Oxidative Cell Damage Research Articles

Mitochondrial metabolic flexibility is critical for CD8+ T cell antitumor immunity.

Mitochondria use different substrates for energy production and intermediatory metabolism according to the availability of nutrients and oxygen levels. The role of mitochondrial metabolic flexibility for CD8+ T cell immune response is poorly understood. Here, we report that the deletion or pharmacological inhibition of protein tyrosine phosphatase, mitochondrial 1 (PTPMT1) significantly decreased CD8+ effector T cell development and clonal expansion. In addition, PTPMT1 deletion impaired stem-like CD8+ T cell maintenance and accelerated CD8+ T cell exhaustion/dysfunction, leading to aggravated tumor growth. Mechanistically, the loss of PTPMT1 critically altered mitochondrial fuel selection-the utilization of pyruvate, a major mitochondrial substrate derived from glucose-was inhibited, whereas fatty acid utilization was enhanced. Persistent mitochondrial substrate shift and metabolic inflexibility induced oxidative stress, DNA damage, and apoptosis in PTPMT1 knockout cells. Collectively, this study reveals an important role of PTPMT1 in facilitating mitochondrial utilization of carbohydrates and that mitochondrial flexibility in energy source selection is critical for CD8+ T cell antitumor immunity.

Растительные радиопротекторы в технологии молочных продуктов

Certain dairy products are known for their antiradiation properties. This article opens with some theoretical aspects of long-term radiation exposure and prevention of free radical processes to move on to the methods that counteract oxidative stress and cell damage in the human body. The empirical part of the research featured the radioprotective properties of milk thistle (Silybum), which were determined by conventional analytical and physico-chemical methods. Milk thistle seed flour was studied for antioxidant activity, which appeared to be 2,400 times as high as that of pasteurized milk. The research objective was to develop a dairy product fortified with milk thistle: to reveal the optimal dose of milk thistle flour, to define the technology that would preserve the antioxidant properties, and to select the most efficient introduction method. The mineral composition of milk thistle flour (100 g) included 1006.66 mg Ca, 457.19 mg Mg, 1082.71 mg K; 1.62 mg Cu, 6.07 mg Z, 8.26 mg Fe, and 701.48 mg P. Eggshells served as a source of calcium to fortify the drink. The resulting fermented dairy product with milk thistle flour proved to be functional as it demonstrated alimentary action against radiostrontium. One glass (200 ml) contained 1,000 mg Calcium, which exceeded the daily physiological need. The study also involved microbiological and sensory evaluation, which proved that the samples fermented with acidophilic starter culture had the optimal sensory profile.

Combination of dimethylmethoxy chromanol and turmeric root extract synergically attenuates ultraviolet-induced oxidative damage by increasing endogenous antioxidants in HaCaT cells.

Repeated exposure to UV generates excessive reactive oxygen species (ROS) and damages the enzymatic antioxidant defense system including quinone oxidoreductase 1 (NQO1) and superoxide dismutase (SOD) in skin. Topical application of antioxidants may prevent the undesired damage of cellular proteins, lipids and DNA in skin. Dimethylmethoxy chromanol (DMC) is a bioinspired molecule, designed to be a structural analog to the γ-tocopherol that is naturally present in vegetables and plants. Turmeric root extract (TRE) is from a plant in South Asia extensively used as a food spice & vegetable, and its main components are turmerones. As both DMC and TRE are strong antioxidants with complementary antioxidation mechanisms, the aim of this study was to investigate the enhanced protective effects of their combination on oxidative damage in HaCaT cells following UVB exposure. The effects of single and combined administrations of DMC and TRE on the SOD activity of HaCaT cells were evaluated by the SOD assay and qPCR. The NQO1 expression in the UVB-treated HaCaT cells was analyzed by the Western Blot. Furthermore, a clinical test involving 24 subjects was conducted to evaluate the in vivo antioxidation efficacies of the serum formulated with the combination of DMC and TRE at the optimal weight ratio. SOD assay showed that pretreating DMC or TRE alone could not preserve the impaired HaCaT SOD activity after UVB treatment. DMC and TRE at 1:1 weight ratio was the optimal combination to enhance the HaCaT SOD activity by approximately more than 1-fold compared with either of the single treated groups. No enhancement effect was observed at other mixing ratios. The 1:1 weight ratio was further proved to be optimal as this combination boosted the NQO1 expression by more than 50%, whereas no boosting effect was observed at other mixing ratios. The clinical test of the serum containing this optimal antioxidant combination demonstrated promising in vivo antioxidation efficacies after 4-week use, including 7.16% improvement in skin lightening, 18.29% reduction in skin redness, 35.68% decrease in TEWL, 19.05% increase in skin gloss and 32.04% enhancement in skin firmness. Collectively, our results indicated that the combination of DMC and TRE at 1:1 weight ratio attenuated the UV-induced oxidative damage by synergistically boosting endogenous antioxidant enzyme activity in HaCaT cells. Therefore, this optimal antioxidant combination is a promising treatment to boost skin antioxidation defense system.

High‐salt diet enhances Helicobacter pylori infection and increases the prevalence of Alzheimer’s disease

AbstractBackgroundThe American Heart Association recommends that adults consume less than 2,300 milligrams of salt (sodium chloride) daily; anything surpassing this limit is classified as a “high‐salt diet (HSD)” [1]. Research has shown that excessive salt intake stimulates the gastric mucosa, favoring Helicobacter pylori (Hp) colonization [2]. In this review, the relationship between HSD and the susceptibility to Hp infection will be discussed. It is proposed that increased salt consumption will cause neurodegeneration, i.e. Alzheimer’s disease (AD) by way of increased expression of Hp strains in the gastric mucosa.MethodsA complex and specific literature search was conducted across various scientific, international databases for English, peer‐reviewed articles and reviews published in the last decade using the following terms: Helicobacter pylori, amyloid‐β, high‐salt diet, and Alzheimer’s disease. Case reports were excluded. The main objectives were predominantly focused on animal‐based studies.ResultsExperimental data shows HSD enhances Hp growth in mice. The subsequent microglial activation containing H. pylori‐specific IgG, IL‐8 and TNF‐α in the cerebrospinal fluid, induces oxidative damage in neuronal cells. In addition, urease in Hp increases cytosolic [Ca2+] apoptosis and autophagy of neurons. Hp filtrate induces tau hyperphosphorylation at AD‐tau phosphorylation sites such as Thr231 and Ser404. Hp ‐infected mice show a significantly larger GFAP‐positive astrocyte area than non‐infected mice. Immunostaining reveals microglia and astrocytes to be found adjacent to amyloid‐β plaques in Hp‐infected AD model mice. Injection of Hp filtrate impairs the maturation of dendritic spines, increasing Aβ42 production in the hippocampus and cortex, and enhancing expression of PS‐2, resulting in delayed spatial learning and impaired memory in rats.ConclusionThis review provides comprehensive evidence of potential synergistic effects of HSD and Hp on the brain resulting in neurodegeneration and AD progression. Understanding the pathologic consequences of salt consumption on this infection may be key in the prevention of dementia and AD. Thus, further research is required for substantiation of causality, the role of antibiotics and to examine other novel therapeutics.

Endoplasmic reticulum stress participates in apoptosis of HeLa cells exposed to TPHP and OH-TPHP via the eIF2α-ATF4/ATF3-CHOP-DR5/P53 signaling pathway.

Triphenyl phosphate (TPHP) is a widely used organophosphate flame retardant, which can be transformed in vivo into diphenyl phosphate (DPHP) and 4-hydroxyphenyl phosphate (diphenyl) ester (OH-TPHP) through biotransformation process. Accumulation of TPHP and its derivatives in biological tissues makes it necessary to investigate their toxicity and molecular mechanism. The present study evaluated the cellular effects of TPHP, DPHP, and OH-TPHP on cell survival, cell membrane damage, oxidative damage, and cell apoptosis using HeLa cells as in vitro model. RNA sequencing and bioinformatics analysis were conducted to monitor the differently expressed genes, and then RT-qPCR and Western bolt were used to identify potential molecular mechanisms and key hub genes. Results showed that OH-TPHP had the most significant cytotoxic effect in HeLa cells, followed by TPHP; and no significant cytotoxic effects were observed for DPHP exposure within the experimental concentrations. Biological function enrichment analysis suggested that TPHP and OH-TPHP exposure may induce endoplasmic reticulum stress (ERS) and cell apoptosis. The nodes filtering revealed that ERS and apoptosis related genes were involved in biological effects induced by TPHP and OH-TPHP, which may be mediated through the eukaryotic translation initiation factor 2α/activating transcription factor 4 (ATF4)/ATF3- CCAAT/ enhancer-binding protein homologous protein (CHOP) cascade pathway and death receptor 5 (DR5) /P53 signaling axis. Above all, these findings indicated that ERS-mediated apoptosis might be one of potential mechanisms for cytotoxicity of TPHP and OH-TPHP.

Luteolin Attenuates Oxidative Stress and Colonic Hypermobility in Water Avoidance Stress Rats by Activating the Nrf2 Signaling Pathway.

Irritable bowel syndrome (IBS) is an intestinal disorder, whose symptoms can be alleviated by certain dietary phytochemicals. This study explores the role and potential mechanisms of a natural flavonoid luteolin (LUT) in alleviating the excessive motility of colonic smooth muscles and reducing oxidative stress in IBS with diarrhea (IBS-D) rats. LUT reduces excessive intestinal motility and lowers reactive oxygen species (ROS) levels in a water avoidance stress (WAS) rat model. Moreover, LUT increases the protein expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1), activates the nuclear translocation of Nrf2, and greatly reduces the hydrogen peroxide (H2 O2 )-induced oxidative damage in intestinal epithelial cells. LUT, a phyto-active component, protects against excessive intestinal motility and diarrhea by regulating the Nrf2 signaling pathway and effectively reduces oxidative stress damage in the colon.

Cytoprotective Effect of Acid-Hydrolyzed Sesame Leaves against Oxidative Stress in HepG2 Cells

In this study, we investigated the cytoprotective effects of acid-treated sesame leaf extracts against oxidative damage in HepG2 cells. Treatment with 0.1 M HCl of sesame leaves significantly increased their verbascoside content (4.398 g/100 g) compared to non-acid-treated leaves (3.950 g/100 g). Acid-treated sesame leaf extract (ASLE) showed no cytotoxicity in HepG2 cells. ASLE conferred a greater cytoprotective effect against oxidative insult than a methanol extract of sesame leaves (SLE), verbascoside, and a vehicle control group. ASLE treatment also significantly inhibited reactive oxygen species generation in response to oxidative stress. Treatment with tert-butyl hydroperoxide increased malondialdehyde (MDA) levels, and depleted reduced glutathione (GSH). However, ASLE treatment significantly ameliorates this MDA and GSH depletion. Moreover, ASLE increased the activities of antioxidant enzymes including catalase, glutathione reductase, and glutathione peroxidase. Phenolic compounds in ASLE and SLE were characterized using UPLC-Q-TOF/MS analysis. A total of 29 iridoid and phenol compounds were tentatively identified in ASLE, and 27 compounds were observed in SLE. These results suggest that acid treatment of sesame leaves enhances the protective effects of their extract against oxidative stress by modulating antioxidant enzymes in HepG2 cells.

The Iron Chaperone Poly C Binding Protein 1 Regulates Iron Efflux through Intestinal Ferroportin in Mice

Iron is an essential nutrient required by all cells but used primarily for red blood cell production. Because humans have no effective mechanism for ridding the body of excess iron, the absorption of dietary iron must be precisely regulated. The critical site of regulation is the transfer of iron from the absorptive enterocyte to the portal circulation via the sole iron efflux transporter, ferroportin (FPN). Here we report that poly(rC)-binding protein 1 (PCBP1), the major cytosolic iron chaperone, is necessary for the regulation of iron flux through FPN in the intestine of mice. PCBP1 binds iron-glutathione complexes in the cytosol of cells and delivers the iron to ferritin, the iron storage protein, to iron centers in enzymes, and to iron-sulfur cluster chaperones. PCBP1 also limits the chemical reactivity of iron, thereby limiting iron-catalyzed oxidative damage in cells. To explore the role of PCBP1 in dietary iron absorption, we developed mice with an inducible, enterocyte-specific deletion of PCBP1. Mice lacking PCBP1 in the intestinal epithelium exhibit low levels of enterocyte iron, poor retention of dietary iron in enterocyte ferritin, and excess efflux of iron through FPN. Kinetic studies of iron transport using a stable isotope ( 57Fe) coupled with a mini-hepcidin that blocks FPN activity demonstrated that PCBP1 deletion had no effect of intestinal iron uptake but caused high rates of iron efflux through FPN. Surprisingly, excess iron efflux occurred despite lower levels of FPN protein in enterocytes and upregulation of the iron regulatory hormone hepcidin. PCBP1 deletion and the resulting unregulated dietary iron absorption led to poor growth, severe anemia on a low iron diet and liver oxidative stress with iron loading on a high iron diet. To investigate the roles of PCBP1 more precisely in enterocytes, we developed 3-D organoid cultures from intestinal epithelium which functionally expressed the major iron trafficking proteins: divalent metal transporter 1, PCBP1, ferritin, transferrin receptor 1 and FPN. Ex vivo culture of wild-type and PCBP1-depleted enteroids demonstrated normal patterns of FPN expression and hepcidin-mediated turnover. However, fluorescence measurements of kinetically labile iron pools in enteroids competent or blocked for FPN iron efflux indicated that PCBP1 dramatically altered efflux activity. PCBP1 functioned as a cytosolic buffer for iron, binding and retaining iron and thereby keeping “free” iron at very low levels. This low concentration of free iron limited its availability for FPN-mediated efflux and allowed hepcidin-mediated changes in FPN levels to regulate the amount of iron exported from the enterocyte. Thus, by binding enterocyte iron, PCBP1 reduces the concentration of unchaperoned, “free” iron to a low level. This low level of cytosolic free iron is necessary for hepcidin-mediated regulation of FPN activity.

Nutraceutical Potential of Grape (Vitis vinifera L.) Seed Oil in Oxidative Stress, Inflammation, Obesity and Metabolic Alterations

Vitis vinifera L. (grapevine) is a perennial plant of the Vitaceae family that is widely used to produce grapes and wines. Grape seed oil is rich in fatty acids such as linoleic acid (65–75%), vitamin E (50 mg), and phytosterols in addition to phenolic compounds, such as catechins (414 mg), epicatechins (130.4 mg), and gallic acid (77 µg), shows promise as a nutritional compound and is outstanding as a therapeutic substance with active properties for health, detected mainly by in vitro studies, as well as some in vivo studies. The benefits of consuming this oil include modulating the expression of antioxidant enzymes, anti-atherosclerotic and anti-inflammatory effects, and protection against oxidative cell damage and some types of cancer. However, experimental findings confirm that therapeutic functions remain scarce; thus, more studies are needed to determine the mechanisms of action involved in the indicated therapeutic qualities.

Heat stress suppresses MnSOD expression via p53-Sp1 interaction and induces oxidative stress damage in endothelial cells: Protective effects of MitoQ10 and Pifithrin-α

AimTo investigate the mechanism of p53-mediated suppression of heat stress-induced oxidative stress damage by manganese superoxide dismutase (MnSOD) in endothelial cells (ECs). MethodsPrimary ECs isolated from mouse aortas were used to examine the effects of heat stress on vascular ECs viability and apoptosis. We measured MnSOD expression, reactive oxygen species (ROS) production, p53 expression, viability, and apoptosis of heat stress-induced ECs. We also tested the protective effects of MitoQ10, a mitochondrial-targeted antioxidant, and Pifithrin-α, a p53 inhibitor, in ECs from a mouse model of heat stroke. ResultsHeat stress increased cellular apoptosis, ROS production, and p53 expression, while reducing cellular viability and MnSOD expression in ECs. We also showed that the suppression of MnSOD expression by heat stress in ECs was mediated by interactions between p53 and Sp1. Furthermore, MitoQ10 and Pifithrin-α alleviated heat stress-induced oxidative stress and apoptosis in ECs. ConclusionOur results revealed that p53-mediated MnSOD downregulation is a key mechanism for heat stress-induced oxidative stress damage in ECs and indicated that MitoQ10 and Pifithrin-α could be potential therapeutic agents for heat stroke.

Erythrocyte labile iron pool indicating concealed iron overload in non-transfusion-dependent β-thalassemia

Abstract Objectives Not only do transfusion-dependent thalassemia (TDT) patients have a risk of clinical consequences arising from iron overload, non-transfusion-dependent thalassemia (NTDT) patients may encounter it also. In this study, we demonstrated the usefulness of intra-erythrocyte labile iron pool (LIP) measurement in NTDT patients with HbE/β-thalassemia in revealing a concealed iron overload and the resultant oxidative cell damage. Methods LIP and ferritin levels were assayed in 20 HbE/β-thalassemia patients, comprising 10 NTDT and 10 TDT patients and 10 healthy individuals. Erythrocyte oxidative stress parameters (intraerythrocyte reactive oxygen species (ROS) levels, numbers of erythrocyte vesicles, and cell apoptosis) were also determined and their correlations to LIP and ferritin levels were analyzed. Results LIP levels (based on different mean fluorescence intensity (MFI) values obtained by flow cytometry) were high in both the NTDT (54 [42–90]) and TDT (71 [68–77]) patients compared to the healthy individuals (43 [31–61]). The ferritin level observed in the NTDT group (2,149 [781–4,071] ng/mL) was lower than that of the TDT group (4,885 [2,343–7,826] ng/mL). The LIP level was significantly correlated with the NTDT patients’ age and all oxidative stress parameters, but the ferritin level was not. Correlation analysis predicted that NTDT patients without receiving any therapy aged 32.5 years old or over are likely at risk of iron overload status and oxidative cell damage. Conclusions The results indicate that LIP may be a helpful alternative parameter for defining the risk of iron overload.

Inhibition mechanism and biological recycling utilization of microalgae culture aging solution

During the process of recovering microalgae culture media, the culture media will age and inhibit the growth of microalgae. When the culture media was reused for the third time, the maximum biomass of Spirulina platensis FACHB-439 was only 56.13% of the fresh culture media. But the inhibitors in the aging solution are not known. In this study, the growth inhibition mechanism of Spirulina platensis aging solution was clarified through the identification of target organic matter by cyclic culture experiment and ion chromatography. The results showed that the growth inhibitors in the aging solution were polysaccharides, mainly including fucose and rhamnose. Further reverse addition experiments confirmed that polysaccharide inhibitors would increase with the increase of repeated use of the culture media. By inhibiting the synthesis of photosynthetic pigments in microalgae, they could cause oxidative damage and membrane peroxidation of microalgae cells, resulting in stress on the growth of microalgae. At the same time, this study established a purification method for reusing aging solution of heterologous microalgae (Chlorella sp. L166) to obtain high lipid and high carbohydrate biomass energy. The results showed that the biomass of Chlorella sp. L166 in the first circulating aging solution of S.platensis FACHB-439 increased by 25%, the carbon utilization rate reached 21.36%, the lipid content per cell increased by 1.61 times, and the carbohydrate content increased by 86.71%. This work is helpful to solve the problem that aging of culture media inhibits carbon sequestration efficiency and biomass yield of microalgae in large-scale production of microalgae. And the results of this study have achieved high utilization rate of water resource for large-scale cultivation of microalgae, which is conducive to realize the scale development of microalgae biotechnology.

Cucurbitacin B protects against myocardial ischemia-reperfusion injury through activating JAK2/STAT3 signaling pathway.

Cucurbitacin B, a tetracyclic triterpenoid compound extracted from various plants, has been proven to exert a vital role in various diseases. However, the effect of cucurbitacin B on myocardial infarction (MI) and ischemia-reperfusion (I/R) injury is still relatively unclear. The main purpose of the present study was to investigate the effect of cucurbitacin B on cell apoptosis and oxidative damage after myocardial I/R injury in vitro and in vivo and elucidate the molecular mechanisms underlying its role. The 56-day-old adult mice and 1-day-old neonatal mice cardiomyocytes were used to construct I/R or oxygen-glucose deprivation/reoxygenation (OGD/R) injury models. The oxidative injury, western blot and TUNEL assay were performed to evaluate cardiomyocyte damage in the present study. In vitro， we confirmed that cucurbitacin B could attenuate LDH release, oxidative stress and cell apoptosis in cardiomyocytes exposed to OGD/R. Besides, we confirmed in an adult I/R mouse model that cucurbitacin B can improve cardiac repair and block cell apoptosis in the acute phase (24 h) post-myocardial I/R injury, as well as promote long-term cardiac function and fiber scar area after 28 days of I/R. Mechanically, we clarify that cucurbitacin B exerts cardiomyocyte protective effects through activating the JAK2/STAT3 signaling pathway. In conclusion, our study elucidates for the first time the protective role of cucurbitacin B in cardiac I/R injury, which provides a novel perspective for better prevention of I/R injury through the JAK2/STAT3 signaling pathway.

Carboxylated Pocoa polysaccharides inhibited oxidative damage and inflammation of HK-2 cells induced by calcium oxalate nanoparticles

The inhibitory effects of Chinese medicine Pocoa (PCPs) with different carboxyl group (-COOH) contents on oxidative damage and inflammatory response of renal epithelial cells and the influence of -COOH content in polysaccharides were investigated. HK-2 cell damage model was established by nanocalcium oxalate crystals (nanoCOM), and then PCPs with -COOH contents of 2.56% (PCP0), 7.48% (PCP1), 12.07% (PCP2), and 17.18% (PCP3) were used to protect the cells. PCPs could inhibit the damage of nanoCOM to HK-2 cells, increase cell viability, restore cytoskeleton and morphology, and improve lysosomal integrity. PCPs can reduce the oxidative stress response of nanoCOM to cells, inhibit the opening of mPTP and cell necrotic apoptosis, reduce the level of Ca2+ ions in cells, the production of ATP and MDA, and increase SOD expression. PCPs can also reduce the cellular inflammatory response caused by oxidative damage, and reduce the expression of nitric oxide (NO), inflammatory factors TNF-α, IL-6, IL-1β and MCP-1, as well as the content of inflammasome NLRP3. After protection, PCPs can inhibit the endocytosis of nanoCOM crystals by cells. With the increase in -COOH content in PCPs, its ability to inhibit nanoCOM cell damage, reduce oxidative stress, reduce inflammatory response, and inhibit crystal endocytosis increases, that is, PCP3 with the highest -COOH content, shows the best biological activity. Inhibiting cell damage and inflammation and reducing a large amount of endocytosis of crystals by cells are beneficial to inhibit the formation of kidney stones.

Preparation of pectin from fingered citron peel and its protective effect on cadmium-induced liver and kidney damage in mice

Citrus pectin has been proved for its ability to bind heavy metals from industrial wastewater. However, few studies have investigated the detoxification effect of citrus pectin on cadmium-induced damage through in vivo experiments. In this study, pectin was extracted from fingered citron peel and subjected to pH-temperature modification, and successful modification of pectin's molecular structure was confirmed by a decrease in the degree of esterification and the increase in the content of free carboxylate groups in the structure. In vitro studies suggested that the modified fingered citron peel pectin (mFCPP) showed higher cadmium removal ability compared to unmodified fingered citron peel pectin (FCPP). A 20-week study in cadmium-exposed mice suggested significant improvement in liver and kidney function with co-treatment of pectin. Co-treatment with FCPP or mFCPP ameliorated the cadmium-induced cell death and oxidative damage in the liver and kidney. Moreover, the study demonstrated that both FCPP and mFCPP were impermeable through the intestinal wall, suggesting their binding with the cadmium ions in the gastrointestinal tract, thus preventing cadmium ions absorption and entry into the systemic circulation.

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.

Composition of Polygonatum zanlanscianense Pamp. Steam and Leaf Phenolic Extract and Its Protective Mechanism on t-BHP-Induced Oxidative Damage of HepG2 Cells.

Plant phenolic compounds have attracted considerable attention because of their health benefits. This study aimed to investigate the composition and antioxidant activity of phenol extracts from Polygonatum zanlanscianense Pamp. steam and leaf (PPP). The FTIR, UPLC-Q-Obtrip-MS, and HPLC-DAD methods were used to analyze the composition of PPP, and 20 phenolic compounds were preliminarily identified. Among them, the contents of hyperin, astragalin, and diosmetin levels were the highest. Treatment with PPP can significantly reduce t-BHP-induced cell damage in HepG2 cells, reactive oxygen species (ROS) accumulation, and malondialdehyde (MDA) content. Meanwhile, the superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and glutathione peroxidase (GSH-Px) activities can be increased. Moreover, PPP enhanced Nrf2 expression, which was consistent with that of heme oxygenase-1 (HO-1), glutamate-cysteine ligase catalytic subunit (GCLC), and NAD(P)H quinone oxidoreductase-1 (NQO1), whereas the expression of Keap1, the Nrf2 inhibitor, was decreased. All findings indicate that PPP can serve as a natural bioactive substance for preventing oxidative stress.

PSVII-21 Protective Effect of Peptide Extract Derived from Beef Protein By Hydrolysis Against Oxidative Damage

Abstract This study was conducted to determine the protective effects of peptide extract with 3 kDa from beef myofibrillar protein by Alkaline-AK enzyme (AK3K) against oxidative damage in SH-SY5Y cells and in the brains of spontaneously hypertensive rats (SHRs). All data were presented as the mean ± standard deviation of three replicates. All statistical analyses were performed using the one-way analysis of variance procedure in SPSS 20.0. A Tukey's multiple comparison test was used to determine significant differences between mean values, and evaluations were based on a significance level of P < 0.05. The AK3K did not affect cytotoxicity in SH-SY5Ycells (Figure 1). The resulting AK3K decrease the apoptotic ratio by 33.25%, DNA fragmentation, and reactive oxygen species (ROS) generation in oxidative damage induced SH-SY5Y cells (Figure 2). The SHR brains treated with the AK3K (400 mg/kg body weight, AK3K400) showed a significant decrease in malondialdehyde and ROS contents at 0.33 and 23.92 μM, respectively (P < 0.05) compared with the control. The SOD activity for AK3K was 61.26%, around 20% greater than the control. Therefore, this study suggest that the peptide extract from beef have neuroprotective effects such as inhibition of apoptotic factors and increment of antioxidant enzyme against oxidative stress and could possibly be used for neuronal hypertension therapy.

Antioxidant, Anticancer, and Neuroprotective Activities and Phytochemical Analysis of Germinated Shoots

This study evaluated the antioxidant, anticancer, and neuroprotective activities of germinated shoots (cotyledon and true leaves) of wild plants and measured their total phenol, flavonoid, quercetin, and vitamin C contents. The ethanol extract of Geum aleppicum (GA) showed high DPPH and ABTS radical scavenging activities. GA treatment also significantly increased cell viability against hydrogen peroxide-induced oxidative stress in SH-SY5Y neuronal cells, indicating that GA had antioxidant and neuroprotective properties. In AGS gastric cancer cells, the cotyledon of Pinus densiflora (PD1) and the true leaves of Chamaecyparis obtusa (CHA2) significantly inhibited cell proliferation, showing that PD1 and CHA2 elicited anticancer effect. The total phenol content was the highest in the shoots of GA, and the total flavonoid content was the highest in the shoots of true leaves of P. densiflora. The quercetin and vitamin C contents were the highest in the CHA2 and the cotyledon of GA, respectively. In conclusion, this study suggested the antioxidant, anticancer, and neuroprotective activities of the germinated shoots of wild plants and their high total phenol, flavonoid, quercetin, and vitamin C contents. These findings were noteworthy in the case of the germinated shoot of GA and provided a basis for studying functional forestry income resources. Practical Applications. Our results demonstrated that GA exerts strong DPPH and ABTS radical scavenging activities. It also plays a neuroprotective role in oxidative stress-induced cell damage. These effects can be linked to their polyphenol and flavonoid contents in the extract. Moreover, PD1 treatment has inhibitory effect on gastric tumor cells growth and exhibited an effective ∙OH radical scavenging property. These findings indicated that germinated shoot extracts have potential for development of functional food with therapeutic applications.

Demethoxymurrapanine, an indole-naphthoquinone alkaloid, inhibits the proliferation of oral cancer cells without major side effects on normal cells.

Antioral cancer drugs need a greater antiproliferative impact on cancer than on normal cells. Demethoxymurrapanine (DEMU) inhibits proliferation in several cancer cells, but an in-depth investigation was necessary. This study evaluated the proliferation-modulating effects of DEMU, focusing on oral cancer and normal cells. DEMU (0, 2, 3, and 4 μg/mL) at 48 h treatments inhibited the proliferation of oral cancer cells (the cell viability (%) for Ca9-22 cells was 100.0 ± 2.2, 75.4 ± 5.6, 26.0 ± 3.8, and 15.4 ± 1.4, and for CAL 27 cells was 100.0 ± 9.4, 77.2 ± 5.9, 57.4 ± 10.7, and 27.1 ± 1.1) more strongly than that of normal cells (the cell viability (%) for S-G cells was 100.0 ± 6.6, 91.0 ± 4.6, 95.0 ± 2.6, and 95.8 ± 5.5), although this was blocked by the antioxidant N-acetylcysteine. The presence of oxidative stress was evidenced by the increase of reactive oxygen species and mitochondrial superoxide and the downregulation of the cellular antioxidant glutathione in oral cancer cells, but these changes were minor in normal cells. DEMU also caused greater induction of the subG1 phase, extrinsic and intrinsic apoptosis (annexin V and caspases 3, 8, and 9), and DNA damage (γH2AX and 8-hydroxy-2-deoxyguanosine) in oral cancer than in normal cells. N-acetylcysteine attenuated all these DEMU-induced changes. Together, these data demonstrate the preferential antiproliferative function of DEMU in oral cancer cells, with the preferential induction of oxidative stress, apoptosis, and DNA damage in these cancer cells, and low cytotoxicity toward normal cells.