GSH) And Glutathione Peroxidase Research Articles

Anti-inflammatory lindenane sesquiterpeniods and dimers from Sarcandra glabra and its upregulating AKT/Nrf2/HO-1 signaling mechanism

Sarcandra glabra (Thunb.) Nakai (Chloranthaceae), grown and cultivated evergreen shrub in south of China, has been used in traditional Chinese medicines (TCMs) to treat bruises, bone fractures and arthritis which were partly due to inflammation. Previous phytochemical and pharmacological researches indicated that flavonoids, coumarins, phenolic acids as its main anti-inflammatory ingredients related to its traditional efficacy. Our present research aimed to elucidate whether the fascinating and abundant lindenane-type sesquiterpeniods are also its anti-inflammatory components and uncover its anti-inflammatory mechanism. On the guidance of results of phytochemical fraction and anti-inflammatory activity evaluation, ten anti-inflammatory lindenane sesquiterpenes with half maximal inhibitory concentration (IC50) values from 8.13 ± 0.37 to 24.06 ± 0.60 μM, including seven dimmers (1-7) and three monomers (8-10) were discovered and characterized from the anti-inflammatory fraction of roots of title plant. Considering the activity and quantity, shizukaol D was selected as the target for further mechanism study. Firstly, shizukaol D could downregulate the expression of inducible nitric oxide synthase (iNOS) and suppress the protein level of nuclear factor kappa B (NF-κB) p65 as well as the nuclear translocation of NF-κB p65. Meanwhile, shizukaol D also decreased the level of reactive oxygen species (ROS) and enhanced the activities of phase II defense enzymes superoxide dismutase (SOD), glutathione (GSH) and glutathione peroxidase (GSH-px) by elevating the expression of heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase 1 (NQO1) via promoting nuclear factor E2-related factor 2 (Nrf2) activation as well as its nuclear translocation, and regulating the pathway of phosphoinositide 3-kinases (PI3K)/ protein kinase B (AKT) rather than mitogen-activated protein kinase (MAPK) to the activation of Nrf2/HO-1 signaling. Taken together, our research provided the phytochemical and pharmacological evidences for that the major sesquiterpenoid dimers can be defined as the anti-inflammatory ingredients of S.glabra and this kind of sesquiterpenoids, such as shizukaol D, can be as an attractive therapeutic candidate for inflammatory diseases.

Protective effects of low-intensity pulsed ultrasound on aluminum overload-induced cerebral damage through epigenetic regulation of brain-derived neurotrophic factor expression.

In consideration of its noninvasive administration and endogenous stimulation property, the enhancement of brain-derived neurotrophic factor (BDNF) via low-intensity pulsed ultrasound (LIPUS) could be a novel strategy for aluminum (Al) overload-induced cerebral damage. LIPUS was pre-treated 7 days before concomitantly given with aluminum chloride (AlCl3) daily for a period of 42 days. Morris water maze and elevated plus maze were performed to analyze spatial learning and memory. Western Blot and immunoprecipitation were used to detect BDNF and histone acetylation of histone H3 lysine 9 (H3K9) and histone H4 lysine 12 (H4K12) in the hippocampus. Assay of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and glutathione peroxidase (GSH-Px) indicated the extent of oxidative damages. Aluminium exposure in rats can cause attenuated spatial learning and memory, followed by up-regulated histone deacetylase 6 (HDAC6) expression, down-regulated H3K9 and H4K12 acetylation at the PIII and PIV promoter of BDNF, all of which will eventually inhibit BDNF expression. LIPUS can recover reduced cognitive function by restoring histone acetylation and BDNF expression, accompanied with increased SOD, GSH, and GSH-Px activity. LIPUS treatment might alleviate aluminium exposure-induced cognitive decline by acetylation regulation of BDNF expression and reducing oxidative stress in the hippocampus.

Structural elucidation and hepatoprotective activities of polysaccharides from a mutant mSM-105 of Catathelasma ventricosum with enhanced production of 1,6-β-glucan

Catathelasma ventricosum is a popular edible officinal mushroom in southwest China. The mycelial polysaccharides from Catathelasma ventricosum (mCVPS) mainly composed of β-glucan which was widely regarded as a kind of prebiotic. In order to improve its yield, a mutant strain (mSM-105) by UV mutagenesis combined with ethyl methane sulfonate (EMS) treatment was developed, which showed a higher β-glucan production than the parent strain (SM-16). Results showed that mSM-105 possessed the yield of β-glucan as high as 85.3% after 15-day cultivation, while the parent strain was about 67% under the same condition. The molecular weight of polysaccharide from SM-16 and mSM-105, determined by gel permeation chromatography and gas chromatograph, was estimated to be from 3.8 × 103 to 2.5 × 107 Da. From the infrared (IR) and methylation analysis, the polysaccharide from mSM-105 referred as mCVPS-M was found to mainly consist of β-d-glucopyranose with 1,6 linkages. And the relative proportion of 1,6-β-d-Glcp estimated on sugar linkage of mCVPS-M was 47% higher than that of mCVPS. Moreover, in mice subjected to CCl4-induced hepatotoxicity, pretreatments with mCVPS and mCVPS-M at the same dose (200 mg/kg/d) both significantly (P < 0.05) decreased the levels of alanine aminotransferase (AST), aspartate aminotransferase (ALT) and malondialdehyde (MDA) and increased antioxidant enzyme activities such as, catalase (CAT), superoxide dismutase (SOD), glutathione (GSH) and glutathione peroxidase (GSH-Px). Hepatic histopathological observation further confirmed that mCVPS-M had stronger hepatoprotection to normalize the histopathological changes. These results suggest that mCVPS-M might possess a more significant protective effect against CCl4 induced hepatocyte damage injury than mCVPS, by mediating antioxidant activities, free radical scavenging effects and alleviation of lipid oxidation, in which a vital role may played by 1,6-β-glucan.

Onjisaponin B prevents cognitive impairment in a rat model of D-galactose-induced aging

In this study, we investigated the potential effect of onjisaponin B (OB) on aging rats induced by D-gal (D-galactose). Sub-acute aging model was established in rats by the subcutaneous injection of D-gal (120 mg/kg) for 42 days, accompanied with OB (10, 20 mg/kg, p.o.) or normal saline intervention for 28 days since the 14th day after the beginning of D-gal stimulation. Morris water maze test and step-down passive avoidance test were conducted to evaluate the cognitive function of the rats. The superoxidase dismutase (SOD), malondialdehyde (MDA), glutathione (GSH) and glutathione peroxidase (GSH-px) contents in hippocampus were measured by according kits, respectively. And the hippocampus levels of inflammatory mediators including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) were assayed by enzyme-linked immunosorbent assay (ELISA). Furthermore, the expressions of SOD1, MDA5, GSH, GSH-px, NF-кB pathway were present by western blot. It revealed that administration of OB was able to significantly attenuate the D-gal-induced changes in the hippocampus, ranging from cognitive capacity, oxidative stress to inflammation response. In a nutshell, our data provided evidence that OB could contribute to the restoration of cognitive ability by improving the antioxidant and anti-inflammatory capacity in D-gal induced aging rats.

Shenxian-Shengmai Oral Liquid Reduces Myocardial Oxidative Stress and Protects Myocardium from Ischemia-Reperfusion Injury

Background/Aims: Shenxian-shengmai (SXSM) oral liquid, a Chinese patent compound medicine, has been used to treat sinus bradyarrhythmias induced by mild sick sinus syndrome in clinical practice. Myocardial ischemia, in particular in serious or right coronary-related heart diseases, can cause bradyarrhythmias and cardiac dysfunction. Moreover, reperfusion of ischemic myocardium is associated with additional myocardial damage known as myocardial ischemia-reperfusion (I/R) injury. This study was designed to evaluate the effects of SXSM on bradyarrhythmias and cardiac dysfunction induced by myocardial I/R injury, and to explore the underlying mechanisms. Methods: Administration of SXSM to adult male Sprague Dawley (SD) rats was achieved orally by gavage and control rats were given equivalent deionized water every day for 14 days. After the last administration, the heart was connected with the Langendorff perfusion apparatus and both groups were subjected to ischemia for 20 min followed by reperfusion for 40 min to induce myocardial I/R injury. Heart rate (HR), left ventricular developed pressure (LVDP), the maximal increase rate of left ventricular pressure (+dp/dt_max) and the maximal decrease rate of left ventricular pressure (-dp/dt_max) were recorded by a physiological signal acquisition system. The heart treated with ischemic preconditioning (IPC) for 3 times at a range of 5 min/time before ischemia served as a positive control group. The hearts without I/R injury served as control group. After reperfusion, superoxide dismutase (SOD), glutathione (GSH) and glutathione peroxidase (GSH-Px) activities in the myocardium were determined by appropriate assay kits. Myocardial SOD1 and glutamate cysteine ligase catalytic subunit (GCLC) expression were assessed by western blot analysis. For the in vitro study, SXSM serum was prepared according to the serum pharmacological method and neonatal rat cardiomyocytes were isolated from the heart of new born SD rats. Neonatal rat cardiomyocytes were pretreated with SXSM serum and subjected to H₂O₂ or anoxia/ reoxygenation (A/R) treatment to induce oxidative damage. Cell viability was evaluated using a Cell Counting Kit-8 (CCK8) assay. Levels of reactive oxygen species (ROS), SOD, GSH and GSH-Px in cardiomyocytes were determined by appropriate assay kits. SOD1 and GCLC expression were assessed by western blot analysis. Buthionine-[S, R]-sulfoximine (BSO), a GCLC inhibitor, and SOD1 siRNA were also used for identifying the cardiac protective targets of SXSM. Results: SXSM and ischemic preconditioning (IPC) significantly increased heart rate during myocardial reperfusion and protected cardiac function against myocardial I/R injury, including an increase in left ventricular diastolic pressure (LVDP), the maximal increase rate of left ventricular pressure (+dp/dt_max) and the maximal decrease rate of left ventricular pressure (-dp/dt_max). We also found that SXSM and IPC improved the expansion of myocardial interstitium, the structural abnormality and morphological changes of cardiomyocytes induced by I/R injury. Meanwhile, SXSM protected cardiomyocytes against the oxidative damage induced by H₂O₂ and A/R injury through reducing intracellular ROS levels. Moreover, SXSM increased SOD activity through enhancing SOD1 expression and increased GSH content through promoting GCLC expression as well as GSH-Px activity. BSO and SOD1 siRNA counteracted anti-arrhythmic and cardiac protective effect of SXSM, suggesting that the therapeutic targets of SXSM might be SOD1 and GCLC. Conclusion: SXSM is effective in protecting the myocardium from I/R injury, with myocardial SOD1 and GCLC being the potential therapeutic targets.

The protective effect of Epimedii Folium and Curculiginis Rhizoma on Alzheimer's disease by the inhibitions of NF-κB/MAPK pathway and NLRP3 inflammasome.

The purpose of the current study was to explore the effects of the water extracts of Epimedii Folium and Curculiginis Rhizoma (EX) on Aβ-induced Alzheimer’s disease. Aβ1-42 was stereotaxically injected bilaterally into the dorsal hippocampus, and then the rats were orally received EX at the doses of 2 g/kg and 6 g/kg for 30 days. Behavior was monitored through Morris water maze test. The neuroprotective effect of EX were examined with methods of histochemistry and biochemistry. EX reduced the contents of pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) in hippocampus and cortex. EX also reduced the levels of malondialdehyde (MDA) and increased superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and glutathione peroxidase (GSH-Px) in the serum. Immunohistochemical analysis demonstrated that EX inhibited the expressions of NLRP3. In addition, we further confirmed that EX suppressed the expression of the NLRP3 inflammasome. EX inhibited the phosphorylations MAPKs, nuclear factor κB (NF-κB), myeloid differentiation factor 88(MyD88), cathepsin B. In conclusion, these results suggest that EX may be a potential agent for treating Alzheimer’s disease.

Is caffeic acid phenethyl ester more protective than doxycycline in experimental periodontitis?

Background and objectivesHost modulation therapies (anti-inflammatory drugs, bone-stimulating agents, anti-proteinase etc.) target the inhibition or stabilization of tissue breakdown. The aim of the present study was to evaluate the effects of caffeic acid phenethyl ester (CAPE) and/or low dose doxycycline (LDD) administrations on alveolar bone loss (ABL), serum cytokines and gingival apoptosis, as well as the levels of oxidants and anti-oxidants in rats with ligature-induced periodontitis. Material and methodsThe animals were randomly divided into five groups: Group C (periodontally healthy), Group PC (Periodontitis+CAPE), Group PD (Periodontitis+LDD), Group PCD (Periodontitis+CAPE+LDD), Group P (Periodontitis). Experimental periodontitis was induced for 14days. Levels of ABL, and the serum cytokines, interleukin (IL)-1 β, IL-6, tumor necrosis factor-α (TNF-α) and IL-10 were assessed as were the levels of the oxidants and anti-oxidants, malondialdehyde (MDA), glutathione (GSH) and glutathione peroxidase (GSH-Px), and levels of gingival apoptosis. ResultsThe lowest ABL levels was evident in the PC group, among the experimental groups. There was also less inflammatory infiltration in the PC group than the PD group. IL-1β, IL-6, and IL-10 were lower in the PC group and higher in the P group in comparison to the levels in the other experiment groups. TNF-α levels in the PD group were higher than levels in the PC and PCD groups. The PC and PCD groups did not differ from the C group in regard to MDA levels. The highest GSH-Px level was found in the PC group. Gingival apoptosis in the PC group was not only lower than the PD and PCD groups, but also lower than in the C group. ConclusionThe present study suggests that CAPE has more anti-inflammatory, anti-oxidant and anti-apoptotic effects than LDD, with no additive benefits of a CAPE+LDD combination being evident in rats with periodontitis.

In vitro non-thermal oxidative stress response after 1800 MHz radiofrequency radiation.

In this study possible connection between radiofrequency exposure (RF) and development of oxidative stress was investigated by measuring impairment in cellular oxidation-reduction balance immediately after RF exposure. Fibroblast cells V79 were exposed for 10, 30 and 60 minutes to 1800 MHz RF radiation. Electric field strength was 30 V/m and specific absorption rate (SAR) was calculated to be 1.6 W/kg. Electromagnetic field was generated within Gigahertz Transversal Electromagnetic Mode cell (GTEM) equipped by signal generator, amplifier and modulator. Cell viability was determined by CCK-8 colorimetric assay and level of reactive oxygen species (ROS) was detected by dihydroethidium staining. Reduced glutathione (GSH) and glutathione peroxidase (GSH-Px) were used to assess cell antioxidant activity while lipid oxidative damage was evaluated measuring concentration of malondialdehyde. Viability of V79 cells remained within normal physiological values regardless of exposure time. Increased level of superoxide radicals was detected after 60-min exposure. Significantly higher GSH level was observed immediately after 10-min exposure with higher but insignificant activity of GSH-Px. Lipid oxidative damage in exposed cell samples was not observed. Short-term RF exposure revealed transient oxidation-reduction imbalance in fibroblast cells following adaptation to applied experimental conditions.

Protective effects of seed melon extract on CCl4-induced hepatic fibrosis in mice

Ethnopharmacological relevanceCitrullus lanatus ssp. vulgaris var. megalaspermus Lin et Chao, was also known as watermelon belongs to family Cucurbitaceae, variously used as healthy food and in the treatment of liver and lungs problems. Currently, Citrullus lanatus has become a major economic crop of medicinal and edible effects with regional characteristics. AimThis study was designed to evaluate the hepatoprotective and antioxidant activity of the seed melon (Citrullus lanatus ssp. vulgaris var. megalaspermus Lin et Chao) extract (SME) against carbon tetrachloride (CCl4) induced hepatic fibrosis in mice. Materials and methodsIn this study, mice were randomly divided into 7 groups, including normal control, model, silymarin tablets as the positive control, SME 100, 200, 400, and 800mg/kg. After 8 weeks, activities of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglycerides (TG), hyaluronic acid (HA) and laminin (LN) were checked. The levels of antioxidant enzymes such as superoxide dismutase (SOD), glutataion (GSH) and glutathione peroxidase (GSH-Px) were determined after SME administration. The hydroxyproline (HYP) levels, malondialdehyde (MDA) levels and histopathologic examinations of hepatocyte fibrosis were also determined. Additionally, effects of SME on alpha-smooth muscle actin (α-SMA) and transforming growth factor beta-1(TGF-β1) protein expressions were determined. ResultsWe found that SME could significantly lower the serum levels of hepatic enzyme markers AST, ALT, HA and LN (P<0.01). Compared with the CCl4-only treatment group, levels of hepatic SOD and GSH-Px were significantly increased, and the MDA levels were remarkably decreased in mice treated by SME at medium dose (400mg/kg) and high dose (800mg/kg) (P<0.01). A histological examination of the liver showed that lesions, including necrosis, lymphocyte infiltration and fatty degeneration, were partially healed by treatment with SME. The results of protein expressions studies displayed that SME could inhibit α-SMA and TGF-β1 protein expression (P<0.01). ConclusionThe present results suggested that protective effect of SME against CCl4-induced hepatic fibrosis may rely on its effect on reducing oxidative stress and improving drug metabolizing enzyme activity in liver.

Protective Effect of the Total Flavonoids from Rosa laevigata Michx Fruit on Renal Ischemia-Reperfusion Injury through Suppression of Oxidative Stress and Inflammation.

Renal ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI). Our previous studies have shown that the total flavonoids (TFs) from Rosa laevigata Michx fruit has various activities, however, there were no papers reporting the role of the TFs against renal IRI. In the present work, a hypoxia/reoxygenation (H/R) model in NRK-52E cells and ischemia-reperfusion model in rats were used. The results showed that the TFs significantly attenuated cell injury and markedly decreased serum creatinine (Cr) and blood urea nitrogen (BUN) levels in rats. Further investigation revealed that the TFs markedly decreased the levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) and glutathione peroxidase (GSH-Px) and intracellular reactive oxygen species (ROS), up-regulated the levels of silent information regulator factor 2-related enzyme 1 (Sirt1), nuclear factor erythroid 2-related factor-2 (Nrf2) and heme oxygenase-1 (HO-1), down-regulated the levels of Kelch like ECH-associated protein-1 (Keap1) and the nuclear translocation of nuclear factor-κBp65 (NF-κBp65), and decreased the mRNA levels of interleukine-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Furthermore, inhibiting Sirt1 by siRNA showed that the role of the natural product in protecting renal IRI was significantly attenuated, suggesting that the effect of the extract against renal IRI depended on Sirt1. Taken together, the TFs has significantly nephroprotective effect against IRI by affecting Sirt1/Nrf2/NF-κB signaling pathway, which should be developed as a new therapeutic agent or food additives to treat acute kidney injury in the future.

Curcumin alleviates lipopolysaccharide induced sepsis and liver failure by suppression of oxidative stress-related inflammation via PI3K/AKT and NF-κB related signaling.

In many liver disorders, oxidative stress-related inflammation and apoptosis are important pathogenic components, finally resulting in acute liver failure. Erythropoietin and its analogues are well known to influence the interaction between apoptosis and inflammation in brain and kidney. The study is to clarify the effect of curcumin, a natural plant phenolic food additive, on lipopolysaccharides (LPS)-induced acute liver injury of mice with endotoxemia and associated molecular mechanism from inflammation, apoptosis and oxidative stress levels. And curcumin, lowered serum cytokines, including Interleukin 1beta (IL-1β), Interleukin 6 (IL-6) and tumor necrosis factor (TNF-α), and improved liver apoptosis through suppressing phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway and inhibiting Cyclic AMP-responsive element-binding protein (CREB)/Caspase expression, and decreased oxidative stress-associated protein expression, mainly involving 2E1 isoform of cytochrome P450/nuclear factor E2-related factor 2/reactive oxygen species (CYP2E/Nrf2/ROS) signaling pathway, as well as liver nitric oxide (NO) production in LPS-induced mice. Moreover, curcumin regulated serum alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP), accelerated liver antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and glutathione peroxidase (GSH-px) levels, and inhibited activation of the mitogen-activated protein kinases/c-Jun NH2-terminal kinase (P38/JNK) cascade in the livers of LPS-induced rats. Thus, curcumin treatment attenuates LPS-induced PI3K/AKT and CYP2E/Nrf2/ROS signaling and liver injury. Strategies to inhibit inflammation and apoptosis signaling may provide alternatives to the current clinical approaches to improve oxidative responses of endotoxemia.

Hepatoprotective standardized EtOH–water extract from the seeds of Fraxinus rhynchophylla Hance

Fraxinus rhynchophylla Hance (Oleaceae), its stem barks are known as Cortex fraxini (秦皮 qín pí) listed in Chinese Pharmacopoeia. Phytochemical study has indicated that methanol extracts from Qinpi has protective effect on acute liver injury. The present study investigates the hepatoprotective activity of EtOH–water extract from the seeds of F. rhynchophylla Hance against carbon tetrachloride-induced liver injury in mice. The EtOH–water extract significantly alleviated liver damage as indicated by the decreased levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), the malondialdehyde (MDA) content, and increased the levels of superoxide dismutase (SOD), glutathione (GSH) and glutathione peroxidase (GSH-Px), and reduced the pathological tissue injury induced by CCl4. Quantitative analysis of seven major constituents (1–7) in EtOH–water extract (EWE) was developed by high performance liquid chromatography-diode-array detector (HPLC-DAD). The current research indicates that the EWE from the seeds of F. rhynchophylla Hance decreased liver index, inhibited the increase of serum aminotransferase induced by CCl4, and decreased hepatic MDA content, SOD and GSH-Px activities. These results suggested that the pretreatment with EWE protected mice against CCl4-induced liver injuries. Based on the results, the EtOH–water extract from the seeds of F. rhynchophylla Hance is efficacious for prevention and treatment of CCl4-induced hepatic injury in mice. Secoiridoid and tyrosol glucosides might be the active ingredients responsible for the biological and pharmacological activities of hepatoprotection.

Oral administration of Moringa oleifera oil but not coconut oil prevents mercury-induced testicular toxicity in rats.

This study was conducted to compare the effects of administration of coconut oil (CO) and Moringa oleifera oil (MO) on testicular oxidative stress, sperm quality and steroidogenesis parameters in rats treated with mercury chloride (HgCl2 ). After 15days of oral administration of CO (2mlkg-1 body weight) and MO (2mlkg-1 body weight) along with intraperitoneal (i.p.) administration of HgCl2 (5mgkg-1 body weight) alone or in combination, we found that CO treatment did not protect against HgCl2 -induced poor sperm quality (motility, count) as well as decreased testosterone level and 17β-hydroxysteroid dehydrogenase (17β-HSD) activity. Treatment with CO alone decreased glutathione (GSH), and glutathione peroxidase (GSH-Px) activities and increased malondialdehyde (MDA) level in rat's testis, whereas MO did not change these parameters. Cotreatment with MO prevented HgCl2 -induced testicular catalase (CAT) and superoxide dismutase (SOD) activities, poor sperm quality and low testosterone level and also blocks the adverse effect of CO+HgCl2 (2mlkg-1 body weight+5mgkg-1 body weight) on the investigated endpoints. In conclusion, MO and not CO decreased the deleterious effects of HgCl2 on sperm quality and steroidogenesis in rats and also strengthen the antioxidant defence of the testes. Therefore, MO is beneficial as an antioxidant in HgCl2 -induced oxidative damage.

Electroacupuncture alleviates cerebral ischemia and reperfusion injury via modulation of the ERK1/2 signaling pathway.

Electroacupuncture (EA) has anti-oxidative and anti-inflammatory actions, but whether the neuroprotective effect of EA against cerebral ischemia-reperfusion (I/R) injury involves modulation of the extracellular regulated kinase 1/2 (ERK1/2) signaling pathway is unclear. Middle cerebral artery occlusion (MCAO) was performed in Sprague-Dawley rats for 2 hours followed by reperfusion for 24 hours. A 30-minute period of EA stimulation was applied to both Baihui (DU20) and Dazhui (DU14) acupoints in each rat (10 mm EA penetration depth, continuous wave with a frequency of 3 Hz, and a current intensity of 1-3 mA) when reperfusion was initiated. EA significantly reduced infarct volume, alleviated neuronal injury, and improved neurological function in rats with MCAO. Furthermore, high mRNA expression of Bax and low mRNA expression of Bcl-2 induced by MCAO was prevented by EA. EA substantially restored total glutathione reductase (GR), glutathione (GSH) and glutathione peroxidase (GSH-Px) levels. Additionally, Nrf2 and glutamylcysteine synthetase (GCS) expression levels were markedly increased by EA. Interestingly, the neuroprotective effects of EA were attenuated when ERK1/2 activity was blocked by PD98059 (a specific MEK inhibitor). Collectively, our findings indicate that activation of the ERK1/2 signaling pathway contributes to the neuroprotective effects of EA. Our study provides a better understanding of the regulatory mechanisms underlying the therapeutic effectiveness of EA.

Curcumin inhibits apoptosis by regulating intracellular calcium release, reactive oxygen species and mitochondrial depolarization levels in SH-SY5Y neuronal cells

Neurological diseases such as Alzheimer’s and Parkinson’s diseases are incurable progressive neurological disorders caused by the degeneration of neuronal cells and characterized by motor and non-motor symptoms. Curcumin, a turmeric product, is an anti-inflammatory agent and an effective reactive oxygen and nitrogen species scavenging molecule. Hydrogen peroxide (H2O2) is the main source of oxidative stress, which is claimed to be the major source of neurological disorders. Hence, in this study we aimed to investigate the effect of curcumin on Ca2+ signaling, oxidative stress parameters, mitochondrial depolarization levels and caspase-3 and -9 activities that are induced by the H2O2 model of oxidative stress in SH-SY5Y neuronal cells. SH-SY5Y neuronal cells were divided into four groups namely, the control, curcumin, H2O2, and curcumin + H2O2 groups. The dose and duration of curcumin and H2O2 were determined from published data. The cells in the curcumin, H2O2, and curcumin + H2O2 groups were incubated for 24 h with 5 µM curcumin and 100 µM H2O2. Lipid peroxidation and cytosolic free Ca2+ concentrations were higher in the H2O2 group than in the control group; however, their levels were lower in the curcumin and curcumin + H2O2 groups than in the H2O2 group alone. Reduced glutathione (GSH) and glutathione peroxidase (GSH-Px) values were lower in the H2O2 group although they were higher in the curcumin and curcumin + H2O2 groups than in the H2O2 group. Caspase-3 activity was lower in the curcumin group than in the H2O2 group. In conclusion, curcumin strongly induced modulator effects on oxidative stress, intracellular Ca2+ levels, and the caspase-3 and -9 values in an experimental oxidative stress model in SH-SY5Y cells.

The Role of Oxidative Stress in Gastrointestinal Tract Tissues Induced by Arsenic Toxicity in Cocks.

Arsenic (As) is a widely distributed trace element which is known to be associated with numerous adverse effects on human beings and animals. Arsenic trioxide (As2O3) is an inorganic arsenical-containing toxic compound. The effect of excessive amounts of As2O3 exposure on gastrointestinal tract tissue damage in cocks is still unknown. This study was conducted to investigate the effect of As2O3 exposure on gastrointestinal tract tissue damage in cocks. In total, 72 1-day-old male Hyline cocks were randomly divided into four groups and fed either a commercial diet or an As2O3 supplement diet containing 7.5, 15, and 30mg/kg As2O3. The experiment lasted for 90days and gastrointestinal tract tissue samples (gizzard, glandular stomach, duodenum, jejunum, ileum, cecum, and rectum) were collected at 30, 60, and 90days. Catalase (CAT), glutathione (GSH), and glutathione peroxidase (GSH-Px) activities; malondialdehyde (MDA) contents; and hydroxyl radical (OH·)-mediated inhibition were examined. Furthermore, the results demonstrated that MDA content in the gastrointestinal tract was increased, while the activities of CAT, GSH, and GSH-Px and the ability to resist OH· was decreased in the As2O3 treatment groups. Extensive damage was observed in the gastrointestinal tract. These findings indicated that As2O3 exposure caused oxidative damage in the gastrointestinal tract of cocks due to alterations in antioxidant enzyme activities and elevation of free radicals.

Sevoflurane preconditioning improving cerebral focal ischemia–reperfusion damage in a rat model via PI3K/Akt signaling pathway

In this study, we aimed to assess the neuroprotective effect of sevoflurane preconditioning in a cerebral focal ischemia–reperfusion rat model. Sixty Sprague Dawley rats were divided into six groups: sham operated group, cerebral focal ischemia–reperfusion (CIR) group, CIR+sevoflurane preconditioning (SP) (2%) group, CIR+sevoflurane preconditioning (2.5%) group, CIR+sevoflurane preconditioning (3%) group, and CIR+sevoflurane preconditioning (3.5%) group. All subjects were euthanized 2days post-surgery and their hippocampus tissues were removed. Tissue malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) and glutathione peroxidase (GSH-Px) levels were measured and hippocampus tissue samples were examined histopathologically. Results showed that significant difference in antioxidant, immunity indexes, and apoptosis-related protein expression was detected in hippocampus tissue between sham-operated control and CIR groups. Sevoflurane preconditioning significantly dose-dependently reduced MDA, IL-1β, IL-6, IL-10 and TNF-α levels and enhanced antioxidant enzyme activities in hippocampus tissue of CIR+SP groups compared to CIR group. In addition, sevoflurane preconditioning significantly dose-dependently upregulated PI3K, p-Akt and Bcl-2 levels and downregulated caspase-3 and Bax levels in hippocampus tissue of CIR+SP groups compared to CIR group. It can be concluded that sevoflurane preconditioning demonstrates a strong and ameliorative effect on cerebral I/R damage in rats. The neuroprotective mechanisms of sevoflurane preconditioning are associated with its properties of anti-apoptosis and anti-oxidation as well as regulation of PI3K and p-Akt signal activation.

Sulforaphane reduces apoptosis and oncosis along with protecting liver injury-induced ischemic reperfusion by activating the Nrf2/ARE pathway.

The purpose of this study was to determine the effect of sulforaphane (SFN) on hepatic ischemia reperfusion injury (HIRI) and to explore the underlying mechanisms. The rat model of HIRI was established. Thirty-two rats were randomly divided into sham (A), SFN (B), HIRI (C), and SFN+HIRI (D) groups. Animals in the HIRI and Sham groups were treated with equal volumes of the vehicle of SPF. Liver functions were evaluated by serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Liver samples were collected for histological examination and determination of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and glutathione peroxidase (GSH-Px) levels. Mitochondrial Na(+)-K(+)-ATPase and Ca(2+)-ATPase were measured by colorimetry. Expression levels of NQO1, Nrf2, and HO-1 in liver tissue were detected by western blot analysis. Additionally, oncosis and apoptosis were detected by Annexin V-FITC/PI immunofluorescent flow cytometry analysis. The HIRI group showed a significant increase in serum levels of liver enzymes (ALT, AST) associated with histopathological damage in the liver. Pre-treatment with SFN could reduce the levels of MDA and MPO in liver tissue and improve the activities of SOD, GSH, GSH-Px, and mitochondrial Na(+)-K(+)-ATPase and Ca(2+)-ATPase in liver tissue. Moreover, SFN could still increase the expression of NQO1, Nrf2, and HO-1 in liver tissue and decrease the oncosis and apoptosis of liver cells. Pre-treatment with SFN could attenuate HIRI via the activation of Nrf2/ARE signaling pathways, ameliorate oxidative stress, and maintain the normal activities of Na(+)-K(+)-ATPase and Ca(2+)-ATPase, thus reducing the occurrence of cell oncosis and apoptosis. Therefore, SFN can be considered a potential candidate as an anti-ischemic medication to minimize HIRI.

Appraisal of Total Phenol, Flavonoid Contents, and Antioxidant Potential of Folkloric Lannea coromandelica Using In Vitro and In Vivo Assays.

The aim of this study was to determine the impending antioxidant properties of different extracts of crude methanolic extract (CME) of leaves of Lannea coromandelica (L. coromandelica) and its two ethyl acetate (EAF) and aqueous (AqF) subfractions by employing various established in vitro systems and estimation of total phenolic and flavonoid content. The results showed that extract and fractions possessed strong antioxidant activity in vitro and among them, EAF had the strongest antioxidant activity. EAF was confirmed for its highest phenolic content, total flavonoid contents, and total antioxidant capacity. The EAF was found to show remarkable scavenging activity on 2,2-diphenylpicrylhydrazyl (DPPH) (EC50 63.9 ± 0.64 µg/mL), superoxide radical (EC50 8.2 ± 0.12 mg/mL), and Fe2+ chelating activity (EC50 6.2 ± 0.09 mg/mL). Based on our in vitro results, EAF was investigated for in vivo antioxidant assay. Intragastric administration of the EAF can significantly increase levels of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and glutathione peroxidase (GSH-Px) levels, and decrease malondialdehyde (MDA) content in the liver and kidney of CCl4-intoxicated rats. These new evidences show that L. coromandelica bared antioxidant activity.

The role of heat shock proteins in oxidative stress damage induced by Se deficiency in chicken livers.

Selenium (Se) is an essential dietary trace element, which acts as an antioxidant. Heat shock proteins (HSPs) are a family of intracellular proteins whose synthesis is greatly increased upon exposure of cells to environmental stressors including oxidative metabolites, heavy metals, amino acid analogues and so on. However, little is known about the role of HSPs in oxidative stress damage induced by Se deficiency in the chicken liver. The aim of this study was to investigate the effects of Se deficiency on the expression levels of HSPs (Hsps27, 40, 60, 70, and 90) and oxidative indexes in the chicken liver. A total of 300 1-day-old sea blue white laying hens were divided into two groups (n = 150/group), and each of those groups was randomly divided into groups so that the trials were conducted in triplicate. The Se-deficient group (-Se) was fed a Se-deficient corn-soy basal diet (the Se content was 0.02 mg/kg); the Se-adequate group as control (+Se) was fed the same basal diet supplemented with Se at 0.2 mg/kg (sodium selenite). The liver tissue was collected and examined for pathological observations, oxidative indexes, mRNA and protein levels of HSPs genes at 15, 25, 35, 45, 55 and 65 days old. The histopathological analysis showed that liver tissues were injured seriously in the Se-deficient group. The oxidative indexes data showed that the malondialdehyde (MDA) level increased and the activity of L-glutathione (GSH) and glutathione peroxidase (GSH-Px) in the chicken liver decreased in Se-deficient group (p < 0.05). Additionally, the mRNA levels of HSPs (27, 40, 60, 70, and 90) increased significantly (p < 0.05) in the Se-deficient group compare to the corresponding control group. Meanwhile, the protein expression of HSPs (60, 70, and 90) also increased significantly (p < 0.05) in the Se-deficient group. These results suggested that oxidative stress and the levels of HSPs expression levels in chicken liver can be influenced by dietary Se deficiency. And HSPs played an important role in the protection of the liver after oxidative stress due to Se deficiency.