Effects of Astragaloside IV combined with the active components of Panax notoginseng on oxidative stress injury and nuclear factor-erythroid 2-related factor 2/heme oxygenase-1 signaling pathway after cerebral ischemia-reperfusion in mice

Objective To explore the mechanism of chromobox 7 (CBX7)-mediated nuclear factor E2-related factor 2 (Nrf2)/hemeoxygenase-1 (HO-1) signaling pathway in the cerebral ischemia/reperfusion (I/R) injury. Methods The experimental wild-type (WT) and CBX7-/- mice were used to establish cerebral I/R models using the middle cerebral artery occlusion (MCAO) surgery to determine CBX7 levels at different time points after MCAO injury. For all mice, neurological behavior, infarct size, water content, and oxidative stress–related indicators were determined, and transferase (TdT)-mediated dUTP-biotin nick-end labeling (terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL)) staining method was employed to observe cell apoptosis, while Western blot to measure the expression of CBX7 and Nrf/HO-1 pathway-related proteins. Results At 6 h, 12 h, 24 h, 3 days, and 7 days after mice with MCAO, CBX7 expression was gradually up-regulated and the peak level was reached at 24 h. Mice in the WT + MCAO group had increased infarct size, with significant increases in the modified neurological severity scores and water content in the brain, as well as the quantity of TUNEL-positive cells. For the oxidative stress-indicators, an increase was seen in the content of MDA (malondial dehyde), but the activity of SOD (superoxide dismutase) and content of GSH-PX (glutathione peroxidase) and CAT (catalase) were decreased; meanwhile, the protein expression of CBX7, HO-1, and nuclear Nrf2 was up-regulated, while the cytoplasmic Nrf2 was down-regulated. Moreover, CBX7 knockout attenuated I/R injury in mice. Conclusion Knockout of CBX7 may protect mice from cerebral I/R injury by reducing cell apoptosis and oxidative stress, possibly via activating the Nrf2/HO-1 pathway.

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Propofol inhibits oxidative stress injury through the glycogen synthase kinase 3 beta/nuclear factor erythroid 2-related factor 2/heme oxygenase-1 signaling pathway

Bioengineered ◽

10.1080/21655979.2021.2021062 ◽

2022 ◽

Vol 13 (1) ◽

pp. 1612-1625

Author(s):

Ziyin Zhang ◽

BaoFeng Yan ◽

Yuguo Li ◽

Shuo Yang ◽

Jinfeng Li

Keyword(s):

Oxidative Stress ◽

Signaling Pathway ◽

Heme Oxygenase ◽

Glycogen Synthase ◽

Glycogen Synthase Kinase ◽

Glycogen Synthase Kinase 3 ◽

Heme Oxygenase 1 ◽

Related Factor ◽

Nuclear Factor ◽

Stress Injury

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(–)-Loliolide Isolated from Sargassum horneri Suppressed Oxidative Stress and Inflammation by Activating Nrf2/HO-1 Signaling in IFN-γ/TNF-α-Stimulated HaCaT Keratinocytes

Antioxidants ◽

10.3390/antiox10060856 ◽

2021 ◽

Vol 10 (6) ◽

pp. 856

Author(s):

Eui-Jeong Han ◽

Ilekuttige Priyan Shanura Fernando ◽

Hyun-Soo Kim ◽

Dae-Sung Lee ◽

Areum Kim ◽

...

Keyword(s):

Oxidative Stress ◽

Nuclear Factor Κb ◽

Sargassum Horneri ◽

Mitogen Activated Protein Kinase ◽

Heme Oxygenase 1 ◽

Related Factor ◽

Nuclear Factor ◽

Hacat Keratinocytes ◽

Tnf Α ◽

Ifn Γ

The present study evaluated the effects of (–)-loliolide isolated from Sargassum horneri (S. horneri) against oxidative stress and inflammation, and its biological mechanism in interferon (IFN)-γ/tumor necrosis factor (TNF)-α-stimulated HaCaT keratinocytes. The results showed that (–)-loliolide improved the cell viability by reducing the production of intracellular reactive oxygen species (ROS) in IFN-γ/TNF-α-stimulated HaCaT keratinocytes. In addition, (–)-loliolide effectively decreased the expression of inflammatory cytokines (interleukin (IL)-4 IL-6, IL-13, IFN-γ and TNF-α) and chemokines (CCL11 (Eotaxin), macrophage-derived chemokine (MDC), regulated on activation, normal T cell expressed and secreted (RANTES), and thymus and activation-regulated chemokine (TARC)), by downregulating the expression of epidermal-derived initial cytokines (IL-25, IL-33 and thymic stromal lymphopoietin (TSLP)). Furthermore, (–)-loliolide suppressed the activation of mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling, whereas it activated nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling. Interestingly, the cytoprotective effects of (–)-loliolide against IFN-γ/TNF-α stimulation were significantly blocked upon inhibition of HO-1. Taken together, these results suggest that (–)-loliolide effectively suppressed the oxidative stress and inflammation by activating the Nrf2/HO-1 signaling in IFN-γ/TNF-α-stimulated HaCaT keratinocytes.

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Ginsenoside Rg1 Protects Cardiomyocytes Against Hypoxia/Reoxygenation Injury via Activation of Nrf2/HO-1 Signaling and Inhibition of JNK

Cellular Physiology and Biochemistry ◽

10.1159/000484578 ◽

2017 ◽

Vol 44 (1) ◽

pp. 21-37 ◽

Cited By ~ 39

Author(s):

Qianhui Li ◽

Yin Xiang ◽

Yu Chen ◽

Yong Tang ◽

Yachen Zhang

Keyword(s):

Oxidative Stress ◽

Antioxidant Properties ◽

Heme Oxygenase 1 ◽

Related Factor ◽

Dependent Manner ◽

Ginsenoside Rg1 ◽

H9c2 Cells ◽

Stress Injury ◽

Mitochondrial Membrane Depolarization ◽

Hypoxia Reoxygenation

Background/Aims: Excessive reactive oxygen species (ROS) disturb the physiology of H9c2 cells, which is regarded as a major cause of H9c2 cardiomyocyte apoptosis. Ginsenoside Rg1 is the main active extract of ginseng, which has important antioxidant properties in various cell models. This project investigated the role of ginsenoside Rg1 in hypoxia/reoxygenation (H/R)-induced oxidative stress injury in cultured H9c2 cells to reveal the underlying signaling pathways. Methods: H9c2 cells were pretreated with ginsenoside Rg1 for 12 h before exposure to H/R. In the absence or presence of Nrf2siRNA, HO-1 inhibitor (ZnPP-IX), and inhibitors of the MAPK pathway (SB203580, PD98059, SP600125), H9c2 cells were subjected to H/R with Rg1 treatment. The effects and mechanisms of H/R-induced cardiomyocyte injury were measured. Results: Ginsenoside Rg1 treatment suppressed H/R-induced apoptosis and caspase-3 activation. Ginsenoside Rg1 treatment decreased ROS production and mitochondrial membrane depolarization by elevating the intracellular antioxidant capacity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and reduced glutathione (GSH). Furthermore, ginsenoside Rg1 stimulation appeared to result in nuclear translocation of NF-E2-related factor 2 (Nrf2), along with enhanced expression of the downstream target gene heme oxygenase-1 (HO-1) in a dose-dependent manner. However, ginsenoside Rg1-mediated cardioprotection was abolished by Nrf2-siRNA and HO-1 inhibitor. H/R treatment increased the levels of phosphorylated c-Jun N-terminal kinases (p-JNK), which was dramatically attenuated by ginsenoside Rg1 and SP600125 (a specific JNK inhibitor). Conclusion: These observations indicate that ginsenoside Rg1 activates the Nrf2/HO-1 axis and inhibits the JNK pathway in H9c2 cells to protect against oxidative stress.

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Cyanate Induces Oxidative Stress Injury and Abnormal Lipid Metabolism in Liver through Nrf2/HO-1

Molecules ◽

10.3390/molecules24183231 ◽

2019 ◽

Vol 24 (18) ◽

pp. 3231 ◽

Cited By ~ 4

Author(s):

Ling Hu ◽

Kuan Tian ◽

Tao Zhang ◽

Chun-Hua Fan ◽

Peng Zhou ◽

...

Keyword(s):

Oxidative Stress ◽

Lipid Metabolism ◽

Protein Modification ◽

Density Lipoprotein ◽

Heme Oxygenase 1 ◽

Related Factor ◽

Uremic Toxin ◽

Stress Injury ◽

Oxidative Stress Injury ◽

Abnormal Lipid Metabolism

Chronic kidney disease (CKD) is problem that has become one of the major issues affecting public health. Extensive clinical data suggests that the prevalence of hyperlipidemia in CKD patients is significantly higher than in the general population. Lipid metabolism disorders can damage the renal parenchyma and promote the occurrence of cardiovascular disease (CVD). Cyanate is a uremic toxin that has attracted widespread attention in recent years. Usually, 0.8% of the molar concentration of urea is converted into cyanate, while myeloperoxidase (MPO) catalyzes the oxidation of thiocyanate to produce cyanate at the site of inflammation during smoking, inflammation, or exposure to environmental pollution. One of the important physiological functions of cyanate is protein carbonylation, a non-enzymatic post-translational protein modification. Carbamylation reactions on proteins are capable of irreversibly changing protein structure and function, resulting in pathologic molecular and cellular responses. In addition, recent studies have shown that cyanate can directly damage vascular tissue by producing large amounts of reactive oxygen species (ROS). Oxidative stress leads to the disorder of liver lipid metabolism, which is also an important mechanism leading to cirrhosis and liver fibrosis. However, the influence of cyanate on liver has remained unclear. In this research, we explored the effects of cyanate on the oxidative stress injury and abnormal lipid metabolism in mice and HL-7702 cells. In results, cyanate induced hyperlipidemia and oxidative stress by influencing the content of total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), superoxide dismutase (SOD), catalase (CAT) in liver. Cyanate inhibited NF-E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and the phosphorylation of adenosine 5′monophosphate-activated protein kinase (AMPK), activated the mTOR pathway. Oxidative stress on the cells reduced significantly by treating with TBHQ, an antioxidant, which is also an activator of Nrf2. The activity of Nrf2 was rehabilitated and phosphorylation of mTOR decreased. In conclusion, cyanate could induce oxidative stress damage and lipid deposition by inhibiting Nrf2/HO-1 pathway, which was rescued by inhibitor of Nrf2.

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Effects of Normobaric Hyperoxia in a Rat Model of Focal Cerebral Ischemia—Reperfusion

Journal of Cerebral Blood Flow & Metabolism ◽

10.1097/00004647-200207000-00011 ◽

2002 ◽

Vol 22 (7) ◽

pp. 861-868 ◽

Cited By ~ 123

Author(s):

Aneesh B. Singhal ◽

Xiaoying Wang ◽

Toshihisa Sumii ◽

Tatsuro Mori ◽

Eng H. Lo

Keyword(s):

Oxidative Stress ◽

Cerebral Ischemia ◽

Focal Cerebral Ischemia ◽

Ischemia Reperfusion ◽

Protein Carbonyl ◽

Blue Dye ◽

Heme Oxygenase 1 ◽

Normobaric Hyperoxia ◽

Cerebral Ischemia Reperfusion ◽

Carbonyl Formation

Recent studies suggest that normobaric hyperoxia can be beneficial, if administered during transient stroke. However, increased oxygenation theoretically may increase oxygen free-radical injury, particularly during reperfusion. In the present study, the authors assessed the benefit and risks of hyperoxia during focal cerebral ischemia and reperfusion. Rats were subjected to hyperoxia (Fio2 100%) or normoxia (Fio2 30%) during 2-hour filament occlusion and 1-hour reperfusion of the middle cerebral artery. At 24 hours, the hyperoxia group showed 70% (total) and 92% (cortical) reduction in infarct volumes as compared to the normoxia group. Levels of oxidative stress were evaluated using three indirect methods. First, since oxygen free radicals increase blood—brain barrier (BBB) damage, Evan's blue dye extravasation was quantified to assess BBB damage. Second, the expression of heme oxygenase-1 (HO-1), a heat shock protein inducible by oxidative stress, was assessed using Western blot techniques. Third, an immunoblot technique (“OxyBlot”) was used to assess levels of protein carbonyl formation as a marker of oxidative stress—induced protein denaturation. At 24 hours, Evan's blue dye extravasation per average lesion volume was similar between groups. There were no significant differences in HO-1 induction and protein carbonyl formation between groups, in the ipsilateral or contralateral hemispheres, at 6 hours and at 24 hours. These results indicate that hyperoxia treatment during focal cerebral ischemia—reperfusion is neuroprotective, and does not increase oxidative stress.

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Astragaloside IV Protects Against Oxidative Stress in Calf Small Intestine Epithelial Cells via NFE2L2-Antioxidant Response Element Signaling

International Journal of Molecular Sciences ◽

10.3390/ijms20246131 ◽

2019 ◽

Vol 20 (24) ◽

pp. 6131 ◽

Cited By ~ 2

Author(s):

Yafang Wang ◽

Fugui Jiang ◽

Haijian Cheng ◽

Xiuwen Tan ◽

Yifan Liu ◽

...

Keyword(s):

Oxidative Stress ◽

Small Intestine ◽

Epithelial Cells ◽

Reactive Oxygen Species Generation ◽

Antioxidant Response ◽

Heme Oxygenase 1 ◽

Related Factor ◽

Antioxidant Response Element ◽

Astragaloside Iv ◽

Response Element

Oxidative stress can damage intestinal epithelial cell integrity and function, causing gastrointestinal disorders. Astragaloside IV (ASIV) exhibits a variety of biological and pharmacological properties, including anti-inflammatory and antioxidant effects. The purpose of this research was to investigate the cytoprotective action of ASIV and its mechanisms in calf small intestine epithelial cells with hydrogen peroxide (H2O2)-induced oxidative stress. ASIV pretreatment not only increased cell survival, but it also decreased reactive oxygen species generation and apoptosis, enhanced superoxide dismutase, catalase, and glutathione peroxidase levels, and it reduced malondialdehyde formation. Furthermore, pretreatment with ASIV elevated the mRNA and protein levels of nuclear factor erythroid 2-related factor 2 (NFE2L2), heme oxygenase-1 (HMOX1), and NAD(P)H quinone dehydrogenase 1 (NQO1). The NFE2L2 inhibitor ML385 inhibited NFE2L2 expression and then blocked HMOX1 and NQO1 expression. These results demonstrate that ASIV treatment effectively protects against H2O2-induced oxidative damage in calf small intestine epithelial cells through the activation of the NFE2L2-antioxidant response element signaling pathway.

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New Insights into the Nrf-2/HO-1 Signaling Axis and Its Application in Pediatric Respiratory Diseases

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/3214196 ◽

2019 ◽

Vol 2019 ◽

pp. 1-9 ◽

Cited By ~ 4

Author(s):

Xueyan Zhang ◽

Ming Ding ◽

Ping Zhu ◽

Huanlei Huang ◽

Quan Zhuang ◽

...

Keyword(s):

Oxidative Stress ◽

Respiratory Diseases ◽

Multiple Organ ◽

Research Progress ◽

Heme Oxygenase 1 ◽

Related Factor ◽

Clinical Value ◽

Organ Protection ◽

Stress Injury ◽

Signaling Axis

Respiratory diseases are one of the most common pediatric diseases in clinical practice. Their pathogenesis, diagnosis, and treatment are thus worthy of further investigation. The nuclear factor erythroid 2-related factor 2/heme oxygenase 1 (Nrf2/HO-1) signaling axis is a multiple organ protection chain that protects against oxidative stress injury. This signaling axis regulates anti-inflammation and antioxidation by regulating calcium ions, mitochondrial oxidative stress, autophagy, ferroptosis, pyroptosis, apoptosis, alkaliptosis, and clockophagy. This review presents an overview of the role of the Nrf2/HO-1 signaling axis in the pathogenesis of pediatric respiratory diseases and the latest research progress on this subject. Overall, the Nrf2/HO-1 signaling axis has an important clinical value in pediatric respiratory diseases, and its protective effect needs further exploration.

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Astragaloside IV ameliorates preeclampsia-induced oxidative stress through the Nrf2/HO-1 pathway in a rat model

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00357.2020 ◽

2020 ◽

Vol 319 (5) ◽

pp. E904-E911 ◽

Cited By ~ 1

Author(s):

Shuangyan Yang ◽

Ruixue Zhang ◽

Baoheng Xing ◽

Ling Zhou ◽

Peipei Zhang ◽

...

Keyword(s):

Oxidative Stress ◽

Rat Model ◽

Target Genes ◽

Heme Oxygenase 1 ◽

Related Factor ◽

Astragaloside Iv ◽

Pregnant Rats ◽

Beneficial Effects ◽

Antioxidative Effects ◽

Protein Serum

Preeclampsia (PE) can cause serious health problems for pregnant women and their infants. Astragaloside IV has been shown to exert cardioprotective, anti-inflammatory, and antioxidative effects on various disorders. We aimed to study the effects of Astragaloside IV on PE symptoms using an NG-nitro-l-arginine methyl ester (l-NAME)-induced rat model of PE. The pregnant rats’ physiological features, including blood pressure, urine protein, serum soluble fms-like tyrosine kinase- 1 ( sFlt - 1)/placental growth factor (PlGF) ratio, and weight of placenta, as well as the weight, length, and survival of pups, were documented. The expression levels of target genes were analyzed by Western blot and qRT-PCR assays. The levels of target secreted proteins were determined by ELISA. We demonstrated that the administration of Astragaloside IV might exert a multitude of beneficial effects on attenuated PE symptoms in a rat model of PE. We further revealed that the effects of Astragaloside IV on PE rats were achieved, at least partially, through elimination of oxidative stress and stimulation of the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway. Our study indicated that Astragaloside IV may serve as a promising candidate for the development of new therapeutic methods for patients with PE.

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