scholarly journals Xanthohumol inhibits PRRSV proliferation and alleviates oxidative stress induced by PRRSV via the Nrf2–HMOX1 axis

2019 ◽  
Vol 50 (1) ◽  
Author(s):  
Xuewei Liu ◽  
Zhongbao Song ◽  
Juan Bai ◽  
Hans Nauwynck ◽  
Yongxiang Zhao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Therapeutic Strategy ◽  
Antioxidant Response ◽  
Economic Losses ◽  
Respiratory Syndrome Virus ◽  
Related Factor ◽  
Nuclear Factor ◽  
Swine Industry ◽  
Therapeutic Drugs ◽  
Swine Pathogen

Abstract Porcine reproductive and respiratory syndrome virus (PRRSV) is a prevalent and endemic swine pathogen that causes significant economic losses in the global swine industry. Commercial vaccines provide limited protection against this virus, and no highly effective therapeutic drugs are yet available. In this study, we first screened a library of 386 natural products and found that xanthohumol (Xn), a prenylated flavonoid found in hops, displayed high anti-PRRSV activity by inhibiting PRRSV adsorption onto and internalization into cells. Transcriptome sequencing revealed that Xn treatment stimulates genes associated with the antioxidant response in the nuclear factor-erythroid 2-related factor 2 (Nrf2) signalling pathway. Xn causes increased expression of Nrf2, HMOX1, GCLC, GCLM, and NQO1 in Marc-145 cells. The action of Xn against PRRSV proliferation depends on Nrf2 in Marc-145 cells and porcine alveolar macrophages (PAMs). This finding suggests that Xn significantly inhibits PRRSV proliferation and decreases viral-induced oxidative stress by activating the Nrf2–HMOX1 pathway. This information should be helpful for developing a novel prophylactic and therapeutic strategy against PRRSV infection.

scholarly journals Differential Yet Integral Contributions of Nrf1 and Nrf2 in the Human HepG2 Cells on Antioxidant Cytoprotective Response against Tert-Butylhydroquinone as a Pro-Oxidative Stressor

Antioxidants ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1610
Author(s):  
Reziyamu Wufuer ◽  
Zhuo Fan ◽  
Keli Liu ◽  
Yiguo Zhang
Keyword(s):  
Oxidative Stress ◽  
Regulatory Networks ◽  
Substantial Reduction ◽  
Normal Growth ◽  
Antioxidant Response ◽  
Related Factor ◽  
Nuclear Factor ◽  
Expression Levels ◽  
Hormetic Effect ◽  
Cytoprotective Response

In the past 25 years, Nrf2 (nuclear factor erythroid 2-related factor 2, also called NFE2L2) had been preferentially parsed as a master hub of regulating antioxidant, detoxification, and cytoprotective genes; albeit as a matter of fact that Nrf1 (nuclear factor erythroid 2-related factor 1, also called NFE2L1)—rather than Nrf2—is indispensable for cell homeostasis and organ integrity during normal growth and development. Herein, distinct genotypic cell lines (i.e., Nrf1α−/−, Nrf2−/−ΔTA, and caNrf2ΔN) are employed to determine differential yet integral roles of Nrf1 and Nrf2 in mediating antioxidant responsive genes to tert-butylhydroquinone (tBHQ) serving as a pro-oxidative stressor. In Nrf1α−/− cells, Nrf2 was highly accumulated but also could not fully compensate specific loss of Nrf1α’s function in its basal cytoprotective response against endogenous oxidative stress, though it exerted partially inducible antioxidant response, as the hormetic effect of tBHQ, against apoptotic damages. By contrast, Nrf2−/−ΔTA cells gave rise to a substantial reduction of Nrf1 in both basal and tBHQ-stimulated expression levels and hence resulted in obvious oxidative stress, but it can still be allowed to mediate a potent antioxidant response, as accompanied by a significantly decreased ratio of GSSG (oxidized glutathione) to GSH (reduced glutathione). Conversely, a remarkable increase of Nrf1 expression resulted from the constitutive active caNrf2ΔN cells, which were not manifested with oxidative stress, whether or not it was intervened with tBHQ. Such inter-regulatory effects of Nrf1 and Nrf2 on the antioxidant and detoxification genes (encoding HO-1, NQO1, GCLC, GCLM, GSR, GPX1, TALDO, MT1E, and MT2), as well on the ROS (reactive oxygen species)-scavenging activities of SOD (superoxide dismutase) and CAT (catalase), were further investigated. The collective results unraveled that Nrf1 and Nrf2 make distinctive yet cooperative contributions to finely tuning basal constitutive and/or tBHQ-inducible expression levels of antioxidant cytoprotective genes in the inter-regulatory networks. Overall, Nrf1 acts as a brake control for Nrf2’s functionality to be confined within a certain extent, whilst its transcription is regulated by Nrf2.

Shenduning Granule Attenuates Renal Injury from Oxidative Stress through the Nuclear Factor Erythroid 2-Related Factor 2/Antioxidant Response Element Pathway

Pharmacology ◽  
2019 ◽  
Vol 103 (5-6) ◽  
pp. 236-245
Author(s):  
Xiao-Jun Fu ◽  
Shuang-Yan Hu
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Response ◽  
Urinary Protein ◽  
Heme Oxygenase 1 ◽  
High Dose ◽  
Related Factor ◽  
Nuclear Factor ◽  
Antioxidant Response Element ◽  
Response Element ◽  
Operation Group

Background: Systemic oxidative stress has been reported to play a central role in the pathogenesis of kidney function decline. The nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway is one of the important endogenous antioxidant stress pathways in cells. This study aims to investigate whether shenduning granule can ameliorate oxidative stress in kidney tissues by activating the Nrf2/ARE pathway, and explores the detailed underlying mechanism. Methods: A total of 120 male Sprague-Dawley rats were randomly assigned to the sham-operated and operation groups. Rats in the operation group underwent 5/6 nephrectomy. Two weeks later, rats in the operation group were further randomly divided into 5 groups: model group, low-dose, medium-dose and high-dose shenduning granule groups, and losartan group. Rats in each group were given the same volume of corresponding liquid orally. Serum creatinine (SCr), blood urea nitrogen (BUN), 24-h urinary protein, malondialdehyde (MDA) and superoxide dismutase (SOD), Nrf2, heme oxygenase-1 (HO-1), and γ-glutamyl-cysteine synthetase (γ-GCS) were determined. Results: Shenduning granule could markedly elevate HO-1, NRF2, γ-GCS and SOD (p < 0.05), and significantly decreased MDA, 24-h urinary protein, SCr and BUN in rats (p < 0.05). Conclusion: Shenduning granule can improve renal antioxidative stress activity in rats, exhibiting a renoprotective effect. The potential mechanism is likely exerted by the activation of the Nrf2/ARE pathway.

scholarly journals Sulforaphane Protects the Male Reproductive System of Mice from Obesity-Induced Damage: Involvement of Oxidative Stress and Autophagy

2019 ◽  
Vol 16 (19) ◽  
pp. 3759 ◽  
Author(s):  
Li Huo ◽  
Yu Su ◽  
Gaoyang Xu ◽  
Lingling Zhai ◽  
Jian Zhao
Keyword(s):  
Oxidative Stress ◽  
Reproductive System ◽  
Sperm Count ◽  
Reproductive Toxicity ◽  
Antioxidant Response ◽  
Male Reproductive System ◽  
Related Factor ◽  
Male Hypogonadism ◽  
Nuclear Factor ◽  
Total Antioxidant

(1) Background: In recent decades, the prevalence of obesity has grown rapidly worldwide, thus causing many diseases, including male hypogonadism. Sulforaphane (SFN), an isothiocyanate compound, has been reported to protect the reproductive system. This research investigated the protective effect of SFN against obesity-induced impairment in the male reproductive system and explored the potential mechanism involved in mice. (2) Methods: One hundred thirty mice were divided into 5 groups (Control, DIO (diet-induced obesity), DIO + SFN 5 mg/kg, DIO + SFN 10 mg/kg, and DIO + SFN 20 mg/kg). The effects of SFN on the male reproductive system were determined based on the sperm count and motility, relative testes and epididymis weights, hormone levels, and pathological analyses. Oxidative stress was determined by measuring malondialdehyde (MDA), total antioxidant capacity (T-AOC), superoxide dismutase (SOD), glutathione (GSH), H2O2, catalase (CAT), and glutathione peroxidase (GSH-PX) levels. Protein expression of nuclear factor erythroid-2 related factor 2 (Nrf2), Kelch-like ECH-associated protein-1 (Keap1), Microtubule-associated protein light chain 3 (LC3), Beclin1, and P62 were determined by western blotting. (3) Results: High-fat diet (HFD)-induced obesity significantly decreased relative testes and epididymis weights, sperm count and motility, and testosterone levels but increased leptin and estradiol levels. SFN supplementation ameliorated these effects. Additionally, SFN administration inhibited the obesity-induced MDA accumulation and increased the SOD level. Western blot indicated that SFN had an important role in the downregulation of Keap1. Moreover, SFN treatment attenuated obesity-induced autophagy, as detected by LC3 and Beclin1. (4) Conclusions: SFN ameliorated the reproductive toxicity associated with obesity by inhibiting oxidative stress mediated by the nuclear factor erythroid-2 related factor 2/ antioxidant response element (Nrf2/ARE) signaling pathway and recovery of normal autophagy.

scholarly journals Elucidating the Role of Nrf2 Factor Interactions in Various Disorders of Human System and It’s Proteomic Approaches: A Novel Study

2021 ◽  
Vol 8 (5) ◽  
Author(s):  
Aparajita Chakraborty
Keyword(s):  
Oxidative Stress ◽  
Protein Interactions ◽  
Leucine Zipper ◽  
Antioxidant Response ◽  
Related Factor ◽  
Nuclear Factor ◽  
Basic Leucine Zipper ◽  
Ring E3 Ligase ◽  
Microbial Infections ◽  
Factor Interactions

Nuclear factor erythroid 2-related factor 2 (Nrf2), which is also known as nuclear factor erythroid-derived-like-2, is a transcription factor which is encoded by the NFE2L2 gene. It is a basic leucine zipper (bZIP) protein which coordinates the basal and stress-inducible activation of a vast array of cytoprotective genes. It modulates a cellular antioxidant response program and plays a major role in the protection against oxidants and electrophiles; extracellular and intracellular oxidant/electrophiles have great contributions to the damages in cellular macromolecules such as proteins, lipids or DNA. Keap1 protein which is a regulator of Nrf2, is a highly redox-sensitive member of BTB-Kelch family assembling with Cul3 protein to form a Cullin-RING E3 ligase complex for Nrf2 degradation. Thus, this factor is a regulator of many processes of life and it’s signalling system (Nrf2-KEAP-1-ARE pathway) has been found to participate in various ocular or eye diseases and even other systemic diseases such as respiratory disease, chronic diseases or cancer. In microbial infections, the host oxidative stress response may lead to the production of cytoprotective molecules, which in turn induces the activation of cellular Nrf2 factor. The crystallins or eye lens proteins, (?B-crystallin being one of them) may possibly interact with Nrf2 factor and regulate oxidative stress, but it is yet to be deciphered. Proteomic studies may provide valuable information, regarding such detailed protein interactions and their pathways especially in case of diseases or infections in the upcoming days.

scholarly journals Pharmacological Applications of Nrf2 Inhibitors as Potential Antineoplastic Drugs

2019 ◽  
Vol 20 (8) ◽  
pp. 2025 ◽  
Author(s):  
Pelin Telkoparan-Akillilar ◽  
Sibel Suzen ◽  
Luciano Saso
Keyword(s):  
Oxidative Stress ◽  
Neurodegenerative Disorders ◽  
Antioxidant Response ◽  
Related Factor ◽  
Antineoplastic Drugs ◽  
Nuclear Factor ◽  
Antioxidant Response Element ◽  
Malignant Cells ◽  
Nrf2 Pathway ◽  
Anti Cancer

Oxidative stress (OS) is associated with many diseases ranging from cancer to neurodegenerative disorders. Nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) is one of the most effective cytoprotective controller against OS. Modulation of Nrf2 pathway constitutes a remarkable strategy in the antineoplastic treatments. A big number of Nrf2-antioxidant response element activators have been screened for use as chemo-preventive drugs in OS associated diseases like cancer even though activation of Nrf2 happens in a variety of cancers. Research proved that hyperactivation of the Nrf2 pathway produces a situation that helps the survival of normal as well as malignant cells, protecting them against OS, anticancer drugs, and radiotherapy. In this review, the modulation of the Nrf2 pathway, anticancer activity and challenges associated with the development of an Nrf2-based anti-cancer treatment approaches are discussed.

scholarly journals Food-Derived Pharmacological Modulators of the Nrf2/ARE Pathway: Their Role in the Treatment of Diseases

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 1016
Author(s):  
Feijie Zhao ◽  
Xinxin Ci ◽  
Xiaxia Man ◽  
Jiajia Li ◽  
Zhentong Wei ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Antioxidant Response ◽  
Experimental Models ◽  
Vital Role ◽  
Related Factor ◽  
Nuclear Factor ◽  
Oxygen Species ◽  
Disease Treatment ◽  
Pharmacological Regulation

Oxidative stress, which refers to unbalanced accumulation of reactive oxygen species (ROS) levels in cells, has been linked to acute and chronic diseases. Nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE) pathway plays a vital role in regulating cytoprotective genes and enzymes in response to oxidative stress. Therefore, pharmacological regulation of Nrf2/ARE pathway is an effective method to treat several diseases that are mainly characterized by oxidative stress and inflammation. Natural products that counteract oxidative stress by modulating Nrf2 have contributed significantly to disease treatment. In this review, we focus on bioactive compounds derived from food that are Nrf2/ARE pathway regulators and describe the molecular mechanisms for regulating Nrf2 to exert favorable effects in experimental models of diseases.

Protective Effect of Swertiamarin on Myocardial Injury Through Activation of Nrf2/HO-1 Pathway in Heart Failure Model of Rats

2020 ◽  
Vol 18 (3) ◽  
pp. 260-265
Author(s):  
Xu Lin ◽  
Zheng Xiaojun ◽  
Lv Heng ◽  
Mo Yipeng ◽  
Tong Hong
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Ejection Fraction ◽  
Protective Effect ◽  
Infarct Size ◽  
Rat Model ◽  
Left Ventricular ◽  
Related Factor ◽  
Nuclear Factor ◽  
Internal Dimension

The purpose of this study was to evaluate the protective effect of swertiamarin on heart failure. To this end, a rat model of heart failure was established via left coronary artery ligation. Infarct size of heart tissues was determined using triphenyl tetrazolium chloride staining. Echocardiography was performed to evaluate cardiac function by the determination of ejection fraction, left ventricular internal dimension in diastole and left ventricular internal dimension in systole. The effect of swertiamarin on oxidative stress was evaluated via enzyme-linked immunosorbent assay. The mechanism was evaluated using western blot. Administration of swertiamarin reduced the infarct size of heart tissues in rat models with heart failure. Moreover, swertiamarin treatment ameliorated the cardiac function, increased ejection fraction and fractional shortening, decreased left ventricular internal dimension in diastole and left ventricular internal dimension in systole. Swertiamarin improved oxidative stress with reduced malondialdehyde, while increased superoxide dismutase, glutathione, and GSH peroxidase. Furthermore, nuclear-factor erythroid 2-related factor 2, heme oxygenase and NAD(P)H dehydrogenase (quinone 1) were elevated by swertiamarin treatment in heart tissues of rat model with heart failure. Swertiamarin alleviated heart failure through suppression of oxidative stress response via nuclear-factor erythroid 2-related factor 2/heme oxygenase-1 pathway providing a novel therapeutic strategy for heart failure.

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