 ± 24.58 µmol of TE g−1), inhibition of peroxides in linoleic acid (85.68 ± 0.21%), and ferric reducing power of 3.11 ± 0.20 ppm gallic acid equivalents. The results suggested that the incorporation of SRA containing enzyme formulation may enhance the recovery of peach peel polyphenols while hydrolysing the glycosidic linkages without deteriorating their antioxidant character.

Abstract 362: MYCN-amplified neuroblastoma is addicted to iron and vulnerable to ferroptosis

Abstract MYCN is amplified in 20% to 25% of neuroblastoma, and MYCN-amplified neuroblastoma contributes to a large percent of pediatric cancer-related deaths. Therapy improvements for this subtype of cancer are a high priority. Ferroptosis is an iron-dependent, oxidative form of cell death that is counteracted mainly by the production of Glutathione Peroxidase 4 (GPX4), a phospholipid hydroperoxidase that is produced through the glutathione pathway. The identification of cancers that may benefit from ferroptosis inducers are just emerging. Here we uncover a MYCN-dependent therapeutic vulnerability in neuroblastoma. Namely, amplified MYCN rewires the cell through expression of key receptors, ultimately enhancing iron influx through increased expression of the iron import transferrin receptor 1 (TFR1). Accumulating iron causes reactive oxygen species (ROS) production, and MYCN-amplified neuroblastomas show enhanced reliance on the system Xc- cystine/glutamate antiporter for ROS detoxification through increased transcription of this receptor. By performing metabolomics, we demonstrate that the transsulfuration pathway is also activated by MYCN. The increased activation of both pathways leads to cysteine accumulation that results in inhibition of lipid peroxidation. Utilizing drugs that target the main components of the glutathione and transsulfuration pathway we sensitize the MYCN neuroblastomas to ferroptotic cell death. These data provide novel insights into how MYCN alters the transcriptome in neuroblastoma to confer growth and survival advantages and simultaneously sheds light on the mechanism of action of ferroptosis inducers with potential application in other types of cancer. Citation Format: Konstantinos V. Floros, Mia O. Johnson-Berro, Richard Kurupi, Carter K. Fairchild, Krista Dalton, Bin Hu, Madhavi Puchalapalli, Mikhail G. Dozmorov, Jennifer E. Koblinski, James A. Olzmann, Lauren A. Cowart, Anthony C. Faber. MYCN-amplified neuroblastoma is addicted to iron and vulnerable to ferroptosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 362.

Design and Synthesis of a Mitochondria-Targeting Radioprotectant for Promoting Skin Wound Healing Combined with Ionizing Radiation Injury.

Wound healing is seriously retarded when combined with ionizing radiation injury, because radiation-induced excessive reactive oxygen species (ROS) profoundly affect cell growth and wound healing. Mitochondria play vital roles not only as cellular energy factories but also as the main source of endogenous ROS, and in this work a mitochondria-targeting radioprotectant (CY-TMP1) is reported for radiation injury-combined wound repair. It was designed, synthesized and screened out from different conjugates between mitochondria-targeting heptamethine cyanine dyes and a peroxidation inhibitor 2,2,6,6-tetramethylpiperidinyloxy (TEMPO). CY-TMP1 specifically accumulated in mitochondria, efficiently mitigated mitochondrial ROS and total intracellular ROS induced by 6 Gy of X-ray ionizing irradiation, thereby exhibiting a notable radioprotective effect. The mechanism study further demonstrated that CY-TMP1 protected mitochondria from radiation-induced injury, including maintaining mitochondrial membrane potential (MMP) and ATP generation, thereby reducing the ratio of cell apoptotic death. Particularly, an in vivo experiment showed that CY-TMP1 could effectively accelerate wound closure of mice after 6 Gy of whole-body ionizing radiation. Immunohistochemical staining further indicated that CY-TMP1 may improve wound repair through angiogenesis and re-epithelialization. Therefore, mitochondria-targeting ROS scavengers may present a feasible strategy to conquer refractory wound combined with radiation injury.

Antioxidant potential of essential oil from Phoenix dactylifera (L.) seed

Oxidative stress has been implicated in the initiation and progression of a plethora of diseases including atherosclerosis, diabetes mellitus, rheumatoid arthritis, neurodegenerative diseases, cardiovascular diseases and cancer. Due to the toxic and mutagenic side effects of some synthetic antioxidant compounds, intense interest is recently converged on natural antioxidants. This study therefore aimed at evaluating the antioxidant potential of essential oil extracted from Phoenix dactylifera seed. Phoenix dactylifera seed essential oil (PDEO) was extracted via steam-distillation technique. The antioxidant activity of the essential oil was assessed by radical scavenging, lipid peroxidation and reduction power assays. From the results obtained in this study, P. dactylifera essential oil showed significant concentration dependent antioxidant potential with maximum activity at 500 µg/ml viz: DPPH radical scavenging (76.24 ± 0.12 %), ABTS radical scavenging (68.97 ± 0.36 %), Nitric oxide radical scavenging (67.86 ± 0.16 %), Hydroxyl radical scavenging (68.70 ± 0.26 %), Fe2+ chelating ability (66.74 ± 0.25 %), Ferric reducing antioxidant power (262.29 ± 0.253 mMol FeSO4/g) and inhibition of lipid peroxidation (67.78 ± 0.29 %). Findings from this study revealed that essential oil from Phoenix dactylifera seed elicits substantial antioxidant activity and may serve as a veritable pharmacological candidate towards prevention of free radical related pathological damages.