Oxidative Insult Research Articles

Therapeutic Potential of Justicia secundaon Oxidative Stress Indices in N‐Acetyl‐P‐Benzoquinone Imine Induced‐ Hepatotoxic Rats

The therapeutic potential of Hot Water Leaf Extract of Justicia secunda(HWEJS) on oxidative stress indices in paracetamol (N‐Acetyl‐p‐Benzoquinone Imine) induced hepatotoxic rats was investigated. Justicia secunda is a blood boosting plant used traditionally with so many medicinal activities. Five groups of 10 rats each were used for the study, GpD was the control given n‐saline and the test grps A,B and C were administered with 2000mg/kg N‐Acetyl‐p‐Benzoquinone Imine (NAPQI) and after 24hrs, groupsB and C were administered with 200 and 400mg/kg of HWEJS respectively for 7 days. The body weights were also measured. Results of the study showed a relative weight loss of all the groups except the control in the first 2 days thereafter a relative increase was observed throughout the duration of the experiment. This could be as a result of the ameliorative effect of the extract against NAPQI overdose. Oxidative stress indices in the animals treated with NAPQI (as shown in the figure) increased the levels of the oxidative enzymes while the 200 and 400mg/kg HWEJS reduced them except in Malondealdehyde which showed a reduced level with NAPQI with increased levels on the treated groups. Gpx showed a significant (p<0.05) decrease at 200mg/kg and 400mg/kg. CAT and SOD decreased significantly (p<0.05) at 400mg/kg and non‐significant (p>0.05) at 200mg/kg respectively relative to control. MDA, an indicator for lipid peroxidation recorded non‐significant (p.>0.05) levels for all the test groups when compared to the control. These results suggest that the oral administration (p.o) of hot water extract of the leaves of J.S have antioxidant activities at the doses of 200 and 400mg/kg in the hepatotoxic rats. The combination of SOD, CAT and GPx enzymes constitute a first line antioxidant defense system that plays a crucial role in total defense mechanisms during metabolic processes. In the extract treated animals, SOD showed that it may have removed superoxide anions from oxidative insult by helping in breaking down potentially cellular harmful oxygen molecules while the CAT and GPX protected the cells from damage due to free radicals like the peroxides. This result could suggest that the hot water extract of Justicia secunda can be used in conditions where harmful oxygen molecules are believed to play a role in a disease or in oxidative stress‐related diseases as a therapeutic agent.

T285 Oxidative insult induced senescence in retinal pigment epithelial cells: A possible mechanism for age-related macular degeneration

T285 Oxidative insult induced senescence in retinal pigment epithelial cells: A possible mechanism for age-related macular degeneration

LC-MS/MS Quantitation of Formaldehyde-Glutathione Conjugates as Biomarkers of Formaldehyde Exposure and Exposure-Induced Antioxidants: A New Look on an Old Topic.

Humans are continuously exposed to formaldehyde via both endogenous and exogenous sources. Prolonged exposure to formaldehyde is associated with many human diseases, such as lung cancer and leukemia. The goal of this study is to develop biomarkers to measure formaldehyde exposure, which could be used to predict the risk of associated diseases. As glutathione (GSH) is well-known for its crucial role in the detoxification of a wide variety of xenobiotics, including formaldehyde, we rigorously quantitated in this study the conjugates formed when formaldehyde reacted with GSH using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) coupled with an isotope dilution method. The results showed for the first time that (S)-1-(((R)-2-amino-3-(carboxymethylamino)-3-oxopropylthio)methyl)-5-oxopyrrolidine-2-carboxylic acid (PGF) and thioproline-glycine (SPro-Gly) are major metabolites in both nonenzymatic reactions and formaldehyde-exposed human cells. In particular, over 35% of the formaldehyde from external sources was found to convert to SPro-Gly in the exposed cells. Interestingly, data showed that these exposure-induced adducts exhibited good antioxidative properties, which can protect cells from hydrogen peroxide mediated oxidative insult. It is anticipated that the findings of this study could shed light on developing PGF and SPro-Gly as dietary supplements and on the development of noninvasive methods to assess health risks associated with formaldehyde exposure.

Oxidative-Induced Angiogenesis Is Modulated by Small Extracellular Vesicle miR-302a-3p Cargo in Retinal Pigment Epithelium Cells.

Extracellular vesicles are released from cells under diverse conditions. Widely studied in cancer, they are associated with different diseases playing major roles. Recent reports indicate that oxidative damage promotes the release of small extracellular vesicle (sEVs) from the retinal pigment epithelium (RPE), with an angiogenic outcome and changes in micro-RNA (miRNA) levels. The aim of this study was to determine the role of the miRNA miR-302a-3p, included within RPE-released sEVs, as an angiogenic regulator in cultures of endothelial cells (HUVEC). ARPE-19 cell cultures, treated with H2O2 to cause an oxidative insult, were transfected with a miR-302a-3p mimic. Later, sEVs from the medium were isolated and added into HUVEC or ARPE-19 cultures. sEVs from ARPE-19 cells under oxidative damage presented a decrease of miR-302a-3p levels and exhibited proangiogenic properties. In contrast, sEVs from miR-302a-3p-mimic transfected cells resulted in control angiogenic levels. The results herein indicate that miR-302a-3p contained in sEVs can modify VEGFA mRNA expression levels as part of its antiangiogenic features.

Social dominance and reproduction result in increased integration of oxidative state in males of an African cichlid fish

Oxidative stress is a potential cost of social dominance and reproduction, which could mediate life history trade-offs between current and future reproductive fitness. However, the evidence for an oxidative cost of social dominance and reproduction is mixed, in part because organisms have efficient protective mechanisms that can counteract oxidative insults. Further, previous studies have shown that different aspects of oxidative balance, including oxidative damage and antioxidant function, vary dramatically between tissue types, yet few studies have investigated oxidative cost in terms of interconnectedness and coordination within the system. Here, we tested whether dominant and subordinate males of the cichlid Astatotilapia burtoni differ in integration of different components of oxidative stress. We assessed 7 markers of oxidative stress, which included both oxidative damage and antioxidant function in various tissue types (total of 14 measurements). Across all oxidative stress measurements, we found more co-regulated clusters in dominant males, suggesting that components of oxidative state are more functionally integrated in dominant males than they are in subordinate males. We discuss how a high degree of functional integration reflects increased robustness or efficiency of the system (e.g. increased effectiveness of antioxidant machinery in reducing oxidative damage), but we also highlight potential costs (e.g. activation of cytoprotective mechanisms may have unwanted pleiotropic effects). Overall, our results suggest that quantifying the extent of functional integration across different components of oxidative stress could reveal insights into the oxidative cost of important life history events.

Effects of a Short-Term Lipopolysaccharides Challenge on Mouse Brain and Liver Peroxisomal Antioxidant and β-oxidative Functions: Protective Action of Argan Oil.

During sepsis, the imbalance between oxidative insult and body antioxidant response causes the dysfunction of organs, including the brain and liver. Exposing mice to bacterial lipopolysaccharides (LPS) results in a similar pathophysiological outcome. The protection offered by argan oil was studied against LPS-induced oxidative stress, dysregulation of peroxisomal antioxidants, and β-oxidation activities in the brain and liver. In a short-term LPS treatment, lipid peroxidation (malonaldehyde assay) increased in the brain and liver with upregulations of proinflammatory tumor necrosis factor (Tnf)-α and anti-inflammatory interleukin (Il)-10 genes, especially in the liver. Although exposure to olive oil (OO), colza oil (CO), and argan oil (AO) prevented LPS-induced lipid peroxidation in the brain and liver, only AO exposure protected against liver inflammation. Remarkably, only exposure to AO prevented LPS-dependent glutathione (GSH) dysregulation in the brain and liver. Furthermore, exposure to AO increased more efficiently than OO and CO in both organs, peroxisomal antioxidant capacity via induction of catalase (Cat) gene, protein and activity expression levels, and superoxide dismutase (Sod1) mRNA and activity levels. Interestingly, LPS decreased protein levels of the peroxisomal fatty acid-ATP binding cassette (ABC) transporters, ABCD1 and ABCD2, and increased acyl-CoA oxidase 1 (ACOX1) protein expression. Moreover, these LPS effects were attenuated for ABCD1 and ACOX1 in the brain of mice pretreated with AO. Our data collectively highlight the protective effects of AO against early oxidative stress caused by LPS in the brain and liver and their reliance on the preservation of peroxisomal functions, including antioxidant and β-oxidation activities, making AO a promising candidate for the prevention and management of sepsis.

IDF21-0158 Aegeline mitigates high glucose induced renal cell fibrosis by alleviating ROS generation & augmenting hydrogen sulphide

Background: Diabetic kidney disease is a complex multifactorial disease, characterised by excessive synthesis and deposition of extracellular matrix proteins (ECM), leading to the glomerulosclerosis and interstitial fibrosis. Innovative treatment strategies to combat DKD are needed in addition to the existing treatment methods as they are not very much effective in preventing the progression of the disease. Previous studies showed the protective role of Aegle marmelos (AM) in the treatment of diabetes mellitus and kidney injury. Aegeline, an active phytochemical identified in the leaves of AM has shown to have antihyperglycemic, antidyslipidemic, and antioxidant properties but no study has explored its molecular mechanisms in combating high glucose induced renal cell injury. So, we aimed to study the efficacy and the molecular mechanism of Aegeline, in high glucose induced renal cell fibrosis. Aim: We aimed to elucidate the role of aegeline in high glucose induced renal cell fibrosis and to study its mechanistic role in the regulation of hydrogen sulphide, a gasotransmitter which attenuates renal cell fibrosis. Method: Expression level of α-SMA (fibrotic marker) was analysed using western blotting. We also analysed fibrotic events such as cell migration, proliferation and trans-well invasion in kidney Proximal Tubular Epithelial Cells (NRK-52E) after Aegeline (10µM) and HG treatment (25mM). Generation of reactive oxygen species was measured using fluorescent probes and NADPH oxidase-4 (NOX4) protein expression was analysed by immunoblotting. Hydrogen sulphide (H2S) level was measured by methylene blue assay and its synthesising enzyme Cystathionine β synthase (CBS) expression level was analysed by immunoblotting. Also, we studied the protein interaction of aegeline with the NOX4 and other related proteins using molecular docking (Auto dock). The statistical analysis was performed using GraphPad Prism software (GraphPad Prism Software, USA). All the experiments were performed for a minimum of three independent experiments. Results: Aegeline treatment alleviates the HG induced fibrosis by significantly reducing the expression level of fibrotic marker (α-SMA) and also impedes the fibrotic events such as migration, invasion and cell proliferation. Additionally, aegeline treatment significantly reduced the high glucose induced ROS generation. Molecular docking studies showed that aegeline had high binding conformation with NOX4 and CBS protein and also exhibit good drug-likeness property. We showed that aegeline treatment significantly reduced the NADPH oxidase activity and NOX4 expression. Further, high glucose treatment significantly decreased the level of H2S which may be the reason for the increase in ROS generation and fibrosis. Aegeline treatment significantly increased the level of H2S and the CBS expression under high glucose condition. Discussion: Oxidative insult and ROS generation are important processes in the progression of renal cell fibrosis under high glucose conditions. H2S exerts promising protective role against renal cell injury by attenuating oxidative stress and inflammation. Hence, an increase in this gasotransmitter (H2S) will eventually diminish the progression of renal cell injury. Here we have observed a protective effect of aegeline in high glucose mediated kidney cell fibrosis by subjugating fibrotic events, ROS generation and by augmenting hydrogen sulphide.

Nervonic Acid Attenuates Accumulation of Very Long-Chain Fatty Acids and is a Potential Therapy for Adrenoleukodystrophy.

Adrenoleukodystrophy (ALD) is an X-linked inherited peroxisomal disorder due to mutations in theALD protein and characterized by accumulation of very long-chain fatty acids (VLCFA), specifically hexacosanoic acid (C26:0). This can trigger other pathological processes such as mitochondrial dysfunction, oxidative stress, and inflammation, which if involves the brain tissues can result in a lethal form of the disease called childhood cerebral ALD. With the recent addition of ALD to the Recommended Uniform Screening Panel, there is an increase in the number of individuals who are identified with ALD. However, currently, there is no approved treatment for pre-symptomatic individuals that can arrest or delay symptom development. Here, we report our observations investigating nervonic acid, a monounsaturated fatty acid as a potential therapy for ALD. Using ALD patient-derived fibroblasts, we examined whether nervonic acid can reverse VLCFA accumulation similar to erucic acid, the active ingredient in Lorenzo's oil, a dietary intervention believed to alter disease course. We have shown that nervonic acid can reverse total lipid C26:0 accumulation in a concentration-dependent manner in ALD cell lines. Further, we show that nervonic acid can protect ALD fibroblasts from oxidative insults, presumably by increasing intracellular ATP production. Thus, nervonic acid can be a potential therapeutic for individuals with ALD, which can alter cellular biochemistry and improve its function.

Antagonistic roles of Ras-MAPK and Akt signaling in integrin-K+ channel complex-mediated cellular apoptosis.

Complexes formed with α5-integrins and the voltage-gated potassium (K+ ) channel KCNB1 (Kv2.1), known as IKCs, transduce the electrical activity at the plasma membrane into biochemical events that impinge on cytoskeletal remodeling, cell differentiation, and migration. However, when cells are subject to stress of oxidative nature IKCs turn toxic and cause inflammation and death. Here, biochemical, pharmacological, and cell viability evidence demonstrates that in response to oxidative insults, IKCs activate an apoptotic Mitogen-activated protein kinase/extracellular signal-regulated kinase (Ras-MAPK) signaling pathway. Simultaneously, wild-type (WT) KCNB1 channels sequester protein kinase B (Akt) causing dephosphorylation of BCL2-associated agonist of cell death (BAD), a major sentinel of apoptosis progression. In contrast, IKCs formed with C73A KCNB1 variant that does not induce apoptosis (IKCC73A ), do not sequester Akt and thus are able to engage cell survival mechanisms. Taken together, these data suggest that apoptotic and survival forces co-exist in IKCs. Integrins send death signals through Ras-MAPK and KCNB1 channels simultaneously sabotage survival mechanisms. Thus, the combined action of integrins and KCNB1 channels advances life or death.

NUTRITIONAL ADVANCES IN PRODUCTION PERFORMANCE AND PRODUCT QUALITY OF POULTRY HUSBANDRY UNDER HEAT STRESS

The objective of this review is to explore the nutritional additives to combat heat stress in high production targeted fowls. Many diseases and stress dynamics are liable for heavy mortality nowadays. High production targets and heat stress initiate free radical injuries and gastrointestinal oxidative insults resulting in poor bioavailability and feed efficiency. Accordingly, the quality of the eggs and meat is compromised along with the bird’s health. Dietary schemes and relevant feed formulation with the provision of vital elements like selenium, zinc, calcium, vitamin E, vitamin C, vitamin A, electrolytes, essential amino acids, and plant extracts can conflict with all sorts of stress in birds and improve the immune system. The occurrence of many contagious diseases, nervous ailments, and metabolic syndromes can be decreased via appropriate feeding routines. It will not only control the bird’s health but also increase the quality and market value of the products and consumer satisfaction. Scientists have struggled to prevent immuno-depression, egg and meat quality impairments by dietary influences. Poultry welfare is facing many problems currently which should be properly coped with innovative nutritional maneuvers. This review anticipates illuminating the probable nutritional approaches to manage stress in poultry birds.

Mitigation of benznidazole toxicity and oxidative stress following ascorbic acid supplementation in an adult traveller with chronic indeterminate Chagas' disease.

Benznidazole is an effective drug in the trypanocidal treatment of acute and chronic indeterminate Chagas' disease (CD). However, adverse drug reactions (ADR) are common and frequently cause patients to discontinue treatment. We hypothesized that antioxidant supplementation could mitigate benznidazole-induced toxicity. We co-supplemented an adult traveller with chronic indeterminate CD who experienced benznidazole ADR with ascorbic acid (AA), 1000 mg/day. We measured selected serum biomarkers of oxidative stress [total antioxidant status (TAS), total oxidative status (TOS), nuclear factor erythroid 2-related factor 2 (Nrf2), malondialdehyde (MDA), extracellular glutathione peroxidase (GPX3), catalase (CAT) and total superoxide dismutase (T-SOD)] at timepoints before and throughout benznidazole treatment and after AA co-supplementation. AA co-supplementation effectively mitigated benznidazole-induced ADR during the aetiological treatment of chronic indeterminate CD. The kinetics of serum biomarkers of oxidative stress suggested significantly decreased oxidative insult in our patient. We hypothesize that the key pathophysiological mechanism of benznidazole-associated toxicity is oxidative stress, rather than hypersensitivity. AA co-supplementation may improve adherence to benznidazole treatment of chronic indeterminate (or acute) CD. Oxidative stress biomarkers have the potential to guide the clinical management of CD. Prospective studies are needed to establish the benefit of antioxidant co-supplementation to benznidazole treatment of CD in reducing benznidazole toxicity, parasite clearance and the prevention of end-organ damage.

Anticolitic activity of prodigiosin loaded with selenium nanoparticles on acetic acid-induced colitis in rats.

Ulcerative colitis (UC) is a chronic autoimmune inflammatory disease associated with extensive mucosal damage. Prodigiosins (PGs) are natural bacterial pigments with well-known antioxidant and immunosuppressive properties. In the current study, we examined the possible protective effect of PGs loaded with selenium nanoparticles (PGs-SeNPs) against acetic acid (AcOH)-induced UC in rats. Thirty-five rats were separated into five equal groups with seven animals/group: control, UC, PGs (300mg/kg), sodium selenite (Na2SeO3, 2mg/kg), PGs-SeNPs (0.5mg/kg), and 5-aminosalicylates (5-ASA, 200mg/kg). Interestingly, PGs-SeNPs administration lessened colon inflammation and mucosal damage as indicated by inhibiting inflammatory markers upon AcOH injection. Furthermore, PGs-SeNPs improved the colonic antioxidant capacity and prevented oxidative insults as evidenced by the upregulation of Nrf2- and its downstream antioxidants along with the decreased pro-oxidants [reactive oxygen species (ROS), carbonyl protein, malondialdehyde (MDA), inducible nitric oxide synthase (iNOS), and nitric oxide (NO] in the colon tissue. Furthermore, PGs-SeNPs protected intestinal cell loss through blockade apoptotic cascade by decreasing pro-apoptotic proteins [Bcl-2-associated X protein (Bax) and caspase-3] and increasing anti-apoptotic protein, B cell lymphoma 2 (Bcl2). Collectively, PGs-SeNPs could be used as an alternative anti-colitic option due to their strong anti-inflammatory, antioxidant, and anti-apoptotic activities.

Glutathione catabolism by Enterobacteriaceae species to hydrogen sulphide adversely affects the viability of host systems in the presence of 5'fluorodeoxyuridine.

Reduced glutathione (GSH) plays an essential role in relieving oxidative insult from the generation of free radicals via normal physiological processes. However, GSH can be exploited by bacteria as a signalling molecule for the regulation of virulence. We describe findings arising from a serendipitous observation that when GSH and Escherichia coli were incubated with 5′fluorodeoxyuridine (FUdR)‐synchronised populations of Caenorhabditis elegans, the nematodes underwent rapid death. Death was mediated by the production of hydrogen sulphide mainly through the action of tnaA, a tryptophanase‐encoding gene in E. coli. Other Enterobacteriaceae species possess similar cysteine desulfhydrases that can catabolise l‐cysteine‐containing compounds to hydrogen sulphide and mediate nematode killing when worms had been pre‐treated with FUdR. When colonic epithelial cell lines were infected, hydrogen sulphide produced by these bacteria in the presence of GSH was also able to inhibit ATP synthesis in these cells particularly when cells had been treated with FUdR. Therefore, bacterial production of hydrogen sulphide could act in concert with a commonly used genotoxic cancer drug to exert host cell impairment. Hydrogen sulphide also increases bacterial adhesion to the intestinal cells. These findings could have implications for patients undergoing chemotherapy using FUdR analogues that could result in intestinal damage.

Maintenance of mitochondrial integrity in midbrain dopaminergic neurons governed by a conserved developmental transcription factor

Progressive degeneration of dopaminergic (DA) neurons in the substantia nigra is a hallmark of Parkinson’s disease (PD). Dysregulation of developmental transcription factors is implicated in dopaminergic neurodegeneration, but the underlying molecular mechanisms remain largely unknown. Drosophila Fer2 is a prime example of a developmental transcription factor required for the birth and maintenance of midbrain DA neurons. Using an approach combining ChIP-seq, RNA-seq, and genetic epistasis experiments with PD-linked genes, here we demonstrate that Fer2 controls a transcriptional network to maintain mitochondrial structure and function, and thus confers dopaminergic neuroprotection against genetic and oxidative insults. We further show that conditional ablation of Nato3, a mouse homolog of Fer2, in differentiated DA neurons causes mitochondrial abnormalities and locomotor impairments in aged mice. Our results reveal the essential and conserved role of Fer2 homologs in the mitochondrial maintenance of midbrain DA neurons, opening new perspectives for modeling and treating PD.

Superoxide Radicals in the Execution of Cell Death.

Superoxide is a primary oxygen radical that is produced when an oxygen molecule receives one electron. Superoxide dismutase (SOD) plays a primary role in the cellular defense against an oxidative insult by ROS. However, the resulting hydrogen peroxide is still reactive and, in the presence of free ferrous iron, may produce hydroxyl radicals and exacerbate diseases. Polyunsaturated fatty acids are the preferred target of hydroxyl radicals. Ferroptosis, a type of necrotic cell death induced by lipid peroxides in the presence of free iron, has attracted considerable interest because of its role in the pathogenesis of many diseases. Radical electrons, namely those released from mitochondrial electron transfer complexes, and those produced by enzymatic reactions, such as lipoxygenases, appear to cause lipid peroxidation. While GPX4 is the most potent anti-ferroptotic enzyme that is known to reduce lipid peroxides to alcohols, other antioxidative enzymes are also indirectly involved in protection against ferroptosis. Moreover, several low molecular weight compounds that include α-tocopherol, ascorbate, and nitric oxide also efficiently neutralize radical electrons, thereby suppressing ferroptosis. The removal of radical electrons in the early stages is of primary importance in protecting against ferroptosis and other diseases that are related to oxidative stress.

Oxidative damage and mitochondrial functionality in hearts from KO UCP3 mice housed at thermoneutrality.

The antioxidant role of mitochondrial uncoupling protein 3 (UCP3) is controversial. This work aimed to investigate the effects of UCP3 on the heart of mice housed at thermoneutral temperature, an experimental condition that avoids the effects of thermoregulation on mitochondrial activity and redox homeostasis, preventing the alterations related to these processes from confusing the results caused by the lack of UCP3. WT and KO UCP3 mice were acclimatized at 30°C for 4weeks and hearts were used to evaluate metabolic capacity and redox state. Tissue and mitochondrial respiration, the activities of the mitochondrial complexes, and the protein expression of mitochondrial complexes markers furnished information on mitochondrial functionality. The levels of lipid and protein oxidative damage markers, the activity of antioxidant enzymes, the reactive oxygen species levels, and the susceptibility to in vitro Fe-ascorbate-induced oxidative stress furnished information on redox state. UCP3 ablation reduced tissue and mitochondrial respiratory capacities, not affecting the mitochondrial content. In KO UCP3 mice, the mitochondrial complexes activities were lower than in WT without changes in their content. These effects were accompanied by an increase in the level of oxidative stress markers, ROS content, and in vitro susceptibility to oxidative stress, notwithstanding that the activities of antioxidant enzymes were not affected by UCP3 ablation. Such modifications are also associated with enhanced activation/phosphorylation of EIF2α, a marker of integrated stress response and endoplasmic reticulum stress (GRP778 BIP). The lack of UCP3 makes the heart more prone to oxidative insult by reducing oxygen consumption and increasing ROS. Our results demonstrate that UCP3 helps the cell to preserve mitochondrial function by mitigating oxidative stress.

Shedding a New Light on Skin Aging, Iron- and Redox-Homeostasis and Emerging Natural Antioxidants.

Reactive oxygen species (ROS) are necessary for normal cell signaling and the antimicrobial defense of the skin. However excess production of ROS can disrupt the cellular redox balance and overwhelm the cellular antioxidant (AO) capacity, leading to oxidative stress. In the skin, oxidative stress plays a key role in driving both extrinsic and intrinsic aging. Sunlight exposure has also been a major contributor to extrinsic photoaging of the skin as its oxidising components disrupt both redox- and iron-homeostasis, promoting oxidative damage to skin cells and tissue constituents. Upon oxidative insults, the interplay between excess accumulation of ROS and redox-active labile iron (LI) and its detrimental consequences to the skin are often overlooked. In this review we have revisited the oxidative mechanisms underlying skin damage and aging by focussing on the concerted action of ROS and redox-active LI in the initiation and progression of intrinsic and extrinsic skin aging processes. Based on these, we propose to redefine the selection criteria for skin antiaging and photoprotective ingredients to include natural antioxidants (AOs) exhibiting robust redox–balancing and/or iron-chelating properties. This would promote the concept of natural-based or bio-inspired bifunctional anti-aging and photoprotective ingredients for skincare and sunscreen formulations with both AO and iron-chelating properties.

Alcohol exacerbated biochemical and biophysical alterations in liver mitochondrial membrane of diabetic male wistar rats – A possible amelioration by green tea

Alcohol exacerbated biochemical and biophysical alterations in liver mitochondrial membrane of diabetic male wistar rats – A possible amelioration by green tea

Carpaine Promotes Proliferation and Repair of H9c2 Cardiomyocytes after Oxidative Insults.

Carpaine has long been identified as the major alkaloid in Carica papaya leaves that possess muscle relaxant properties. Limited study on the molecular signaling properties of carpaine urges us to conduct this study that aims to elucidate the mechanism underlying the cardioprotective effect of carpaine in embryonic cardiomyocytes of the H9c2 cell line. The 50% inhibitory concentration (IC50) of carpaine was first determined using a colorimetric MTT assay to establish the minimum inhibitory concentration for the subsequent test. Using a 1 µM carpaine treatment, a significant increase in the H9c2 proliferation rate was observed following 24 and 48 h of incubation. A Western blot analysis also revealed that carpaine promotes the upregulation of the cell cycle marker proteins cyclin D1 and PCNA. Carpaine-induced H9c2 cell proliferation is mediated by the activation of the FAK-ERK1/2 and FAK-AKT signaling pathways. In the setting of ischemia-reperfusion injury (IRI), carpaine provided a significant protective role to recover the wounded area affected by the hydrogen peroxide (H2O2) treatment. Furthermore, the oxidative-stress-induced reduction in mitochondrial membrane potential (MMP) and overproduction of reactive oxygen species (ROS) were attenuated by carpaine treatment. The current study revealed a novel therapeutic potential of carpaine in promoting in vitro cardiomyocyte proliferation and repair following injury.

The alleviative effect of flavonol-type Nrf2 activator rhamnazin from Physalis alkekengi L. var. franchetii (Mast.) Makino on pulmonary disorders.

Rhamnazin (RN) is a flavonol isolated from the calyxes and fruits of Physalis alkekengi L. var. franchetii (Mast.) Makino, which has been used for treating pulmonary diseases in traditional Chinese medicine. The nuclear factor erythroid 2-related factor 2 (Nrf2) is a therapeutic target for pulmonary diseases. In the present study, the underlying mechanism and pharmacological effect of RN against pulmonary disorders are investigated. Human lung epithelial Beas-2B cell and RAW 264.7 murine macrophage-based cell models, and a cigarette smoke (CS)-induced pulmonary impairment mice model are adopted for investigation in vitro and in vivo. RN is identified to be an Nrf2 activator, which promotes Nrf2 dissociation from Keap1 via reacting with the Cys151 cysteine residue of Keap1, and suppresses Nrf2 ubiquitination. In addition, RN is able to attenuate toxicant-stimulated oxidative stress and inflammatory response in vitro. Importantly, RN significantly relieves CS-induced oxidative insult and inflammation, and RN-induced inhibition of inflammation is related to inhibition of nuclear transcription factor-κB (NF-κB) and induction of cell autophagy. In conclusion, our data indicate that RN is an activator of the Nrf2 pathway and evidently alleviates pulmonary disorders via restricting NF-κB activation and promoting autophagy. RN is a promising candidate for the therapy of pulmonary disorders.