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Oxidative stress is closely related to the pathogenesis of ischemic stroke. Protocatechualdehyde (PCA) is a phenolic acid compound that has the putative antioxidant activities. The present study was aimed to investigate the molecular mechanisms involved in the antioxidative effect of PCA against cerebral ischemia/reperfusion (I/R) injury. The experiment stroke model was produced in Sprague-Dawley rats via middle cerebral artery occlusion (MCAO). To model ischemia-like conditions in vitro, differentiated SH-SY5Y cells were exposed to transient oxygen and glucose deprivation (OGD). Treatment with PCA significantly improved neurologic score, reduced infarct volume and necrotic neurons, and also decreased reactive oxygen species (ROS) production, 4-hydroxynonenal (4-HNE), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) contents at 24 h after reperfusion. Meanwhile, PCA significantly increased the transcription nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expressions in the ischemic cerebral cortex as shown by immunofluorescence staining and Western blot analysis. In vitro experiment showed that PCA protected differentiated SH-SY5Y cells against OGD-induced injury. Likewise, PCA also increased markedly the Nrf2 and HO-1 expressions in a dose-dependent manner. The neuroprotection effect of PCA was abolished by knockdown of Nrf2 and HO-1. Moreover, knockdown of protein kinase Cε (PKCε) also blocked PCA-induced Nfr2 nuclear translocation, HO-1 expression, and neuroprotection. Taken together, these results provide evidences that PCA can protect against cerebral ischemia-reperfusion-induced oxidative injury, and the neuroprotective effect involves the PKCε/Nrf2/HO-1 pathway.

Oxidative stress plays a key role in the pathogenesis of diabetic myopathy. Celastrol provides a wide range of health benefits, including antioxidant, anti-inflammatory and antitumor effects. We hypothesized that celastrol may exert an antioxidant effect in the skeletal muscle of diabetic rats. In the present study, MnSOD activity was determined by spectrophotometry. The protein levels were evaluated by western blot analysis and mRNA content was quantified by RT‑qPCR. We firstly found that the levels of AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor coactivator 1α (PGC1α), silent mating-type information regulation 2 homolog 3 (Sirt3) and manganese superoxide dismutase (MnSOD) were all decreased in the skeletal muscle of diabetic patients. Male rats with diabetes were also treated with the vehicle or with celastrol at 1, 3 and 6 mg/kg/day for 8 weeks. The administration of celastrol at 3 and 6 mg/kg attenuated the deterioration of skeletal muscle, as shown by histological analysis, decreased the malondialdehyde (MDA) level and increased the glutathione (GSH) level assayed by enzyme-linked immunosorbent assay (ELISA) method. It also enhanced the enzyme activity and increased the expression of MnSOD, and increased the AMPK phosphorylation level, as well as PGC1α and Sirt3 expression. The findings of our study suggest that the expression of AMPK, PGC1α, Sirt3 and MnSOD are decreased in the skeletal muscle of diabetic patients. Celastrol exerted antioxidant effects on skeletal muscle partly by regulating the AMPK-PGC1α-Sirt3 signaling pathway.

Objectives: The purpose of this study is to investigate the antifibrosis and antioxidation of ShenKang injection (SKI) in vivo and in vitro and to evaluate potential mechanisms involved in the treatment of chronic kidney disease (CKD)., Methods: In experimental animal studies, CKD was established by 5/6 nephrectomy (5/6Nx). Serum creatinine (Scr) and blood urea nitrogen (BUN) were determined. Histopathological tests were performed by H&E and Masson trichrome stained. The protein expressions of fibronectin (FN), collagen Ι, α-smooth muscle actin (α-SMA) and transforming growth factor-β (TGF-β) and phosphorylation of Smad3 were measured in 5/6Nx rats. In Human kidney proximal tubular cell line (HK-2) cells, the effects of TGF-β/Smad3 signalling pathway on renal fibrosis and oxidative injury were examined., Key Findings: 5/6Nx induced severe renal damages. Treatment of rats with SKI markedly reduced levels of Scr and BUN, alleviated expression of fibrosis-associated signalling molecules and reduced expression of TGF-β and phosphorylated Smad3. Meanwhile, in HK-2 cells, after exposure to TGF-β and H2 O2 , the protein expression of renal fibrosis was significantly increased. The generation of oxidative stress was also elevated. The severity of fibrosis and oxidative damage appears to be reduced after treatment with SKI., Conclusion: SKI inhibits renal fibrosis and oxidative stress through downregulation of TGF-β/Smad3 signalling pathway., (© 2015 Royal Pharmaceutical Society.)

Patients with type 2 diabetes have increased cardiovascular disease risk compared with those without diabetes. Hyperglycemia can induce reactive oxygen species (ROS) generation, which contributes to the development of diabetic cardiomyopathy. Our previous study has demonstrated that the total saponins of Aralia taibaiensis (sAT), a frequently-used antidiabetic medicine in traditional Chinese medicine (TCM), can scavenge free radicals in vitro and have good anti-oxidant ability on lipid peroxidation of rat liver microsomes. This work was designed to investigate whether sAT could protect the heart while it was used in the treatment of diabetes. Oxidative stress was induced in H9c2 cells by high glucose (33 mM) and glucose oxidase (15 mU, G/GO) and the protective effects of sAT were evaluated. Treatment of H9c2 cells with G/GO resulted in an increase in cell death, intracellular ROS level and cell oxidative injury, which were markedly reduced by sAT treatment. Further study revealed that sAT induced the nuclear translocation of Nrf2 and expression of its downstream targets. Moreover, Nrf2 siRNA markedly abolished the cytoprotective effects of sAT. sAT exerted cytoprotective effects against oxidative stress induced by hyperglycemia and the cardioprotective effects of sAT might be through the Nrf2/ARE pathway. Thus, sAT might be a promising candidate for the treatment of diabetic cardiomyopathy.

Alzheimer's disease (AD) is prone to onset and progression under oxidative stress conditions. Hericium coralloides (HC) is an edible medicinal fungus that contains various nutrients and possesses antioxidant properties. In the present study, the nutritional composition and neuroprotective effects of HC on APP/PS1 mice were examined. Behavioral experiments showed that HC improved cognitive dysfunction in APP/PS1 mice. Immunohistochemical and Western blotting results showed that HC reduced the levels of p-tau and amyloid-β deposition in the brain. By altering the composition of the gut microbiota, HC promoted the growth of short-chain fatty acid-producing bacteria and suppressed the growth of Helicobacter. Metabolomic results showed that HC decreased D-glutamic acid and oxidized glutathione levels. In addition, HC reduced the levels of reactive oxygen species, enhanced the secretion of superoxide dismutase, catalase, and glutathione peroxidase, inhibited the production of malondialdehyde and 4-hydroxynonenal, and activated the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. Collectively, HC demonstrated antioxidant activity by activating Nrf2 signaling and regulating gut microbiota, further exerting neuroprotective effects. This study confirms that HC has the potential to be a clinically effective AD therapeutic agent and offers a theoretical justification for both the development and use of this fungus. [ABSTRACT FROM AUTHOR]

We have recently reported that epigallocatechin gallate (EGCG) could extend lifespan in healthy rats. This study aimed to investigate the effects and mechanisms of a high dose of EGCG in extending the lifespan of obese rats. Ninety adult male Wistar rats were randomly divided into the control (NC), high‐fat (HF) and EGCG groups. Serum glucose and lipids, inflammation and oxidative stress were dynamically determined from adulthood to death, and the transcriptome and proteome of the liver were also examined. The median lifespans of the NC, HF and EGCG groups were 693, 599 and 683 days, respectively, and EGCG delayed death by 84 days in obese rats. EGCG improved serum glucose and lipids and reduced inflammation and oxidative stress associated with aging in obese rats induced by a high‐fat diet. EGCG also significantly decreased the levels of total free fatty acids (FFAs), SFAs and the n‐6/n‐3 ratio but significantly increased the n‐3 FFAs related to longevity. The joint study of the transcriptome and proteome in liver found that EGCG exerted its effects mainly by regulating the suppression of hydrogen peroxide and oxygen species metabolism, suppression of oxidative stress, activation of fatty acid transport and oxidation and cholesterol metabolism. EGCG significantly increased the protein expression of FOXO1, Sirt1, CAT, FABP1, GSTA2, ACSL1 and CPT2 but significantly decreased NF‐κB, ACC1 and FAS protein levels in the livers of rats. All the results indicate that EGCG extends lifespan by improving FFA metabolism and reducing the levels of inflammatory and oxidative stress in obese rats. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study is to investigate the antifibrosis and anti‐oxidation of rhein in vivo and in vitro, and to evaluate potential mechanisms involved in the treatment of chronic kidney disease (CKD). Methods: In experimental animal studies, CKD was established by 5/6 nephrectomy (5/6Nx). Serum creatinine (Scr) and blood urea nitrogen (BUN) were determined. Histopathologic tests were performed by HE and Masson trichrome stained. The level of ROS was investigated by fluorescence microplate with the probe 2′, 7′‐dichlorofluorescein diacetate (DCFH‐DA). The protein expressions of p47phox and gp91phox were measured in 5/6Nx rats. In HK‐2 cells, the expression of SIRT3 and Foxo3α was measured in SIRT3 knockdown conditions. The indicators of oxidation and fibrosisi were measured in SIRT3 knockdown conditions. Key findings: The results showed that, in addition to reducing renal interstitial pathologic injury and collagen fibrils, rhein administration improved renal function. The protective mechanisms were attributed to active SIRT3/FOXO3α signalling pathway and then play the anti‐oxidative capacity of rhein, as well as to subsequent antifibrotic effect. Conclusion: Taken together, rhein protected kidney through SIRT3/FOXO3a involvement. The anti‐oxidative capacity of rhein contributed to the protective effects including the subsequent antifibrotic responses. [ABSTRACT FROM AUTHOR]

Halophilic methanogens play an important role in the carbon cycle in hypersaline environments, but are under-represented in culture collections. In this study, we describe a novel Methanohalophilus strain that was isolated from the sulfide-rich brine-seawater interface of Kebrit Deep in the Red Sea. Based on physiological and phylogenomic features, strain RSK, which is the first methanogenic archaeon to be isolated from a deep hypersaline anoxic brine lake of the Red Sea, represents a novel species of this genus. In order to compare the genetic traits underpinning the adaptations of this genus in diverse hypersaline environments, we sequenced the genome of strain RSK and compared it with genomes of previously isolated and well characterized species in this genus (Methanohalophilus mahii , Methanohalophilus halophilus , Methanohalophilus portucalensis , and Methanohalophilus euhalobius). These analyses revealed a highly conserved genomic core of greater than 93% of annotated genes (1490 genes) containing pathways for methylotrophic methanogenesis, osmoprotection through salt-out strategy, and oxidative stress response, among others. Despite the high degree of genomic conservation, species-specific differences in sulfur and glycogen metabolisms, viral resistance, amino acid, and peptide uptake machineries were also evident. Thus, while Methanohalophilus species are found in diverse extreme environments, each genotype also possesses adaptive traits that are likely relevant in their respective hypersaline habitats. [ABSTRACT FROM AUTHOR]

Objectives The purpose of this study is to investigate the antifibrosis and antioxidation of ShenKang injection ( SKI) in vivo and in vitro and to evaluate potential mechanisms involved in the treatment of chronic kidney disease ( CKD). Methods In experimental animal studies, CKD was established by 5/6 nephrectomy (5/ 6Nx). Serum creatinine ( Scr) and blood urea nitrogen ( BUN) were determined. Histopathological tests were performed by H&E and Masson trichrome stained. The protein expressions of fibronectin ( FN), collagen Ι, α-smooth muscle actin (α- SMA) and transforming growth factor-β ( TGF-β) and phosphorylation of Smad3 were measured in 5/ 6Nx rats. In Human kidney proximal tubular cell line ( HK-2) cells, the effects of TGF-β/ Smad3 signalling pathway on renal fibrosis and oxidative injury were examined. Key findings 5/ 6Nx induced severe renal damages. Treatment of rats with SKI markedly reduced levels of Scr and BUN, alleviated expression of fibrosis-associated signalling molecules and reduced expression of TGF-β and phosphorylated Smad3. Meanwhile, in HK-2 cells, after exposure to TGF-β and H2O2, the protein expression of renal fibrosis was significantly increased. The generation of oxidative stress was also elevated. The severity of fibrosis and oxidative damage appears to be reduced after treatment with SKI. Conclusion SKI inhibits renal fibrosis and oxidative stress through downregulation of TGF-β/ Smad3 signalling pathway. [ABSTRACT FROM AUTHOR]

Fatigue is a common physiological response that is closely related to energy metabolism. Polysaccharides, as excellent dietary supplements, have been proven to have a variety of pharmacological activities. In this study, A 23.007 kDa polysaccharide from Armillaria gallica (AGP) was purified and performed structural characterization, including analysis of homogeneity, molecular weight and monosaccharide composition. Methylation analysis is used to analyze the glycosidic bond composition of AGP. The mouse model of acute fatigue was used to evaluate the anti-fatigue effect of AGP. AGP-treatment improved exercise endurance in mice and reduced fatigue symptoms caused by acute exercise. AGP regulated the levels of adenosine triphosphate, lactic acid, blood urea nitrogen and lactate dehydrogenase, muscle glycogen and liver glycogen of acute fatigue mice. AGP affected the composition of intestinal microbiota, the changes of some intestinal microorganisms are correlated with fatigue and oxidative stress indicators. Meanwhile, AGP reduced oxidative stress levels, increased antioxidant enzyme activity and regulated the AMP-dependent protein kinase/nuclear factor erythroid 2-related factor 2 signaling pathway. AGP exerted an anti-fatigue effect through modulation of oxidative stress, which is related to intestinal microbiota. [ABSTRACT FROM AUTHOR]

Aims: High levels of circulating free fatty acids (FFAs), inflammation and oxidative stress are important causes for insulin resistance (IR) and type 2 diabetes mellitus. The aim of this study was to investigate the mechanisms of EGCG in alleviating IR in HepG2 cells.Methods: HepG2 cells were treated with 25 mM glucose, 0.25 mM palmitic acid (PA), or 50 μM EGCG for 24 h.Results: EGCG increased glucose uptake and decreased glucose content. EGCG markedly decreased the levels of inflammatory and oxidative stress factors including nuclear factor κB (NF-κB), tumor necrosis factor-α, interleukin-6, reactive oxygen species, malondialdehyde and p53 protein, and markedly increased superoxide dismutases (SOD), glutathione peroxidase and SOD2 protein. EGCG significantly downregulated the levels of FFAs, triacylglycerol and cholesterol in HepG2 cells. The glucose transporter 2 (GLUT2) protein and its downstream proteins peroxisome proliferator-activated receptor γ coactivator (PGC)-1β were significantly increased, and sterol regulatory element-binding-1c (SREBP-1c) protein, and fatty acid synthase (FAS) were significantly decreased by EGCG in HepG2. Moreover, the foregoing effects were reversed by siRNA-mediated knockdown of GLUT2.Conclusion: Our data demonstrated that EGCG improved IR, possibly through ameliorating glucose (25 mM) and PA (0.25 mM)-induced inflammation, oxidative stress, and FFAs via the GLUT2/PGC-1β/SREBP-1c/FAS pathway in HepG2 cells. [ABSTRACT FROM AUTHOR]