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Keywords = tert-butyl hydroperoxide (TBHP)

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16 pages, 2736 KB  
Article
Curcumin and Resveratrol vs. Ferrocene-Modified Polyphenols: Role in Enhancing Protective Properties in Human Keratinocytes
by Marina Miletić, Veronika Kovač, Lidija Barišić, Alen Supičić, Bruno Doskočil, Irena Landeka Jurčević, Jelka Pleadin, Branimir Šimić, Ivana Kmetič and Teuta Murati
Pharmaceutics 2025, 17(12), 1511; https://doi.org/10.3390/pharmaceutics17121511 - 22 Nov 2025
Viewed by 643
Abstract
Background/Objectives: Resveratrol (RSV) and curcumin (CRC) have antioxidant, anti-inflammatory, photoprotective, and cell-repairing properties. We selected them to investigate the potential role involved in human keratinocyte protection. Additionally, we tried to overcome the limitations of their application due to poor pharmacokinetics by introducing [...] Read more.
Background/Objectives: Resveratrol (RSV) and curcumin (CRC) have antioxidant, anti-inflammatory, photoprotective, and cell-repairing properties. We selected them to investigate the potential role involved in human keratinocyte protection. Additionally, we tried to overcome the limitations of their application due to poor pharmacokinetics by introducing ferrocene into their structure. Methods: The multiple cellular endpoints—viability (determined by MTT and Trypan Blue method), ROS (reactive oxygen species) formation (evaluated by fluorescence intensity measurement), apoptosis and autophagy (assessed using flow cytometry) of trans-3,5,4′-tri(4-ferrocenylbutanoyloxy)-stilbene (RF) and (E)-5-(4-hydroxy-3-methoxyphenyl)-1-ferrocenylpent-4-ene-1,3-dione (CF), as well as of RSV and CRC, were evaluated in the HaCaT cell line. Results: RF and CF showed significantly lower antiproliferative activity, and cell survival was markedly pronounced compared to RSV or CRC-treated cells. CRC exerted the highest cytotoxicity, and cell viability was almost completely impaired at >50 µM. All compounds showed a beneficial effect on the reduction of ROS induced by tBHP (tert-butyl hydroperoxide), while in UV (ultraviolet) experiments, results were inconclusive (variable depending on dose). CRC and CF had the most prominent antioxidant capacity. Cytofluorimetry showed that CRC has a diverse range of targets in HaCaT cells, including cell proliferation arrest, apoptosis, and autophagy induction. RF at the lowest dose (5 µM) slightly induced autophagy, while treatment with CF even led to a decrease in the autophagy induction ratio. Conclusions: Based on the results, introducing ferrocene into natural compounds is an appropriate approach to protect skin cells, considering the low cytotoxicity of ferrocene-modified polyphenols and their retained antioxidant ability. However, caution should be exercised with CRC at ≥20 µM as it significantly impairs cell viability and induces cell death. Full article
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27 pages, 7998 KB  
Article
Tert-Butyl Hydroperoxide in Human Adult Mesenchymal Stem Cells Isolated from Dermis: A Stress-Induced Premature Senescence Model
by Luca Pampanella, Giovannamaria Petrocelli, Provvidenza Maria Abruzzo, Riccardo Tassinari, Beatrice Bassoli, Rossella Sgarzani, Margherita Maioli, Carlo Ventura, Silvia Canaider and Federica Facchin
Cells 2025, 14(19), 1563; https://doi.org/10.3390/cells14191563 - 8 Oct 2025
Viewed by 1155
Abstract
Stem cell (SC)-based therapy exploits the ability of cells to migrate to damaged tissues and repair them. In this context, there is a strong interest in the use of mesenchymal stem cells (MSCs), multipotent SCs that are easy to obtain and are able [...] Read more.
Stem cell (SC)-based therapy exploits the ability of cells to migrate to damaged tissues and repair them. In this context, there is a strong interest in the use of mesenchymal stem cells (MSCs), multipotent SCs that are easy to obtain and are able to differentiate into various cell lineages. However, MSCs undergo cellular senescence during in vitro expansion, and may also become senescent in vivo, influenced by multiple molecular, cellular, and environmental interactions. Therefore, the development of in vitro cell models is crucial to study the mechanisms underlying senescence in MSCs. This study aimed to investigate the effects of tert-butyl hydroperoxide (t-BHP) as a senescence inducer in human dermal MSCs (hDMSCs), a promising tool for tissue repair. t-BHP induced a pro-senescent effect on hDMSCs greater than hydrogen peroxide (H2O2), as evidenced by ROS production, DNA damage, cell cycle arrest, inhibition of cell proliferation, changes in cellular and nuclear morphology, and cytoskeletal reorganization, as well as the increase in other senescence markers, including senescence-associated β-galactosidase (SA-β-Gal)-positive cells, and senescence-associated secretory phenotype (SASP). These results indicate that t-BHP could be a promising compound for inducing stress-induced premature senescence (SIPS) in hDMSCs, providing a valuable tool to investigate this process and evaluate the efficacy of senolytic compounds. Full article
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12 pages, 916 KB  
Article
Comparative Hepatoprotective Effects of Esculetin and Its Derivatives Against Oxidative Stress
by Yoonjeong Kim, Jihyun Kwon, Jae-Hwan Kwak, In-hwan Baek and Younghwa Kim
Antioxidants 2025, 14(7), 787; https://doi.org/10.3390/antiox14070787 - 26 Jun 2025
Cited by 1 | Viewed by 1120
Abstract
In this study, we evaluated the antioxidant activities of esculetin and four synthesized derivatives (E1, 2-oxo-2H-1-benzopyran-6,7-diyl diacetate; E2, 7-hydroxy-2-oxo-2H-1-benzopyran-6-yl acetate; E3, 7-(methoxymethoxy)-2-oxo-2H-1-benzopyran-6-yl acetate; E4, 7-hydroxy-2-oxo-2H-1-benzopyran-6-yl 2,4-dinitrobenzene-1-sulfonate) against oxidative stress in hepatocytes. In HepG2 cells, treatment with 1 mM tert-butyl hydroperoxide (TBHP) reduced [...] Read more.
In this study, we evaluated the antioxidant activities of esculetin and four synthesized derivatives (E1, 2-oxo-2H-1-benzopyran-6,7-diyl diacetate; E2, 7-hydroxy-2-oxo-2H-1-benzopyran-6-yl acetate; E3, 7-(methoxymethoxy)-2-oxo-2H-1-benzopyran-6-yl acetate; E4, 7-hydroxy-2-oxo-2H-1-benzopyran-6-yl 2,4-dinitrobenzene-1-sulfonate) against oxidative stress in hepatocytes. In HepG2 cells, treatment with 1 mM tert-butyl hydroperoxide (TBHP) reduced cell viability to 40%, while co-treatment with esculetin restored cell viability. Among the esculetin derivatives, E2 exhibited the most significant cytoprotective effect, while E4 showed the lowest. Furthermore, E2 at 25 µM concentration showed the similar effects to esculetin in reducing ROS generation and preventing glutathione depletion. The treatment of E2 also enhanced the expression of HO-1 and GCLC proteins against oxidative stress. On the other hand, TBHP-induced oxidative stress decreased antioxidant activities including glutathione reductase, glutathione peroxidase, and catalase; however, E2 significantly increased these antioxidant activities. These findings suggest that the esculetin derivative, particularly E2, possesses potential as an antioxidant aimed at enhancing physiological functions. Full article
(This article belongs to the Special Issue Antioxidant Capacity of Natural Products—2nd Edition)
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16 pages, 4979 KB  
Article
Tetrahydrocurcumin Outperforms Curcumin in Preventing Oxidative Stress-Induced Dysfunction in Tert-Butyl Hydroperoxide-Stimulated Cardiac Fibroblasts
by Patrícia dos Santos Azeredo, Charity Fix, Laena Pernomian, Camilla F. Wenceslau, Gerardo G. Piroli, Cristina Pontes Vicente and Wayne E. Carver
Int. J. Mol. Sci. 2025, 26(13), 5964; https://doi.org/10.3390/ijms26135964 - 21 Jun 2025
Viewed by 1609
Abstract
Oxidative stress is a common feature of various pathological conditions, including tissue remodeling and dysfunction. Cardiac fibroblasts, which play a key role in maintaining extracellular matrix homeostasis, are sensitive to oxidative injury. Curcumin and tetrahydrocurcumin are plant-derived polyphenols with antioxidant properties, yet their [...] Read more.
Oxidative stress is a common feature of various pathological conditions, including tissue remodeling and dysfunction. Cardiac fibroblasts, which play a key role in maintaining extracellular matrix homeostasis, are sensitive to oxidative injury. Curcumin and tetrahydrocurcumin are plant-derived polyphenols with antioxidant properties, yet their relative efficacy in preventing oxidative stress–induced dysfunction in cardiac fibroblasts remains unclear. In this study, cardiac fibroblasts were treated with curcumin or tetrahydrocurcumin prior to exposure to tert-butyl hydroperoxide (t-BHP), a widely used inducer of oxidative stress. Cell viability, apoptosis, reactive oxygen species (ROS) production, and Tgfb1 expression were assessed. Both curcuminoids significantly attenuated oxidative stress–induced cell death, decreased cell viability, and reduced Tgfb1 expression. Notably, tetrahydrocurcumin demonstrated superior protective effects across most parameters. These findings suggest that both compounds help mitigate oxidative-stress–induced cellular dysfunction in cardiac fibroblasts and highlight tetrahydrocurcumin as a potentially more effective antioxidant. Further studies are needed to explore their role in the context of tissue remodeling and fibrotic progression. Full article
(This article belongs to the Special Issue Drug Discovery Based on Natural Products)
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14 pages, 3148 KB  
Article
Pomegranate Extract Modulates Oxidative Stress by Reducing Basal ROS Levels and Protecting White Blood Cells from Induced Oxidative Damage in Aging Mice
by David Verdú, Alicia Valls, Marta Serna-García, Guadalupe Herrera, Mustafa Ezzeddin-Ayoub, Maria D. Mauricio, José Viña and Eva Serna
Int. J. Mol. Sci. 2025, 26(13), 5957; https://doi.org/10.3390/ijms26135957 - 20 Jun 2025
Cited by 2 | Viewed by 1516
Abstract
Aging is associated with increased oxidative stress, which contributes to cellular dysfunction and age-related diseases. Pomegranate extract (PE), rich in antioxidant polyphenols, may help mitigate oxidative damage. This study evaluated whether PE supplementation modulates oxidative stress by reducing reactive oxygen species (ROS) levels [...] Read more.
Aging is associated with increased oxidative stress, which contributes to cellular dysfunction and age-related diseases. Pomegranate extract (PE), rich in antioxidant polyphenols, may help mitigate oxidative damage. This study evaluated whether PE supplementation modulates oxidative stress by reducing reactive oxygen species (ROS) levels in white blood cells of aging mice. Aged mice (18 months) were supplemented with PE for four months, and cytoplasmic and mitochondrial ROS levels were assessed in leukocytes under basal conditions and oxidative stress conditions induced by tert-butyl hydroperoxide (t-BHP) using flow cytometry. Our results indicate that aged mice exhibit increased basal ROS levels in both the mitochondrial and cytoplasmic compartments, which were mitigated by PE supplementation. Furthermore, PE reversed the increase in hydrogen peroxide levels induced by τ-BHP and protected neutrophils by reducing mitochondrial ROS levels. These findings suggest that PE supplementation modulates the oxidative stress response, potentially improving immune function in aging. Given the central role of oxidative stress in age-related decline, PE may represent a valuable nutritional strategy to promote healthy aging. Full article
(This article belongs to the Special Issue Natural Antioxidants in Human Health and Disease, 2nd Edition)
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16 pages, 4749 KB  
Article
Neuroprotective Effects of Peanut Skin Extract Against Oxidative Injury in HT-22 Neuronal Cells
by Jinlan Huang, Yue Zhou, Hui Xu and Mingfu Wang
Pharmaceuticals 2025, 18(4), 544; https://doi.org/10.3390/ph18040544 - 8 Apr 2025
Cited by 1 | Viewed by 1670
Abstract
Background: Oxidative stress is a key therapeutic target in neurological disorders. As processing wastes from the peanut industry, peanut skins are great sources of antioxidants and possess potential in neuroprotection. Methods: We prepared a peanut skin extract (PSE) and investigated its protective effects [...] Read more.
Background: Oxidative stress is a key therapeutic target in neurological disorders. As processing wastes from the peanut industry, peanut skins are great sources of antioxidants and possess potential in neuroprotection. Methods: We prepared a peanut skin extract (PSE) and investigated its protective effects against tert-butyl hydroperoxide (t-BHP)-induced oxidative injury in HT-22 neuronal cells. Results: PSE was rich in phenolic compounds (123.90 ± 0.46 mg GAE/g), comprising flavonoids (75.97 ± 0.23 mg RE/g) and proanthocyanidins (53.34 ± 1.58 mg PE/g), and displayed potent radical scavenging activities in chemical-based assays. In HT-22 cells, PSE pretreatment restored oxidative balance and endogenous antioxidant defense disrupted by t-BHP, as evidenced by significant reductions in ROS generation and lipid peroxidation levels, along with enhanced endogenous antioxidants. Specifically, 25 μg/mL PSE pretreatment reduced ROS levels by 53.03%, decreased MDA content by 78.82%, enhanced superoxide dismutase (SOD) activity by 12.42%, and improved the ratio of glutathione (GSH) to oxidized glutathione (GSSG) by 80.34% compared to the t-BHP group. Furthermore, PSE rescued mitochondrial membrane potential collapse, inhibited cytochrome c (Cyt.c) release, and prevented subsequent apoptotic death. Notably, the neuroprotective efficacy of PSE was comparable to that of edaravone, an approved neuroprotective drug. Mechanistic investigations combining network pharmacology and experimental validation revealed that the PI3K/Akt/Nrf2 signaling pathway played a pivotal role in mediating the neuroprotective effects of PSE. Compared to t-BHP-treated cells, 25 µg/mL PSE pretreatment significantly upregulated PI3K/Akt phosphorylation, the expression of Nrf2, and its downstream antioxidant proteins heme oxygenase-1 (HO-1) and NAD(P)H dehydrogenase quinone 1 (NQO1). Conclusions: Collectively, these findings demonstrate the potential of PSE as a natural protective agent against oxidative-related neurological disorders. Full article
(This article belongs to the Special Issue NeuroImmunoEndocrinology)
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19 pages, 6227 KB  
Article
Comparative Study of Greener Alkene Epoxidation Using a Polymer-Supported Mo(VI) Complex: Performance Evaluation and Optimisation via Response Surface Methodology
by Md Masud Rana Bhuiyan and Basudeb Saha
Reactions 2025, 6(2), 22; https://doi.org/10.3390/reactions6020022 - 24 Mar 2025
Viewed by 1124
Abstract
A heterogeneous polybenzimidazole-supported Mo(VI) catalyst and tert-butyl hydroperoxide (TBHP) as an oxidising reagent have been utilised to establish a more environmentally friendly and greener alkene epoxidation process. A polybenzimidazole-supported Mo(VI) complex (PBI.Mo) has been prepared, characterised and evaluated successfully. The stability and [...] Read more.
A heterogeneous polybenzimidazole-supported Mo(VI) catalyst and tert-butyl hydroperoxide (TBHP) as an oxidising reagent have been utilised to establish a more environmentally friendly and greener alkene epoxidation process. A polybenzimidazole-supported Mo(VI) complex (PBI.Mo) has been prepared, characterised and evaluated successfully. The stability and catalytic activity of the produced catalyst have been evaluated for the epoxidation of 1,7-octadiene and 1,5-hexadiene in a jacketed stirred batch reactor to assess its performance towards these alkenes. The suitability and efficiency of the catalyst have been compared by studying the effect of reaction temperature, feed mole ratio of alkene to TBHP, catalyst loading, and reaction time on the yield of 1,2-epoxy-5-hexene and 1,2-epoxy-7-octene. Response surface methodology (RSM) using Box–Behnken Design (BBD) has been employed to design experimental runs and study the catalytic performance of the PBI.Mo catalyst for all batch experimental results. A quadratic regression model has been developed representing an empirical relationship between reaction variables and response, which is the yield of epoxides. The numerical optimisation technique concluded that the maximum yield that can be reached is 66.22% for 1,7-octadiene and 64.2% for 1,5-hexadiene. The reactivity of alkenes was observed to follow the sequence 1,5-hexadiene > 1,7-octadiene. The findings of this study confirm that the optimal reaction conditions vary between the two reactions, indicating differences in catalytic performance for each alkene. Full article
(This article belongs to the Special Issue Feature Papers in Reactions in 2025)
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16 pages, 2977 KB  
Article
Protective Effects of Oleanolic Acid on Human Keratinocytes: A Defense Against Exogenous Damage
by Marzia Vasarri, Maria Camilla Bergonzi, Manuela Leri, Rebecca Castellacci, Monica Bucciantini, Lucia De Marchi and Donatella Degl’Innocenti
Pharmaceuticals 2025, 18(2), 238; https://doi.org/10.3390/ph18020238 - 11 Feb 2025
Cited by 6 | Viewed by 5546
Abstract
Background/objectives: Aging leads to increased oxidative stress and chronic inflammation in the skin, which contribute to various disorders such as dermatitis and cancer. This study explores the cytoprotective effects of oleanolic acid (OA), a natural triterpenoid compound known for its potential in mitigating [...] Read more.
Background/objectives: Aging leads to increased oxidative stress and chronic inflammation in the skin, which contribute to various disorders such as dermatitis and cancer. This study explores the cytoprotective effects of oleanolic acid (OA), a natural triterpenoid compound known for its potential in mitigating oxidative damage, on human keratinocyte (HaCaT) cells exposed to oxidative stress from tert-butyl hydroperoxide (tBHP). Methods: Using in vitro experiments, we assessed cell viability, reactive oxygen species (ROS) levels, nitric oxide (NO) production, and protein expression following OA pre-treatment. Advanced imaging techniques were employed to visualize protein localization. Results: Results demonstrated that OA significantly improved cell viability and reduced intracellular ROS levels compared with those in controls. Additionally, OA inhibited inducible nitric oxide synthase (iNOS) expression and subsequent nitric oxide release, indicating a modulation of inflammatory responses. Notably, while tBHP activated the Nrf2/HO-1 signaling pathway, OA did not enhance this response, suggesting that OA exerts cytoprotective effects through mechanisms independent of Nrf2 activation. Conclusion: OA shows promise in protecting HaCaT cells from tBHP-induced oxidative stress, highlighting its potential role in promoting skin health and addressing aging-related damage. The study proposes that OA operates through pathways distinct from Nrf2 and MAPKs, paving the way for new therapeutic strategies aimed at improving skin health against oxidative stress. Full article
(This article belongs to the Special Issue Natural-Based Skincare Solutions)
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15 pages, 2711 KB  
Article
Melatonin Pre-Treatment Protects Erythrocytes Against Subsequent Oxidative Damage
by Tomas Jasenovec, Rastislav Vazan, Dominika Radosinska, Roman Gardlik and Jana Radosinska
Molecules 2025, 30(3), 658; https://doi.org/10.3390/molecules30030658 - 1 Feb 2025
Viewed by 1580
Abstract
Research on the effects of melatonin on erythrocyte deformability has yielded mixed results. While some studies reported improvements, others found no effect, and a few even noted a deterioration in deformability. Moreover, the impact of melatonin may vary between healthy erythrocytes and those [...] Read more.
Research on the effects of melatonin on erythrocyte deformability has yielded mixed results. While some studies reported improvements, others found no effect, and a few even noted a deterioration in deformability. Moreover, the impact of melatonin may vary between healthy erythrocytes and those subjected to oxidative stress. This study investigated the dose-dependent effects of melatonin on erythrocytes under baseline conditions and oxidative stress, using both pre- and post-stress incubation protocols. Oxidative damage was induced with tert-butyl hydroperoxide (TBHP), and its extent was assessed via dichlorofluorescein fluorescence. Erythrocyte deformability was measured using ektacytometry, and osmotic resistance was assessed through hemolytic assays. The results showed that incubation with TBHP led to a dose-dependent decline in both erythrocyte deformability and osmotic resistance. While melatonin treatment had no observable effect on intact erythrocytes, it enhanced deformability in oxidatively damaged erythrocytes when administered before oxidative stress was induced. However, the beneficial effect was not evident when melatonin was applied after oxidative damage. Additionally, melatonin incubation had no impact on the ability of erythrocytes to resist the hypotonic environment. In conclusion, this study supports the notion that the antioxidant properties of melatonin can improve erythrocyte functional status, as reflected by enhanced deformability, but not osmotic resistance. Notably, this effect was observed only in erythrocytes that were exposed to oxidative damage after melatonin incubation, not in intact cells. Full article
(This article belongs to the Section Medicinal Chemistry)
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9 pages, 1259 KB  
Article
Heterogenous Epoxidation of Isobutene Selectively Enabled by MoSe2 in Hexafluoroisopropanol (HFIP)
by Xiaodao Liang, Chenghao Zhang, Yaorong He, Yanxiong Fang, Hongyu Chen, Hongbing Ji and Yan Yang
Molecules 2024, 29(24), 5844; https://doi.org/10.3390/molecules29245844 - 11 Dec 2024
Viewed by 1547
Abstract
Herein, a high selective epoxidation of isobutene was achieved by heterogeneously dispersed MoSe2 with tert-butyl hydroperoxide (TBHP), which further showed versatile substrate scopes and well-retained activity among recycling tests. A rational mechanism is proposed based on extensive control experiments and electron paramagnetic [...] Read more.
Herein, a high selective epoxidation of isobutene was achieved by heterogeneously dispersed MoSe2 with tert-butyl hydroperoxide (TBHP), which further showed versatile substrate scopes and well-retained activity among recycling tests. A rational mechanism is proposed based on extensive control experiments and electron paramagnetic resonance spectroscopy, surprisingly unveiling the metal–oxo and radical mediated pathways dramatically accelerated by hydrogen bonds of hexafluoroisopropanol (HFIP). Full article
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26 pages, 9253 KB  
Article
The Efficient and Environmentally Friendly Chlorination of Arene, Alcohol, Halobenzene, and Peroxide Catalyzed by Fe–Ba Binary Oxides Using Hydrochloric Acid as Chlorine Source and Aqueous H2O2 as Oxidant
by Sidra Chaudhary, Qin Pan, Yong Wu, Zainab Bibi, Xiaoyong Li, Qinxiang Jia and Yang Sun
Molecules 2024, 29(22), 5451; https://doi.org/10.3390/molecules29225451 - 19 Nov 2024
Viewed by 2308
Abstract
A series of Fe–Ba mixed oxides, including a pure Fe-containing sample as a reference, have been synthesized via a sol–gel process using Fe3+ or Fe2+ salts and BaSO4 as raw materials, with Pluronic P123 serving as a template. These oxides [...] Read more.
A series of Fe–Ba mixed oxides, including a pure Fe-containing sample as a reference, have been synthesized via a sol–gel process using Fe3+ or Fe2+ salts and BaSO4 as raw materials, with Pluronic P123 serving as a template. These oxides have been thoroughly characterized and subsequently utilized as catalysts for the chlorination of various organic molecules. Commercial hydrochloric acid, known for its relative safety, and environmentally friendly aqueous hydrogen peroxide were employed as the chlorine source and oxidant, respectively. The pure Fe-containing catalyst displays excellent thermal stability between 600 and 800 °C and exhibited moderate to high conversions in the chlorination of toluene, benzene, and tert-butyl hydroperoxide, with remarkable ortho-selectivity in chlorination of toluene. The combination of Fe3+ salt with BaSO4 in the sol–gel process results in a Fe–Ba mixed oxide catalyst composed of BaO2, BaFe4O7, and Fe2O3, significantly enhancing the chlorination activity compared to that displayed by the pure Fe catalyst. Notably, the chlorination of tert-butyl hydroperoxide (TBHP) does not require additional oxidants such as H2O2, and involves both electrophilic substitution and nucleophilic addition. Notably, the chlorination of bromobenzene yields chlorobenzene as the sole product, a transformation that has not been previously reported. Overall, this catalytic chlorination system holds promise for advancing the chlorination industry and enhancing pharmaceutical production. Full article
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13 pages, 1635 KB  
Article
Modulation of Urea Transport Attenuates TLR2-Mediated Microglial Activation and Upregulates Microglial Metabolism In Vitro
by Najlaa A. Al-Thani, Dylan Zinck, Gavin S. Stewart and Derek A. Costello
Metabolites 2024, 14(11), 634; https://doi.org/10.3390/metabo14110634 - 17 Nov 2024
Cited by 5 | Viewed by 1970
Abstract
Background: Alzheimer’s disease (AD) is a neurodegenerative disorder traditionally characterised by the presence of amyloid beta (Aβ) plaques and neurofibrillary tau tangles in the brain. However, emerging research has highlighted additional metabolic hallmarks of AD pathology. These include the metabolic reprogramming of microglia [...] Read more.
Background: Alzheimer’s disease (AD) is a neurodegenerative disorder traditionally characterised by the presence of amyloid beta (Aβ) plaques and neurofibrillary tau tangles in the brain. However, emerging research has highlighted additional metabolic hallmarks of AD pathology. These include the metabolic reprogramming of microglia in favour of glycolysis over oxidative phosphorylation. This shift is attributed to an ‘M1′-like pro-inflammatory phenotype, which exacerbates neuroinflammation and contributes to neuronal damage. The urea cycle also presents as an altered metabolic pathway in AD, due to elevated urea levels and altered expression of urea cycle enzymes, metabolites, and transporters in the brain. However, to date, these changes remain largely unexplored. Methods: This study focuses on understanding the effects of extracellular urea and urea transporter-B (UT-B) inhibition on inflammatory changes in lipoteichoic acid (LTA)-stimulated BV2 microglia and on the viability of SH-SY5Y neuronal cells under oxidative stress and neurotoxic conditions. Results: In BV2 microglia, UT-B inhibition demonstrated a notable anti-inflammatory effect by reducing the formation of nitric oxide (NO) and the expression of tumour necrosis factor α (TNFα) and CCL2 in response to stimulation with the toll-like receptor (TLR)2 agonist, lipoteichoic acid (LTA). This was accompanied by a reduction in extracellular urea and upregulation of UT-B expression. The application of exogenous urea was also shown to mediate the inflammatory profile of BV2 cells in a similar manner but had only a modest impact on UT-B expression. While exposure to LTA alone did not alter the microglial metabolic profile, inhibition of UT-B upregulated the expression of genes associated with both glycolysis and fatty acid oxidation. Conversely, neither increased extracellular urea nor UT-B inhibition had a significant impact on cell viability or cytotoxicity in SH-SY5Y neurones exposed to oxidative stressors tert-butyl hydroperoxide (t-BHP) and 6-hydroxydopamine (6-OHDA). Conclusions: This study further highlights the involvement of urea transport in regulating the neuroinflammation associated with AD. Moreover, we reveal a novel role for UT-B in maintaining microglial metabolic homeostasis. Taken together, these findings contribute supporting evidence to the regulation of UT-B as a therapeutic target for intervention into neuroinflammatory and neurodegenerative disease. Full article
(This article belongs to the Section Cell Metabolism)
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25 pages, 5673 KB  
Article
Thymus spp. Aqueous Extracts and Their Constituent Salvianolic Acid A Induce Nrf2-Dependent Cellular Antioxidant Protection Against Oxidative Stress in Caco-2 Cells
by Carlos Martins-Gomes, Fernando M. Nunes and Amélia M. Silva
Antioxidants 2024, 13(11), 1287; https://doi.org/10.3390/antiox13111287 - 24 Oct 2024
Cited by 6 | Viewed by 2258
Abstract
The increasing incidence of colorectal cancer and inflammatory diseases poses a major health concern, with oxidative stress playing a significant role in the onset of these pathologies. Factors such as excessive consumption of sugar-rich and fatty foods, synthetic food additives, pesticides, alcohol, and [...] Read more.
The increasing incidence of colorectal cancer and inflammatory diseases poses a major health concern, with oxidative stress playing a significant role in the onset of these pathologies. Factors such as excessive consumption of sugar-rich and fatty foods, synthetic food additives, pesticides, alcohol, and tobacco contribute to oxidative stress and disrupt intestinal homeostasis. Functional foods arise as a potential tool to regulate redox balance in the intestinal tract. Herbs (such as Thymus spp.) have long been screened for their antioxidant properties, but their use as antioxidants for medicinal purposes requires validation in biological models. In this study, we addressed the potential antioxidant protection and preventive effects of extracts from two thyme species at the intestinal level, as well as their molecular mechanisms of action. Caco-2 cells were pre-exposed (4 h) to aqueous (AD) and hydroethanolic (HE) extracts of Thymus carnosus and Thymus capitellatus, followed by a recovery period in culture medium (16 h), and then treated with tert-butyl-hydroperoxide (TBHP; 4 h), before analyzing cell viability. The effect of the extracts’ main components was also analysed. Cellular oxidative stress, cell-death markers, and the expression of antioxidant-related proteins were evaluated using flow cytometry on cells pre-exposed to the AD extracts and salvianolic acid A (SAA). Results showed that pre-exposure to AD extracts or SAA reduced TBHP-induced oxidative stress and cell death, mediated by increased levels of nuclear factor erythroid 2-related factor 2 (Nrf2) protein. The protective activity of T. capitellatus AD extract was shown to be dependent on NAD(P)H quinone dehydrogenase 1 (NQO1) protein expression and on increased glutathione (GSH) content. Furthermore, ursolic acid induced cytotoxicity and low cellular antioxidant activity, and thus the presence of this triterpenoid impaired the antioxidant effect of HE extracts. Thus, AD extracts show high potential as prophylactic dietary agents, while HE extracts arise as a source of nutraceuticals with antioxidant potential. Full article
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12 pages, 2512 KB  
Article
Protective Effect of Epigallocatechin-3-gallate against Hepatic Oxidative Stress Induced by tert-Butyl Hhydroperoxide in Yellow-Feathered Broilers
by Xinyan Ma, Junli Ni, Wei Wang, Yongwen Zhu, Yuqing Zhang and Mingfei Sun
Antioxidants 2024, 13(10), 1153; https://doi.org/10.3390/antiox13101153 - 24 Sep 2024
Cited by 1 | Viewed by 1545
Abstract
Recent studies have shown that epigallocatechin-3-gallate (EGCG), as an effective antioxidant, could attenuate the oxidative damage, inflammation and necrosis in the liver in response to oxidative stress. The present study investigated whether oral administration of EGCG could effectively alleviate the hepatic histopathological changes [...] Read more.
Recent studies have shown that epigallocatechin-3-gallate (EGCG), as an effective antioxidant, could attenuate the oxidative damage, inflammation and necrosis in the liver in response to oxidative stress. The present study investigated whether oral administration of EGCG could effectively alleviate the hepatic histopathological changes and oxidative damage in yellow-feathered broilers induced by tert-butyl hydroperoxide (t-BHP). Broilers were exposed to 600 μmol t-BHP/kg body weight (BW) to induce oxidative stress by intraperitoneal injection every five days, followed by oral administration of different doses of EGCG (0, 20, 40 and 60 mg/kg BW) and 20 mg vitamin E (VE)/kg BW every day during 5–21 days of age. The results showed that t-BHP injection decreased (p < 0.05) body weight and the relative weight of the spleen; the enzyme activities of total antioxidant capacity (T-AOC), catalase (CAT) and total superoxide dismutase (SOD); and gene mRNA expressions of nuclear factor erythroid 2-related factor 2 (Nrf2), CAT, SOD1, SOD2 and acetyl-CoA carboxylase (ACACA); as well as increased (p < 0.05) necrosis formation, malondialdehyde (MDA) content, reactive oxygen species (ROS)accumulation, and peroxisome proliferator activates receptor-α (PPARα) mRNA expression in the liver of yellow-feathered female broilers at 21 days of age. Treatment with 60 mg EGCG/kg BW orally could enhance antioxidant enzyme activities and reverse the hepatic damage induced by t-BHP injection by reducing the accumulation of ROS and MDA in the liver and activating the Nrf2 and PPARα pathways related to the induction of antioxidant gene expression (p < 0.05). In conclusion, intraperitoneal injection of t-BHP impaired body growth and induced hepatic ROS accumulation, which destroyed the antioxidant system and led to oxidative damage in the liver of yellow-feathered broilers from 5 to 21 days of age. It is suggested that EGCG may play an antioxidant role through the Nrf2 and PPARα signaling pathways to effectively protect against t-BHP-induced hepatic oxidative damage in broilers, and the appropriate dose was 60 mg EGCG/kg BW by oral administration. Full article
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13 pages, 2823 KB  
Article
Instant and Multifunctional Nanofibers Loaded with Proanthocyanidins and Hyaluronic Acid for Skincare Applications
by Xuan Yang, Pengcheng Gu, Qiang Jiang, Xiting Cheng, Jia Fan and Yan Bai
Biomedicines 2024, 12(7), 1584; https://doi.org/10.3390/biomedicines12071584 - 17 Jul 2024
Cited by 6 | Viewed by 1915
Abstract
Hyaluronic-acid- and silk-fibroin-based nanofibrous mats loaded with proanthocyanidins and collagen peptides were fabricated as multifunctional facial masks using electrospinning. Their morphology, hygroscopicity and moisture retention, DPPH, ABTS free radical scavenging abilities, and cytocompatibility were investigated. The results showed that the nanofibrous mats were [...] Read more.
Hyaluronic-acid- and silk-fibroin-based nanofibrous mats loaded with proanthocyanidins and collagen peptides were fabricated as multifunctional facial masks using electrospinning. Their morphology, hygroscopicity and moisture retention, DPPH, ABTS free radical scavenging abilities, and cytocompatibility were investigated. The results showed that the nanofibrous mats were dense and uniform, with an average diameter ranging from 300 to 370 nm. The nanofibrous mats exhibited satisfactory moisture retention, oxidation resistance, biocompatibility, especially excellent DPPH, and ABTS free radical scavenging capacities. DPPH free radical scavenging activity was 90% with 15 mg/L nanofibers, and ABTS free radical scavenging activity was 90% with 0.005 mg/L nanofibers. The nanofibrous mats protected fibroblasts from oxidative stress damage induced by tert-butyl hydroperoxide (t-BHP) and significantly promoted their proliferation. Compared with traditional liquid masks and semi-solid facial masks, the multifunctional nanofibrous mats prepared in this study contained fewer additives, which has significant advantages in terms of safety. The nanofibrous mats were rapidly dissolved within 5 s after being sprayed with water, which facilitated the release and penetration of active ingredients for skincare. Therefore, the multifunctional nanofibrous mats displayed excellent moisture retention, oxidation resistance, and biocompatibility, indicating promising translational potential as facial masks and providing a valuable reference for skincare. Full article
(This article belongs to the Topic Advanced Functional Materials for Regenerative Medicine)
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