Alaa Ahmed Alsiddig Hassan, Young Hun Jin, Jae-Hyung Mah
This study investigated the impact of Pediococcus pentosaceus strains not only on biogenic amine (BA) content, but also on antioxidant indices, including 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity and total phenolic content, in kisra, an African sourdough flatbread. Among forty-six lactic acid bacteria (LAB) strains isolated from naturally fermented kisra sourdough, two strains (K-B21, K-B01) identified as P. pentosaceus, were selected due to their low BA-producing and high BA-degrading ability for kisra fermentation. Inoculation with P. pentosaceus K-B21 or P. pentosaceus K-B01 completely prevented the formation of tyramine and cadaverine during kisra fermentation. The levels of putrescine, histamine, spermine, and spermidine in kisra were reduced by about 90%, >31%, 55-61%, and 9-25%, respectively, by the two strains, compared to the control (natural fermentation). Additionally, DPPH scavenging activity was 83-84% in the control and inoculated groups of kisra. The total phenolic content was 1977.60 μg/g in the control and insignificantly lower in the inoculated groups (1850-1880 μg/g) than the control. These results suggest that P. pentosaceus K-B21 and K-B01 are promising candidates for use as sourdough starter cultures to produce kisra bread of higher quality, including both its safety and health functionality.
本研究调查了五胜肽球菌(Pediococcus pentosaceus)菌株不仅对生物胺(BA)含量的影响,还对非洲酸面团(kisra)中的抗氧化指数(包括 2,2-二苯基-1-苦基肼(DPPH)清除活性和总酚含量)的影响。在从自然发酵的基斯拉酸面团中分离出的 46 株乳酸菌(LAB)中,有两株(K-B21 和 K-B01)被鉴定为戊糖杆菌,它们具有低 BA 产出和高 BA 降解能力,因此被选中用于基斯拉发酵。接种 P. pentosaceus K-B21 或 P. pentosaceus K-B01 能完全阻止基斯拉发酵过程中酪胺和尸胺的形成。与对照组(自然发酵)相比,这两种菌株可使 kisra 中的腐胺、组胺、精胺和亚精胺的含量分别减少约 90%、31%、55%-61% 和 9%-25%。此外,对照组和接种组基斯拉的 DPPH 清除活性为 83-84%。对照组的总酚含量为 1977.60 μg/g,接种组的总酚含量(1850-1880 μg/g)显著低于对照组。这些结果表明,P. pentosaceus K-B21 和 K-B01 有希望用作酸包粉起始培养物,以生产出更高质量的基斯拉面包,包括其安全性和保健功能。
{"title":"Influence of <i>Pediococcus pentosaceus</i> Starter Cultures on Biogenic Amine Content and Antioxidant Activity in African Sourdough Flatbread Fermentation.","authors":"Alaa Ahmed Alsiddig Hassan, Young Hun Jin, Jae-Hyung Mah","doi":"10.3390/antiox13101204","DOIUrl":"10.3390/antiox13101204","url":null,"abstract":"<p><p>This study investigated the impact of <i>Pediococcus pentosaceus</i> strains not only on biogenic amine (BA) content, but also on antioxidant indices, including 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity and total phenolic content, in kisra, an African sourdough flatbread. Among forty-six lactic acid bacteria (LAB) strains isolated from naturally fermented kisra sourdough, two strains (K-B21, K-B01) identified as <i>P. pentosaceus,</i> were selected due to their low BA-producing and high BA-degrading ability for kisra fermentation. Inoculation with <i>P. pentosaceus</i> K-B21 or <i>P. pentosaceus</i> K-B01 completely prevented the formation of tyramine and cadaverine during kisra fermentation. The levels of putrescine, histamine, spermine, and spermidine in kisra were reduced by about 90%, >31%, 55-61%, and 9-25%, respectively, by the two strains, compared to the control (natural fermentation). Additionally, DPPH scavenging activity was 83-84% in the control and inoculated groups of kisra. The total phenolic content was 1977.60 μg/g in the control and insignificantly lower in the inoculated groups (1850-1880 μg/g) than the control. These results suggest that <i>P. pentosaceus</i> K-B21 and K-B01 are promising candidates for use as sourdough starter cultures to produce kisra bread of higher quality, including both its safety and health functionality.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"13 10","pages":""},"PeriodicalIF":6.0,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11504419/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493372","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}
With the development of society and the improvement of people's health consciousness, the demand for antioxidants is increasing. As a natural antioxidant with no toxic side effects, antioxidant peptides are widely used in food, cosmetics, medicine, and other fields because of their strong antioxidant capacity and easy absorption by the human body. Plant-derived antioxidant peptides have attracted more attention than animal-derived antioxidant peptides because plants are more diverse than animals and produce a large number of protein-rich by-products during the processing of their products, which are the main source of antioxidant peptides. In this review, we summarize the source, structure and activity, other biological functions, mechanism of action, and comprehensive applications of plant antioxidant peptides, and look forward to their future development trends, which will provide a reference for further research and development of plant antioxidant peptides.
{"title":"Antioxidant Function and Application of Plant-Derived Peptides.","authors":"Zhengqing Zhu, Ziwu Xu, Yuhang Li, Yutong Fan, Yingqian Zhou, Kaixin Song, Lei Meng","doi":"10.3390/antiox13101203","DOIUrl":"10.3390/antiox13101203","url":null,"abstract":"<p><p>With the development of society and the improvement of people's health consciousness, the demand for antioxidants is increasing. As a natural antioxidant with no toxic side effects, antioxidant peptides are widely used in food, cosmetics, medicine, and other fields because of their strong antioxidant capacity and easy absorption by the human body. Plant-derived antioxidant peptides have attracted more attention than animal-derived antioxidant peptides because plants are more diverse than animals and produce a large number of protein-rich by-products during the processing of their products, which are the main source of antioxidant peptides. In this review, we summarize the source, structure and activity, other biological functions, mechanism of action, and comprehensive applications of plant antioxidant peptides, and look forward to their future development trends, which will provide a reference for further research and development of plant antioxidant peptides.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"13 10","pages":""},"PeriodicalIF":6.0,"publicationDate":"2024-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11505357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493356","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}
Cesidio Giuliani, Giulia Di Dalmazi, Ines Bucci, Giorgio Napolitano
Quercetin is the most abundant flavonoid present in fruits and vegetables. For its antiproliferative, antiviral, anti-inflammatory and antioxidants activities, it is an active ingredient of several herbal remedies and is available as a nutraceutical. Experimental studies performed in vitro have demonstrated that quercetin inhibits growth and function in normal thyroid cells and may act as a thyroid disruptor. These effects have also been confirmed in vivo using rodent models. Some studies have reported the ability of quercetin to interfere with the metabolism of thyroid hormones, since it inhibits the 5'-deiodinase type 1 (D1) activity in the thyroid, as well as in the liver. Besides the effects on normal thyroid cells, several experiments performed in vitro have shown a potential therapeutic role of quercetin in thyroid cancer. Indeed, quercetin inhibits the growth, the adhesion and the migration of thyroid cancer cells, and it also has redifferentiation properties in some thyroid cancer cell lines. In conclusion, these data suggest that, although its effects can be of benefit in hyperthyroidism and thyroid cancer, caution is required in the use of high doses of quercetin due to its anti-thyroid properties. Further in vivo studies are certainly needed to confirm these hypotheses.
{"title":"Quercetin and Thyroid.","authors":"Cesidio Giuliani, Giulia Di Dalmazi, Ines Bucci, Giorgio Napolitano","doi":"10.3390/antiox13101202","DOIUrl":"10.3390/antiox13101202","url":null,"abstract":"<p><p>Quercetin is the most abundant flavonoid present in fruits and vegetables. For its antiproliferative, antiviral, anti-inflammatory and antioxidants activities, it is an active ingredient of several herbal remedies and is available as a nutraceutical. Experimental studies performed in vitro have demonstrated that quercetin inhibits growth and function in normal thyroid cells and may act as a thyroid disruptor. These effects have also been confirmed in vivo using rodent models. Some studies have reported the ability of quercetin to interfere with the metabolism of thyroid hormones, since it inhibits the 5'-deiodinase type 1 (D1) activity in the thyroid, as well as in the liver. Besides the effects on normal thyroid cells, several experiments performed in vitro have shown a potential therapeutic role of quercetin in thyroid cancer. Indeed, quercetin inhibits the growth, the adhesion and the migration of thyroid cancer cells, and it also has redifferentiation properties in some thyroid cancer cell lines. In conclusion, these data suggest that, although its effects can be of benefit in hyperthyroidism and thyroid cancer, caution is required in the use of high doses of quercetin due to its anti-thyroid properties. Further in vivo studies are certainly needed to confirm these hypotheses.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"13 10","pages":""},"PeriodicalIF":6.0,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11505551/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493435","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}
Nowadays, interest in natural antioxidants (especially phenolics) for the prevention of oxidative stress-related diseases is increasing due to their fewer side effects and more potent activity than some of their synthetic analogues. New chemical and pharmacological studies of well-known herbal substances are among the current trends in medicinal plant research. Meadowsweet (Filipendula ulmaria) is a popular herb used in traditional medicine to treat various diseases (including rheumatic-, inflammatory- and tumor-related disease, etc.). The dry tincture of Filipendulae ulmariae herba, collected from the Bulgarian flora, was analyzed using the HPLC method and bioassayed for antioxidant, antiproliferative and DNA-protective activities against oxidative damage. The HPLC phenolic profile showed 12 phenolics, of which salicylic acid (18.84 mg/g dry extract), rutin (9.97 mg/g de), p-coumaric acid (6.80 mg/g de), quercetin (4.47 mg/g de), rosmarinic acid (4.01 mg/g de) and vanillic acid (3.82 mg/g de) were the major components. The high antioxidant potential of the species was confirmed by using four methods, best expressed by the results of the CUPRAC assay (10,605.91 μM TE/g de). The present study reports for the first time the highly protective activities of meadowsweet dry tincture against oxidative DNA damage and its antiproliferative effect against hepatocellular carcinoma (HepG2 cell line). Meadowsweet dry tincture possesses great potential to prevent diseases caused by oxidative stress.
{"title":"DNA-Protective, Antioxidant and Anti-Carcinogenic Potential of Meadowsweet (<i>Filipendula ulmaria</i>) Dry Tincture.","authors":"Tsvetelina Andonova, Yordan Muhovski, Elena Apostolova, Samir Naimov, Silviya Mladenova, Iliya Slavov, Ivayla Dincheva, Vasil Georgiev, Atanas Pavlov, Ivanka Dimitrova-Dyulgerova","doi":"10.3390/antiox13101200","DOIUrl":"10.3390/antiox13101200","url":null,"abstract":"<p><p>Nowadays, interest in natural antioxidants (especially phenolics) for the prevention of oxidative stress-related diseases is increasing due to their fewer side effects and more potent activity than some of their synthetic analogues. New chemical and pharmacological studies of well-known herbal substances are among the current trends in medicinal plant research. Meadowsweet (<i>Filipendula ulmaria</i>) is a popular herb used in traditional medicine to treat various diseases (including rheumatic-, inflammatory- and tumor-related disease, etc.). The dry tincture of <i>Filipendulae ulmariae herba</i>, collected from the Bulgarian flora, was analyzed using the HPLC method and bioassayed for antioxidant, antiproliferative and DNA-protective activities against oxidative damage. The HPLC phenolic profile showed 12 phenolics, of which salicylic acid (18.84 mg/g dry extract), rutin (9.97 mg/g de), <i>p</i>-coumaric acid (6.80 mg/g de), quercetin (4.47 mg/g de), rosmarinic acid (4.01 mg/g de) and vanillic acid (3.82 mg/g de) were the major components. The high antioxidant potential of the species was confirmed by using four methods, best expressed by the results of the CUPRAC assay (10,605.91 μM TE/g de). The present study reports for the first time the highly protective activities of meadowsweet dry tincture against oxidative DNA damage and its antiproliferative effect against hepatocellular carcinoma (HepG2 cell line). Meadowsweet dry tincture possesses great potential to prevent diseases caused by oxidative stress.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"13 10","pages":""},"PeriodicalIF":6.0,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11504252/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493280","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}
Muthipeedika Nibin Joy, Igor S Kovalev, Olga V Shabunina, Sougata Santra, Grigory V Zyryanov
A series of 16 (hetero)aryl compounds based on coumarin and equol has been efficiently synthesized by exploring the palladium-catalyzed Suzuki cross-coupling reactions. Polyphenol based on coumarin (4-methyl-7-hydroxy coumarin) was initially converted to corresponding coumarin imidazylate and then subjected to Suzuki coupling reaction with 4-methoxyphenylboronic acid to obtain the coupled product. This modified approach was later developed into a one-pot methodology by directly reacting the polyphenol with 1,1-sulfonyldiimidazole (SDI) and boronic acid in situ to obtain the Suzuki coupled product in one step. Moreover, an array of (poly)phenols based on coumarin and equol were later converted to diverse (hetero)aryl compounds by this optimized step-economic protocol. The synthesized compounds were then subjected to the screening of their potential antioxidant activities by 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. In our investigation, the compounds 4ah, 4eh, 4gh and 4hh exhibited promising antioxidant potential when compared to the reference standard, butylated hydroxytoluene (BHT). Structure activity relationship (SAR) studies revealed the importance of the presence of electron-donating substituents in enhancing the antioxidant activity of the synthesized compounds.
{"title":"Facile One-Pot Conversion of (poly)phenols to Diverse (hetero)aryl Compounds by Suzuki Coupling Reaction: A Modified Approach for the Synthesis of Coumarin- and Equol-Based Compounds as Potential Antioxidants.","authors":"Muthipeedika Nibin Joy, Igor S Kovalev, Olga V Shabunina, Sougata Santra, Grigory V Zyryanov","doi":"10.3390/antiox13101198","DOIUrl":"10.3390/antiox13101198","url":null,"abstract":"<p><p>A series of 16 (hetero)aryl compounds based on coumarin and equol has been efficiently synthesized by exploring the palladium-catalyzed Suzuki cross-coupling reactions. Polyphenol based on coumarin (4-methyl-7-hydroxy coumarin) was initially converted to corresponding coumarin imidazylate and then subjected to Suzuki coupling reaction with 4-methoxyphenylboronic acid to obtain the coupled product. This modified approach was later developed into a one-pot methodology by directly reacting the polyphenol with 1,1-sulfonyldiimidazole (SDI) and boronic acid in situ to obtain the Suzuki coupled product in one step. Moreover, an array of (poly)phenols based on coumarin and equol were later converted to diverse (hetero)aryl compounds by this optimized step-economic protocol. The synthesized compounds were then subjected to the screening of their potential antioxidant activities by 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. In our investigation, the compounds <b>4ah</b>, <b>4eh</b>, <b>4gh</b> and <b>4hh</b> exhibited promising antioxidant potential when compared to the reference standard, butylated hydroxytoluene (BHT). Structure activity relationship (SAR) studies revealed the importance of the presence of electron-donating substituents in enhancing the antioxidant activity of the synthesized compounds.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"13 10","pages":""},"PeriodicalIF":6.0,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11504026/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493317","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}
Javier Marqués, Elena Ainzúa, Josune Orbe, María Martínez-Azcona, José Martínez-González, Guillermo Zalba
NADPH oxidases (NOXs) have been described as critical players in vascular remodeling, a mechanism modulated by matrix metalloproteinases. In this study, we describe for the first time the upregulation of MMP-10 through the activation of NOX5 in endothelial cells. In a chronic NOX5 overexpression model in human endothelial cells, MMP-10 production was measured at different levels: extracellular secretion, gene expression (mRNA and protein levels), and promoter activity. Effects on cell migration were quantified using wound healing assays. NOX5 overexpression increased MMP-10 production, favoring cell migration. In fact, NOX5 and MMP-10 silencing prevented this promigratory effect. We showed that NOX5-mediated MMP-10 upregulation involves the redox-sensitive JNK/AP-1 signaling pathway. All these NOX5-dependent effects were enhanced by angiotensin II (Ang II). Interestingly, MMP-10 protein levels were found to be increased in the hearts of NOX5-expressing mice. In conclusion, we described that NOX5-generated ROS may modulate the MMP-10 expression in endothelial cells, which leads to endothelial cell migration and may play a key role in vascular remodeling.
{"title":"NADPH Oxidase 5 (NOX5) Upregulates MMP-10 Production and Cell Migration in Human Endothelial Cells.","authors":"Javier Marqués, Elena Ainzúa, Josune Orbe, María Martínez-Azcona, José Martínez-González, Guillermo Zalba","doi":"10.3390/antiox13101199","DOIUrl":"10.3390/antiox13101199","url":null,"abstract":"<p><p>NADPH oxidases (NOXs) have been described as critical players in vascular remodeling, a mechanism modulated by matrix metalloproteinases. In this study, we describe for the first time the upregulation of MMP-10 through the activation of NOX5 in endothelial cells. In a chronic NOX5 overexpression model in human endothelial cells, MMP-10 production was measured at different levels: extracellular secretion, gene expression (mRNA and protein levels), and promoter activity. Effects on cell migration were quantified using wound healing assays. NOX5 overexpression increased MMP-10 production, favoring cell migration. In fact, NOX5 and MMP-10 silencing prevented this promigratory effect. We showed that NOX5-mediated MMP-10 upregulation involves the redox-sensitive JNK/AP-1 signaling pathway. All these NOX5-dependent effects were enhanced by angiotensin II (Ang II). Interestingly, MMP-10 protein levels were found to be increased in the hearts of NOX5-expressing mice. In conclusion, we described that NOX5-generated ROS may modulate the MMP-10 expression in endothelial cells, which leads to endothelial cell migration and may play a key role in vascular remodeling.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"13 10","pages":""},"PeriodicalIF":6.0,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11504164/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493400","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}
Fatemeh Jamali, Katherine Lan, Paul Daniel, Kevin Petrecca, Siham Sabri, Bassam Abdulkarim
Glioblastoma (GBM) is an incurable primary brain cancer characterized by increased reactive oxygen species (ROS) production. The redox-sensitive tumor suppressor gene TP53, wild-type (wt) for 70% of patients, regulates redox homeostasis. Glioblastoma stem cells (GSCs) increase thioredoxin (Trx) and glutathione (GSH) antioxidant systems as survival redox-adaptive mechanisms to maintain ROS below the cytotoxic threshold. Auranofin, an FDA-approved anti-rheumatoid drug, inhibits thioredoxin reductase 1 (TrxR1). L-buthionine sulfoximine (L-BSO) and the natural product piperlongumine (PPL) inhibit the GSH system. We evaluated the cytotoxic effects of Auranofin alone and in combination with L-BSO or PPL in GBM cell lines and GSCs with a known TP53 status. The Cancer Genome Atlas/GBM analysis revealed a significant positive correlation between wtp53 and TrxR1 expression in GBM. Auranofin induced ROS-dependent cytotoxicity within a micromolar range in GSCs. Auranofin decreased TrxR1 expression, AKT (Ser-473) phosphorylation, and increased p53, p21, and PARP-1 apoptotic cleavage in wtp53-GSCs, while mutant-p53 was decreased in a mutant-p53 GSC line. Additionally, p53-knockdown in a wtp53-GSC line decreased TrxR1 expression and significantly increased sensitivity to Auranofin, suggesting the role of wtp53 as a negative redox-sensitive mechanism in response to Auranofin in GSCs. The combination of Auranofin and L-BSO synergistically increased ROS, decreased IC50s, and induced long-term cytotoxicity irrespective of p53 in GBM cell lines and GSCs. Intriguingly, Auranofin increased the expression of glutathione S-transferase pi-1 (GSTP-1), a target of PPL. Combining Auranofin with PPL synergistically decreased IC50s to a nanomolar range in GSCs, supporting the potential to repurpose Auranofin and PPL in GBM.
{"title":"Synergistic Dual Targeting of Thioredoxin and Glutathione Systems Irrespective of p53 in Glioblastoma Stem Cells.","authors":"Fatemeh Jamali, Katherine Lan, Paul Daniel, Kevin Petrecca, Siham Sabri, Bassam Abdulkarim","doi":"10.3390/antiox13101201","DOIUrl":"10.3390/antiox13101201","url":null,"abstract":"<p><p>Glioblastoma (GBM) is an incurable primary brain cancer characterized by increased reactive oxygen species (ROS) production. The redox-sensitive tumor suppressor gene <i>TP53</i>, wild-type (wt) for 70% of patients, regulates redox homeostasis. Glioblastoma stem cells (GSCs) increase thioredoxin (Trx) and glutathione (GSH) antioxidant systems as survival redox-adaptive mechanisms to maintain ROS below the cytotoxic threshold. Auranofin, an FDA-approved anti-rheumatoid drug, inhibits thioredoxin reductase 1 (TrxR1). L-buthionine sulfoximine (L-BSO) and the natural product piperlongumine (PPL) inhibit the GSH system. We evaluated the cytotoxic effects of Auranofin alone and in combination with L-BSO or PPL in GBM cell lines and GSCs with a known <i>TP53</i> status. The Cancer Genome Atlas/GBM analysis revealed a significant positive correlation between wtp53 and TrxR1 expression in GBM. Auranofin induced ROS-dependent cytotoxicity within a micromolar range in GSCs. Auranofin decreased TrxR1 expression, AKT (Ser-473) phosphorylation, and increased p53, p21, and PARP-1 apoptotic cleavage in wtp53-GSCs, while mutant-p53 was decreased in a mutant-p53 GSC line. Additionally, p53-knockdown in a wtp53-GSC line decreased TrxR1 expression and significantly increased sensitivity to Auranofin, suggesting the role of wtp53 as a negative redox-sensitive mechanism in response to Auranofin in GSCs. The combination of Auranofin and L-BSO synergistically increased ROS, decreased IC50s, and induced long-term cytotoxicity irrespective of p53 in GBM cell lines and GSCs. Intriguingly, Auranofin increased the expression of glutathione S-transferase pi-1 (GSTP-1), a target of PPL. Combining Auranofin with PPL synergistically decreased IC50s to a nanomolar range in GSCs, supporting the potential to repurpose Auranofin and PPL in GBM.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"13 10","pages":""},"PeriodicalIF":6.0,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11504866/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493448","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}
Melatonin (5-methoxy-N-acetyltryptamine) is an indoleamine compound that plays a critical role in the regulation of circadian rhythms. While melatonin is primarily synthesized from the amino acid tryptophan in the pineal gland of the brain, it can also be produced locally in various tissues, such as the skin and intestines. Melatonin's effects in target tissues can be mediated through receptor-dependent mechanisms. Additionally, melatonin exerts various actions via receptor-independent pathways. In biological systems, melatonin and its endogenous metabolites often produce similar effects. While injuries are common in daily life, promoting optimal wound healing is essential for patient well-being and healthcare outcomes. Beyond regulating circadian rhythms as a neuroendocrine hormone, melatonin may enhance wound healing through (1) potent antioxidant properties, (2) anti-inflammatory actions, (3) infection control, (4) regulation of vascular reactivity and angiogenesis, (5) analgesic (pain-relieving) effects, and (6) anti-pruritic (anti-itch) effects. This review aims to provide a comprehensive overview of scientific studies that demonstrate melatonin's potential roles in supporting effective wound healing.
{"title":"Melatonin's Impact on Wound Healing.","authors":"Eun-Hwa Sohn, Su-Nam Kim, Sung-Ryul Lee","doi":"10.3390/antiox13101197","DOIUrl":"10.3390/antiox13101197","url":null,"abstract":"<p><p>Melatonin (5-methoxy-N-acetyltryptamine) is an indoleamine compound that plays a critical role in the regulation of circadian rhythms. While melatonin is primarily synthesized from the amino acid tryptophan in the pineal gland of the brain, it can also be produced locally in various tissues, such as the skin and intestines. Melatonin's effects in target tissues can be mediated through receptor-dependent mechanisms. Additionally, melatonin exerts various actions via receptor-independent pathways. In biological systems, melatonin and its endogenous metabolites often produce similar effects. While injuries are common in daily life, promoting optimal wound healing is essential for patient well-being and healthcare outcomes. Beyond regulating circadian rhythms as a neuroendocrine hormone, melatonin may enhance wound healing through (1) potent antioxidant properties, (2) anti-inflammatory actions, (3) infection control, (4) regulation of vascular reactivity and angiogenesis, (5) analgesic (pain-relieving) effects, and (6) anti-pruritic (anti-itch) effects. This review aims to provide a comprehensive overview of scientific studies that demonstrate melatonin's potential roles in supporting effective wound healing.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"13 10","pages":""},"PeriodicalIF":6.0,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11504849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493380","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}
Riccardo Barbari, Vera Bruggink, Robert Klaus Hofstetter, Chiara Tupini, Sofia Fagnani, Erika Baldini, Elisa Durini, Ilaria Lampronti, Silvia Vertuani, Anna Baldisserotto, Oliver Werz, Stefano Manfredini
A current trend in healthcare research is to discover multifunctional compounds, able to interact with multiple biological targets, in order to simplify multi-drug therapies and improve patient compliance. The aim of this work was to outline the growing demand for innovative multifunctional compounds, achieved through the synthesis, characterisation and SAR evaluation of a series of 2-styrylbenzothiazole derivatives. The six synthesised compounds were studied for their potential as photoprotective, antioxidant, antiproliferative, and anti-inflammatory agents. In order to profile antioxidant activity against various radical species, in vitro DPPH, FRAP and ORAC assays were performed. UV-filtering activity was studied, first in solution and then in formulation (standard O/W sunscreen containing 3% synthesised molecules) before and after irradiation. Compound BZTst6 proved to be photostable, suitable for broad-spectrum criteria, and is an excellent UVA filter. In terms of antioxidant activity, only compound BZTst4 can be considered a promising candidate, due to the potential of the catechol moiety. Both also showed exceptional inhibitory action against the pro-inflammatory enzyme 5-lipoxygenase (LO), with IC50 values in the sub-micromolar range in both activated neutrophils and under cell-free conditions. The results showed that the compounds under investigation are suitable for multifunctional application purposes, underlining the importance of their chemical scaffolding in terms of different biological behaviours.
{"title":"Synthesis and Biological Activity Assessment of 2-Styrylbenzothiazoles as Potential Multifunctional Therapeutic Agents.","authors":"Riccardo Barbari, Vera Bruggink, Robert Klaus Hofstetter, Chiara Tupini, Sofia Fagnani, Erika Baldini, Elisa Durini, Ilaria Lampronti, Silvia Vertuani, Anna Baldisserotto, Oliver Werz, Stefano Manfredini","doi":"10.3390/antiox13101196","DOIUrl":"10.3390/antiox13101196","url":null,"abstract":"<p><p>A current trend in healthcare research is to discover multifunctional compounds, able to interact with multiple biological targets, in order to simplify multi-drug therapies and improve patient compliance. The aim of this work was to outline the growing demand for innovative multifunctional compounds, achieved through the synthesis, characterisation and SAR evaluation of a series of 2-styrylbenzothiazole derivatives. The six synthesised compounds were studied for their potential as photoprotective, antioxidant, antiproliferative, and anti-inflammatory agents. In order to profile antioxidant activity against various radical species, in vitro DPPH, FRAP and ORAC assays were performed. UV-filtering activity was studied, first in solution and then in formulation (standard O/W sunscreen containing 3% synthesised molecules) before and after irradiation. Compound <b>BZTst6</b> proved to be photostable, suitable for broad-spectrum criteria, and is an excellent UVA filter. In terms of antioxidant activity, only compound <b>BZTst4</b> can be considered a promising candidate, due to the potential of the catechol moiety. Both also showed exceptional inhibitory action against the pro-inflammatory enzyme 5-lipoxygenase (LO), with IC<sub>50</sub> values in the sub-micromolar range in both activated neutrophils and under cell-free conditions. The results showed that the compounds under investigation are suitable for multifunctional application purposes, underlining the importance of their chemical scaffolding in terms of different biological behaviours.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"13 10","pages":""},"PeriodicalIF":6.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11504387/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493449","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}
Vitamin C (ascorbate; Asc) is a biologically important antioxidant that scavenges reactive oxygen species such as deleterious alkylperoxyl radicals (ROO•), which are generated by radical-mediated oxidation of biomolecules in the presence of oxygen. The radical trapping proprieties of Asc are conventionally attributed to its ability to undergo single-electron transfers with reactive species. According to this mechanism, the reaction between Asc and ROO• results in the formation of dehydroascorbate (DHA) and the corresponding hydroperoxides (ROOH). When studying the reactivity of DNA 5-(2'-deoxyuridinyl)methylperoxyl radicals, we discovered a novel pathway of ROO• scavenging by Asc. The purpose of this study is to elucidate the underlying mechanism of this reaction with emphasis on the characterization of intermediate and final decomposition products. We show that the trapping of ROO• by Asc leads to the formation of an alcohol (ROH) together with an unstable cyclic oxalyl-l-threonate intermediate (cOxa-Thr), which readily undergoes hydrolysis into a series of open-chain oxalyl-l-threonic acid regioisomers. The structure of products was determined by detailed MS and NMR analyses. The above transformation can be explained by initial peroxyl radical addition (PRA) onto the C2=C3 enediol portion of Asc. Following oxidation of the resulting adduct radical, the product subsequently undergoes Baeyer-Villiger rearrangement, which releases ROH and generates the ring expansion product cOxa-Thr. The present investigation provides robust clarifications of the peroxide-mediated oxidation chemistry of Asc and DHA that has largely been obscured in the past by interference with autooxidation reactions and difficulties in analyzing and characterizing oxidation products. Scavenging of ROO• by PRA onto Asc may have beneficial consequences since it directly converts ROO• into ROH, which prevents the formation of potentially deleterious ROOH, although it induces the breakdown of Asc into fragments of oxalyl-l-threonic acid.
{"title":"Scavenging of Alkylperoxyl Radicals by Addition to Ascorbate: An Alternative Mechanism to Electron Transfer.","authors":"Gabriel Robert, J Richard Wagner","doi":"10.3390/antiox13101194","DOIUrl":"10.3390/antiox13101194","url":null,"abstract":"<p><p>Vitamin C (ascorbate; Asc) is a biologically important antioxidant that scavenges reactive oxygen species such as deleterious alkylperoxyl radicals (ROO<sup>•</sup>), which are generated by radical-mediated oxidation of biomolecules in the presence of oxygen. The radical trapping proprieties of Asc are conventionally attributed to its ability to undergo single-electron transfers with reactive species. According to this mechanism, the reaction between Asc and ROO<sup>•</sup> results in the formation of dehydroascorbate (DHA) and the corresponding hydroperoxides (ROOH). When studying the reactivity of DNA 5-(2'-deoxyuridinyl)methylperoxyl radicals, we discovered a novel pathway of ROO<sup>•</sup> scavenging by Asc. The purpose of this study is to elucidate the underlying mechanism of this reaction with emphasis on the characterization of intermediate and final decomposition products. We show that the trapping of ROO<sup>•</sup> by Asc leads to the formation of an alcohol (ROH) together with an unstable cyclic oxalyl-l-threonate intermediate (cOxa-Thr), which readily undergoes hydrolysis into a series of open-chain oxalyl-l-threonic acid regioisomers. The structure of products was determined by detailed MS and NMR analyses. The above transformation can be explained by initial peroxyl radical addition (PRA) onto the C2=C3 enediol portion of Asc. Following oxidation of the resulting adduct radical, the product subsequently undergoes Baeyer-Villiger rearrangement, which releases ROH and generates the ring expansion product cOxa-Thr. The present investigation provides robust clarifications of the peroxide-mediated oxidation chemistry of Asc and DHA that has largely been obscured in the past by interference with autooxidation reactions and difficulties in analyzing and characterizing oxidation products. Scavenging of ROO<sup>•</sup> by PRA onto Asc may have beneficial consequences since it directly converts ROO<sup>•</sup> into ROH, which prevents the formation of potentially deleterious ROOH, although it induces the breakdown of Asc into fragments of oxalyl-l-threonic acid.</p>","PeriodicalId":7984,"journal":{"name":"Antioxidants","volume":"13 10","pages":""},"PeriodicalIF":6.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11504153/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493444","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}