Direct Scavenging Research Articles

N-acetylecysteine: The multiuse antioxidant

N-acetylcysteine (NAC) is an acetylated variant of the amino acid L-cysteine, is an effective antidote able to increase cell protection against oxidative stress , it acts as an antioxidant by restoring the pool of intracellular reduced glutathione, which is often depleted as a consequence of increased status of oxidative stress and inflammation. It has reducing and antioxidant properties, acting as a direct scavenger of ROS (reactive oxygen species). NAC is available in different dosage forms for different indications.Many studies stated other uses of NAC such as mucolytic action which is useful in obstructive airway , nasal sinus diseases as it liquefies bacterial biofilms ( antibacterial action), decrease radio contrast induced kidney disease, treatment of many neuropsychiatric diseases like Alzheimer's disease, bipolar disorder, major depressive disorder, obsessive-compulsive disorder, schizophrenia, specific drug addictions (cocaine) and a certain form of epilepsy (progressive myoclonic) through central mechanisms, and improved fertility outcome in both males and females.

Priming with L-arginine reduces oxidative damages in Carthamus tinctorius seedlings under the toxic levels of lead

Lead (Pb) stress adversely affects plant nutrient homeostasis and metabolism when present at an elevated concentrations in the surrounding media. In this research, the effects of 1mM Pb(NO3)2 on 14-day-old Carthamus tinctorius seedlings pretreated with arginine (Arg) as nitric oxide (NO) precursor, methylene blue (MB), a nitric oxide scavenger and Nω-nitro-L-Arg-methyl ester (LNAME) and a nitric oxide biosynthetic inhibitor, were investigated in the greenhouse of the Department of Biology, Shahid Bahonar University of Kerman, Iran. Pb exposure caused oxidative stress, reduced root and shoot growth and elevated malondialdehyde (MDA) content of the seedlings. Pb stress also increased the ascorbate peroxidase activity while decreasing the activity of the catalase (CAT) enzyme. Arg pretreatment decreased the harmful effects of Pb stress by increasing the root and shoot length and reducing the MDA content. Additionally, Pb-induced reduction of CAT enzyme activity in roots was reversed by the Arg pretreatment of the plants. In many characteristics which we measured, the effects of Arg pretreatment on alleviation of Pb-induced oxidative stress were reversed by LNAME and methylene blue pretreatments. Therefore, it seems that Arg induces a positive effect through NO production. Data showed that in the presence of Arg, the uptake and translocation of Pb declined and the application of Arg with LNAME or MB reversed these positive effects of Arg. It seems that Arg can alleviate lead toxicity in plants through the prevention of Pb uptake and promoting the direct scavenging of reactive oxygen species or activating antioxidant enzymes. Also, results from the use of LNAME and MB indicated that the positive effect of Arg is probably related to its role in NO production.

Ethyl acetate fraction from Nymphaea hybrida Peck modulates inflammatory responses in LPS-stimulated RAW 264.7 cells and acute inflammation murine models

Ethnopharmacological relevanceNymphaea hybrida Peck is used as a traditional medicinal herb for treating pain and inflammatory diseases, and known for its ornamental value and as a hot drink. However, the effects of N. hybrida polar fractions on lipopolysaccharide (LPS)-induced in vitro inflammation model and acute inflammation murine models have yet to be evaluated.Aim of the study: The aim of this study was to elucidate the anti-inflammatory effects of N. hybrida ethanol extract (NHE) and its polar fractions: petroleum ether (PE), methylene chloride (MC), ethyl acetate (EA), methanol (ME), and water (WA). The underlying molecular mechanisms of active fraction in LPS-stimulated RAW 264.7 murine macrophages were further investigated. Material and methodsFractions with potential anti-inflammatory effects were screened using direct nitric oxide (NO) radical scavenging and cyclooxygenase (COX)-2 inhibition assays in vitro. The anti-inflammatory properties of potential fraction were evaluated in LPS-stimulated RAW264.7 cells, xylene-induced ear edema, carrageenan-induced paw edema and xylene-induced Evans blue exudation of acute inflammation murine models. The regulation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways were investigated using western blotting and immunofluorescence. ResultsCompared to other polar fractions, NHE-EA displayed higher phenol and flavonoid content, and exerted greater activity in direct NO radical scavenging and COX-2 inhibition assay in vitro. NHE-EA markedly decreased the levels of inflammatory mediators, NO and prostaglandin E2 (PGE2), by suppressing the over-expression of inducible nitric oxide synthase (iNOS) and COX-2 in LPS-stimulated RAW264.7 cells. The NHE-EA fraction dose-dependently alleviated over-elevation of LPS-associated intracellular calcium and decreased the abnormal secretion of pro-inflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, and interferon-γ (IFN-γ). The combination with NHE-EA effectively attenuated the activation and nuclear translocation of NF-κB p65, and the phosphorylation of extracellular signal-regulated kinases (ERK), c-Jun N-terminal kinases (JNK), and p38 kinases of MAPK pathways. NHE-EA could significantly ameliorate the degree of swelling of the mice ear and paw, the skin exudation of Evans blue and the excessive secretion of inflammatory cytokines. ConclusionOur results demonstrated that NHE-EA was the most active polar fraction of N. hybrida extracts. It inhibited the LPS-associated inflammatory response by blocking the activation of NF-κB and MAPKs pathways in RAW264.7 cells. It also effectively alleviated the inflammatory response of acute inflammation. These results indicated the role of NHE-EA as adjuvants and their potential role in alternative strategy for the treatment of inflammatory diseases.

Evaluation of licorice (Glycyrrhiza glabra L.) as a novel microgreen from the anti-inflammatory potential of polyphenols

Literature on microgreens, an emerging new functional food crop, remains limited. Further study on microgreens as a promising dietary component for potential use in diet-based disease prevention is, therefore, essential. Given that the anti-inflammatory and anti-oxidant properties of mature licorice root material are well-documented, the objective of the present, preliminary study was to present licorice (<em>Glycyrrhiza glabra</em> L.) as a novel, edible fresh-food microgreen candidate. The effect of leaf, stem and root polyphenol extracts of 20-day old licorice microgreen seedlings on cell proliferation and viability of Caco-2 cells (simulating the intestinal epithelium), after pro-inflammatory induction of lipopolysaccharide (LPS), was examined and then compared to the polyphenol, flavonoid and anti-radical activities of the respective tissue extracts. Root extracts contained a two-fold less polyphenol (including flavonoid) content compared to leaf extracts, but with a five-fold lower anti-radical scavenging activity. Only the root extracts provided functional protection in terms of preserving cell proliferation and viability of LPS-treated Caco-2 cells. Some protection was also afforded by the stems, but the young leaf material offered no anti-inflammatory protection. Results point to a differing composition of anti-inflammatory polyphenols between the root and leaf, suggesting that the protective efficacy of the root extracts (and to some degree, the stem extracts) resides in inhibiting the pro-inflammatory cascade and resultant cytotoxic effects as opposed to a direct anti-radical scavenging activity. Potential use of licorice as a microgreen is promising, but will necessitate further study.

Burr marigold (Bidens tripartita L.) roots directly and immediately scavenge rhizosphere methane with highly exuded hydrogen peroxide via a rhizosphere Fenton reaction

The major factors controlling the soil methane (CH4) concentration and CH4 emissions of various plant (mainly wetland) species were identified. Five plant species (Oryza sativa, Zizania latifolia, Phragmites australis, Sesbania cannabina, and Bidens tripartita) were separately cultivated under the flooded soil conditions. The direct CH4 scavenging potential of B. tripartita roots was also measured in conjunction with in vitro CH4 scavenging experiments using H2O2 and several transition metal ions. CH4 emissions from the soil-cultivated plants did not depend on the maximum CH4 emission potential for each plant species but on the soil CH4 concentrations, which were positively correlated with the CH4 production potential of the soil and negatively correlated with soil Eh values. Bidens tripartita roots possessed the highest increasing soil Eh potential and a direct, immediate, and continuous CH4 scavenging potential via the Fenton reaction using a considerably high concentration of root apoplastic H2O2 and rhizosphere Fe2+. Bidens tripartita presented the highest soil Eh ascending potential. The in vitro experiments suggested the involvement of・OH/FeIVO2+ via the newly termed rhizosphere Fenton reaction as a strong destructive power for CH4. To our knowledge, this is the first report on direct CH4 scavenging by high H2O2-exuding plant roots.

Astaxanthin protects mesenchymal stem cells from oxidative stress by direct scavenging of free radicals and modulation of cell signaling

Recent evidence has shown that mesenchymal stem cells (MSCs) play vital roles in cell therapy of ischemia/hypoxia damaged tissues. However, after the transplantation, they might undergo apoptosis due to oxidative stress. Thus, some strategies have been developed to support stem cells in harsh conditions, including pre-treatment of the cells with antioxidants. Of various antioxidants, in this study, astaxanthin (ATX) was used to protect adipose-derived MSCs against oxidative stress. The MSCs were exposed to different doses of hydrogen peroxide, and then the expression of key genes involved in the redox signaling pathway was studied, including nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NADPH quinine oxidoreductase 1 (NQO1). The balance of intracellular reactive oxygen species was detected with the H2DCFDA molecular probe. Additionally, for the detection of apoptosis and protective effect of ATX, the DAPI/Phallacidin and annexin V cell staining were performed. The results of cellular studies revealed that ATX reduced the H2O2-induced cell apoptosis and oxidative stress. Furthermore, after the induction of oxidative stress, the cells’ native antioxidants (HO-1 and NQO1) were overexpressed but they were modulated with ATX treatments (p < 0.023). Based on our findings, ATX could increase the expression of Nrf2 as a key transcription factor of antioxidant enzymes (p < 0.05). These findings support the notion that ATX can act as an effective antioxidant in the pre-treatment of MSCs before cell therapy. Thus, to enhance the viability of stem cells during the transplantation in harsh conditions, the concurrent use of ATX in cell therapy modalities is proposed.

Nanocrystals Continuously Releasing Nitric Oxide: Promoting Cell Migration and Increasing Cell Survival against Oxidative Stress

Antioxidants offer a potential cure for certain diseases caused by reactive oxygen species (ROS); unfortunately, conventional antioxidants have poor long-term targeting and bioavailability. Here, we report NO-releasing crystals (NOCs) to achieve direct ROS scavenging as well as enhance cell survival, based on their long-term NO supply. Despite the controversial functions of NO, in order to achieve the goal, NOCs can supply a constant level of NO over 4 days, owing to the thermally stable form of C-diazeniumdiolate-based NO donor. NOCs are controllable for their size, aspect ratio, and NO loading by the crystallization temperature; the nanosized NOCs enhanced cytocompatibility and cell migration owing to their excellent distribution and supply of NO at physiological levels. In addition, NOCs exhibited efficient and continuous radical scavenging compared to ascorbic acid (AA) as a function of the NO release amount. An in vitro test on the antioxidative activity of NO was investigated via two methods: pretreatment of antioxidants prior to oxidative stress and antioxidant treatment in the presence of the oxidants. It was found that 10–20 μM of NO from NOC was optimal for cell protection under oxidative stress. These findings demonstrate the controlled NO system and potential utility of NO as an effective antioxidation tool for treating diseases induced by ROS overproduction.

A Mechanistic Evaluation of Antioxidant Nutraceuticals on Their Potential against Age-Associated Neurodegenerative Diseases.

Nutraceuticals have been extensively studied worldwide due to its neuroprotective effects in in vivo and in vitro studies, attributed by the antioxidative properties. Alzheimer (AD) and Parkinson disease (PD) are the two main neurodegenerative disorders that are discussed in this review. Both AD and PD share the similar involvement of oxidative stress in their pathophysiology. Nutraceuticals exert their antioxidative effects via direct scavenging of free radicals, prevent damage to biomolecules, indirectly stimulate the endogenous antioxidative enzymes and gene expressions, inhibit activation of pro-oxidant enzymes, and chelate metals. In addition, nutraceuticals can act as modulators of pro-survival, pro-apoptotic, and inflammatory signaling pathways. They have been shown to be effective particularly in preclinical stages, due to their multiple mechanisms of action in attenuating oxidative stress underlying AD and PD. Natural antioxidants from food sources and natural products such as resveratrol, curcumin, green tea polyphenols, and vitamin E are promising therapeutic agents in oxidative stress-mediated neurodegenerative disease as they have fewer adverse effects, more tolerable, cheaper, and sustainable for long term consumption.

Antioxidant and anti-inflammatory effects of piperine on UV-B-irradiated human HaCaT keratinocyte cells

The increase in intracellular reactive oxygen and nitrogen species plays a key role in ultraviolet B (UV-B)-induced inflammatory responses in the human skin. Piperine exhibits many pharmacological benefits. In the present study, the photoprotective effects and the possible underlying mechanisms of the anti-inflammatory effects of piperine on UV-B-irradiated keratinocytes were investigated. Piperine exerted strong, direct scavenging effects on DPPH radicals and exhibited free radical scavenging capabilities as demonstrated by the DCFH-DA and Griess assays. Consistent with these results, 10, 20, and 40 μM piperine pretreatments attenuated UV-B irradiation-induced keratinocyte cytotoxicity as reported by the resazurin assay. The highest concentration of piperine inhibited UV-B irradiation-induced cell apoptosis, as revealed by Hoechst 33342 staining. Moreover, we demonstrated the anti-inflammatory effects of piperine using western blot analysis, real-time PCR, and ELISA. Pretreatment with piperine suppressed the activation of phosphorylated p38, JNK, and AP-1 as well as the levels of COX-2/PGE2 and iNOS synthesis, while UV-B-irradiated cells triggered the induction of these signaling molecules. These results indicated that the inhibition of these inflammatory signaling pathways might play a key role in the regulation of the anti-inflammatory effects of piperine. In addition, piperine showed stronger anti-inflammatory effects than celecoxib which served as a positive control at the same concentration. All these results suggested that the anti-inflammatory properties of piperine protected keratinocytes from UV-B-induced damage, which might be due to its antioxidant properties. Therefore, piperine may be an effective therapeutic candidate compound for the treatment of UV irradiation-induced skin inflammation.

Amifostine ameliorates induction of experimental autoimmune encephalomyelitis: Effect on reactive oxygen species/NLRP3 pathway

Multiple sclerosis (MS) is an autoimmune disease for which conventional treatments have limited efficacy or side effects. Free radicals are primarily involved in blood–brain barrier disruption and induce neuronal and axonal damage, thus promoting the development of MS. Amifostine, a radioprotective drug used as a cytoprotective agent, attenuates oxidative stress and improves radiation damage by acting as a direct scavenger of reactive oxygen and nitrogen species. The aim of this study was to evaluate the effects of amifostine on MS in a mouse model of experimental autoimmune encephalomyelitis (EAE), which was developed by immunizing C57BL/6 mice with myelin oligodendrocyte glycoprotein and pertussis toxin. EAE mice received intraperitoneal injections of amifostine prior to onset of clinical symptoms and were monitored up to day 15 post induction. We observed abnormal clinical behavioral scores and a decrease in body weight. Histological analysis showed severe inflammatory infiltration and demyelination in the brain and spinal cord lumbar enlargements where significant upregulation of the mRNA expression of the pro-inflammatory cytokines interleukin-6 and interleukin-8, downregulation of the anti-inflammatory cytokine interleukin-10, and obvious microgliosis were also observed. Amifostine treatment potently reversed these abnormal changes. The anti-inflammatory effect of amifostine was associated with the inhibition of reactive oxygen species generation. Furthermore, the expression of proteins involved in the NLRP3 signaling pathway and pyroptosis was decreased. In conclusion, our study showed that amifostine ameliorates induction of experimental autoimmune encephalomyelitis via anti-inflammatory and anti-pyroptosis effects, providing further insights into the use of amifostine for the treatment of MS.

Potential use of n-3 PUFAs to prevent oxidative stress-derived ototoxicity caused by platinum-based chemotherapy

Platinum-based compounds are widely used for the treatment of different malignancies due to their high effectiveness. Unfortunately, platinum-based treatment may lead to ototoxicity, an often-irreversible side effect without a known effective treatment and prevention plan. Platinum-based compound-related ototoxicity results mainly from the production of toxic levels of reactive oxygen species (ROS) rather than DNA-adduct formation, which has led to test strategies based on direct ROS scavengers to ameliorate hearing loss. However, favorable clinical results have been associated with several complications, including potential interactions with chemotherapy efficacy. To understand the contribution of the different cytotoxic mechanisms of platinum analogues on malignant cells and auditory cells, the particular susceptibility and response of both kinds of cells to molecules that potentially interfere with these mechanisms, is fundamental to develop innovative strategies to prevent ototoxicity without affecting antineoplastic effects. The n-3 long-chain polyunsaturated fatty acids (n-3 PUFAs) have been tried in different clinical settings, including with cancer patients. Nevertheless, their use to decrease cisplatin-induced ototoxicity has not been explored to date. In this hypothesis paper, we address the mechanisms of platinum compounds-derived ototoxicity, focusing on the differences between the effects of these compounds in neoplastic versus auditory cells. We discuss the basis for a strategic use of n-3 PUFAs to potentially protect auditory cells from platinum-derived injury without affecting neoplastic cells and chemotherapy efficacy.

Immunomodulatory Activity and Phytochemical Profile of Infusions from Cleavers Herb

Extracts from aerial parts of G. aparine (cleavers) constitute a herbal remedy with monography in British Herbal Pharmacopeia. On the European market, there are several drugs and food supplements consisting of Galium extracts. In folk medicine, cleavers was used topically in Europe, Asia, and the Americas to treat skin diseases. In several remedies, cleavers is also listed as an immunomodulatory active herb influencing the defense response of the human body. The aim of this study was to investigate the immunostimulatory activity and antioxidant potential in vitro of a raw infusion of cleavers and bioactive fractions. The functional activity of lymphocytes in the reaction of the lymphocyte blast transformation (RLBT) method was used for immunomodulatory activity assays and direct scavenging of 2,2-diphenyl-1-picrylhydrazyl (DPPH), nitric oxide (NO), and hydrogen peroxide (H2O2) was chosen for the examination of antioxidant activity. It was shown that both the raw extract and fractions show significant immunostimulatory and scavenging activities. The obtained data partially justify the traditional use of cleavers as topical remedy for skin infections and for wounds.

Antioxidant Mechanisms in the Neuroprotective Action of Cemtirestat: Studies in Chemical Models, Liposomes and Rat Brain Cortical Slices

Neuroprotective action of the novel aldose reductase (AR) inhibitor cemtirestat (CMT), 2-(3-thioxo-2H-[1,2,4]triazino[5,6-b]indol-5(3H)-yl)acetic acid, was recently proved in experimental rat models of diabetes. The in vivo results indicated that the antioxidant activity of this compound might have participated on its effects. The aim of this study was to explore in a greater detail the putative antioxidant mechanisms potentially involved in CMT mediated neuroprotection. Antioxidant efficacy per se of CMT was proved by a ferric reducing antioxidant power (FRAP) test and CMT was found to scavenge reactive oxygen species (ROS) generated in water phase chemically with decreasing efficacy as follows ROO > H2O2 > O2−. Studies in liposomes revealed the ability of CMT to inhibit lipid peroxidation more efficiently than melatonin, yet less effectively than Trolox. In the rat brain cortical slices, CMT reduced the loss of cell viability/mitochondrial function induced by quinolinic acid (QUIN), and inhibited lipid peroxidation. In addition, CMT normalized the GSH/GSSG ratio which could be explained, at least partially, by the ability of this compound to release free GSH from the pool of endogenously bound disulfides. Neuronal cell damage induced by QUIN or H2O2 was reduced by CMT as proved by significant drop in propidium iodide incorporation into cells. On balance then, our results corroborated the notion of a multifunctional action of CMT as a drug combining AR inhibition with direct antioxidant and ROS scavenging activity. Moreover, the ability of CMT to restore thiol-disulfide homeostasis was proved.

The emerging antioxidant paradigm of mesenchymal stem cell therapy.

Mesenchymal stem cells (multipotent stromal cells; MSCs) have been under investigation for the treatment of diverse diseases, with many promising outcomes achieved in animal models and clinical trials. The biological activity of MSC therapies has not been fully resolved which is critical to rationalizing their use and developing strategies to enhance treatment efficacy. Different paradigms have been constructed to explain their mechanism of action, including tissue regeneration, trophic/anti‐inflammatory secretion, and immunomodulation. MSCs rarely engraft and differentiate into other cell types after in vivo administration. Furthermore, it is equivocal whether MSCs function via the secretion of many peptide/protein ligands as their therapeutic properties are observed across xenogeneic barriers, which is suggestive of mechanisms involving mediators conserved between species. Oxidative stress is concomitant with cellular injury, inflammation, and dysregulated metabolism which are involved in many pathologies. Growing evidence supports that MSCs exert antioxidant properties in a variety of animal models of disease, which may explain their cytoprotective and anti‐inflammatory properties. In this review, evidence of the antioxidant effects of MSCs in in vivo and in vitro models is explored and potential mechanisms of these effects are discussed. These include direct scavenging of free radicals, promoting endogenous antioxidant defenses, immunomodulation via reactive oxygen species suppression, altering mitochondrial bioenergetics, and donating functional mitochondria to damaged cells. Modulation of the redox environment and oxidative stress by MSCs can mediate their anti‐inflammatory and cytoprotective properties and may offer an explanation to the diversity in disease models treatable by MSCs and how these mechanisms may be conserved between species.

Use of Melatonin in Oxidative Stress Related Neonatal Diseases.

Reactive oxygen species have a crucial role in the pathogenesis of perinatal diseases. Exposure to inflammation, infections, or high oxygen concentrations is frequent in preterm infants, who have high free iron levels that enhance toxic radical generation and diminish antioxidant defense. The peculiar susceptibility of newborns to oxidative stress supports the prophylactic use of melatonin in preventing or decreasing oxidative stress-mediated diseases. Melatonin, an effective direct free-radical scavenger, easily diffuses through biological membranes and exerts pleiotropic activity everywhere. Multiple investigations have assessed the effectiveness of melatonin to reduce the “oxygen radical diseases of newborn” including perinatal brain injury, sepsis, chronic lung disease (CLD), and necrotizing enterocolitis (NEC). Further studies are still awaited to test melatonin activity during perinatal period.

Restoration of antitumor immunity through anti-MICA antibodies elicited with a chimeric protein

BackgroundNatural killer and cytotoxic CD8+ T cells are major players during antitumor immunity. They express NKG2D, an activating receptor that promotes tumor elimination through recognition of the MHC class I...

Polyethylene glycol functionalized cerium oxide nanoparticle confer protection against UV- induced oxidative damage in skin: evidences for a new class of UV filter

Acute exposure to high dose of ultraviolet (UV) radiations is known to cause significant harm to skin, primarily due to the generation of free radicals and damage to DNA, which often culminate in rapid aging of the skin, or cancers. Keratinocytes being the most abundant skin’s cells are affected most by UV. Although a degree of endogenous protection is present, the vulnerability of UV-induced damaged can be minimized using protective agents. A few UV filters (organic and inorganic) have been successfully commercialized, yet, due to prevailing disadvantages such as low solubility, photostability, and aesthetic sense, suitable and more efficient UV filters continue to be explored as potential ingredients of cosmaceutical agents. A recently studied antioxidant enzyme mimetic cerium oxide nanoparticles showed emerging piece of evidence on benefits under environmental stress. However, its protective abilities as potential UV filter and therefore applicability in cosmaceutical has not yet been completely explored. This study provides a piece of evidence in support of beneficial effects of this new class of UV filters, polyethyleneglycol functionalized nanoceria (PEG-CNP) against UV - induced damage in vitro and in vivo. The nanomolar concentration of PEG-CNPs in the cell culture showed significant protection from UV exposure, by direct ROS scavenging, the rescue of cells from cell cycle arrest and DNA damage. Further, a proof of the concept study in dehaired rat skin showed that the topical application of 50 μM PEG-CNPs prevented the initial signs of UV induced damage. Unlike conventional UV filters, PEG-CNPs confer protection by internalizing the cells, and scavenging the radicals.

3-Hydroxytyrosol Promotes Angiogenesis In Vitro by Stimulating Endothelial Cell Migration.

Cardiovascular diseases, followed by strokes, represent the leading cause of mortality worldwide. Despite its success in preventing cardiovascular diseases, the therapeutic potential of 3-Hydroxytyrosol (HT) for treating ischemic diseases is yet to be investigated in detail, especially with regard to ischemic heart disease, which is a major challenge for humans. We assessed that low concentrations (1–5 µM) of HT, generally achieved after the ingestion of olive oil, stimulate endothelial cells migration and angiogenesis in an in vitro model. At early time points (1–6 h), HT induces the expression of different proteins such as proto-oncogene tyrosine-protein kinase Src (Src), rho-associated protein kinase (ROCK) and matrix metalloproteinase-2 (MMP-2) protein influencing cell adhesion, cytoskeletal dynamics and cell migration. We observed that at the same time, HT induces prominent vascular formation in the tube formation assay, accompanied by an increase in the expression of the vascular endothelial growth factor receptor (VEGF-R2) and PI3K-Akt-eNOS protein pathways, which are recognized for their central role in angiogenesis. Therefore, in addition to the proven capability of HT to regulate reactive oxygen species (ROS) levels, through both direct scavenging properties and indirect antioxidant efficacy, our results revealed that HT promotes angiogenesis, arguing in favor of great pharma-nutritional potential in ischemic injuries.

An optically active isochroman-2H-chromene conjugate potently suppresses neuronal oxidative injuries associated with the PI3K/Akt and MAPK signaling pathways.

Increasing evidence suggests that the use of potent neuroprotective agents featured with novel pharmacological mechanism would offer a promising strategy to delay or prevent the progression of neurodegeneration. Here, we provide the first demonstration that the chiral nonracemic isochroman-2H-chromene conjugate JE-133, a novel synthetic 1,3-disubstituted isochroman derivative, possesses superior neuroprotective effect against oxidative injuries. Pretreatment with JE-133 (1-10 μM) concentration-dependently prevented H2O2-induced cell death in SH-SY5Y neuroblastoma cells and rat primary cortical neurons. Pretreatment with JE-133 significantly alleviated H2O2-induced apoptotic changes. These protective effects could not be simply attributed to the direct free radical scavenging as JE-133 had moderate activity in reducing DPPH free radical. Further study revealed that pretreatment with JE-133 (10 μM) significantly decreased the phosphorylation of MAPK pathway proteins, especially ERK and P38, in the neuronal cells. In addition, blocking PI3K/Akt pathway using LY294002 partially counteracted the cell viability-enhancing effect of JE-133. We conclude that JE-133 exerts neuroprotection associated with dual regulative mechanisms and consequently activating cell survival and inhibiting apoptotic changes, which may provide important clues for the development of effective neuroprotective drug lead/candidate.

Effects of N-acetylcysteine on Pulmonary Functions in Patients with Systemic Sclerosis: A Randomized Double Blind, Placebo Controlled Study.

Systemic sclerosis (SSc) is a systematic and rare autoimmune disease that affects many organs. N-acetylcysteine (NAC), thiol-containing compound, can act both as the precursor of reduced glutathione and direct scavenger of reactive oxygen species. We assessed the clinical effect of NAC on the pulmonary function test of patients with diffuse scleroderma. This study is a randomized double-blind clinical trial that was done on 25 patients with diffuse SSc without lung involvement on primary chest high-resolution computed tomography. Placebo was administered for 13 patients and 1200 milligram NAC for 12 patients. Body plethysmography parameters were assessed at the beginning of the study and after 24 weeks. Patients in the two groups were matched in the basic demographic data like age, duration of disease, and modified Rodnan skin score. The analysis showed no significant differences in parameters of plethysmography between the two groups. After importing the data of 2 patients in the placebo-treated group, who developed interstitial lung disease, DLCO in the placebo-treated group was 90.69 ± 21.29 milliliter at the end of the study, which significantly decreased compared with the beginning of the study (102.30 ± 13.83 ml). Also, changes of DLCO between the two groups were significantly different. In this trial, the sensitivity of DLCO as the first marker in the evaluation of pulmonary function in patients with SSc was confirmed. On the other hand, NAC had no effect versus placebo in a period of 24 weeks.