scholarly journals Notoginsenoside R1 attenuates sevoflurane-induced neurotoxicity

2020 ◽  
Vol 11 (1) ◽  
pp. 215-226
Author(s):  
Yibing Zhang ◽  
Yong Zhao ◽  
Yongwang Ran ◽  
Jianyou Guo ◽  
Haifeng Cui ◽  
...  
Keyword(s):  
Neuronal Degeneration ◽  
Apoptotic Cell ◽  
Volatile Anesthetic ◽  
Adenosine Monophosphate ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Sprague Dawley ◽  
Quinone Oxidoreductase ◽  
Neuroprotective Effects ◽  
Cell Counts

AbstractBackgroundSevoflurane, a volatile anesthetic, is known to induce widespread neuronal degeneration and apoptosis. Recently, the stress-inducible protein sestrin 2 and adenosine monophosphate-activated protein kinase (AMPK) have been found to regulate the levels of intracellular reactive oxygen species (ROS) and suppress oxidative stress. Notoginsenoside R1 (NGR1), a saponin isolated from Panax notoginseng, has been shown to exert neuroprotective effects. The effects of NGR1 against neurotoxicity induced by sevoflurane were assessed.MethodsSprague-Dawley rat pups on postnatal day 7 (PD7) were exposed to sevoflurane (3%) anesthesia for 6 h. NGR1 at doses of 12.5, 25, or 50 mg/kg body weight was orally administered to pups from PD2 to PD7.ResultsPretreatment with NGR1 attenuated sevoflurane-induced generation of ROS and reduced apoptotic cell counts. Western blotting revealed decreased cleaved caspase 3 and Bad and Bax pro-apoptotic protein expression. NGR1 substantially upregulated nuclear factor erythroid 2-related factor 2 (Nrf2) expression along with increased heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase-1 levels, suggesting Nrf2 signaling activation. Enhanced sestrin-2 and phosphorylated AMPK expression were noticed following NGR1 pretreatment.ConclusionThis study revealed the neuroprotective effects of NGR1 through effective suppression of apoptosis and ROS via regulation of apoptotic proteins and activation of Nrf2/HO-1 and sestrin 2/AMPK signaling cascades.

scholarly journals Thymoquinone Prevents Dopaminergic Neurodegeneration by Attenuating Oxidative Stress Via the Nrf2/ARE Pathway

2021 ◽  
Vol 11 ◽  
Author(s):  
Jianjian Dong ◽  
Xiaoming Zhang ◽  
Shijing Wang ◽  
Chenchen Xu ◽  
Manli Gao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nuclear Translocation ◽  
Nigella Sativa ◽  
Drug Candidate ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Protective Effects ◽  
Quinone Oxidoreductase ◽  
Neuroprotective Effects ◽  
Antioxidant Genes

Studies have indicated that oxidative stress plays a crucial role in the development of Parkinson’s disease (PD) and other neurodegenerative conditions. Research has also revealed that nuclear factor erythroid 2-related factor 2 (Nrf2) triggers the expression of antioxidant genes via a series of antioxidant response elements (AREs), thus preventing oxidative stress. Thymoquinone (TQ) is the bioactive component of Nigella sativa, a medicinal plant that exhibits antioxidant and neuroprotective effects. In the present study we examined whether TQ alleviates in vivo and in vitro neurodegeneration induced by 1-methyl-4-phenylpyridinium (MPP+) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) by acting as an activator of the Nrf2/ARE cascade. We showed that TQ significantly reduced MPP+-mediated cell death and apoptosis. Moreover, TQ significantly elevated the nuclear translocation of Nrf2 and significantly increased the subsequent expression of antioxidative genes such as Heme oxygenase 1 (HO-1), quinone oxidoreductase (NQO1) and Glutathione-S-Transferase (GST). The application of siRNA to silence Nrf2 led to an abolishment in the protective effects of TQ. We also found that the intraperitoneal injection of TQ into a rodent model of PD ameliorated oxidative stress and effectively mitigated nigrostriatal dopaminergic degeneration by activating the Nrf2-ARE pathway. However, these effects were inhibited by the injection of a lentivirus wrapped Nrf2 siRNA (siNrf2). Collectively, these findings suggest that TQ alleviates progressive dopaminergic neuropathology by activating the Nrf2/ARE signaling cascade and by attenuating oxidative stress, thus demonstrating that TQ is a potential novel drug candidate for the treatment of PD.

scholarly journals Neuroprotective Effects and Mechanisms of Procyanidins In Vitro and In Vivo

Molecules ◽  
2021 ◽  
Vol 26 (10) ◽  
pp. 2963
Author(s):  
Juan Chen ◽  
Yixuan Chen ◽  
Yangfan Zheng ◽  
Jiawen Zhao ◽  
Huilin Yu ◽  
...  
Keyword(s):  
Antioxidant Activities ◽  
Antioxidant Response ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Quinone Oxidoreductase ◽  
Neuroprotective Effects ◽  
Glutamate Cysteine Ligase ◽  
Pheochromocytoma Cells

This study evaluated the neuroprotective effects and mechanisms of procyanidins (PCs). In vitro, rat pheochromocytoma cells (PC12 cells) were exposed to PCs (1, 2 or 4 μg/mL) or N-Acetyl-L-cysteine (NAC) (20 μM) for 24 h, and then incubated with 200 μM of H2O2 for 24 h. Compared with H2O2 alone, PCs significantly increased antioxidant activities (e.g., glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT)), decreased levels of reactive oxygen species (ROS) and malondialdehyde (MDA), and increased nuclear factor-erythroid 2-related factor 2 (Nrf2) accumulation and increased the expression of quinone oxidoreductase 1 (NQO1), heme oxygenase 1 (HO-1), glutamate-cysteine ligase modifier subunit (GCLM), and glutamate-cysteine ligase catalytic subunit (GCLC). In vivo, zebrafish larvae (AB strain) 3 days post-fertilization (dpf) were exposed to NAC (30 μM) or PCs (4, 8 or 16 μg/mL) in the absence or presence of 300 μM of H2O2 for 4 days. Compared with H2O2 alone, PCs enhanced antioxidant activities (e.g., GSH-Px, CAT, and SOD), decreased levels of ROS and MDA, and enhanced Nrf2/ antioxidant response element (ARE) activation and raised expression levels of NQO1, HO-1, GCLM, and GCLC. In conclusion, these results indicated that PCs exerted neuroprotective effects via activating the Nrf2/ARE pathway and alleviating oxidative damage.

Sodium tanshinone IIA sulfate protects myocardium against paraquat-induced toxicity through activating the Nrf2 signaling pathway in rats

2018 ◽  
Vol 38 (2) ◽  
pp. 247-254 ◽  
Author(s):  
WX Zhang ◽  
XY Xiao ◽  
CG Peng ◽  
WL Chen ◽  
S Xie ◽  
...  
Keyword(s):  
Tanshinone Iia ◽  
Control Group ◽  
Heme Oxygenase 1 ◽  
Intragastric Administration ◽  
Related Factor ◽  
Dependent Manner ◽  
Myocardial Cells ◽  
Sprague Dawley ◽  
Nrf2 Pathway ◽  
Nrf2 Signaling Pathway

Objective: To investigate the therapeutic effect and mechanism of sodium tanshinone IIA sulfate (STS) on paraquat (PQ)-induced myocardial injuries in a rat model. Methods: Healthy adult Sprague Dawley rats were randomly divided into normal control, PQ, and PQ + STS groups. PQ group was given a single intragastric administration of PQ (80 mg/kg). PQ + STS group was intraperitoneally injected with STS (1 ml/kg) at 30 min following PQ exposure. Rats in control and PQ groups were injected with equal amount of saline. After 12, 24, 48, and 72 h, rats were killed, and the apoptosis of myocardial cells was detected. Myocardial expression of Bax and Bcl-2 was measured. The activity of the nuclear erythroid 2-related factor 2 (Nrf2) pathway was assessed by Western blot. Results: The apoptotic cells in PQ group were significantly increased in a time-dependent manner compared with the control group ( p < 0.01). The rats in PQ group exhibited significantly lower Bcl-2 expression, but notably higher Bax expression at 12, 24, 48, and 72 h after PQ exposure ( p < 0.05 or 0.01). STS intervention markedly reduced the proportion of apoptotic myocardial cells, increased Bcl-2 expression, and decreased Bax expression at 24, 48, and 72 h after treatment ( p < 0.05 or 0.01). The expression of phosphorylated Nrf2 and heme oxygenase 1 in PQ + STS group was significantly increased compared with PQ and control groups ( p < 0.05 or 0.01). Conclusion: STS effectively inhibits PQ-induced myocardial cell apoptosis in rats via modulating the Nrf2 pathway, suggesting its potential as a promising therapeutic agent for PQ-induced myocardium damage.

scholarly journals Bovine Herpesvirus 1 Productive Infection Led to Inactivation of Nrf2 Signaling through Diverse Approaches

2019 ◽  
Vol 2019 ◽  
pp. 1-14
Author(s):  
Xiaotian Fu ◽  
Dongmei Chen ◽  
Yan Ma ◽  
Weifeng Yuan ◽  
Liqian Zhu
Keyword(s):  
Signaling Pathway ◽  
Bovine Herpesvirus ◽  
Productive Infection ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Quinone Oxidoreductase ◽  
Herpesvirus Type ◽  
Nrf2 Signaling Pathway ◽  
Mdbk Cells ◽  
Bovine Herpesvirus Type 1

Bovine herpesvirus type 1 (BoHV-1) is a significant cofactor for bovine respiratory disease complex (BRDC), the most important inflammatory disease in cattle. BoHV-1 infection in cell cultures induces overproduction of pathogenic reactive oxygen species (ROS) and the depletion of nuclear factor erythroid 2 p45-related factor 2 (Nrf2), a master transcriptional factor regulating a panel of antioxidant and cellular defense genes in response to oxidative stress. In this study, we reported that the virus productive infection in MDBK cells at the later stage significantly decreased the expression levels of heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase-1 (NQO1) proteins, the canonical downstream targets regulated by Nrf2, inhibited Nrf2 acetylation, reduced the accumulation of Nrf2 proteins in the nucleus, and relocalized nuclear Nrf2 proteins to form dot-like staining patterns in confocal microscope assay. The differential expression of Kelch-like ECH associated protein 1 (KEAP1) and DJ-1 proteins as well as the decreased association between KEAP1 and DJ-1 promoted Nrf2 degradation through the ubiquitin proteasome pathway. These data indicated that the BoHV-1 infection may significantly suppress the Nrf2 signaling pathway. Moreover, we found that there was an association between Nrf2 and LaminA/C, H3K9ac, and H3K18ac, and the binding ratios were altered following the virus infection. Taken together, for the first time, we provided evidence showing that BoHV-1 infection inhibited the Nrf2 signaling pathway by complicated mechanisms including promoting Nrf2 degradation, relocalization of nuclear Nrf2, and inhibition of Nrf2 acetylation.

scholarly journals Defatted Rice Bran Supplementation in Diets of Finishing Pigs: Effects on Physiological, Intestinal Barrier, and Oxidative Stress Parameters

Animals ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 449
Author(s):  
Lijuan Fan ◽  
Ruihua Huang ◽  
Chengwu Wu ◽  
Yang Cao ◽  
Taoran Du ◽  
...  
Keyword(s):  
Rice Bran ◽  
Waste Product ◽  
Intestinal Barrier ◽  
Control Group ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Mrna Levels ◽  
Finishing Pigs ◽  
Quinone Oxidoreductase ◽  
Defatted Rice Bran

Rice bran is a waste product with low cost and high fiber content, giving it an added advantage over corn and soybean meal, which have to be purchased and always at a relatively higher cost. Under the background of increased attention to sustainable agriculture, it is significant to find alternative uses for this byproduct. A total of 35 finishing pigs were allotted to five dietary treatments: a control group with basal diet and four experimental diets where corn was equivalently substituted by 7%, 14%, 21%, and 28% defatted rice bran (DFRB), respectively. With increasing levels of DFRB, the neutrophil to lymphocyte ratio (NLR) linearly decreased (p < 0.05). In the jejunum, the mRNA level of nuclear factor erythroid-2 related factor-2 (Nrf2) exhibited a quadratic response (p < 0.01) with incremental levels of DFRB. In the colon, the mRNA levels of mucin 2 (MUC2), Nrf2, and NAD(P)H: quinone oxidoreductase 1 (NQO1) were upregulated (linear, p < 0.05) and heme oxygenase-1 (HO-1) was upregulated (linear, p < 0.01). Overall, using DFRB to replace corn decreased the inflammatory biomarkers of serum and showed potential function in modulating the intestinal barrier by upregulating the mRNA expression levels of MUC2 and downregulating that of Nrf2, NQO1, and HO-1 in the colon.

scholarly journals Cinnamaldehyde Ameliorates Vascular Dysfunction in Diabetic Mice by Activating Nrf2

2020 ◽  
Vol 33 (7) ◽  
pp. 610-619 ◽  
Author(s):  
Peijian Wang ◽  
Yi Yang ◽  
Dan Wang ◽  
Qiyuan Yang ◽  
Jindong Wan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Vascular Dysfunction ◽  
Mesenteric Arteries ◽  
Heme Oxygenase 1 ◽  
No Production ◽  
Related Factor ◽  
Diabetic Mice ◽  
Quinone Oxidoreductase ◽  
Nrf2 Signaling Pathway

Abstract BACKGROUND Oxidative stress is known to be associated with the development of diabetes. Cinnamaldehyde (CA) is a spice compound in cinnamon that enhances the antioxidant defense against reactive oxygen species (ROS) by activating nuclear factor erythroid-related factor 2 (Nrf2), which has been shown to have a cardioprotection effect. However, the relationship between CA and Nrf2 in diabetic vascular complications remains unclear. METHODS Leptin receptor-deficient (db/db) mice were fed normal chow or diet containing 0.02% CA for 12 weeks. The vascular tone, blood pressure, superoxide level, nitric oxide (NO) production, renal morphology, and function were measured in each group. RESULTS CA remarkably inhibited ROS generation, preserved NO production, increased phosphorylated endothelial nitric oxide synthase (p-eNOS), attenuated the upregulation of nitrotyrosine, P22 and P47 in aortas of db/db mice, and apparently ameliorated the elevation of type IV collagen, TGF-β1, P22, and P47 in kidney of db/db mice. Feeding with CA improved endothelium-dependent relaxation of aortas and mesenteric arteries, and alleviated the remodeling of mesenteric arteries in db/db mice. Additionally, dietary CA ameliorated glomerular fibrosis and renal dysfunction in diabetic mice. Nrf2 and its targeted genes heme oxygenase-1 (HO-1) and quinone oxidoreductase-1 (NQO-1) were slightly increased in db/db mice and further upregulated by CA. However, these protective effects of CA were reversed in Nrf2 downregulation mice. CONCLUSIONS A prolonged diet of CA protects against diabetic vascular dysfunction by inhibiting oxidative stress through activating of Nrf2 signaling pathway in db/db mice.

scholarly journals Polygonatum sibiricum Polysaccharides Protect against MPP-Induced Neurotoxicity via the Akt/mTOR and Nrf2 Pathways

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Si Huang ◽  
Haiyan Yuan ◽  
Wenqun Li ◽  
Xinyi Liu ◽  
Xiaojie Zhang ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Neuronal Loss ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Dependent Manner ◽  
Quinone Oxidoreductase ◽  
Glutamate Cysteine Ligase ◽  
Dopaminergic Neuronal Loss

Polygonatum sibiricum, a well-known life-prolonging tonic in Chinese medicine, has been widely used for nourishing nerves in the orient, but the underlying molecular mechanisms remain unclear. In this study, we found that P. sibiricum polysaccharides (PSP) ameliorated 1-methyl-4-phenyl-1,2.3,6-tetrahydropyridine- (MPTP-) induced locomotor activity deficiency and dopaminergic neuronal loss in an in vivo Parkinson’s disease (PD) mouse model. Additionally, PSP pretreatment inhibited N-methyl-4-phenylpyridine (MPP+) induced the production of reactive oxygen species, increasing the ratio of reduced glutathione/oxidized glutathione. In vitro experiments showed that PSP promoted the proliferation of N2a cells in a dose-dependent manner, while exhibiting effects against oxidative stress and neuronal apoptosis elicited by MPP+. These effects were found to be associated with the activation of Akt/mTOR-mediated p70S6K and 4E-BP1 signaling pathways, as well as nuclear factor erythroid 2-related factor 2- (Nrf2-) mediated NAD(P)H quinone oxidoreductase 1 (NQO1), heme oxygenase-1 (HO-1), glutamate-cysteine ligase catalytic subunit (Gclc), and glutamate-cysteine ligase modulatory subunit (Gclm), resulting in antiapoptotic and antioxidative effects. Meanwhile, PSP exhibited no chronic toxicity in C57BJ/6 mice. Together, our results suggest that PSP can serve as a promising therapeutic candidate with neuroprotective properties in preventing PD.

scholarly journals Efficacy of Minocycline in Neural Stem Cells Proliferation after Traumatic Brain Injury

2020 ◽  
Vol 8 (A) ◽  
pp. 59-64
Author(s):  
R. R. Suzy Indharty ◽  
Iskandar Japardi ◽  
Andre M. P. Siahaan ◽  
Steven Tandean ◽  
Michael Lumintang Loe
Keyword(s):  
Traumatic Brain Injury ◽  
Stem Cells ◽  
Brain Injury ◽  
Neural Stem Cells ◽  
Inflammatory Responses ◽  
Closed Head Injury ◽  
Related Factor ◽  
Sprague Dawley ◽  
Proliferation Capacity ◽  
Cell Counts

BACKGROUND: Neuroinflammation is an important secondary injury mechanism that contributes to neurological impairments after traumatic brain injury (TBI). There is a robust evidence that neuroinflammation will diminish neurogenesis after TBI. Therefore, strategies to attenuate the inflammatory responses are potential to increase neurogenesis following TBI. Minocycline, a second-generation tetracycline antibiotic derivate, has potent anti-inflammatory effect by reducing microglial activation and suppressing some pro-inflammatory cytokines. AIM: The aim of this study is to investigate if minocycline could enhance neurogenesis after TBI. METHODS: Thirty Sprague Dawley rats were randomized into three treatments group, i.e., sham-operated controls, closed head injury (CHI), and CHI with minocycline. We used the modified Feeney’s weight-drop model for making CHI. For the treatment group, we gave minocycline per oral (50 mg/kg) twice daily for the first 2 days followed by 25 mg/kg once daily for 3 consecutive days. Animals were sacrificed on day 5. To assess the proliferation capacity of neural stem cells (NSC), we performed immunohistochemistry staining with SOX2, brain-derived neurotropic factor (BDNF), and NFR. Cell counts were carried out using light microscope with 1000 times magnification in 20 high-power fields. RESULTS: SOX2, NF-E2-related factor 2 (NRF-2), and BDNF were upregulated in the CHI group compared to the sham-operated group (p < 0.05). NRF-2, BDNF, and SOX2 were upregulated also significantly in the CHI+ minocycline group compared to the sham-operated group and the CHI group (p < 0.05). CONCLUSION: Minocycline increased the proliferation capacity of NSC.

scholarly journals Upregulation of antioxidant nuclear factor erythroid 2-related factor 2 and its dependent genes associated with enhancing renal ischemic preconditioning renoprotection using levosimendan and cilostazol in an ischemia/reperfusion rat model

2021 ◽  
Vol 18 (2) ◽  
pp. 1-34
Author(s):  
Mona Tawfik ◽  
Samy Makary ◽  
Mohammed Keshawy
Keyword(s):  
Ischemic Preconditioning ◽  
Rat Model ◽  
Ischemia Reperfusion ◽  
Blood Oxygenation ◽  
Renal Ischemia ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Nuclear Factor ◽  
Quinone Oxidoreductase ◽  
Antioxidant Genes

IntroductionIschemic preconditioning (Ipre) provides protection against renal ischemia-reperfusion (I/R) injury with its associated remote organ damage. This study examined the enhancing protective effect of Ipre with levosimendan or cilostazol in I/R-induced kidney and lung injury in a rat model.Material and methodsRats were divided into: sham-operated, I/R control, Ipre control, I/R + cilostazol or levosimendan and Ipre + cilostazol or levosimendan. Drugs were given 30 min before left renal I/R or 4 cycles of Ipre just before renal ischemia.ResultsThe Ipre combined with the implemented drugs enhanced physio­logical antioxidant defense genes including renal nuclear factor erythroid 2-related factor 2 (Nrf2) and its dependent genes heme oxygenase-1 (HO-1) and NADPH-quinone oxidoreductase-1 (NQO-1) and improved malondialdehyde and superoxide dismutase renal tissue levels. The combined effect improved I/R consequences for blood urea, creatinine, and creatinine clearance and improved blood oxygenation and metabolic acidosis. Moreover, the combination improved the renal soluble intercellular adhesion molecule (ICAM), tumor necrosis factor α (TNF-α) and interlukin-6 (IL-6) with histopathological improvement of tubular necrosis with a decrease in the apoptotic marker caspase-3 and an increase in the anti-apoptotic Bcl-2 expression.ConclusionsCilostazol or levosimendan potentiates the renoprotective effect of Ipre against renal I/R injury, associated with upregulation of antioxidant genes Nrf2, HO-1, and NOQ-1 expression.

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