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17 pages, 3149 KiB

Open AccessArticle

Anti-Wrinkling Effect of 3,4,5-tri-O-caffeoylquinic Acid from the Roots of Nymphoides peltata through MAPK/AP-1, NF-κB, and Nrf2 Signaling in UVB-Irradiated HaCaT Cells

by Tae-Young Kim, No-June Park, Beom-Geun Jo, Bum Soo Lee, Min-Ji Keem, Taek-Hwan Kwon, Ki Hyun Kim, Su-Nam Kim and Min Hye Yang

Antioxidants 2023, 12(10), 1899; https://doi.org/10.3390/antiox12101899 - 23 Oct 2023

Cited by 1 | Viewed by 1371

Abstract

Nymphoides peltata has been widely used pharmacologically in traditional Chinese medicine to treat heat strangury and polyuria. The aim of this study was to isolate the bioactive components from N. peltata and evaluate their potential use as antioxidant and anti-wrinkle agents. Phytochemical investigation [...] Read more.

Nymphoides peltata has been widely used pharmacologically in traditional Chinese medicine to treat heat strangury and polyuria. The aim of this study was to isolate the bioactive components from N. peltata and evaluate their potential use as antioxidant and anti-wrinkle agents. Phytochemical investigation of the methanolic extract of N. peltata roots led to the isolation of 15 compounds (1–15), which were structurally determined as α-spinasterol (1), 3-O-β-D-glucopyranosyl-oleanolic acid 28-O-β-D-glucuronopyranoside (2), 4-hydroxybenzoic acid (3), protocatechuic acid (4), vanillic acid (5), p-coumaric acid (6), caffeic acid (7), ferulic acid (8), neochlorogenic acid (neo-CQA) (9), chlorogenic acid (CQA) (10), cryptochlorogenic acid (crypto-CQA) (11), isochlorogenic acid B (3,4-DCQA) (12), isochlorogenic acid A (3,5-DCQA) (13), isochlorogenic acid C (4,5-DCQA) (14), and 3,4,5-tri-O-caffeoylquinic acid (TCQA) (15). Of these 15 compounds, compound 2 was a new oleanane saponin, the chemical structure of which was characterized by 1D and 2D nuclear magnetic resonance (NMR) spectroscopic data and high-resolution electrospray ionization mass spectrometry (HRESIMS), as well as chemical reaction. Biological evaluation of the isolated compounds revealed that 3,4,5-tri-O-caffeoylquinic acid (TCQA) significantly improved Nrf2 levels in an Nrf2–ARE reporter HaCaT cell screening assay. TCQA was found to potently inhibit the Nrf2/HO-1 pathway and to possess strong anti-wrinkle activity by modulating the MAPK/NF-κB/AP-1 signaling pathway and thus inhibiting MMP-1 synthesis in HaCaT cells exposed to UVB. Our results suggest that TCQA isolated from N. peltata might be useful for developing effective antioxidant and anti-wrinkle agents. Full article

(This article belongs to the Special Issue Nrf2 Antioxidative Pathway and NF-κB Signaling)

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13 pages, 3230 KiB

Open AccessArticle

Effect of Purple Sweet Potato Using Different Cooking Methods on Cytoprotection against Ethanol-Induced Oxidative Damage through Nrf2 Activation in HepG2 Cells

by Dagyeong Kim, Yoonjeong Kim and Younghwa Kim

Antioxidants 2023, 12(8), 1650; https://doi.org/10.3390/antiox12081650 - 21 Aug 2023

Cited by 2 | Viewed by 1376

Abstract

The aim of this study was to investigate the effects of different cooking methods on the hepatoprotective effects of purple sweet potatoes against alcohol-induced damage in HepG2 cells. Purple sweet potatoes (Ipomeoea batatas L. Danjami) were subjected to different cooking methods, including [...] Read more.

The aim of this study was to investigate the effects of different cooking methods on the hepatoprotective effects of purple sweet potatoes against alcohol-induced damage in HepG2 cells. Purple sweet potatoes (Ipomeoea batatas L. Danjami) were subjected to different cooking methods, including steaming, roasting, and microwaving. Steaming resulted in a higher cytoprotective effect against alcohol damage than the other cooking methods. Additionally, the highest inhibition of glutathione depletion and production of reactive oxygen species against alcohol-induced stress were observed in raw and/or steamed purple sweet potatoes. Compared to roasted and/or microwaved samples, steamed samples significantly increased the expression of NADPH quinone oxidoreductase 1, heme oxygenase 1, and gamma glutamate-cysteine ligase in alcohol-stimulated HepG2 cells via the activation of nuclear factor erythroid 2-related factor 2. Moreover, ten anthocyanins were detected in the raw samples, whereas five, two, and two anthocyanins were found in the steamed, roasted, and microwaved samples, respectively. Taken together, steaming purple sweet potatoes could be an effective cooking method to protect hepatocytes against alcohol consumption. These results provide useful information for improving the bioactive properties of purple sweet potatoes using different cooking methods. Full article

(This article belongs to the Special Issue Nrf2 Antioxidative Pathway and NF-κB Signaling)

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24 pages, 2776 KiB

Open AccessArticle

Copper(II) Complexes with Carnosine Conjugates of Hyaluronic Acids at Different Dipeptide Loading Percentages Behave as Multiple SOD Mimics and Stimulate Nrf2 Translocation and Antioxidant Response in In Vitro Inflammatory Model

by Francesco Bellia, Valeria Lanza, Irina Naletova, Barbara Tomasello, Valeria Ciaffaglione, Valentina Greco, Sebastiano Sciuto, Pietro Amico, Rosanna Inturri, Susanna Vaccaro, Tiziana Campagna, Francesco Attanasio, Giovanni Tabbì and Enrico Rizzarelli

Antioxidants 2023, 12(8), 1632; https://doi.org/10.3390/antiox12081632 - 18 Aug 2023

Cited by 2 | Viewed by 1262

Abstract

A series of copper(II) complexes with the formula [Cu²⁺Hy(x)Car%] varying the molecular weight (MW) of Hyaluronic acid (Hy, x = 200 or 700 kDa) conjugated with carnosine (Car) present at different loading were synthesized and characterized via different spectroscopic [...] Read more.

A series of copper(II) complexes with the formula [Cu²⁺Hy(x)Car%] varying the molecular weight (MW) of Hyaluronic acid (Hy, x = 200 or 700 kDa) conjugated with carnosine (Car) present at different loading were synthesized and characterized via different spectroscopic techniques. The metal complexes behaved as Cu, Zn-superoxide dismutase (SOD1) mimics and showed some of the most efficient reaction rate values produced using a synthetic and water-soluble copper(II)-based SOD mimic reported to date. The increase in the percentage of Car moieties parallels the enhancement of the I₅₀ value determined via the indirect method of Fridovich. The presence of the non-functionalized Hy OH groups favors the scavenger activity of the copper(II) complexes with HyCar, recalling similar behavior previously found for the copper(II) complexes with Car conjugated using β-cyclodextrin or trehalose. In keeping with the new abilities of SOD1 to activate protective agents against oxidative stress in rheumatoid arthritis and osteoarthritis diseases, Cu²⁺ interaction with HyCar promotes the nuclear translocation of erythroid 2-related factor that regulates the expressions of target genes, including Heme-Oxigenase-1, thus stimulating an antioxidant response in osteoblasts subjected to an inflammatory/oxidative insult. Full article

(This article belongs to the Special Issue Nrf2 Antioxidative Pathway and NF-κB Signaling)

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18 pages, 7631 KiB

Open AccessArticle

CCN2 Activates RIPK3, NLRP3 Inflammasome, and NRF2/Oxidative Pathways Linked to Kidney Inflammation

by Sandra Rayego-Mateos, Laura Marquez-Exposito, Pamela Basantes, Lucia Tejedor-Santamaria, Ana B. Sanz, Tri Q. Nguyen, Roel Goldschmeding, Alberto Ortiz and Marta Ruiz-Ortega

Antioxidants 2023, 12(8), 1541; https://doi.org/10.3390/antiox12081541 - 31 Jul 2023

Cited by 1 | Viewed by 1258

Abstract

Inflammation is a key characteristic of both acute and chronic kidney diseases. Preclinical data suggest the involvement of the NLRP3/Inflammasome, receptor-interacting protein kinase-3 (RIPK3), and NRF2/oxidative pathways in the regulation of kidney inflammation. Cellular communication network factor 2 (CCN2, also called CTGF in [...] Read more.

Inflammation is a key characteristic of both acute and chronic kidney diseases. Preclinical data suggest the involvement of the NLRP3/Inflammasome, receptor-interacting protein kinase-3 (RIPK3), and NRF2/oxidative pathways in the regulation of kidney inflammation. Cellular communication network factor 2 (CCN2, also called CTGF in the past) is an established fibrotic biomarker and a well-known mediator of kidney damage. CCN2 was shown to be involved in kidney damage through the regulation of proinflammatory and profibrotic responses. However, to date, the potential role of the NLRP3/RIPK3/NRF2 pathways in CCN2 actions has not been evaluated. In experimental acute kidney injury induced with folic acid in mice, CCN2 deficiency diminished renal inflammatory cell infiltration (monocytes/macrophages and T lymphocytes) as well as the upregulation of proinflammatory genes and the activation of NLRP3/Inflammasome-related components and specific cytokine products, such as IL-1β. Moreover, the NRF2/oxidative pathway was deregulated. Systemic administration of CCN2 to C57BL/6 mice induced kidney immune cell infiltration and activated the NLRP3 pathway. RIPK3 deficiency diminished the CCN2-induced renal upregulation of proinflammatory mediators and prevented NLRP3 modulation. These data suggest that CCN2 plays a fundamental role in sterile inflammation and acute kidney injury by modulating the RIKP3/NLRP3/NRF2 inflammatory pathways. Full article

(This article belongs to the Special Issue Nrf2 Antioxidative Pathway and NF-κB Signaling)

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17 pages, 4172 KiB

Open AccessArticle

Hepatitis Delta Virus Antigens Trigger Oxidative Stress, Activate Antioxidant Nrf2/ARE Pathway, and Induce Unfolded Protein Response

by Olga A. Smirnova, Olga N. Ivanova, Furkat Mukhtarov, Vladimir T. Valuev-Elliston, Artemy P. Fedulov, Petr M. Rubtsov, Natalia F. Zakirova, Sergey N. Kochetkov, Birke Bartosch and Alexander V. Ivanov

Antioxidants 2023, 12(4), 974; https://doi.org/10.3390/antiox12040974 - 21 Apr 2023

Cited by 2 | Viewed by 1961

Abstract

Hepatitis delta virus (HDV) is a viroid-like satellite that may co-infect individuals together with hepatitis B virus (HBV), as well as cause superinfection by infecting patients with chronic hepatitis B (CHB). Being a defective virus, HDV requires HBV structural proteins for virion production. [...] Read more.

Hepatitis delta virus (HDV) is a viroid-like satellite that may co-infect individuals together with hepatitis B virus (HBV), as well as cause superinfection by infecting patients with chronic hepatitis B (CHB). Being a defective virus, HDV requires HBV structural proteins for virion production. Although the virus encodes just two forms of its single antigen, it enhances the progression of liver disease to cirrhosis in CHB patients and increases the incidence of hepatocellular carcinoma. HDV pathogenesis so far has been attributed to virus-induced humoral and cellular immune responses, while other factors have been neglected. Here, we evaluated the impact of the virus on the redox status of hepatocytes, as oxidative stress is believed to contribute to the pathogenesis of various viruses, including HBV and hepatitis C virus (HCV). We show that the overexpression of large HDV antigen (L-HDAg) or autonomous replication of the viral genome in cells leads to increased production of reactive oxygen species (ROS). It also leads to the upregulated expression of NADPH oxidases 1 and 4, cytochrome P450 2E1, and ER oxidoreductin 1α, which have previously been shown to mediate oxidative stress induced by HCV. Both HDV antigens also activated the Nrf2/ARE pathway, which controls the expression of a spectrum of antioxidant enzymes. Finally, HDV and its large antigen also induced endoplasmic reticulum (ER) stress and the concomitant unfolded protein response (UPR). In conclusion, HDV may enhance oxidative and ER stress induced by HBV, thus aggravating HBV-associated pathologies, including inflammation, liver fibrosis, and the development of cirrhosis and hepatocellular carcinoma. Full article

(This article belongs to the Special Issue Nrf2 Antioxidative Pathway and NF-κB Signaling)

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14 pages, 3646 KiB

Open AccessArticle

LncRNA MHRT Prevents Angiotensin II-Induced Myocardial Oxidative Stress and NLRP3 Inflammasome via Nrf2 Activation

by Pinyi Liu, Xiaoming Dong, Chao Dong, Guowen Hou, Wenyun Liu, Xin Jiang and Ying Xin

Antioxidants 2023, 12(3), 672; https://doi.org/10.3390/antiox12030672 - 09 Mar 2023

Cited by 4 | Viewed by 2061

Abstract

The development of angiotensin II (Ang II)-induced cardiomyopathies is reportedly mediated via oxidative stress and inflammation. Nuclear factor erythroid 2-related factor (Nrf2) is an important regulator of cellular antioxidant defense, and reactive oxygen species (ROS) can activate the NLRP3 inflammasome. MHRT is a [...] Read more.

The development of angiotensin II (Ang II)-induced cardiomyopathies is reportedly mediated via oxidative stress and inflammation. Nuclear factor erythroid 2-related factor (Nrf2) is an important regulator of cellular antioxidant defense, and reactive oxygen species (ROS) can activate the NLRP3 inflammasome. MHRT is a newly discovered lncRNA exhibiting cardioprotective effects, demonstrated by inhibiting myocardial hypertrophy via Brg1 and myocardial apoptosis via Nrf2 upregulation. However, the underlying mechanism of MHRT remains unclear. We explored the potential protective effects of MHRT against Ang II-induced myocardial oxidative stress and NLRP3-mediated inflammation by targeting Nrf2. Chronic Ang II administration induced NLRP3 inflammasome activation (increased NLRP3, caspase-1 and interleukin-1β expression), oxidative stress (increased 3-nitrotyrosine and 4-hydroxy-2-nonenal), cardiac dysfunction and decreased MHRT and Nrf2 expression. Lentivirus-mediated MHRT overexpression inhibited Ang II (100 nM)-induced oxidative stress and NLRP3 inflammasome activation in AC16 human cardiomyocyte cells. Mechanistically, MHRT overexpression upregulated the expression and function of Nrf2, as determined by the increased transcription of downstream genes HO-1 and CAT, subsequently decreasing intracellular ROS accumulation and inhibiting the expression of thioredoxin-interacting protein (NLRP3 activator) and its direct binding to NLRP3. Accordingly, MHRT could protect against Ang II-induced myocardial injury by decreasing oxidative stress and NLRP3 inflammasome activation via Nrf2 activation. Full article

(This article belongs to the Special Issue Nrf2 Antioxidative Pathway and NF-κB Signaling)

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14 pages, 3709 KiB

Open AccessArticle

Cyanidin Alleviated CCl₄-Induced Acute Liver Injury by Regulating the Nrf2 and NF-κB Signaling Pathways

by Bulei Wang, Shumao Cui, Bingyong Mao, Qiuxiang Zhang, Fengwei Tian, Jianxin Zhao, Xin Tang and Wei Chen

Antioxidants 2022, 11(12), 2383; https://doi.org/10.3390/antiox11122383 - 01 Dec 2022

Cited by 13 | Viewed by 1585

Abstract

Acute liver injury has multiple causes and can result in liver failure. In this study, we evaluated the hepatoprotective ability of cyanidin (Cy) and investigated its associated mechanisms. Cy administration significantly and dose-dependently ameliorated acute liver injury induced by carbon tetrachloride (CCl₄ [...] Read more.

Acute liver injury has multiple causes and can result in liver failure. In this study, we evaluated the hepatoprotective ability of cyanidin (Cy) and investigated its associated mechanisms. Cy administration significantly and dose-dependently ameliorated acute liver injury induced by carbon tetrachloride (CCl₄). High-dose Cy showed effects comparable to those achieved by the positive control (silymarin). Severe oxidative stress and inflammatory responses in the liver tissue induced by CCl₄ were significantly mitigated by Cy supplementation. The total antioxidant capacity and the activity of superoxide dismutase, catalase, and glutathione peroxidase were increased and the content of malondialdehyde, lipid peroxide, tumor necrosis factor α, interleukin-1β, and interleukin-6 were decreased. Additionally, the Nrf2 and NF-κB signaling pathways, which regulate antioxidative and inflammatory responses, were analyzed using quantitative real-time polymerase chain reaction and western blot assay. Cy treatment not only increased Nrf2 transcription and expression but also decreased NF-κB signaling. Moreover, molecular docking simulation indicated that Cy had high affinity for Keap1 and NF-κB/p65, which may promote nuclear translocation of Nrf2 and inhibit that of NF-κB. In summary, Cy treatment exerted antioxidative and anti-inflammatory effects and ameliorated liver injury by increasing Nrf2 and inhibiting the NF-κB pathway, demonstrating the potential of Cy as a therapeutic agent in liver injury. Full article

(This article belongs to the Special Issue Nrf2 Antioxidative Pathway and NF-κB Signaling)

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15 pages, 4771 KiB

Open AccessArticle

Melatonin Suppresses LPS-Induced Oxidative Stress in Dendritic Cells for Inflammatory Regulation via the Nrf2/HO-1 Axis

by Tao Qin, Danni Feng, Bangyue Zhou, Lirong Bai and Yinyan Yin

Antioxidants 2022, 11(10), 2012; https://doi.org/10.3390/antiox11102012 - 11 Oct 2022

Cited by 10 | Viewed by 2127

Abstract

Melatonin, an indoleamine synthesized in the pineal gland of mammals, is a natural bioactive compound with powerful antioxidant and anti-inflammatory properties. Here, we evaluated whether melatonin has the capacity to moderate the oxidative stress of dendritic cells (DCs) for inflammatory control in an [...] Read more.

Melatonin, an indoleamine synthesized in the pineal gland of mammals, is a natural bioactive compound with powerful antioxidant and anti-inflammatory properties. Here, we evaluated whether melatonin has the capacity to moderate the oxidative stress of dendritic cells (DCs) for inflammatory control in an acute lung injury (ALI) model. Our findings showed that melatonin remarkably inhibited total nitric oxide synthase (T-NOS) activity, nitric oxide (NO) production, intracellular reactive oxygen species (ROS) levels, and lipid peroxidation (MDA detection) levels in both an LPS-induced murine ALI model and LPS-induced DCs. Meanwhile, the reduced glutathione (GSH) level and the GSH/GSSG ratio were recovered. In addition, antioxidant enzymes, such as glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD), were increased in these processes. Moreover, melatonin also inhibited the LPS-induced secretions of IL-1β, IL-6, and TGF-β in vivo and in vitro. Finally, we found that the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) axis was required in the inhibition of LPS-induced oxidative stress in DCs by melatonin. Altogether, these data indicate that melatonin strongly suppresses the LPS-induced oxidative stress in DCs, which is a promising DC-targeted strategy via inflammatory control for ALI treatment. Full article

(This article belongs to the Special Issue Nrf2 Antioxidative Pathway and NF-κB Signaling)

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Review

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33 pages, 859 KiB

Open AccessReview

N-Acetylcysteine and Its Immunomodulatory Properties in Humans and Domesticated Animals

by Sophie Tieu, Armen Charchoglyan, Lauryn Paulsen, Lauri C. Wagter-Lesperance, Umesh K. Shandilya, Byram W. Bridle, Bonnie A. Mallard and Niel A. Karrow

Antioxidants 2023, 12(10), 1867; https://doi.org/10.3390/antiox12101867 - 16 Oct 2023

Cited by 2 | Viewed by 3787

Abstract

N-acetylcysteine (NAC), an acetylated derivative of the amino acid L-cysteine, has been widely used as a mucolytic agent and antidote for acetaminophen overdose since the 1960s and the 1980s, respectively. NAC possesses antioxidant, cytoprotective, anti-inflammatory, antimicrobial, and mucolytic properties, making it a promising [...] Read more.

N-acetylcysteine (NAC), an acetylated derivative of the amino acid L-cysteine, has been widely used as a mucolytic agent and antidote for acetaminophen overdose since the 1960s and the 1980s, respectively. NAC possesses antioxidant, cytoprotective, anti-inflammatory, antimicrobial, and mucolytic properties, making it a promising therapeutic agent for a wide range of diseases in both humans and domesticated animals. Oxidative stress and inflammation play a major role in the onset and progression of all these diseases. NAC’s primary role is to replenish glutathione (GSH) stores, the master antioxidant in all tissues; however, it can also reduce levels of pro-inflammatory tumor necrosis factor-alpha (TNF-∝) and interleukins (IL-6 and IL-1β), inhibit the formation of microbial biofilms and destroy biofilms, and break down disulfide bonds between mucin molecules. Many experimental studies have been conducted on the use of NAC to address a wide range of pathological conditions; however, its effectiveness in clinical trials remains limited and studies often have conflicting results. The purpose of this review is to provide a concise overview of promising NAC usages for the treatment of different human and domestic animal disorders. Full article

(This article belongs to the Special Issue Nrf2 Antioxidative Pathway and NF-κB Signaling)

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18 pages, 1665 KiB

Open AccessReview

The Complex Genetic and Epigenetic Regulation of the Nrf2 Pathways: A Review

by Joe M. McCord, Bifeng Gao and Brooks M. Hybertson

Antioxidants 2023, 12(2), 366; https://doi.org/10.3390/antiox12020366 - 03 Feb 2023

Cited by 9 | Viewed by 3558

Abstract

Nrf2 is a major transcription factor that significantly regulates—directly or indirectly—more than 2000 genes. While many of these genes are involved in maintaining redox balance, others are involved in maintaining balance among metabolic pathways that are seemingly unrelated to oxidative stress. In the [...] Read more.

Nrf2 is a major transcription factor that significantly regulates—directly or indirectly—more than 2000 genes. While many of these genes are involved in maintaining redox balance, others are involved in maintaining balance among metabolic pathways that are seemingly unrelated to oxidative stress. In the past 25 years, the number of factors involved in the activation, nuclear translocation, and deactivation of Nrf2 has continued to expand. The purpose of this review is to provide an overview of the remarkable complexity of the tortuous sequence of stop-and-go signals that not only regulate expression or repression, but may also modify transcriptional intensity as well as the specificity of promoter recognition, allowing fluidity of its gene expression profile depending on the various structural modifications the transcription factor encounters on its journey to the DNA. At present, more than 45 control points have been identified, many of which represent sites of action of the so-called Nrf2 activators. The complexity of the pathway and the synergistic interplay among combinations of control points help to explain the potential advantages seen with phytochemical compositions that simultaneously target multiple control points, compared to the traditional pharmaceutical paradigm of “one-drug, one-target”. Full article

(This article belongs to the Special Issue Nrf2 Antioxidative Pathway and NF-κB Signaling)

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