scholarly journals Induction of antioxidant and detoxifying enzymes by oriental bezoar

2021 ◽  
Author(s):  
Tomoe Tsubonoya ◽  
Eiji Inoue ◽  
Yasuharu Shimizu ◽  
Keiichi Sudo
Keyword(s):  
Underlying Mechanism ◽  
Luciferase Reporter ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Dependent Manner ◽  
Detoxifying Enzymes ◽  
Antioxidative Effect ◽  
Quinone Oxidoreductase ◽  
Traditional Use

AbstractOriental bezoar, a gallstone formed in the gall sac of Bos taurus Linné var. domesticus Gmelin (Bovidae), has been used as an antipyretic, sedative, antispasmodic, and detoxifying drug in oriental medicine. It reportedly has an antioxidative effect; however, its underlying mechanism remains unclear. Therefore, we investigated the effects of oriental bezoar and its main components on the nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway, which transcriptionally regulates the gene encoding an antioxidant enzyme, heme oxygenase-1 (HO-1), and detoxifying enzymes glutathione-S-transferase alpha 1 (GSTA1) and quinone oxidoreductase 1 (NQO1) in vitro. Using a dual-luciferase reporter assay and real-time PCR, oriental bezoar and its main constituent bilirubin were shown to induce ARE activity and up-regulate the expression of HO-1, GSTA1, and NQO1 in HepG2 cells in a dose-dependent manner. These results suggest that activation of the Nrf2-ARE pathway is partially involved in the antioxidative effect of oriental bezoar, thus providing a scientific basis for oriental bezoar’s traditional use for detoxification.

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 Protective Effect of Decursin Extracted fromAngelica gigasin Male Infertility via Nrf2/HO-1 Signaling Pathway

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Woong Jin Bae ◽  
U. Syn Ha ◽  
Jin Bong Choi ◽  
Kang Sup Kim ◽  
Su Jin Kim ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Semen Quality ◽  
Antioxidant Activities ◽  
Control Group ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Dependent Manner ◽  
Testicular Weight ◽  
Unilateral Cryptorchidism

Higher testicular temperature results in altered spermatogenesis due to heat-related oxidative stress. We examined the effects of decursin extracted fromAngelica gigasNakai on antioxidant activityin vitroand in a cryptorchidism-induced infertility rat model. TM3 Leydig cell viability was measured based on oxidative stress according to treatment. Either distilled water or AG 400 mg/kg ofA. gigasextract was administered orally for 4 weeks after unilateral cryptorchidism was induced. After 1, 2, and 4 weeks, six rats from the control group and six rats from treatment group were sacrificed. Testicular weight, semen quality, antioxidant activities, nuclear factor erythroid 2-related factor 2 (Nrf2) protein, and mRNA expression of Nrf2-regulated genes were analyzed. Treatment withA. gigasextract (1) protected TM3 cells against oxidative stress in a dose-dependent manner, (2) improved the mean weight of the cryptorchid testis, (3) maintained sperm counts, motility, and spermatogenic cell density, (4) decreased levels of 8-hydroxy-2-deoxyguanosine (8-OHdG) and increased levels of superoxide dismutase (SOD), (5) significantly increased Nrf2 and heme oxygenase-1 (HO-1), and (6) significantly decreased apoptosis. This study suggests that decursin extracted fromA. gigasis a supplemental agent that can reduce oxidative stress by Nrf2-mediated upregulation of HO-1 in rat experimentally induced unilateral cryptorchidism and may improve cryptorchidism-induced infertility.

scholarly journals Circ_0001367 inhibits glioma proliferation, migration and invasion by sponging miR-431 and thus regulating NRXN3

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Liang Liu ◽  
Peng Zhang ◽  
Xuchen Dong ◽  
Haoran Li ◽  
Suwen Li ◽  
...  
Keyword(s):  
Close Correlation ◽  
Underlying Mechanism ◽  
Vital Role ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Dependent Manner ◽  
Glioma Growth

AbstractMany studies have reported that circular RNAs play a vital role in the malignant progression of human cancers. However, the role and underlying mechanism of circRNAs in the development of gliomas have not been fully clarified. In this study, we found that circ_0001367 was downregulated in glioma tissues and showed a close correlation with glioma patient survival. Functional assays demonstrated that upregulation of circ_0001367 could suppress the proliferation, migration and invasion of glioma cells in vitro and inhibit glioma growth in vivo. Furthermore, bioinformatics analysis, luciferase reporter assay and RNA immunoprecipitation assay indicated that circ_0001367 can serve as a sponge for miR-431 and that miR-431 acts as an oncogene by regulating neurexin 3 (NRXN3). In addition, rescue experiments verified that circ_0001367 could regulate both the expression and function of NRXN3 in a miR-431-dependent manner. In conclusion, circ_0001367 functions as an suppressor in glioma by targeting the miR-431/NRXN3 axis and may be a promising therapeutic target against gliomas.

Mifepristone-inducible recombinant adenovirus attenuates paraquat-induced lung injury in rats

2014 ◽  
Vol 34 (1) ◽  
pp. 32-43 ◽  
Author(s):  
G-L Hong ◽  
Q-Q Cai ◽  
J-P Tan ◽  
X-Z Jiang ◽  
G-J Zhao ◽  
...  
Keyword(s):  
Lung Injury ◽  
Recombinant Adenovirus ◽  
Antioxidant Response ◽  
Nuclear Factor Κb ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Dependent Manner ◽  
Nuclear Factor ◽  
Quinone Oxidoreductase ◽  
Protein Levels

Objective: To investigate the effects of overexpression of nuclear factor E2-related factor-2 (NRF2) on lung injury in rats exposed to paraquat (PQ) poisoning. Methods: A mifepristone (RU486)-inducible recombinant adenoviral vector carrying the human NRF2 gene (Ad-RUNRF2) was constructed and transfected via airway into the rats 7 days before the administration of RU486. Rats were orally challenged with PQ at 20 mg/kg 24 h after the injection of RU486. On days 0.5, 3 and 21 after PQ poisoning, the expressions of NRF2 and cytokines related to inflammation and oxidation in lung tissue were examined. Results: RU486 remarkably enhanced NRF2 mRNA and NRF2 protein levels in Ad-RUNRF2-transfected rats in a dose-dependent manner ( p < 0.01). PQ stimulated compensatory overexpression of NRF2, heme oxygenase 1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO-1) in lungs on days 0.5 and 3 after exposure ( p < 0.05), but depleted the expression of catalase (CAT), glutathione peroxidase (GSH-Px) and glutathione (GSH), with an increased malondialdehyde (MDA) ( p < 0.05). However, pretreatment with Ad-RUNRF2 and RU486 strongly enhanced the expression levels of NRF2, HO-1, NQO-1, CAT and GSH-Px in the lungs of PQ intoxicated rats, with increased GSH and decreased MDA ( p < 0.05). Pretreatment with Ad-RUNRF2 and RU486 also strongly suppressed the PQ-induced activation of nuclear factor κB (NF-κB) and decreased the levels of tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). In addition, Ad-RUNRF2 and RU486 induction significantly reduced PQ-induced pathological changes in lungs and attenuated lung oedema and protein leakage caused by PQ ( p < 0.05). Conclusion: RU486-induced overexpression of NRF2 in lungs transfected with Ad-RUNRF2 can ameliorate PQ-induced lung injury by the activation of the NRF2-antioxidant response element (ARE) pathway.

Roles of oxidative stress, apoptosis, and heme oxygenase-1 in ethylbenzene-induced renal toxicity in NRK-52E cells

2016 ◽  
Vol 32 (12) ◽  
pp. 1952-1960
Author(s):  
Ming Zhang ◽  
Yanrang Wang ◽  
Xiaojun Wang ◽  
Jing Liu ◽  
Jingshu Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heme Oxygenase ◽  
Messenger Rna ◽  
Renal Toxicity ◽  
Control Group ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Dependent Manner ◽  
Dose Dependent

Ethylbenzene is an important industrial chemical, but its potential toxicity is a recent concern. Our previous study investigated the renal toxicity of ethylbenzene in vivo. Rat renal epithelial cells (NRK-52E cells) were incubated with 0, 30, 60, and 90 µmol/L of ethylbenzene for 24 h in vitro to investigate ethylbenzene-induced oxidative stress, apoptosis, and the expression of heme oxygenase 1 (HO-1) and nuclear factor (erythroid 2)-related factor 2 (Nrf2). The cell survival rate in the ethylbenzene-treated groups was significantly lower than the control group. Ethylbenzene significantly increased intracellular reactive oxygen species and apoptosis. Malondialdehyde levels were significantly elevated compared with the control group, while glutathione levels and glutathione peroxidase activities were decreased in ethylbenzene-treated groups. The activities of catalase and superoxide dismutase were also markedly reduced. A significant dose-dependent increase in HO-1 and Nrf2 messenger RNA expression levels was observed in ethylbenzene-treated groups compared with the control group. Similarly, ethylbenzene treatment enhanced protein expression of HO-1 and Nrf2 in a dose-dependent manner. Our results indicated that ethylbenzene induced oxidative stress, apoptosis, and upregulation of HO-1 and Nrf2 in NRK-52E cells, which contributes to ethylbenzene-induced renal toxicity.

scholarly journals Anti-Inflammatory and Anti-Oxidative Effects of luteolin-7-O-glucuronide in LPS-Stimulated Murine Macrophages through TAK1 Inhibition and Nrf2 Activation

2020 ◽  
Vol 21 (6) ◽  
pp. 2007 ◽  
Author(s):  
Young-Chang Cho ◽  
Jiyoung Park ◽  
Sayeon Cho
Keyword(s):  
Heme Oxygenase 1 ◽  
No Production ◽  
Related Factor ◽  
Dependent Manner ◽  
Nuclear Factor ◽  
Quinone Oxidoreductase ◽  
Murine Macrophages ◽  
Nrf2 Activation ◽  
Anti Inflammatory ◽  
Oxidative Effects

Various herbal extracts containing luteolin-7-O-glucuronide (L7Gn) have been traditionally used to treat inflammatory diseases. However, systemic studies aimed at elucidating the anti-inflammatory and anti-oxidative mechanisms of L7Gn in macrophages are insufficient. Herein, the anti-inflammatory and anti-oxidative effects of L7Gn and their underlying mechanisms of action in macrophages were explored. L7Gn inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages by transcriptional regulation of inducible NO synthase (iNOS) in a dose-dependent manner. The mRNA expression of inflammatory mediators, including cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), IL-1β, and tumor necrosis factor-α (TNF-α), was inhibited by L7Gn treatment. This suppression was mediated through transforming growth factor beta-activated kinase 1 (TAK1) inhibition that leads to reduced activation of nuclear factor-κB (NF-κB), p38, and c-Jun N-terminal kinase (JNK). L7Gn also enhanced the radical scavenging effect and increased the expression of anti-oxidative regulators, including heme oxygenase-1 (HO-1), glutamate-cysteine ligase catalytic subunit (GCLC), and NAD(P)H quinone oxidoreductase 1 (NQO1), by nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) activation. These results indicate that L7Gn exhibits anti-inflammatory and anti-oxidative properties in LPS-stimulated murine macrophages, suggesting that L7Gn may be a suitable candidate to treat severe inflammation and oxidative stress.

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.

scholarly journals Pinocembrin ameliorates post-infarct heart failure through activation of Nrf2/HO-1 signaling pathway

2021 ◽  
Author(s):  
Xiuhuan Chen ◽  
Weiguo Wan ◽  
Yan Guo ◽  
Tianxin Ye ◽  
Yuhong Fo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Border Zone ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Dependent Manner ◽  
Ros Scavenging ◽  
Artery Ligation ◽  
Cardiac Functions

Abstract Background Oxidative stress is an important factor involved in the progress of heart failure. The current study was performed to investigate whether pinocembrin was able to ameliorate post-infarct heart failure (PIHF) and the underlying mechanisms. Methods Rats were carried out left anterior descending artery ligation to induce myocardial infarction and subsequently raised for 6 weeks to produce chronic heart failure. Then pinocembrin was administrated every other day for 2 weeks. The effects were evaluated by echocardiography, western blot, Masson’s staining, biochemical examinations, immunohistochemistry, and fluorescence. In vitro we also cultured H9c2 myocytes to further testify the mechanisms. Results We found that PIHF-induced deteriorations of cardiac functions were significantly ameliorated by administrating pinocembrin. In addition, the pinocembrin treatment also attenuated collagen deposition and augmented vascular endothelial growth factor receptor 2 in infarct border zone along with an attenuated apoptosis, which were related to an amelioration of oxidative stress evidenced by reduction of reactive oxygen species (ROS) in heart tissue and malondialdehyde (MDA) in serum, and increase of superoxide dismutase (SOD). This were accompanied by upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2)/ heme oxygenase-1 (HO-1) pathway. In vitro experiments we found that non-specific Nrf2 inhibitor significantly reversed the effects resulted from pinocembrin including antioxidant, anti-apoptosis, anti-fibrosis and neovascularization, which further indicated the amelioration of PIHF by pinocembrin was in a Nrf2/HO-1 pathway-dependent manner. Conclusion Pinocembrin ameliorated cardiac functions and remodeling resulted from PIHF by ROS scavenging and Nrf2/HO-1 pathway activation which further attenuated collagen fibers deposition and apoptosis, and facilitated angiogenesis.

scholarly journals Tanshinone I exerts cardiovascular protective effects in vivo and in vitro through inhibiting necroptosis via Akt/Nrf2 signaling pathway

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Youqiong Zhuo ◽  
Renyikun Yuan ◽  
Xinxin Chen ◽  
Jia He ◽  
Yangling Chen ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protective Effect ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
H9c2 Cells ◽  
Quinone Oxidoreductase ◽  
Interacting Protein ◽  
Tnf Α

Abstract Background Tanshinone I (TI) is a primary component of Salvia miltiorrhiza Bunge (Danshen), which confers a favorable role in a variety of pharmacological activities including cardiovascular protection. However, the exact mechanism of the cardiovascular protection activity of TI remains to be illustrated. In this study, the cardiovascular protective effect and its mechanism of TI were investigated. Methods In this study, tert-butyl hydroperoxide (t-BHP)-stimulated H9c2 cells model was employed to investigate the protective effect in vitro. The cell viability was determined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay and lactate dehydrogenase (LDH) kit. The reactive-oxygen-species (ROS) level and mitochondrial membrane potential (MMP) were investigated by the flow cytometry and JC-1 assay, respectively. While in vivo experiment, the cardiovascular protective effect of TI was determined by using myocardial ischemia–reperfusion (MI/R) model including hematoxylin–eosin (H&E) staining assay and determination of superoxide dismutase (SOD) and malondialdehyde (MDA). Tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) release were detected by Enzyme-linked immunosorbent assay (ELISA). Receptor interacting protein kinase 1 (RIP1), receptor interacting protein kinase 3 (RIP3), receptor interacting protein kinase 3 (MLKL), protein kinase B (Akt), Nuclear factor erythroid 2 related factor 2 (Nrf2), Heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase-1 (NQO-1) were determined by western blotting. Results Our data demonstrated that TI pretreatment attenuated t-BHP and MI/R injury-induced necroptosis by inhibiting the expression of p-RIP1, p-RIP3, and p-MLKL. TI activated the Akt/Nrf2 pathway to promote the expression of antioxidant-related proteins such as phosphorylation of Akt, nuclear factor erythroid 2 related factor 2 (Nrf2), quinone oxidoreductase-1 (NQO-1) and heme oxygenase-1 (HO-1) expression in t-BHP-stimulated H9c2 cells. TI relieved oxidative stress by mitigating ROS generation and reversing MMP loss. In vivo experiment, TI made electrocardiograph (ECG) recovery better and lessened the degree of myocardial tissue damage. The counts of white blood cell (WBC), neutrophil (Neu), lymphocyte (Lym), and the release of TNF-α and IL-6 were reversed by TI treatment. SOD level was increased, while MDA level was decreased by TI treatment. Conclusion Collectively, our findings indicated that TI exerted cardiovascular protective activities in vitro and in vivo through suppressing RIP1/RIP3/MLKL and activating Akt/Nrf2 signaling pathways, which could be developed into a cardiovascular protective agent.

scholarly journals Z-ligustilide reduces cisplatin-induced nephrotoxicity via activation of NRF2/HO-1 signaling pathways

2020 ◽  
Vol 19 (7) ◽  
pp. 1359-1364
Author(s):  
Xu Chen ◽  
Yingjie Cao ◽  
Naifeng Guo ◽  
Guoyuan Lu
Keyword(s):  
Oxidative Stress ◽  
Cell Viability ◽  
Underlying Mechanism ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Dependent Manner ◽  
Protein Levels ◽  
Proximal Tubular Epithelial Cells ◽  
Ldh Release ◽  
Induced Apoptosis

Purpose: To investigate the effect of Z-ligustilide (Z-lig) on cisplatin-induced nephrotoxicity and examine whether NRF2 signaling mediates the underlying mechanism of action.Methods: Human proximal tubular epithelial cells (HK-2) were pretreated with 20 or 100 μM Z-lig for 2 h, followed by 10 μM cisplatin treatment for 24 h. Cell viability was measured using (3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. A commercial kit was used todetermine lactate dehydrogenase (LDH) release. Apoptosis was determined by flow cytometry while Western blotting was used to evaluate protein levels. Levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and glutathione peroxidase (GSH-Px) were assessed by enzymelinked immunosorbent assay (ELISA).Results: Cisplatin decreased HK-2 cell viability and increased LDH release, while Z-lig increased cell viability and decreased LDH release in a dose-dependent manner (p < 0.05). Moreover, Z-lig reduced cisplatin-induced apoptosis (p < 0.01), and alleviated cellular oxidative stress caused by cisplatin (p < 0.05). Furthermore, Z-lig activated NRF2/HO-1 signaling in cells treated with cisplatin (p < 0.05).Conclusion: Z-lig reduces cisplatin-induced nephrotoxicity via activation of NRF2/HO-1 signaling. Thus, Z-lig is a potential drug for the treatment of nephrotoxicity caused by cisplatin. Keywords: Z-ligustilide, Cisplatin, Nephrotoxicity, Oxidative stress, Apoptosis, Nuclear factor erythroid 2-related factor 2, Heme oxygenase-1

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