Ignacija Vlašić, Antonio Krstačić-Galić, Anđela Horvat, Nada Oršolić, Anja Sadžak, Lucija Mandić, Suzana Šegota, Maja Jazvinšćak Jembrek
Although commonly appreciated for their anti-oxidative and neuroprotective properties, flavonoids can also exhibit pro-oxidative activity, potentially reducing cell survival, particularly in the presence of metal ions. Disrupted copper homeostasis is a known contributor to neuronal dysfunction through oxidative stress induction. This study investigated the effects of myricitrin (1-20 μg/mL) on copper-induced toxicity (0.5 mM CuSO4) in the neuroblastoma SH-SY5Y cell line. At non-toxic concentrations, myricitrin exacerbated copper's toxic effects. The myricitrin-induced decrease in survival was accompanied with increased reactive oxygen species (ROS) production, reduced superoxide dismutase activity, and a lower GSH/GSSG ratio. In combination with copper, myricitrin also activated caspase-3/7, promoted nuclear chromatin changes, and compromised membrane integrity. At the protein level, myricitrin upregulated p53 and PUMA expression. The toxic effects of myricitrin were alleviated by the p38 inhibitor SB203580, the intracellular calcium chelator BAPTA-AM, and the NMDA receptor blocker MK-801, highlighting the significant role of the ROS/p53/p38 axis in cell death and the critical involvement of calcium ions in apoptosis induction. The atomic force microscopy was used to assess the surface morphology and nanomechanical properties of SH-SY5Y cells, revealing changes following myricitrin treatment. This research highlights the toxic potential of myricitrin and emphasizes the need for caution when considering flavonoid supplementation in conditions with elevated copper levels.
{"title":"Neurotoxic Effect of Myricitrin in Copper-Induced Oxidative Stress Is Mediated by Increased Intracellular Ca<sup>2+</sup> Levels and ROS/p53/p38 Axis.","authors":"Ignacija Vlašić, Antonio Krstačić-Galić, Anđela Horvat, Nada Oršolić, Anja Sadžak, Lucija Mandić, Suzana Šegota, Maja Jazvinšćak Jembrek","doi":"10.3390/antiox14010046","DOIUrl":"10.3390/antiox14010046","url":null,"abstract":"<p><p>Although commonly appreciated for their anti-oxidative and neuroprotective properties, flavonoids can also exhibit pro-oxidative activity, potentially reducing cell survival, particularly in the presence of metal ions. Disrupted copper homeostasis is a known contributor to neuronal dysfunction through oxidative stress induction. This study investigated the effects of myricitrin (1-20 μg/mL) on copper-induced toxicity (0.5 mM CuSO<sub>4</sub>) in the neuroblastoma SH-SY5Y cell line. At non-toxic concentrations, myricitrin exacerbated copper's toxic effects. The myricitrin-induced decrease in survival was accompanied with increased reactive oxygen species (ROS) production, reduced superoxide dismutase activity, and a lower GSH/GSSG ratio. In combination with copper, myricitrin also activated caspase-3/7, promoted nuclear chromatin changes, and compromised membrane integrity. At the protein level, myricitrin upregulated p53 and PUMA expression. The toxic effects of myricitrin were alleviated by the p38 inhibitor SB203580, the intracellular calcium chelator BAPTA-AM, and the NMDA receptor blocker MK-801, highlighting the significant role of the ROS/p53/p38 axis in cell death and the critical involvement of calcium ions in apoptosis induction. The atomic force microscopy was used to assess the surface morphology and nanomechanical properties of SH-SY5Y cells, revealing changes following myricitrin treatment. This research highlights the toxic potential of myricitrin and emphasizes the need for caution when considering flavonoid supplementation in conditions with elevated copper levels.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 1","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11763042/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143036104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Congenital heart disease (CHD) represents the major cause of infant mortality related to congenital anomalies globally. The etiology of CHD is mostly multifactorial, with environmental determinants, including maternal exposure to ambient air pollutants, assumed to contribute to CHD development. While particulate matter (PM) is responsible for millions of premature deaths every year, overall ambient air pollutants (PM, nitrogen and sulfur dioxide, ozone, and carbon monoxide) are known to increase the risk of adverse pregnancy outcomes. In this literature review, we provide an overview regarding the updated evidence related to the association between maternal exposure to outdoor air pollutants and CHD occurrence, also exploring the underlying biological mechanisms from human and experimental studies. With the exception of PM, for which there is currently moderate evidence of its positive association with overall CHD risk following exposure during the periconception and throughout pregnancy, and for ozone which shows a signal of association with increased risk of pooled CHD and certain CHD subtypes in the periconceptional period, for the other pollutants, the data are inconsistent, and no conclusion can be drawn about their role in CHD onset. Future epidemiological cohort studies in countries with different degree of air pollution and experimental research on animal models are warranted to gain a comprehensive picture of the possible involvement of ambient air pollutants in CHD etiopathogenesis. While on the one hand this information could also be useful for timely intervention to reduce the risk of CHD, on the other hand, it is mandatory to scale up the use of technologies for pollutant monitoring, as well as the use of Artificial Intelligence for data analysis to identify the non-linear relationships that will eventually exist between environmental and clinical variables.
{"title":"Ambient Air Pollution and Congenital Heart Disease: Updated Evidence and Future Challenges.","authors":"Francesca Gorini, Alessandro Tonacci","doi":"10.3390/antiox14010048","DOIUrl":"10.3390/antiox14010048","url":null,"abstract":"<p><p>Congenital heart disease (CHD) represents the major cause of infant mortality related to congenital anomalies globally. The etiology of CHD is mostly multifactorial, with environmental determinants, including maternal exposure to ambient air pollutants, assumed to contribute to CHD development. While particulate matter (PM) is responsible for millions of premature deaths every year, overall ambient air pollutants (PM, nitrogen and sulfur dioxide, ozone, and carbon monoxide) are known to increase the risk of adverse pregnancy outcomes. In this literature review, we provide an overview regarding the updated evidence related to the association between maternal exposure to outdoor air pollutants and CHD occurrence, also exploring the underlying biological mechanisms from human and experimental studies. With the exception of PM, for which there is currently moderate evidence of its positive association with overall CHD risk following exposure during the periconception and throughout pregnancy, and for ozone which shows a signal of association with increased risk of pooled CHD and certain CHD subtypes in the periconceptional period, for the other pollutants, the data are inconsistent, and no conclusion can be drawn about their role in CHD onset. Future epidemiological cohort studies in countries with different degree of air pollution and experimental research on animal models are warranted to gain a comprehensive picture of the possible involvement of ambient air pollutants in CHD etiopathogenesis. While on the one hand this information could also be useful for timely intervention to reduce the risk of CHD, on the other hand, it is mandatory to scale up the use of technologies for pollutant monitoring, as well as the use of Artificial Intelligence for data analysis to identify the non-linear relationships that will eventually exist between environmental and clinical variables.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 1","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11761577/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143036215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mario de la Fuente-Muñoz, Marta Román-Carmena, Sara Amor, María C Iglesias-de la Cruz, Patricia Martorell, Sonia Guilera-Bermell, Reme García Bou, Antonio M Inarejos-García, Ángel L García-Villalón, Miriam Granado
Arterial hypertension has a high prevalence in the population and is considered both a cardiovascular disease and an important risk factor for the development of other cardiovascular diseases. Tea consumption shows antihypertensive effects due to its composition in terms of bioactive substances such as flavan-3-ols and xanthines. The aim of this study was to assess the possible beneficial effects of two tea extracts, one of white tea (ADM® White Tea; WTE) and another one composed of a mixture of black tea and green tea (ADM® Tea Complex; CTE), on the cardiovascular alterations induced by angiotensin II (AngII) infusion in mice. For this purpose, four groups of C57BL/6J male mice were used: (1) mice fed on a standard diet for 8 weeks and infused with saline for the last 4 weeks (controls); (2) mice fed on a standard diet for 8 weeks and infused with AngII for the last 4 weeks (AngII); (3) mice fed on a standard diet supplemented with 1.6% WTE and infused with AngII for the last 4 weeks (AngII + WTE); (4) mice fed on a standard diet supplemented with 1.6% TC and infused with AngII for the last 4 weeks (AngII + CTE). Both tea extracts exerted anti-inflammatory and antioxidant effects in arterial tissue and reduced AngII-induced endothelial dysfunction in aorta segments. Moreover, supplementation with WTE or CTE reduced the Ang-II-induced overexpression of AT1R and increased AngII-induced downregulation of AT2R in arterial tissue. However, only supplementation with CTE significantly increased the circulating levels of angiotensin 1-7 and reduced systolic blood pressure. In the heart, supplementation with both tea extracts attenuated AngII-induced cardiac hypertrophy and reduced ischemia-reperfusion-induced oxidative stress and apoptosis in myocardial tissue. In conclusion, supplementation with WTE or CTE attenuates AngII-induced cardiovascular damage through their anti-inflammatory, antioxidant, and antiapoptotic effects. In addition, supplementation with CTE also exerts antihypertensive effects, and so it may constitute an avenue through which to support cardiovascular health.
{"title":"Supplementation with Standardized Green/Black or White Tea Extracts Attenuates Hypertension and Ischemia-Reperfusion-Induced Myocardial Damage in Mice Infused with Angiotensin II.","authors":"Mario de la Fuente-Muñoz, Marta Román-Carmena, Sara Amor, María C Iglesias-de la Cruz, Patricia Martorell, Sonia Guilera-Bermell, Reme García Bou, Antonio M Inarejos-García, Ángel L García-Villalón, Miriam Granado","doi":"10.3390/antiox14010047","DOIUrl":"10.3390/antiox14010047","url":null,"abstract":"<p><p>Arterial hypertension has a high prevalence in the population and is considered both a cardiovascular disease and an important risk factor for the development of other cardiovascular diseases. Tea consumption shows antihypertensive effects due to its composition in terms of bioactive substances such as flavan-3-ols and xanthines. The aim of this study was to assess the possible beneficial effects of two tea extracts, one of white tea (ADM<sup>®</sup> White Tea; WTE) and another one composed of a mixture of black tea and green tea (ADM<sup>®</sup> Tea Complex; CTE), on the cardiovascular alterations induced by angiotensin II (AngII) infusion in mice. For this purpose, four groups of C57BL/6J male mice were used: (1) mice fed on a standard diet for 8 weeks and infused with saline for the last 4 weeks (controls); (2) mice fed on a standard diet for 8 weeks and infused with AngII for the last 4 weeks (AngII); (3) mice fed on a standard diet supplemented with 1.6% WTE and infused with AngII for the last 4 weeks (AngII + WTE); (4) mice fed on a standard diet supplemented with 1.6% TC and infused with AngII for the last 4 weeks (AngII + CTE). Both tea extracts exerted anti-inflammatory and antioxidant effects in arterial tissue and reduced AngII-induced endothelial dysfunction in aorta segments. Moreover, supplementation with WTE or CTE reduced the Ang-II-induced overexpression of AT1R and increased AngII-induced downregulation of AT2R in arterial tissue. However, only supplementation with CTE significantly increased the circulating levels of angiotensin 1-7 and reduced systolic blood pressure. In the heart, supplementation with both tea extracts attenuated AngII-induced cardiac hypertrophy and reduced ischemia-reperfusion-induced oxidative stress and apoptosis in myocardial tissue. In conclusion, supplementation with WTE or CTE attenuates AngII-induced cardiovascular damage through their anti-inflammatory, antioxidant, and antiapoptotic effects. In addition, supplementation with CTE also exerts antihypertensive effects, and so it may constitute an avenue through which to support cardiovascular health.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 1","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143036228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hao Wu, Baochun Qin, Guang Yang, Pengyun Ji, Yu Gao, Lu Zhang, Bingyuan Wang, Guoshi Liu
As the global climate changes, high temperatures will cause heat stress, which significantly affects the productive efficiency of livestock. Currently, there is a lack of efficient methods to use in targeting this issue. In this study, we report that melatonin supplementation may represent an alternative method to reduce the negative impact of heat stress on livestock, particularly in Hainan black goats. Our results show that melatonin treatment increased the average daily gain of Hainan black goats that were exposed to constantly high temperatures for two months compared to controls. Our mechanistic exploration revealed that melatonin treatment not only reduced the oxidative stress and inflammatory reaction caused by heat stress but also improved goats' metabolic capacity, promoting their growth and development. More importantly, for the first time, we observed that melatonin treatment modified the abundance of the intestinal microflora, altering the metabolism of the goats, which further improved their tolerance to constant heat stress.
{"title":"The Protective Effects of Melatonin on Hainan Black Goats Under Heat Stress: Understanding Its Actions and Mechanisms.","authors":"Hao Wu, Baochun Qin, Guang Yang, Pengyun Ji, Yu Gao, Lu Zhang, Bingyuan Wang, Guoshi Liu","doi":"10.3390/antiox14010044","DOIUrl":"10.3390/antiox14010044","url":null,"abstract":"<p><p>As the global climate changes, high temperatures will cause heat stress, which significantly affects the productive efficiency of livestock. Currently, there is a lack of efficient methods to use in targeting this issue. In this study, we report that melatonin supplementation may represent an alternative method to reduce the negative impact of heat stress on livestock, particularly in Hainan black goats. Our results show that melatonin treatment increased the average daily gain of Hainan black goats that were exposed to constantly high temperatures for two months compared to controls. Our mechanistic exploration revealed that melatonin treatment not only reduced the oxidative stress and inflammatory reaction caused by heat stress but also improved goats' metabolic capacity, promoting their growth and development. More importantly, for the first time, we observed that melatonin treatment modified the abundance of the intestinal microflora, altering the metabolism of the goats, which further improved their tolerance to constant heat stress.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 1","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11760882/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143036241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The relationship between oxidative stress and cancer has been extensively studied and highlighted, along with its role in various aspects of angiogenesis. The modulation of oxidative levels and the adaptive mechanisms of oxidative stress in cancer systems are attractive research themes for developing anti-cancer strategies. Reactive oxygen species (ROS) are involved in various pathophysiological processes and play crucial roles in DNA damage and angiogenesis. Although cancer cells have developed various adaptive defense mechanisms against oxidative stress, excessive ROS production has been proposed as an anti-cancer strategy to induce cellular apoptosis. In particular, natural-source-based antioxidants have been identified as effective against cancers, and various delivery platforms have been developed to enhance their efficacy. In this review, we highlighted the anti-cancer components (plumbagin, quercetin, resveratrol, curcumin, xanthatin, carvacrol, telmisartan, and sulforaphane) that modulate ROS levels and the recent targeting platforms used to increase the application of anti-cancer drugs and the developed delivery platforms with diverse mechanisms of action. Further, we summarized the actual doses used and the effects of these drug candidates in various cancer systems. Overall, this review provides beneficial research themes for expanding cancer-targeting fields and addressing limited applications in diverse cancer types.
{"title":"Prominent Naturally Derived Oxidative-Stress-Targeting Drugs and Their Applications in Cancer Treatment.","authors":"Eunsun Lee, Dongki Yang, Jeong Hee Hong","doi":"10.3390/antiox14010049","DOIUrl":"10.3390/antiox14010049","url":null,"abstract":"<p><p>The relationship between oxidative stress and cancer has been extensively studied and highlighted, along with its role in various aspects of angiogenesis. The modulation of oxidative levels and the adaptive mechanisms of oxidative stress in cancer systems are attractive research themes for developing anti-cancer strategies. Reactive oxygen species (ROS) are involved in various pathophysiological processes and play crucial roles in DNA damage and angiogenesis. Although cancer cells have developed various adaptive defense mechanisms against oxidative stress, excessive ROS production has been proposed as an anti-cancer strategy to induce cellular apoptosis. In particular, natural-source-based antioxidants have been identified as effective against cancers, and various delivery platforms have been developed to enhance their efficacy. In this review, we highlighted the anti-cancer components (plumbagin, quercetin, resveratrol, curcumin, xanthatin, carvacrol, telmisartan, and sulforaphane) that modulate ROS levels and the recent targeting platforms used to increase the application of anti-cancer drugs and the developed delivery platforms with diverse mechanisms of action. Further, we summarized the actual doses used and the effects of these drug candidates in various cancer systems. Overall, this review provides beneficial research themes for expanding cancer-targeting fields and addressing limited applications in diverse cancer types.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 1","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11760868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143036130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Min Jiang, Xuekai Zhang, Xiao Jin, Binlin Shi, Yuanqing Xu, Zheqi Wang
Artemisia ordosica Krasch, a traditional Chinese herbal medicine, possesses antibacterial, antiviral, and anti-inflammatory properties. The aim of this experiment was to investigate the therapeutic effect of Artemisia ordosica Krasch extraction (AOE) in treating colitis induced by dextran sulfate sodium (DSS) in mice. The in vitro antioxidant activity of AOE was evaluated by assessing its iron reduction capacity and scavenging capacity towards 1,1-diphenyl-2-picrylhydrazyl (DPPH) and hydroxyl radicals (·OH). The protective effect of AOE on colitis in mice was determined by monitoring key indicators such as body weight, colon length, and survival rate in mice, as well as by assessing the expression of colon-related genes and cytokine levels. We evaluated the impact of AOE on intestinal microbiota by measuring the 16s sequencing of cecal contents and bile acid metabolism. The results showed that the iron reduction capacity of AOE was positively correlated with its concentration. The half-maximal inhibitory concentrations (IC50) for scavenging DPPH and hydroxyl radicals were 3.126 mg/mL and 6.139 mg/mL, with a 95% confidence interval of 95%. In vivo studies demonstrated that AOE reduced DSS-induced colitis in mice by increasing the colon length, enhancing antioxidant enzyme activity, inhibiting inflammatory cell infiltration, suppressing the formation of TNF-α and IL-6, and reducing malondialdehyde (MDA) levels. qPCR analysis revealed that AOE reversed the down-regulation of Claudin mRNA expression, and altered the composition of cecal microbiota, thus mitigating DSS-induced colitis. AOE plays a crucial role in alleviating colitis in mice and effectively improves DSS-induced colitis, highlighting its potential as a therapeutic agent for inflammatory bowel diseases.
{"title":"Relieving Effect of <i>Artemisia ordosica Krasch</i> Extract on DSS-Induced Colitis by Regulating Immunity, Antioxidant Function, Gut Microbiota, and Bile Acid Metabolism in Mice.","authors":"Min Jiang, Xuekai Zhang, Xiao Jin, Binlin Shi, Yuanqing Xu, Zheqi Wang","doi":"10.3390/antiox14010045","DOIUrl":"10.3390/antiox14010045","url":null,"abstract":"<p><p><i>Artemisia ordosica Krasch</i>, a traditional Chinese herbal medicine, possesses antibacterial, antiviral, and anti-inflammatory properties. The aim of this experiment was to investigate the therapeutic effect of <i>Artemisia ordosica Krasch</i> extraction (AOE) in treating colitis induced by dextran sulfate sodium (DSS) in mice. The in vitro antioxidant activity of AOE was evaluated by assessing its iron reduction capacity and scavenging capacity towards 1,1-diphenyl-2-picrylhydrazyl (DPPH) and hydroxyl radicals (·OH). The protective effect of AOE on colitis in mice was determined by monitoring key indicators such as body weight, colon length, and survival rate in mice, as well as by assessing the expression of colon-related genes and cytokine levels. We evaluated the impact of AOE on intestinal microbiota by measuring the 16s sequencing of cecal contents and bile acid metabolism. The results showed that the iron reduction capacity of AOE was positively correlated with its concentration. The half-maximal inhibitory concentrations (IC<sub>50</sub>) for scavenging DPPH and hydroxyl radicals were 3.126 mg/mL and 6.139 mg/mL, with a 95% confidence interval of 95%. In vivo studies demonstrated that AOE reduced DSS-induced colitis in mice by increasing the colon length, enhancing antioxidant enzyme activity, inhibiting inflammatory cell infiltration, suppressing the formation of TNF-α and IL-6, and reducing malondialdehyde (MDA) levels. qPCR analysis revealed that AOE reversed the down-regulation of <i>Claudin</i> mRNA expression, and altered the composition of cecal microbiota, thus mitigating DSS-induced colitis. AOE plays a crucial role in alleviating colitis in mice and effectively improves DSS-induced colitis, highlighting its potential as a therapeutic agent for inflammatory bowel diseases.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 1","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143036150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mitochondria are found, with rare exceptions [...].
{"title":"Mitochondrial Management of ROS in Physiological and Pathological Conditions.","authors":"Paola Venditti, Gaetana Napolitano","doi":"10.3390/antiox14010043","DOIUrl":"10.3390/antiox14010043","url":null,"abstract":"<p><p>Mitochondria are found, with rare exceptions [...].</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 1","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11761860/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143036028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Blanca Martínez-Inda, Nerea Jiménez-Moreno, Irene Esparza, Carmen Ancín-Azpilicueta
Cocoa and coffee are two of the world's most important crops. Therefore, their by-products are generated in large quantities. This work proposes a simple method for the valorization of these residues by obtaining phenolic compounds and melanoidins by solid-liquid extraction using different hydroalcoholic solutions as extracting solvents (0, 25, 50, 75, 100% ethanol). Extracts of both by-products presented the highest antioxidant capacity and total phenolic and melanoidin content when using 50-75% ethanol in the solvent. Among all the extracts, those obtained from spent coffee grounds at 75% ethanol showed the highest concentrations of total phenolic compounds (13.5 ± 1.3 mmol gallic acid equivalents/g dry matter) and melanoidins (244.4 ± 20.1 mg/g dry matter). Moreover, the sun protection factor values of the coffee extracts obtained with 50 and 75% of ethanol as extraction solvent (7.8 ± 0.9 and 8.5 ± 0.7, respectively) showed their potential for use in the cosmetic sector. The most important phenolic compounds identified in the coffee by-products extracts were phenolic acids, and most of them were found in higher concentration in extracts obtained with lower percentages of ethanol (0-25%). Protocatechuic acid was the most abundant phenolic in cocoa extracts, with concentrations ranging from 18.49 ± 2.29 to 235.35 ± 5.55 µg/g dry matter, followed by 4-hydroxybenzoic acid, (-)-epicatechin and (+)-catechin. Esculetin was found in both coffee and cocoa extracts, which had not been reported to date in these residues. In summary, the use of 75% ethanol as an extraction solvent seems a good strategy to obtain extracts rich in phenolic compounds from food by-products rich in melanoidins, such as coffee and cocoa by-products. The high antioxidant potential of these extracts makes them of great interest for the cosmetic and nutraceutical industries.
{"title":"Coffee and Cocoa By-Products as Valuable Sources of Bioactive Compounds: The Influence of Ethanol on Extraction.","authors":"Blanca Martínez-Inda, Nerea Jiménez-Moreno, Irene Esparza, Carmen Ancín-Azpilicueta","doi":"10.3390/antiox14010042","DOIUrl":"10.3390/antiox14010042","url":null,"abstract":"<p><p>Cocoa and coffee are two of the world's most important crops. Therefore, their by-products are generated in large quantities. This work proposes a simple method for the valorization of these residues by obtaining phenolic compounds and melanoidins by solid-liquid extraction using different hydroalcoholic solutions as extracting solvents (0, 25, 50, 75, 100% ethanol). Extracts of both by-products presented the highest antioxidant capacity and total phenolic and melanoidin content when using 50-75% ethanol in the solvent. Among all the extracts, those obtained from spent coffee grounds at 75% ethanol showed the highest concentrations of total phenolic compounds (13.5 ± 1.3 mmol gallic acid equivalents/g dry matter) and melanoidins (244.4 ± 20.1 mg/g dry matter). Moreover, the sun protection factor values of the coffee extracts obtained with 50 and 75% of ethanol as extraction solvent (7.8 ± 0.9 and 8.5 ± 0.7, respectively) showed their potential for use in the cosmetic sector. The most important phenolic compounds identified in the coffee by-products extracts were phenolic acids, and most of them were found in higher concentration in extracts obtained with lower percentages of ethanol (0-25%). Protocatechuic acid was the most abundant phenolic in cocoa extracts, with concentrations ranging from 18.49 ± 2.29 to 235.35 ± 5.55 µg/g dry matter, followed by 4-hydroxybenzoic acid, (-)-epicatechin and (+)-catechin. Esculetin was found in both coffee and cocoa extracts, which had not been reported to date in these residues. In summary, the use of 75% ethanol as an extraction solvent seems a good strategy to obtain extracts rich in phenolic compounds from food by-products rich in melanoidins, such as coffee and cocoa by-products. The high antioxidant potential of these extracts makes them of great interest for the cosmetic and nutraceutical industries.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 1","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762683/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143036308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhen Yang, Jingyuan Man, Haoyu Liu, Di Wu, Qiangwen Gu, Hongjuan Zhang, Yu Liu, Dan Shao, Baocheng Hao, Shengyi Wang
Oxidative stress refers to the phenomenon in which the redox balance of the body is disrupted in response to stimuli, leading to an excessive accumulation of reactive oxygen species in vivo, which can lead to a variety of diseases. In contrast to artificial antioxidants, whose safety is controversial, natural antioxidants, which are widely available, pharmacologically active, and have little toxic side effects, are expected to be candidates for the treatment of oxidative stress-related diseases. Polygonum viviparum L. (PV) is a natural herbal medicine with antioxidant properties and is used as a traditional medicine in the Tibetan Plateau region. However, there are few studies that have focused on its antioxidant activity and mechanism of action in vitro and in vivo. Therefore, the present study firstly demonstrated that PV could exert good in vitro antioxidant effects by scavenging DPPH radicals and inhibiting the production of hydroxyl radicals through in vitro experiments. Secondly, PV was proven to attenuate the effects of oxidative stress on body weight gain and thymus development by establishing the Senna leaf-induced diarrhea model in rats, as well as to increase the activity of antioxidant enzymes and the content of non-enzymatic antioxidants in the intestinal tract and to enhance the rats' own antioxidant defenses, to mitigate the oxidative damage caused by diarrhea. Subsequently, the application of the cellular oxidative stress model evidenced that PV could play a protective role against cellular oxidative stress by inhibiting the overaccumulation of ROS in macrophages. Furthermore, the candidate antioxidant targets of PV were analyzed and screened using a comprehensive network pharmacology method, and their expression were then examined at the mRNA level and protein level. Our results suggest that PV may protect against H2O2-induced oxidative damage in macrophages by activating BCL2L1 and inhibiting ESR1, JAK2/STAT3, and MMP2. These findings open new perspectives on the antioxidant mechanism of PV and the prospect of developing it as a novel natural antioxidant drug.
{"title":"Study on the In Vitro and In Vivo Antioxidant Activity and Potential Mechanism of <i>Polygonum viviparum</i> L.","authors":"Zhen Yang, Jingyuan Man, Haoyu Liu, Di Wu, Qiangwen Gu, Hongjuan Zhang, Yu Liu, Dan Shao, Baocheng Hao, Shengyi Wang","doi":"10.3390/antiox14010041","DOIUrl":"10.3390/antiox14010041","url":null,"abstract":"<p><p>Oxidative stress refers to the phenomenon in which the redox balance of the body is disrupted in response to stimuli, leading to an excessive accumulation of reactive oxygen species in vivo, which can lead to a variety of diseases. In contrast to artificial antioxidants, whose safety is controversial, natural antioxidants, which are widely available, pharmacologically active, and have little toxic side effects, are expected to be candidates for the treatment of oxidative stress-related diseases. <i>Polygonum viviparum</i> L. (PV) is a natural herbal medicine with antioxidant properties and is used as a traditional medicine in the Tibetan Plateau region. However, there are few studies that have focused on its antioxidant activity and mechanism of action in vitro and in vivo. Therefore, the present study firstly demonstrated that PV could exert good in vitro antioxidant effects by scavenging DPPH radicals and inhibiting the production of hydroxyl radicals through in vitro experiments. Secondly, PV was proven to attenuate the effects of oxidative stress on body weight gain and thymus development by establishing the Senna leaf-induced diarrhea model in rats, as well as to increase the activity of antioxidant enzymes and the content of non-enzymatic antioxidants in the intestinal tract and to enhance the rats' own antioxidant defenses, to mitigate the oxidative damage caused by diarrhea. Subsequently, the application of the cellular oxidative stress model evidenced that PV could play a protective role against cellular oxidative stress by inhibiting the overaccumulation of ROS in macrophages. Furthermore, the candidate antioxidant targets of PV were analyzed and screened using a comprehensive network pharmacology method, and their expression were then examined at the mRNA level and protein level. Our results suggest that PV may protect against H<sub>2</sub>O<sub>2</sub>-induced oxidative damage in macrophages by activating BCL2L1 and inhibiting ESR1, JAK2/STAT3, and MMP2. These findings open new perspectives on the antioxidant mechanism of PV and the prospect of developing it as a novel natural antioxidant drug.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 1","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762547/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143036223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mehboob Ahmed, Umair Riaz, Haimiao Lv, Muhammad Amjad, Sohail Ahmed, Shaokat Ali, Muhammad Usman Ghani, Guohua Hua, Liguo Yang
Inflammation disrupts the normal function of granulosa cells (GCs), which leads to ovarian dysfunction and fertility decline. Inflammatory conditions such as polycystic ovary syndrome (PCOS), primary ovarian insufficiency (POI), endometriosis, and age-related ovarian decline are often associated with chronic low-grade inflammation. Nicotinamide mononucleotide (NMN) is an important precursor of NAD+ and has gained attention for its potential to modulate cellular metabolism, redox homeostasis, and mitigate inflammation. This study investigated the protective roles of NMN against lipopolysaccharide LPS-mediated inflammation in GCs. The results of this experiment demonstrated that LPS had negative effects on GCs in term of reduced viability and proliferation rates and upregulated the production of pro-inflammatory cytokines, including interleukin-1 beta (IL-1β), interleukin-6 (IL-6), cyclooxygenase-2 (Cox-2), and tumor necrosis factor-alpha (TNF-α). Notably, the levels of NAD+ and NAD+/NADH ratio in GCs were reduced in response to inflammation. On the other hand, NMN supplementation restored the NAD+ levels and the NAD+/NADH ratio in GCs and significantly reduced the expression of pro-inflammatory markers at both mRNA and protein levels. It also enhanced cell viability and proliferation rates of GCs. Furthermore, NMN also reduced apoptosis rates in GCs by downregulating pro-apoptotic markers, including Caspase-3, Caspase-9, and Bax while upregulating anti-apoptotic marker Bcl-2. NMN supplementation significantly reduced reactive oxygen species ROS and improved steroidogenesis activity by restoring the estradiol (E2) and progesterone (P4) levels in LPS-treated GCs. Mechanistically, this study found that NMN suppressed the activation of the TLR4/NF-κB/MAPK signaling pathways in GCs, which regulates inflammatory processes. In conclusion, the findings of this study revealed that NMN has the potential to reduce LPS-mediated inflammatory changes in GCs by modulating NAD+ metabolism and inflammatory signaling pathways. NMN supplementation can be used as a potential therapeutic agent for ovarian inflammation and related fertility disorders.
{"title":"Nicotinamide Mononucleotide Restores NAD<sup>+</sup> Levels to Alleviate LPS-Induced Inflammation via the TLR4/NF-κB/MAPK Signaling Pathway in Mice Granulosa Cells.","authors":"Mehboob Ahmed, Umair Riaz, Haimiao Lv, Muhammad Amjad, Sohail Ahmed, Shaokat Ali, Muhammad Usman Ghani, Guohua Hua, Liguo Yang","doi":"10.3390/antiox14010039","DOIUrl":"10.3390/antiox14010039","url":null,"abstract":"<p><p>Inflammation disrupts the normal function of granulosa cells (GCs), which leads to ovarian dysfunction and fertility decline. Inflammatory conditions such as polycystic ovary syndrome (PCOS), primary ovarian insufficiency (POI), endometriosis, and age-related ovarian decline are often associated with chronic low-grade inflammation. Nicotinamide mononucleotide (NMN) is an important precursor of NAD<sup>+</sup> and has gained attention for its potential to modulate cellular metabolism, redox homeostasis, and mitigate inflammation. This study investigated the protective roles of NMN against lipopolysaccharide LPS-mediated inflammation in GCs. The results of this experiment demonstrated that LPS had negative effects on GCs in term of reduced viability and proliferation rates and upregulated the production of pro-inflammatory cytokines, including interleukin-1 beta (IL-1β), interleukin-6 (IL-6), cyclooxygenase-2 (Cox-2), and tumor necrosis factor-alpha (TNF-α). Notably, the levels of NAD<sup>+</sup> and NAD<sup>+</sup>/NADH ratio in GCs were reduced in response to inflammation. On the other hand, NMN supplementation restored the NAD<sup>+</sup> levels and the NAD<sup>+</sup>/NADH ratio in GCs and significantly reduced the expression of pro-inflammatory markers at both mRNA and protein levels. It also enhanced cell viability and proliferation rates of GCs. Furthermore, NMN also reduced apoptosis rates in GCs by downregulating pro-apoptotic markers, including Caspase-3, Caspase-9, and Bax while upregulating anti-apoptotic marker Bcl-2. NMN supplementation significantly reduced reactive oxygen species ROS and improved steroidogenesis activity by restoring the estradiol (E2) and progesterone (P4) levels in LPS-treated GCs. Mechanistically, this study found that NMN suppressed the activation of the TLR4/NF-κB/MAPK signaling pathways in GCs, which regulates inflammatory processes. In conclusion, the findings of this study revealed that NMN has the potential to reduce LPS-mediated inflammatory changes in GCs by modulating NAD<sup>+</sup> metabolism and inflammatory signaling pathways. NMN supplementation can be used as a potential therapeutic agent for ovarian inflammation and related fertility disorders.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"14 1","pages":""},"PeriodicalIF":6.0,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143035622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}