T-AOC Levels Research Articles

Alleviative effects of Ginkgo biloba extract on oxidative stress, inflammatory response and immune suppression induced by long-term glyphosate exposure in tilapia (Oreochromis niloticus)

Ginkgo biloba extract (GBE), a common herbal medicine, possesses antioxidative, anti-inflammatory and hepatoprotective properties. It has been wildly used as a feed additive in aquaculture to improve fish health. In the present study, we aimed to investigate the protective effects of GBE on glyphosate (Gly) chronic toxicity and explore its possible mechanisms in tilapia (Oreochromis niloticus). The tilapia was fed on diets containing GBE at doses of 0, 0.5, 1 and 4 g /kg and exposed to 16 mg/L Gly for 60 days. The control group was fed on 0 g/kg GBE and unexposed to Gly. The results showed that, in serum, compared with Gly alone treatment, 0.5 and/or 1 g/kg GBE treatments significantly inhibited the increase of TC, ALT and AST, while 1 and 4 g/kg GBE treatments significantly inhibited the decrease of HDL-C. Antioxidative status data showed that GBE treatments improved T-AOC and GSH levels in serum, T-AOC, CAT and GSH levels in liver, and SOD and GSH levels in gills when compared to Gly group. Also, GBE treatments suppressed the formation of MDA induced by Gly exposure in liver and gills. Meanwhile, GBE treatments blocked the downregulation of autoxidation-genes (nrf-2, gst, ho-1 and nqo1) induced by Gly exposure in gills and/or liver. Furthermore, compared with the Gly group, the inflammation-related genes (nf-kb, il-1β and/or tnf-α) were clearly downregulated in GBE-fed groups, while the immune-related genes (igm, hsp70 and/or c3) were apparently upregulated in 0.5 and/or 1 g/kg GBE-fed groups. Overall, these results indicated that GBE could alleviate the chronic toxicity of Gly exposure by improving antioxidative status, suppressing inflammation and enhancing immune function in tilapia.

Immunomodulatory effects of Nigella sativa seed polysaccharides by gut microbial and proteomic technologies

Cyclophosphamide (CTX) was used to establish the immunosuppressive mice model. The immune organ viscera index, phagocytes vitality, the levels of cytokines in serum, the oxidative stress resistance, proteomics and intestinal flora in mice were investigated to evaluate the effect of immune regulation of Nigella sativa seed polysaccharide (NSSP). The results showed that the high-dose NSSP group could significantly increase the thymus and spleen index. The levels of ACP, LDH, T-AOC, SOD, IL-2, IL-4 and IL-6 were significantly increased and the levels of TNF-α and MDA were reduced. All evidences indicated that NSSP could improve the immune effects of the immunosuppressed mice. Proteomics investigation showed that NSSP could improve the immune by regulating the differential proteins of PI3K and PTEN, and regulating the metabolism-related pathways such as autoimmune diseases and PI3K-Akt signaling pathway. of Gut microbes analysis showed that NSSP could exert immunomodulatory effects by improving the structure of the intestinal flora, increasing the diversity of the flora, and regulating metabolic pathways such as lipid metabolism, polysaccharide synthesis and signal transduction by the prediction of flora metabolic functions. In addition, NSSP could regulate intestinal environment by regulating the content of short chain fatty acids.

Mangiferin attenuates cigarette smoke-induced chronic obstructive pulmonary disease in male albino rats

We analyzed the ability of mangiferin to suppress cigarette smoke-induced chronic obstructive pulmonary disease. Control rats showed a marked decrease in the ratio of the forced expiratory volume at 0.1 s to forced vital capacity. The decreases in the peak expiratory flow and maximal mid-expiratory flow indicated airway remodeling and enlargement. The expression levels of superoxide dismutase (SOD), heme oxygenase-1 (HO-1), γ-glutamylcysteine synthetase, nuclear factor erythroid 2-related factor 2, and activating transcription factor 4 were increased in the control rats. The levels of oxidative stress, malondialdehyde, and reactive oxygen species peaked after 24 weeks, whereas the SOD and HO-1 levels and the total antioxidant capacity were reduced in control rats. Mangiferin restored the levels of reactive oxygen species, malondialdehyde, SOD, HO-1, and T-AOC to near normal. Increased numbers of infiltrating inflammatory cells were observed in control rats but were significantly reduced by mangiferin. In addition, edema and airway inflammation were reduced by mangiferin.

Effects of Cold-Pressing and Hydrodistillation on the Active Non-volatile Components in Lemon Essential Oil and the Effects of the Resulting Oils on Aging-Related Oxidative Stress in Mice.

The aim of this study was to analyze the non-volatile composition and antioxidant differences of lemon essential oils (LEOs) obtained by cold-pressing vs. hydrodistillation. Pathological observations showed that LEO effectively inhibited liver injury caused by oxidative stress, and CPLEO was more effective than HDLEO. CPLEO increased serum T-AOC, SOD, GSH, and GSH-Px levels while decreasing NO, COX-2, IL-6, IL-1β, IFN-γ, and TNF-α levels in mice with oxidative damage. The effects of CPLEO were stronger than those of HDLEO and similar to those of vitamin C. CPLEO upregulated mRNA and protein expressions of Cu/Zn-SOD, Mn-SOD, CAT, HO-1, Nrf2, and NQO1 while downregulating nNOS, iNOS, IL-1β, COX-2, TNF-α, and NF-κB mRNA expression and nNOS, eNOS, iNOS, and COX-2 protein expression in mice with oxidative damage. The results demonstrate that LEO has good antioxidant effects and that CPLEO has a better antioxidant effect than HDLEO as it retains more active non-volatile substances.

Evaluation of toxic effects induced by arsenic trioxide or/and antimony on autophagy and apoptosis in testis of adult mice.

Arsenic trioxide (ATO) and antimony (Sb) are well-known ubiquitous environmental contaminants and cause unpromising male reproductive effects in target and non-target exposed organisms. The main objective of this study was to investigate the effects of ATO or/and Sb on process of autophagy, apoptosis, and reproductive organ in adult mice. For this reason, a total of 32 adult mice were randomly divided into different groups like control group, ATO-treated group, Sb-treated group, and combined group. The duration of current experimental trial was 2 months. Various adverse effects of ATO or/and Sb on sperm parameters, oxidative stress, autophagy, and apoptosis were determined in testis of mice. Results indicated that parameters of sperm quality for organ coefficient, sperm count, ratio of sperm survival, testosterone level, and germ cells were significantly decreased, while malformation rate and vacuolization significantly increased in mice exposed to different treatments. Furthermore, the status of antioxidant index of T-AOC, SOD, and MsrB1 levels was reduced, while MDA increased significantly in ATO + Sb group. Results on TEM investigation determined that the autophagosomes, autolysosome, nuclear pyknosis, and chromatin condensation were prominent ailments, and the levels of autophagy and pro-apoptosis indictors including Beclin1, Atg-5, LC3B/LC3A, caspase-8, cytc, cleaved caspase-3, p53, and Bax were up-regulated in treated group, while the content of an anti-apoptosis maker (Bcl-2) was down-regulated. In conclusion, the results of our experiment suggested that abnormal process of autophagy and apoptosis was triggered by arsenic and antimony, and intensity of toxic effects increased in combined treatments of ATO and Sb.

Bioflocs attenuates lipopolysaccharide-induced inflammation, immunosuppression and oxidative stress in Channa argus

The regulation of C/N in aquaculture water is an important means of environmental regulation, of which the most common is bioflocs technology (BFT). Here, an eight-week feeding experiment and a lipopolysaccharide (LPS) challenge test were proceed to investigate the growth, oxidative stress, immunosuppression and GR–NF–κB related genes expression of Channa argus rearing in the BFT. Four groups were set, the control group was a basic diet (C/N = 7.6:1), and the other three groups were adjusted by glucose, which was C/N 10: 1, C/N 15: 1 and C/N 20:1, respectively. And we detected the two-stage test indexes of C. argus before and after the LPS challenge. The results showed that the bioflocs of C/N 15:1 group significantly (P < 0.05) promoted the growth performance. Similarly, the trend of immune enzyme activity was the same before and after LPS challenge, but decreased after challenge (except AKP and IgM). The best group is still treatment C/N 15:1. Liver and intestine SOD, CAT, GPX, ASA and T-AOC levels of juveniles in treatment C/N 15:1 were markedly increased (P < 0.05) compared to control before and after the LPS challenge. Simultaneously, the content of MDA in control group was considerably higher than that in treatment C/N 15:1 (P < 0.05). Furthermore, C/N 15:1 group significantly down-regulated the expression level of pro-inflammatory factors (NF-κB, TNF-α, IL-1β and IL-8), and up-regulated IκBα, GR, HSP70 and HSP90 expression levels considerably (P < 0.05). Also, intestinal morphology appeared injury in control group, while intestinal integrity was better in treatment C/N 10:1 and C/N 15:1 after challenge. Taken together, these upshot indicated that bioflocs could enhance growth and alleviate C. argus from LPS-induced oxidative stress, immunosuppression and inflammation through restraining GR–NF–κB signaling pathway. The best C/N ratio for alleviating LPS is 15:1.

Protective Effects of Silymarin Against D-Gal/LPS-Induced Organ Damage and Inflammation in Mice.

AimSilymarin contains various flavonoids and exhibits antioxidative, anti-inflammatory, and anticancer effects, in addition to other pharmacological properties. This study explored the alleviating effect of silymarin on multiple-organ damage induced by D-galactose/lipopolysaccharide in Kunming mice.MethodsKunming mice were injected intraperitoneally with D-galactose (30 mg/kg·BW)/LPS (3 μg/kg·BW) and then treated using silymarin with different doses (75 mg/kg·bw and 150 mg/kg·bw) via intragastric administration. Changes in organ indexes, pathological changes, liver-function index, biochemical indexes, molecular biological indexes, and genes related to the oxidation and inflammation of main organs were evaluated.ResultsAfter the mice were treated with silymarin, their body weight showed no significant change, and the liver, kidney, and lung indexes of the treated mice were higher than those of the model group; meanwhile, the corresponding histopathological formation was reduced. Compared with the model group, the silymarin-treated group showed reductions in ALT, AST, and liver function indexes in the mouse serum. Silymarin treatment also increased the SOD, CAT, GSH, GSH-Px, T-AOC, IL-10, and IL-12 levels, as well as reduced the MDA, NO, IL-6, IL-1β, TNF-α, IFN-γ levels in the mouse serum and liver tissues. In addition, quantitative polymerase chain reaction analysis indicated that the mRNA expression levels of SOD1, SOD2, CAT, GSH-Px, IL-10, Nrf2, HO-1, NQO1, Trx, and IκB-α were higher in the liver tissue of the silymarin-treated mice than in those of the model group; meanwhile, the mRNA expression levels of IL-6, IL-1β, TNF-α, IFN-γ, NF-κB, NLRP3, COX2, and p38 were lower than those in the model group.ConclusionSilymarin, which exhibits antioxidative and anti-inflammatory effects, can alleviate the liver, lung, and kidney damage induced by D-galactose/lipopolysaccharide. High-dose (150 mg/kg·bw) silymarin can more effectively inhibit organ damage, compared with low-dose silymarin (75 mg/kg·bw) in Kunming mice.

Bioflocs attenuate Mn-induced bioaccumulation, immunotoxic and oxidative stress via inhibiting GR-NF-κB signalling pathway in Channa asiatica

Manganese (Mn) is a relatively common element in aquatic ecosystems and can be bio-concentration, but the mechanism of manganese poisoning on fish health is unclear. Here, this study's objective was to evaluate the potential mechanisms of bioflocs in ameliorating Mn-induced toxicity in Channa asiatica. Three hundred sixty juveniles were randomly divided into 12 tanks. Four C:N ratios in triplicate tanks were tried: C/N = 7.6:1 with a commercial diet (control), C/N 10:1, C/N 15:1 and C/N 20:1, and the bio-accumulation, immunotoxic, oxidative stress, GR-NF-κB related genes expression and intestinal histomorphology were assessed in three different periods after Mn exposure (0 h, 48 h and 96 h). The results showed that bioflocs had a significant protective effect on Mn poisoning by preventing alterations in bio-accumulation levels, LSZ, AKP, C3, C4 and IgM, of which the C/N 15:1 group had the best relief effect. Furthermore, bioflocs also assisted in the recovery of liver T-SOD, CAT, GPX and T-AOC levels while decreasing the content of MDA. Moreover, C/N 15:1 group significantly down-regulated the expression level of NF-κB, TNF-α, IL-1β and IL-8 and up-regulated significantly IκBα, GR, HSP70 and HSP90 expression levels considerably (P < 0.05). From the intestinal section, the C/N 15:1 group resistance was the best one, and there was no difference between C/N 20:1 group and control group. These results revealed that administration of bioflocs (C/N 15:1) has the potential to combat Mn toxicity in C. asiatica, and the specific pathway may be GR-NF-κB.

Albicanol Alleviates D-Galactose-Induced Aging and Improves Behavioral Ability Via by Alleviating Oxidative Stress-Induced Damage.

Albicanol is a natural terpenoid derived from Dryopteris fragrans. Herein, we assessed the ability of Albicanol to protect against oxidative stress-induced senescence. Using a murine model of D-galactose (D-gal)-induced aging, we determined that Albicanol treatment can reverse D-gal-mediated learning impairments and behavioral changes, while also remediating brain tissue damage in treated mice. We found that serum SOD, CAT, GSH-Px, and T-AOC levels were significantly decreased in aging mice, and that Albicanol treatment significantly increased the serum levels of these antioxidant enzymes. We additionally evaluated the impact of Albicanol treatment on the Keap1/Nrf2/ARE signaling pathway, and found that it was able to decrease Keap1 expression while increasing the expression of Nrf2, thereby activating this signaling pathway, suppressing oxidative damage, and enhancing the expression of downstream target genes including SOD, GSH, GST, HO-1, and NQO1 in this murine aging model system. Albicanol treatment also inhibited the secretion of inflammatory TNF-a and IL-1b. Together, these data indicated that Albicanol can activate Nrf2 pathway-related genes, thereby inhibition of delayed aging by alleviating oxidative stress-induced damage.

Rosmarinic acid ameliorates septic-associated mortality and lung injury in mice via GRP78/IRE1α/JNK pathway.

Acute lung injury (ALI) is the major complication of sepsis, and no effective treatment is available now. Recently, rosmarinic acid (RA), a water-soluble polyphenolic phytochemical, exerts a potential role on ALI with anti-inflammation, and antioxidant properties. However, there is still no evidence on its protective effect on cell apoptosis in sepsis. Here, we investigated the protective effect of RA in septic-associated mortality and lung injury based on apoptosis. Male C57BL/6 mice were administered with lipopolysaccharide (LPS) (15 mg/kg, ip) to establish ALI mice model. Preteatment of RA (20 or 40 mg/kg, ip) was performed once daily for five consecutive days. The mortality was monitored for seven days after injection of LPS. RA (40 mg/kg) significantly decreased mortality and alleviated septic-associated lung injury. Meanwhile, RA significantly reversed LPS induced decrease in serum T-aoc level and superoxide dismutase (SOD) activity, and increase in malondialdehyde (MDA) activity. Furthermore, RA pretreatment significantly inhibited lung cell apoptosis, as well as decreased p53 level in sepsis mice. Finally, the LPS induced activation of GRP78/IRE1α/JNK pathway was suppressed by RA pretreatment. These findings indicated that RA could be beneficial to septic-associated lung injury through anti-apoptosis effect.

Effects of dietary supplementation recombined PtALF8 protein (rPtALF8) on the growth performance, antioxidant capacity and gut microbial composition in swimming crab, Portunus trituberculatus

An 8 weeks feeding trial was performed to determine the effects of dietary supplementation with rPtALF8 on the growth performance, antioxidant capacity and gut microbial composition in Portunus trituberculatus. Four experimental diets were carried out with addition of 0 (control), 10 (D10), 20 (D20), and 40 (D40) mg kg−1 rPtALF8 in diet. Three hundred and sixty crabs were randomly divided into four groups and each group contained three replicates. No significant difference was found in survival rate in each group (P > 0.05). Weight gain rate (WGR) and specific growth rate (SGR) in the D20 group were significantly higher than control group (P < 0.05). The activity of LZM in D10 and D20 groups were significantly higher than control group (P < 0.05), but there was no significant difference found between D10 and D20 group (P > 0.05). While rPtALF8 was added at 20 mg kg−1 in diet, the activity of ACP in the plasma reached the highest, significantly higher than that in the other groups (P < 0.05). In the D20 group, the T-AOC levels and the activity of SOD in the hepatopancreas were increased significantly (P < 0.05), whereas the MDA level was significantly lower than other three groups (P < 0.05). After being challenged with Vibrio alginolyticus, the cumulative mortality of D20 group and D40 group at 6 h and 12 h was significantly lower than that of the control group (P < 0.05). At 18 h and 24 h, the cumulative mortality rate of the D20 group was significantly lower than that of the control group (P < 0.05). However, no significant difference was detected between D40 and control groups (P > 0.05). In terms of gut microbiota, rPtALF8 could significantly affect the α-diversity and community composition of intestinal bacteria of P. trituberculatus. Proteobacteria, Bacteroidetes, and Firmicutes were the dominant bacteria in the gut of P. trituberculatus among groups. Highest relative abundance of Proteobacteria and lowest relative abundance of Firmicutes were observed in D40 group. Besides, supplementation of rPtALF8 in diet also significantly decrease the relative abundance of Thermobifida and Saccharomonospora. The results indicated that dietary supplementation with 20–40 mg kg−1 rPtALF8 could improve the WGR and SGR, enhance the antioxidant capacity and innate immunity of P. trituberculatus. In conclusion, rPtALF8 can be used as a novel antibiotic substitute in P. trituberculatus farming.

ShengMai-San Attenuates Cardiac Remodeling in Diabetic Rats by Inhibiting NOX-Mediated Oxidative Stress.

Background and PurposeShengMai-San (SMS) is traditionally used to treat ischemic cardiovascular and cerebrovascular diseases. Recently, several studies have reported the cardioprotective effects of SMS in diabetic animals. However, the potential mechanisms have not yet been fully elucidated. In this study, we investigated whether SMS exerts a beneficial effect in diabetic cardiomyopathy (DCM) by alleviating NADPH oxidase (NOX)-mediated oxidative stress.MethodsSD rats were randomly divided into a negative control group (NC), diabetes mellitus group (DM) and SMS-treated group (SMS). The myocardial structure alterations, apoptosis and biomarkers of oxidative stress were observed. Moreover, to explore the protective mechanism of SMS, the activation of AMPKα, expression and translocation of NOX-related proteins were assessed.ResultsDiabetes led to excessive collagen content, fibrosis, and apoptosis in the myocardium. Oxidative stress in diabetic hearts was indicated by low levels of T-AOC, high levels of 8-iso-PGF2α and 8-OHdG, inactivation of AMPKα, elevated expression of NOX2 and NOX4 and translocation of NOX isoforms p47phox and p67phox. Treatment with SMS for 10 weeks resulted in the alleviation of diabetes-associated myocardial structure abnormalities and apoptosis. Additionally, SMS attenuated the accumulation of oxidative stress markers in myocardial tissue. Further investigation showed that SMS was able to reverse the levels of oxidative stress-associated proteins NOX2 and NOX4 in the DM rats. Moreover, SMS treatment blunted the translocation of NADPH oxidase isoforms p47phox and p67phox as well. Furthermore, SMS promoted the activation of AMPK in the cardiac tissue of diabetic rats.ConclusionThese findings indicate that SMS exhibits therapeutic properties against diabetic cardiomyopathy by attenuating myocardial oxidative damage via activation of AMPKα and inhibition of NOX signaling.

Environmental contaminant BPA causes intestinal damage by disrupting cellular repair and injury homeostasis in vivo and in vitro

Our previous studies have shown that the environmental contaminant bisphenol A (BPA) exhibits strong intestinal toxicity and can readily cause intestinal barrier dysfunction. However, the causal relationship between adverse biological processes of BPA-induced intestinal tissue and the role of key signaling molecules in it requires further investigation. In this study, we established a mouse and intestinal epithelial cell model of BPA treatment to determine the underlying molecular mechanisms of BPA-induced intestinal injury. The results showed that the BPA treatment increased the intestinal permeability and disrupted the barrier function by increasing the chemical marker content and tight junction expression in intestinal tissues and blood circulation. BPA also altered the oxidative and antioxidant status of intestinal epithelial cells by increasing ROS and RNS contents and decreasing the activity levels of SOD, GPx, CAT, and T-AOC. BPA further induced inflammatory responses by upregulating the gene abundance of key factors of the innate immune system (TLR2, TLR4, MyD88, and NF-κB), the transcriptional activity of NF-kB, and the secretion of pro-inflammatory cytokines (IL-1β, IL-6, IL-8, and TNF-α). Moreover, apoptosis was activated by BPA, whereas cell proliferation was inhibited by BPA. Mechanistically, co-treatment of intestinal epithelial cells with BPA using the oxidative stress scavenger NAC, the NF-κB-specific inhibitor JSH-23, and the apoptosis inhibitor Z-VAD-FMK, respectively, showed that BPA activates the innate immune response by inducing oxidative stress. Consequently, apoptosis is promoted, and cell proliferation is inhibited, ultimately disrupting the intestinal barrier function. Our findings provide insight into the pathogenesis of BPA-induced gut injury.

Dietary Probiotics or Synbiotics Supplementation During Gestation, Lactation, and Nursery Periods Modifies Colonic Microbiota, Antioxidant Capacity, and Immune Function in Weaned Piglets.

This study was conducted to investigate the effect of dietary probiotics or synbiotics supplementation on colonic microbiota, antioxidant capacity, and immune function in weaned piglets. A total of 64 pregnant Bama mini-sows and then 128 of their weaned piglets were randomly assigned into control group, antibiotics group, probiotics group, or synbiotics group. The results showed that colonic Firmicutes and Bifidobacterium abundances in the probiotics group and total bacteria, Bacteroidetes, and Lactobacillus abundances in the synbiotics group were increased (P < 0.05), while Escherichia coli abundance in the synbiotics group was decreased (P = 0.061) compared with the control group. Firmicutes, Bifidobacterium, and total bacteria abundances were increased (P < 0.05) in the probiotics and synbiotics groups compared with the antibiotics group. Probiotics supplementation up-regulated (P < 0.05) the mRNA expression of GPR109A compared with the control and antibiotics groups. Dietary probiotics or synbiotics supplementation improved the antioxidant capacity by increasing (P < 0.05) the colonic CAT, GSH-Px, SOD, and T-AOC levels and plasma CAT, GSH, GSH-Px, and SOD levels and by decreasing (P < 0.05) the colonic and plasma MDA and H2O2 levels. Compared to the control group, the colonic IL-10, IFN-α, and sIgA concentrations and plasma IgA and IgM concentrations were significantly increased (P < 0.05) in the probiotics and synbiotics groups. Spearman's correlation analysis showed that the changed colonic microbiota, such as Lactobacillus and Bifidobacterium were correlated with the alteration of antioxidant indexes, cytokines, and immunoglobulins. In conclusion, dietary probiotics or synbiotics supplementation during gestation, lactation, and nursery periods could be used as an alternative for antibiotics in terms of gut health of weaned piglets.

The BRD4 inhibitor JQ1 protects against chronic obstructive pulmonary disease in mice by suppressing NF-κB activation.

To examine the effect of the BRD4 inhibitor JQ1 on mice with chronic obstructive pulmonary disease (COPD) via NF-κB. COPD models constructed by exposure to cigarette smoke and intratracheal instillation of lipopolysaccharides (LPS) in mice were treated with JQ1 (15, 25 or 50 mg/kg). HE staining was performed to observe histopathological changes in the lung tissues. Enzyme-linked immunosorbent assays (ELISAs) were used to measure the levels of IL-10, IFN-γ, IL-17, IL-1β, IL-6, TNF-α, MMP-2, MMP-9, MDA, SOD, T-AOC and HO-1, and gelatin zymography assays were used to examine MMP-2 and MMP-9 activity. A TransAMTM NF-κB p65 detection kit was used to test NF-κB p65/DNA binding activity. Western blotting was conducted to analyze NF-κB p65 in the nucleus and its acetylation. JQ1 dose-dependently improved the histopathological changes in the lung tissues and decreased the mean linear intercept (MLI), destructive index and inflammatory score of the mice with COPD. The mice with COPD showed increased levels of MMP-2, MMP-9, IFN-γ, IL-17, IL-1β, IL-6 and TNF-α with decreased IL-10 level; these changes were reversed by JQ1 in a dose-dependent manner. In addition, JQ1 reduced the MDA level and increased the SOD, HO-1 and T-AOC levels in mice with COPD, with suppression of NF-κB p65 expression in the nucleus, NF-κB/p65 (Lys310) acetylation and NF-κB p65/DNA binding activity in the lung tissues. The BRD4 inhibitor JQ1 can downregulate MMP-2 and MMP-9 expression, reduce inflammatory responses, and alleviate oxidative stress in mice with COPD, and this mechanism might be related to the inhibition of NF-κB.

Effects of dietary baicalin supplementation on growth performance, antioxidative status and protection against oxidative stress-induced liver injury in GIFT tilapia (Oreochromis niloticus)

Baicalin, a main bioactive compound of Scutellaria baicalensis, has a variety of pharmacological activities including antioxidation, anti-inflammation and hepatoprotection. However, there are few reports on these biological activities in fish. Therefore, the aim of this study was to assess the effects of baicalin on growth performance, antioxidative status and hepatoprotection in tilapia. The fish were fed on different doses of baicalin (0, 0.4, 0.8 and 1.6 g/kg diet). After feeding 60 days, parts of fishes were netted, and the blood, liver, gills and muscle tissues were collected to analyze the antioxidative effect. The remaining fishes were injected with saline or hydrogen peroxide (H2O2) for challenge test. The results showed that the specific growth rate of fish was slightly increased in three baicalin treatments, and the feed efficiency was clearly improved in 0.4 g/kg baicalin treatment. Meanwhile, the antioxidative capacity in blood, liver and/or gill was enhanced in treatments with 0.4, 0.8 and/or 1.6 g/kg baicalin. After challenge test, the pre-treatments with baicalin effectively alleviated H2O2-induced liver injury. In serum and liver, pre-treatments with 0.8 and/or 1.6 g/kg baicalin suppressed the oxidative damage induced by H2O2, as evidenced by improvement of the levels of SOD, T-AOC and GSH and the decline of MDA level. More important, pre-treatments with 0.4, 0.8 and/or 1.6 g/kg baicalin blocked the upregulation of mRNA levels of tlr1, myd88, irak4, rela, tnf-α and il-1β in H2O2-induced liver injury. In summary, dietary baicalin supplementation could improve feed efficiency, enhance antioxidative ability and alleviate oxidative stress-induced hepatotoxicity in tilapia.

Amelioration by Idesia polycarpa Maxim. var. vestita Diels. of Oleic Acid-Induced Nonalcoholic Fatty Liver in HepG2 Cells through Antioxidant and Modulation of Lipid Metabolism.

Idesia polycarpa Maxim. var. vestita Diels (I. polycarpa) is well known as an edible oil plant which contains abundant linoleic acid and polyphenols. The objective of this study was to maximize the by-product of defatted fruit of I. polycarpa. We found that the fraction D of ethyl acetate extract (EF-D) contained more polyphenols, which contribute to its strong antioxidant activity by antioxidant assays (DPPH, ABTS, and FRAP). Meanwhile, EF-D showed a significant lipid-lowering effect on oleic acid- (OA-) induced hepatic steatosis in HepG2 cells through enhancing antioxidant activity, reducing liver damage, and regulating lipid metabolism, antioxidant, and inflammation-related gene expression. The SOD and T-AOC levels significantly increased, but the levels of MDA, AST, and ALT decreased obviously when treated with EF-D. In general, EF-D improved the antioxidant enzyme activities and decreased the hepatic injury activities. Besides, treatment with EF-D for NAFLD influenced lipid metabolism and inflammation by activating PPARα which was associated with the increased expression of CPT1 and decreased expression of SCD, NF-κB, and IL-1. Moreover, EF-D improved the oxidative stress system through activation of the Nrf2 antioxidant signal pathways and upregulated its target genes of HO-1, NQO1, and GSTA2. The results highlighted the EF-D from the defatted fruit of I. polycarpa regarding lipid-lowering, proving it to be a potential drug resource of natural products for treating the nonalcoholic fatty liver disease (NAFLD).

Chronic exposure of hydrogen peroxide alters redox state, apoptosis and endoplasmic reticulum stress in common carp (Cyprinus carpio)

Hydrogen peroxide (H2O2) appears to be ubiquitous in natural water. Higher level of H2O2 can cause physiological stress, immunosuppression and even death in aquatic animals, but the physiological and molecular mechanisms of H2O2 toxicity are not well studied. Thus, the aim of the present study was to exposure potential toxic mechanisms of H2O2 via assessing the effects on redox state, apoptosis and endoplasmic reticulum (ER) stress in common carp. The fish were subjected to four concentrations of H2O2 (0, 0.25, 0.5 and 1 mM) for 14 days. And then, the tissues including blood, liver, muscle, gills, intestines, heart, kidney and spleen were collected to measure biochemical parameter and gene expression. The results showed that H2O2 exposure suppressed the majority antioxidative parameters in serum, liver, muscle and intestines, but enhanced T-SOD, CAT and T-AOC levels in gills. In all tested tissues, the MDA content was significantly promoted by H2O2 exposure. The oxidative stress-related genes including nrf2, gstα, sod, cat and/or gpx1 were upregulated in liver, gills, muscle, intestines, and/or kidney, but downregulated in heart after H2O2 exposure. Moreover, the ho-1 mRNA level was inhibited by H2O2 exposure in all tissues except intestines and spleen. After 14 days of exposure, H2O2 induced ER stress and initiated IRE1 and PERK pathways, which activated downstream genes, including chop, grp78 and/or xbp1s, to regulate UPR in liver, gills, muscle and/or heart. Meanwhile, H2O2 exposure activated MAPK pathway to regulate mitochondria-related genes including bcl-2, bax and cytc, which further triggered cas-8, cas-9 and cas-3, and accelerated apoptosis in liver, gills, muscle and heart. Importantly, in different tissues, the genes associated with oxidative stress, ER stress and apoptosis showed a different influence, and more significant influence was observed in the muscle, gills and liver. Overall results suggested that long-term H2O2 exposure induced oxidative stress, ER stress and apoptosis in the majority of tested tissues of common carp. The Nrf2, IRE1, PERK and MAPK pathways played important roles in H2O2-induced toxicity in fish. These data enriched the toxicity mechanism of H2O2 in fish, which might contribute to the risk assessment of H2O2 in aquatic environment.

Terpenoids of Ganoderma lucidum reverse cognitive impairment through attenuating neurodegeneration via suppression of PI3K/AKT/mTOR expression in vivo model

Abstract This study investigated effects of triterpenoids derived from Ganoderma lucidum (GLT) on the ability to attenuate cognitive impairment and reduce oxidative stress and inflammation induced by D-galactose using an aged rats model. The data revealed that dietary GLT intervention improved the memory of aged rats in a water maze experiment. A reduction in inflammation was also achieved as GLT decreased the levels of MDA, AGEs, NO, TNF-α and AChE activity, and increased the activity of T-AOC, GSH-Px, T-SOD, CAT and IL-2 level in serum. The GLT intervention revised hepatocyte cellular arrangement and binucleation of the liver status, and even hippocampal neurons morphology. GLT upregulated the expression of FOXO4, SIRT1, and downregulated the expression of GFAP, iNOS, PI3K, AKT, mTOR and IL-6 with activation of PI3K/AKT/mTOR pathway. The current study highlights a promising dietary approach for prevention or alleviation of oxidative stress, inflammation and cognitive impairment induced by age-related conditions.

Magnesium supplementation enhances insulin sensitivity and decreases insulin resistance in diabetic rats.

Objective(s):Diabetes mellitus has been suggested to be the most common metabolic disorder associated with magnesium deficiency. This study aimed to investigate the effects and mechanisms of magnesium supplementation on insulin receptor activity in elderly type 2 diabetes using a rat model and to provide experimental evidence for insulin resistance improvement by magnesium supplementation. Materials and Methods:Rat model of type 2 diabetes was developed using a high-fat diet along with low dose streptozotocin (STZ) treatment. Magnesium supplement was given orally by mixing with the high-fat diet. Serum insulin level, insulin sensitivity, and insulin receptor affinity were assessed using radioimmunoassay (RIA). Insulin receptor, insulin receptor substrate (IRS-2), and β-Arrestin-2 gene and protein expression levels were measured using immunohistochemistry and RT-PCR. Xanthine oxidase assay, thiobarbituric acid reactive substance assay (TCA method), colorimetric assay, and ELISA were used to determine the serum SOD, MDA, T-AOC, and ox-LDL levels, respectively. Results:Magnesium supplementation enhanced insulin sensitivity and decreased insulin resistance in diabetic rats mainly through increasing insulin receptor expression, affinity, and augmenting insulin receptor signaling. Magnesium supplementation also inhibited lipid peroxidation in diabetic rats and protected against pancreatic cell injury in diabetic rats. In addition, we found that β-arrestin-2 gene expression was suppressed in diabetes, which was possibly attributed to gene methylation modification, as β-arrestin 2 promotor was rich in methylation-regulating sites. Magnesium supplementation could affect β-arrestin-2 gene expression and methylation.Conclusion:Magnesium supplementation has a positive effect on insulin receptor activity and insulin sensitivity in type 2 diabetes.