Antioxidants

26 pages, 1183 KiB

Open AccessReview

Astaxanthin as a Potent Antioxidant for Promoting Bone Health: An Up-to-Date Review

by Iswari Davan, Sharida Fakurazi, Ekram Alias, Nurul ‘Izzah Ibrahim, Ng Min Hwei and Haniza Hassan

Antioxidants 2023, 12(7), 1480; https://doi.org/10.3390/antiox12071480 - 24 Jul 2023

Cited by 3 | Viewed by 4427

Abstract

In recent years, bone loss and its associated diseases have become a significant public health concern due to increased disability, morbidity, and mortality. Oxidative stress and bone loss are correlated, where oxidative stress suppresses osteoblast activity, resulting in compromised homeostasis between bone formation [...] Read more.

In recent years, bone loss and its associated diseases have become a significant public health concern due to increased disability, morbidity, and mortality. Oxidative stress and bone loss are correlated, where oxidative stress suppresses osteoblast activity, resulting in compromised homeostasis between bone formation and resorption. This event causes upregulation of bone remodeling turnover rate with an increased risk of fractures and bone loss. Therefore, supplementation of antioxidants can be proposed to reduce oxidative stress, facilitate the bone remodeling process, suppress the initiation of bone diseases, and improve bone health. Astaxanthin (3,3′-dihydroxy-4-4′-diketo-β-β carotene), a potent antioxidant belonging to the xanthophylls family, is a potential ROS scavenger and could be a promising therapeutic nutraceutical possessing various pharmacological properties. In bone, astaxanthin enhances osteoblast differentiation, osteocytes numbers, and/or differentiation, inhibits osteoclast differentiation, cartilage degradation markers, and increases bone mineral density, expression of osteogenic markers, while reducing bone loss. In this review, we presented the up-to-date findings of the potential anabolic effects of astaxanthin on bone health in vitro, animal, and human studies by providing comprehensive evidence for its future clinical application, especially in treating bone diseases. Full article

(This article belongs to the Special Issue Women’s Special Issue Series: Antioxidants in Human Health)

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24 pages, 1343 KiB

Open AccessReview

Urolithin A in Health and Diseases: Prospects for Parkinson’s Disease Management

by Olga Wojciechowska and Małgorzata Kujawska

Antioxidants 2023, 12(7), 1479; https://doi.org/10.3390/antiox12071479 - 24 Jul 2023

Cited by 3 | Viewed by 4752

Abstract

Parkinson’s disease (PD) is a chronic and progressive neurodegenerative disorder characterized by a complex pathophysiology and a range of symptoms. The prevalence increases with age, putting the ageing population at risk. Disease management includes the improvement of symptoms, the comfort of the patient’s [...] Read more.

Parkinson’s disease (PD) is a chronic and progressive neurodegenerative disorder characterized by a complex pathophysiology and a range of symptoms. The prevalence increases with age, putting the ageing population at risk. Disease management includes the improvement of symptoms, the comfort of the patient’s life, and palliative care. As there is currently no cure, growing evidence points towards the beneficial role of polyphenols on neurodegeneration. Numerous studies indicate the health benefits of the family of urolithins, especially urolithin A (UA). UA is a bacterial metabolite produced by dietary ellagitannins and ellagic acid. An expanding body of literature explores the involvement of the compound in mitochondrial health, and its anti-inflammatory, anti-oxidant, and anti-apoptotic properties. The review organizes the existing knowledge on the role of UA in health and diseases, emphasizing neurodegenerative diseases, especially PD. We gathered data on the potential neuroprotective effect in in vivo and in vitro models. We discussed the possible mechanisms of action of the compound and related health benefits to give a broader perspective of potential applications of UA in neuroprotective strategies. Moreover, we projected the future directions of applying UA in PD management. Full article

(This article belongs to the Special Issue Natural Antioxidants and Their Sources in Food)

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Catabolic pathway of ellagitannins and ellagic acid to urolithins. 5-OH, 4-OH, 3-OH, 2-OH, and 1-OH refer to the number of hydroxyl groups for each urolithin group—penta-, tetra-, tri-, di- and monohydroxy urolithins, respectively. The blue font refers to new urolithins generated by a bacterial 3-dehydroxylase. The purple and red circles designate the final urolithins produced in UM-A and UM-B, respectively. Uro-AR can be found in both metabotypes. Adapted from [<a href="#B7-antioxidants-12-01479" class="html-bibr">7</a>]. Full article ">Figure 2
Urolithin A mechanisms of action. Ellagitannins and ellagic acid are polyphenols that occur naturally in dietary products like pomegranates, berries, and nuts. The compounds are substrates of colonic bacteria transformed into urolithins. However, it is estimated that only 40% of individuals could naturally convert the polyphenolic precursors to UA. Thus, UA administration is proposed as an answer for urolithin non-producers. In vivo and in vitro experiments suggest the health-promoting activity of UA. The effects of the compound are related to different mechanisms of action, including engagement in mitochondrial function and the process of mitophagy, inflammation, oxidative stress, and the modulation of the apoptosis process. Created with BioRender.com. Full article ">Figure 3
Urolithin A’s activity in Parkinson’s disease model studies. UA’s beneficial activity may include potential favorable effects of UA on brain health. The current research explores the potential neuroprotective effects of the compound in PD models. The beneficial role of the compound can be related to the reduction in neuroinflammation, loss of dopaminergic neurons, a-synuclein aggregation, and apoptosis, as well as improved mitochondrial, motor, and cognitive function. Created with BioRender.com. Full article ">

17 pages, 3707 KiB

Open AccessArticle

Teneligliptin Co-Infusion Alleviates Morphine Tolerance by Inhibition of Spinal Microglial Cell Activation in Streptozotocin-Induced Diabetic Rats

by Yaswanth Kuthati, Vaikar Navakanth Rao, Wei-Hsiu Huang, Prabhakar Busa and Chih-Shung Wong

Antioxidants 2023, 12(7), 1478; https://doi.org/10.3390/antiox12071478 - 24 Jul 2023

Cited by 2 | Viewed by 1407

Abstract

Morphine (MOR) is a commonly prescribed drug for the treatment of moderate to severe diabetic neuropathic pain (DNP). However, long-term MOR treatment is limited by morphine analgesic tolerance (MAT). The activation of microglial cells and the release of glia-derived proinflammatory cytokines are known [...] Read more.

Morphine (MOR) is a commonly prescribed drug for the treatment of moderate to severe diabetic neuropathic pain (DNP). However, long-term MOR treatment is limited by morphine analgesic tolerance (MAT). The activation of microglial cells and the release of glia-derived proinflammatory cytokines are known to play an important role in the development of MAT. In this study, we aimed to investigate the effects of the dipeptidyl peptidase-4 inhibitor (DPP-4i) teneligliptin (TEN) on MOR-induced microglial cell activation and MAT in DNP rats. DNP was induced in four groups of male Wistar rats through a single intraperitoneal injection of streptozotocin (STZ) (50 mg/kg, freshly dissolved in 5 mmol/L citrate buffer, pH 4.5). Sham rats were administered with the vehicle. Seven days after STZ injection, all rats were implanted with an intrathecal (i.t) catheter connected to a mini-osmotic pump, divided into five groups, and infused with the following combinations: sham + saline (1 µL/h, i.t), DNP + saline (1 µL/h, i.t), DNP + MOR (15 µg/h, i.t), DNP + TEN (2 µg/h, i.t), and DNP + MOR (15 µg/h, i.t) + TEN (2 µg/h, i.t) for 7 days at a rate of 1 μL/h. The MAT was confirmed through the measurement of mechanical paw withdrawal threshold and tail-flick tests. The mRNA expression of neuroprotective proteins nuclear factor erythroid 2-related factor (Nrf2) and heme oxygenase-1 (HO-1) in the dorsal horn was evaluated by quantitative PCR (qPCR). Microglial cell activation and mononucleate cell infiltration in the spinal cord dorsal horn were assessed by immunofluorescence assay (IFA) and Western blotting (WB). The results showed that co-infusion of TEN with MOR significantly attenuated MAT in DNP rats through the restoration of neuroprotective proteins Nrf2 and HO-1 and suppression of microglial cell activation in the dorsal horn. Though TEN at a dose of 2 μg has mild antinociceptive effects, it is highly effective in limiting MAT. Full article

(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)

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11 pages, 1015 KiB

Open AccessReview

Complex II Biology in Aging, Health, and Disease

by Eric Goetzman, Zhenwei Gong, Bob Zhang and Radhika Muzumdar

Antioxidants 2023, 12(7), 1477; https://doi.org/10.3390/antiox12071477 - 24 Jul 2023

Cited by 9 | Viewed by 2449

Abstract

Aging is associated with a decline in mitochondrial function which may contribute to age-related diseases such as neurodegeneration, cancer, and cardiovascular diseases. Recently, mitochondrial Complex II has emerged as an important player in the aging process. Mitochondrial Complex II converts succinate to fumarate [...] Read more.

Aging is associated with a decline in mitochondrial function which may contribute to age-related diseases such as neurodegeneration, cancer, and cardiovascular diseases. Recently, mitochondrial Complex II has emerged as an important player in the aging process. Mitochondrial Complex II converts succinate to fumarate and plays an essential role in both the tricarboxylic acid (TCA) cycle and the electron transport chain (ETC). The dysfunction of Complex II not only limits mitochondrial energy production; it may also promote oxidative stress, contributing, over time, to cellular damage, aging, and disease. Intriguingly, succinate, the substrate for Complex II which accumulates during mitochondrial dysfunction, has been shown to have widespread effects as a signaling molecule. Here, we review recent advances related to understanding the function of Complex II, succinate signaling, and their combined roles in aging and aging-related diseases. Full article

(This article belongs to the Special Issue Mitochondrial Oxidative Stress in Aging and Disease)

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Graphical abstract

Graphical abstract
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Structure and functional role of mitochondrial Complex II. Complex II is composed of four nuclear-encoded subunits SDHA, SDHB, SDHC, and SDHD (labeled “A”, “B”, “C”, and “D” in the figure).Under normal physiological conditions, SDHA serves to oxidize succinate to fumarate, transporting electrons first to the FAD cofactor on SDHA (depicted in yellow rings), then to a series of three iron-sulfur clusters (Fe-S) embedded in SDHB, and ending with transfer to ubiquinone (Q) at the interface of SDHC/D and the inner mitochondrial membrane (IMM). Malonate and oxaloacetate are naturally occurring inhibitors that compete with succinate for binding to the active site. A series of fungicides are known Complex II inhibitors via the ubiquinone binding site. Other abbreviations: OMM, outer mitochondrial membrane; IMS, inter-membrane space; III, respiratory chain Complex III; IV, respiratory chain Complex IV; V, respiratory chain Complex V (ATP synthase); CytC, cytochrome C; TCA, tricarboxylic acid cycle. Figure created with <a href="http://BioRender.com" target="_blank">BioRender.com</a> (accessed on 9 June 2023). Full article ">Figure 2
Complex II produces ROS under three contexts. (1) When succinate is at normal physiological concentrations, the binding site is often left unoccupied while the FAD cofactor is in the reduced state (electrons indicated as pink circles). This allows oxygenated solvent access to steal electrons from the FAD cofactor. (2) Inborn errors of Complex II genes, Complex II assembly factors, or acquired mutations in cancer can disrupt the functional integrity of the complex, promoting electron leak from either the FAD or from the iron-sulfur (Fe-S) clusters. (3) Reverse electron transport can be a robust source of ROS under conditions of high succinate concentrations. Here, succinate saturates the SDHA biding site, preventing oxygen from stealing electrons, but the ubiquinone system cannot keep up and becomes highly reduced (QH2), leading to electrons flowing upstream to Complex I, where they react with oxygen to form ROS. Other abbreviations: IMM, inner mitochondrial membrane; III, respiratory chain Complex III; A,B,C,D, succinate dehydrogenase subunits SDHA, SDHB, SDHC, and SDHD. Figure created with <a href="http://BioRender.com" target="_blank">BioRender.com</a> (accessed on 9 June 2023). Full article ">

19 pages, 5469 KiB

Open AccessArticle

Effects of Tannic Acid Supplementation on the Intestinal Health, Immunity, and Antioxidant Function of Broilers Challenged with Necrotic Enteritis

by Huiping Xu, Xiaodan Zhang, Peng Li, Yimeng Luo, Jianyang Fu, Lu Gong, Zengpeng Lv and Yuming Guo

Antioxidants 2023, 12(7), 1476; https://doi.org/10.3390/antiox12071476 - 24 Jul 2023

Cited by 5 | Viewed by 2200

Abstract

Clostridium perfringens causes necrotic enteritis (NE) after proliferation in the intestine of poultry, resulting in considerable losses to the poultry industry. This study aimed to investigate the impact of tannic acid on the antioxidant, immunity, and gut health of broilers with NE. In [...] Read more.

Clostridium perfringens causes necrotic enteritis (NE) after proliferation in the intestine of poultry, resulting in considerable losses to the poultry industry. This study aimed to investigate the impact of tannic acid on the antioxidant, immunity, and gut health of broilers with NE. In the experiment, 630 one-day-old Cobb500 male chicks were randomly divided into six treatment groups, with seven replicate cages and with fifteen birds in each cage. The treatment groups were as follows: control group (NC), challenged group (PC), and challenged NE chickens treated with 250, 500, 750, and 1000 mg/kg tannic acid (PTA1, PTA2, PTA3, and PTA4, respectively). To induce NE, coccidia vaccine and Clostridium perfringens were administered on day 19 and days 22–28, respectively. Indexes related to antioxidant, immune, and intestinal health were measured on days 28 and 35. During the infection period, we observed significant increases in fecal water content, D-LA, TNF-α, and malondialdehyde concentrations (p < 0.05). Conversely, significant decreases were noted in chyme pH and in T-AOC, IL-4, and IL-10 concentrations (p < 0.05). The addition of tannic acid exhibited a linear decrease in fecal water content and TNF-α concentration (p < 0.05). Furthermore, tannic acid supplementation resulted in a quadratic curve decrease in D-LA concentration and linear increases in T-AOC, IL-4, and IL-10 (p < 0.05). Cecal microbiological analysis revealed that Ruminococcaceae and Butyricimona were dominant in PTA3. In conclusion, the dietary addition of tannic acid may reduce the negative effects of NE by increasing antioxidant and anti-inflammatory capacity, improving the intestinal barrier, and regulating the intestinal flora. Full article

(This article belongs to the Special Issue Natural Antioxidants in Animal Immunity—2nd Edition)

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19 pages, 3297 KiB

Open AccessArticle

Ultrasound-Assisted Deep Eutectic Solvent Extraction of Phenolic Compounds from Thinned Young Kiwifruits and Their Beneficial Effects

by Ding-Tao Wu, Wen Deng, Jie Li, Jin-Lei Geng, Yi-Chen Hu, Liang Zou, Yi Liu, Hong-Yan Liu and Ren-You Gan

Antioxidants 2023, 12(7), 1475; https://doi.org/10.3390/antiox12071475 - 23 Jul 2023

Cited by 5 | Viewed by 1627

Abstract

Fruit thinning is a common practice employed to enhance the quality and yield of kiwifruits during the growing period, and about 30–50% of unripe kiwifruits will be thinned and discarded. In fact, these unripe kiwifruits are rich in nutrients and bioactive compounds. Nevertheless, [...] Read more.

Fruit thinning is a common practice employed to enhance the quality and yield of kiwifruits during the growing period, and about 30–50% of unripe kiwifruits will be thinned and discarded. In fact, these unripe kiwifruits are rich in nutrients and bioactive compounds. Nevertheless, the applications of thinned young kiwifruits and related bioactive compounds in the food and functional food industry are still limited. Therefore, to promote the potential applications of thinned young kiwifruits as value-added health products, the extraction, characterization, and evaluation of beneficial effects of phenolic compounds from thinned young fruits of red-fleshed Actinidia chinensis cv ‘HY’ were examined in the present study. A green and efficient ultrasound-assisted deep eutectic solvent extraction (UADE) method for extracting phenolic compounds from thinned young kiwifruits was established. A maximum yield (105.37 ± 1.2 mg GAE/g DW) of total phenolics extracted from thinned young kiwifruits by UADE was obtained, which was significantly higher than those of conventional organic solvent extraction (CSE, about 14.51 ± 0.26 mg GAE/g DW) and ultrasound-assisted ethanol extraction (UAEE, about 43.85 ± 1.17 mg GAE/g DW). In addition, 29 compounds, e.g., gallic acid, chlorogenic acid, neochlorogenic acid, catechin, epicatechin, procyanidin B1, procyanidin B2, quercetin-3-rhamnoside, and quercetin-3-O-glucoside, were identified in the kiwifruit extract by UPLC-MS/MS. Furthermore, the contents of major phenolic compounds in different kiwifruit extracts prepared by conventional organic solvent extraction (EE), ultrasound-assisted ethanol extraction (UEE), and ultrasound-assisted deep eutectic solvent extraction (UDE) were compared by HPLC analysis. Results revealed that the content of major phenolics in UDE (about 15.067 mg/g DW) was significantly higher than that in EE (about 2.218 mg/g DW) and UEE (about 6.122 mg/g DW), suggesting that the UADE method was more efficient for extracting polyphenolics from thinned young kiwifruits. In addition, compared with EE and UEE, UDE exhibited much higher antioxidant and anti-inflammatory effects as well as inhibitory effects against α-glucosidase and pancreatic lipase, which were closely associated with its higher content of phenolic compounds. Collectively, the findings suggest that the UADE method can be applied as an efficient technique for the preparation of bioactive polyphenolics from thinned young kiwifruits, and the thinned young fruits of red-fleshed A. chinensis cv ‘HY’ have good potential to be developed and utilized as functional foods and nutraceuticals. Full article

(This article belongs to the Special Issue Antioxidant Capacity of Phenolic Compounds in Foods, Plants and Related By-Products)

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Effects of water content in DES solution (A), ultrasonic power (B), ultrasonic time (C), and liquid–solid ratio (D) on the yield of total phenolics extracted from of thinned young kiwifruits by ultrasound-assisted deep eutectic solvent extraction. TPC indicates total phenolic content; different letters (a–e) indicate significant differences at p < 0.05 determined by ANOVA. Full article ">Figure 2
Three-dimensional response surface plots (A,C,E) and 2D contour plots (B,D,F) of ultrasound-assisted deep eutectic solvent extraction. (A–F) indicate interactions among ultrasonic time, water content in DES, and liquid–solid ratio, respectively. Full article ">Figure 3
UPLC-MS/MS extracted ions chromatogram (A) and HPLC chromatograms of mixed standards (B–D) and the thinned young kiwifruit extract (E–G). Compounds 1–29 are the same as in <a href="#antioxidants-12-01475-t003" class="html-table">Table 3</a>. Full article ">Figure 4
Antioxidant capacities and inhibitory effects on digestive enzymes of the thinned young kiwifruit extracts: (A), the ferric-reducing antioxidant power; (B), the ABTS radical scavenging ability; (C), the DPPH radical scavenging ability; (D), the hydroxyl radical scavenging ability; (E), the inhibitory effect against pancreatic lipase; (F), the inhibitory effect against α-glucosidase. UDE, the thinned kiwifruit extract prepared by ultrasound-assisted deep eutectic solvent extraction; UEE, the thinned kiwifruit extract prepared by ultrasound-assisted ethanol extraction; EE, the thinned kiwifruit extract prepared by conventional organic solvent extraction; different letters (a–c) indicate statistically significant differences (p < 0.05). Full article ">Figure 5
Pearson correlation matrix of phenolics, antioxidant capacities, inhibitory effects on digestive enzymes, and anti-inflammatory effects. The correlation coefficients are proportional to the circular size and color intensity; * Stands for significant correlation at p < 0.05. Full article ">Figure 6
In vitro anti-inflammatory effects of the thinned young kiwifruit extracts: (A), the effect of different thinned young kiwifruit extracts on the cell viability of RAW 264.7 cells; (B), the effect of different thinned young kiwifruit extracts on the NO production from LPS-stimulated RAW 264.7 cells. UDE, the thinned kiwifruit extract prepared by ultrasound-assisted deep eutectic solvent extraction; UEE, the thinned kiwifruit extract prepared by ultrasound-assisted ethanol extraction; EE, the thinned kiwifruit extract prepared by conventional organic solvent extraction; different letters (a, b) indicate statistically significant differences (p < 0.05) among different kiwifruit extracts; significant differences in cell viability and NO production in LPS and kiwifruit extracts vs. control are shown by ** p < 0.01. Full article ">

19 pages, 3700 KiB

Open AccessArticle

Natural Extracts Mitigate the Deleterious Effects of Prolonged Intense Physical Exercise on the Cardiovascular and Muscular Systems

by Marc Yehya, Doria Boulghobra, Pierre-Edouard Grillet, Pablo R. Fleitas-Paniagua, Patrice Bideaux, Sandrine Gayrard, Pierre Sicard, Jérome Thireau, Cyril Reboul and Olivier Cazorla

Antioxidants 2023, 12(7), 1474; https://doi.org/10.3390/antiox12071474 - 22 Jul 2023

Cited by 3 | Viewed by 1510

Abstract

Muscle fatigue is a common symptom induced by exercise. A reversible loss of muscle force is observed with variable rates of recovery depending on the causes or underlying mechanisms. It can not only affect locomotion muscles, but can also affect the heart, in [...] Read more.

Muscle fatigue is a common symptom induced by exercise. A reversible loss of muscle force is observed with variable rates of recovery depending on the causes or underlying mechanisms. It can not only affect locomotion muscles, but can also affect the heart, in particular after intense prolonged exercise such as marathons and ultra-triathlons. The goal of our study was to explore the effect of four different natural extracts with recognized antioxidant properties on the contractile function of skeletal (locomotion) and cardiac muscles after a prolonged exhausting exercise. Male Wistar rats performed a bout of exhausting exercise on a treadmill for about 2.5 h and were compared to sedentary animals. Some rats received oral treatment of a natural extract (rosemary, buckwheat, Powergrape^®, or rapeseed) or the placebo 24 h and 1 h before exercise. Experiments were performed 30 min after the race and after 7 days of recovery. All natural extracts had protective effects both in cardiac and skeletal muscles. The extent of protection was different depending on muscle type and the duration post-exercise (just after and after one-week recovery), including antiarrhythmic effect and anti-diastolic dysfunction for the heart, and faster recovery of contractility for the skeletal muscles. Moreover, the muscular protective effect varied between natural extracts. Our study shows that an acute antioxidant supplementation can protect against acute abnormal endogenous ROS toxicity, induced here by prolonged exhausting exercise. Full article

(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)

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Effects of the 4 different natural extracts on the isometric strength of soleus after exhausting exercise and one week of recovery. (A) Soleus muscles were isolated from Sedentary (Base), 30 min post-exercise (Exer), and after one-week recovery (Recov). (B) Force–frequency relationships of soleus muscles measured in vitro from Sedentary (black square), 30 min post-exercise (black circle), and after one week of recovery (open circle, dash line) placebo groups. Results are expressed as mean ± SEM, (n = 10–13 animals/group). * p < 0.05 Placebo post-exercise vs. Basal. (C,D) reveal the different contractile characteristics measured in vitro of the Soleus muscles in groups of animals fed with the 4 different natural extracts (rosemary, buckwheat, Powergrape, and rapeseed), either immediately post-exercise or one week later. (C) represents the force induced by a single twitch, and (D) represents the tetanic contraction or peak specific force. Results are expressed as mean ± SEM, (n = 7–13 in each group). $ p < 0.05 vs. basal, * p < 0.05 recovery vs. post-exercise. Full article ">Figure 2
Effects of the 4 different natural extracts on the soleus fatigability after exercise and recovery. (A) Test of fatigue in vitro on soleus muscles in sedentary rats (control, black square), placebo post-exercise (black circle), and placebo one-week recovery (open circle) groups. (B) Effects of rosemary (blue square), buckwheat (red triangle), Powergrape® (green triangle), and rapeseed (pink diamond) on in vitro post-exercise muscle fatigue test in soleus compared with placebo (open circle) and controls (black square). (C–E) Effects of the natural extracts on the in vitro muscle fatigue test one week after exercise compared with the placebo (open circle) and controls (black square). (D) Muscle fatigue was also expressed relative to the level of force of the placebo group at each time point. (E) Time to 1/2 loss of maximum strength during fatigue test in the different groups after one week of recovery. (n = 7–13 animals per group). * p < 0.05 placebo vs. Control, rosemary, buckwheat, Powergrape®, and rapeseed groups. Full article ">Figure 3
Effect of natural extracts on aortic endothelium-dependent and endothelium-independent vasorelaxation after prolonged exhausting exercise. (A) Schematic representation of the experimental design. Dose–response curves (B) and maximal response (C) to acetylcholine (ACh) obtained in aortic rings pre-contracted with phenylephrine (PE, 10−6 M) (n = 13–15 aortic rings from 5–6 different rats per condition) for control (Ctrl, black square), placebo (open circle), Rosemary (blue circle), Buckwheat (red circle), grape (green circle), and rapeseed (pink circle). Each dot is one preparation. Dose–response curves (D) and maximal response (E) to sodium nitroprusside (SNO) obtained in aortic rings pre-contracted with phenylephrine (PE, 10−6 M) (n = 13–15 aortic rings from 5–6 different rats per condition). All values are the mean ± SEM. Full article ">Figure 4
Effects of natural extracts on in vivo cardiac function after exercise. (A) The cardiac function was evaluated in vivo by echocardiography at baseline (base, black square), 30 min after PEE (Exer, black circle), and 1 week after exercise (Recov, open circle) in placebo and extract-treated animals. (B) The function of contraction or systole was indexed by the ejection fraction. The phase of relaxation or diastole of the heart was indexed by the E/A ratios of early diastolic and atrial transmitral inflow velocities (C), as well as the E′/A′ ratios obtained by tissue Doppler imaging (D). (n = 10/group). * p < 0.05 repeated measures ANOVA. Full article ">Figure 5
Effects of natural extracts on ex vivo cardiac function after exhausting exercise. (A) Schematic representation of the experimental design. (B) Representative trace of the left ventricular (LV) pressure (upper panel) and its first derivative (lower panel) obtained from Langendorff hearts isolated from Ctrl and Placebo-exercised rats. (C) LV developed pressure obtained from hearts 30 min after exhausting exercise in rats treated or not treated with 4 different natural extracts (n = 7–13 hearts per condition). Maximal first derivative of LV pressure (dP/dtmax) (D) and minimal first derivative of LV pressure (dP/dtmin) (E) obtained from Langendorff isolated hearts 30 min after exhausting exercise in rats treated or not treated with 4 different natural extracts (n = 7–13 hearts per condition). * p < 0.05 vs. Ctrl ANOVA followed by adjusted t-test; All values are the mean ± SEM. Full article ">Figure 6
Effects of natural extracts on in vivo electrical cardiac function after exercise. (A) The ECG was recorded in vivo for the same rat at baseline (base, black square), 30 min after PEE (Exer, black circle), and 1 week after exercise (Recov, open circle) in placebo and extract-treated animals. (B) Heart rate (RR interval in ms) and (C) QT duration (in ms) were analyzed. (D) Example of ECG recording of a rat with ventricular extrasystole. (E) Number of ventricular extrasystoles (number/30 min) in extract-treated animals. (n = 8/group). * p < 0.05 repeated measures ANOVA. Full article ">

16 pages, 4730 KiB

Open AccessArticle

Synthesis, Characterization and Evaluation of a Novel Tetraphenolic Compound as a Potential Antioxidant

by Mengqi Xu, Pengcheng Meng, Hongyan Wang, Jun Liu, Tao Guo, Zhenjie Zhu and Yanlan Bi

Antioxidants 2023, 12(7), 1473; https://doi.org/10.3390/antiox12071473 - 22 Jul 2023

Cited by 3 | Viewed by 1773

Abstract

A novel antioxidant containing four hydroxyl groups, namely 2,2′-(2-methylpropane-1,3-diyl)bis(hydroquinone) (MPBHQ), was synthesized using hydroquinone and methylallyl alcohol as the raw materials, phosphoric acid as the catalyst, and toluene as the solvent system. The structure of MPBHQ was characterized by mass spectrometry, nuclear magnetic [...] Read more.

A novel antioxidant containing four hydroxyl groups, namely 2,2′-(2-methylpropane-1,3-diyl)bis(hydroquinone) (MPBHQ), was synthesized using hydroquinone and methylallyl alcohol as the raw materials, phosphoric acid as the catalyst, and toluene as the solvent system. The structure of MPBHQ was characterized by mass spectrometry, nuclear magnetic resonance, ultraviolet spectroscopy, and infrared spectroscopy. The results showed that MPBHQ has a good radical scavenging effect, as measured by the ORAC assay, DPPH radical scavenging assay, ABST radical scavenging assay, and Rancimat test. In fatty acid methyl ester and lard without exogenous antioxidants, MPBHQ showed better antioxidant performance than butylated hydroxytoluene (BHT), hydroquinone (HQ), tert-butyl hydroquinone (TBHQ), and propyl gallate (PG), meeting the need for a new antioxidant with better properties to ensure the oxidative stability of lipids and biodiesel. Full article

(This article belongs to the Special Issue Antioxidants and Oxidative Stability in Fats and Oils)

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Graphical abstract
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(a) Possible products in the synthesis reaction. (b) Ultraviolet spectrogram of MPBHQ solution and the mixture of MPBHQ and KOH. (c) The FTIR spectra of MPBHQ, HQ and TBHQ. Full article ">Figure 2
The primary (a) and secondary (b) ion mass spectra of MPBHQ. Full article ">Figure 3
NMR spectra of MPBHQ, including 1H NMR (a), 13C NMR (b), 1H-1H COSY-NMR (c), 13C-1H HSQC-NMR (d), and 13C-1H HMBC-NMR (e). Full article ">Figure 3 Cont.
NMR spectra of MPBHQ, including 1H NMR (a), 13C NMR (b), 1H-1H COSY-NMR (c), 13C-1H HSQC-NMR (d), and 13C-1H HMBC-NMR (e). Full article ">Figure 4
(a) DPPH radical scavenging activity of different antioxidants. (b) ABTS radical scavenging activity of different antioxidants. (c) The attenuation curve of fluorescence intensity of Trolox solution. (d) ORAC values of different antioxidants. The different lowercase letters in the graph, including a, b, c, d, e, and f, indicate the significant difference of EC50 values of the same substance at different concentrations (p < 0.05). Full article ">Figure 5
(a) Changes in Pf values of lard containing 0.02 wt.% of antioxidants at different temperatures. (b) Changes in Pf values of lard containing different antioxidants concentrations at 120 °C. (c) Changes in Pf values of fatty acid methyl ester containing 0.02 wt.% of antioxidants at different temperatures. (d) Changes in Pf values of fatty acid methyl ester containing different antioxidants concentrations at 120 °C. The chemical structure of the five antioxidants is shown below. The different lowercase letters in the graph, including a, b, c, d, e, and f, indicate the significant difference of Pf values of the different substances at same condition (p < 0.05). Full article ">Scheme 1
Flowchart on the synthesis and harvest process of MPBHQ crude products. Full article ">

25 pages, 367 KiB

Open AccessReview

Olive Oil Phenolic Compounds’ Activity against Age-Associated Cognitive Decline: Clinical and Experimental Evidence

by Anna Boronat, Gabriele Serreli, Jose Rodríguez-Morató, Monica Deiana and Rafael de la Torre

Antioxidants 2023, 12(7), 1472; https://doi.org/10.3390/antiox12071472 - 22 Jul 2023

Cited by 2 | Viewed by 2374

Abstract

Epidemiological studies have shown that consuming olive oil rich in phenolic bioactive compounds is associated with a lower risk of neurodegenerative diseases and better cognitive performance in aged populations. Since oxidative stress is a common hallmark of age-related cognitive decline, incorporating exogenous antioxidants [...] Read more.

Epidemiological studies have shown that consuming olive oil rich in phenolic bioactive compounds is associated with a lower risk of neurodegenerative diseases and better cognitive performance in aged populations. Since oxidative stress is a common hallmark of age-related cognitive decline, incorporating exogenous antioxidants could have beneficial effects on brain aging. In this review, we firstly summarize and critically discuss the current preclinical evidence and the potential neuroprotective mechanisms. Existing studies indicate that olive oil phenolic compounds can modulate and counteract oxidative stress and neuroinflammation, two relevant pathways linked to the onset and progression of neurodegenerative processes. Secondly, we summarize the current clinical evidence. In contrast to preclinical studies, there is no direct evidence in humans of the bioactivity of olive oil phenolic compounds. Instead, we have summarized current findings regarding nutritional interventions supplemented with olive oil on cognition. A growing body of research indicates that high consumption of olive oil phenolic compounds is associated with better preservation of cognitive performance, conferring an additional benefit, independent of the dietary pattern. In conclusion, the consumption of olive oil rich in phenolic bioactive compounds has potential neuroprotective effects. Further research is needed to understand the underlying mechanisms and potential clinical applications. Full article

(This article belongs to the Special Issue Olive Antioxidants: Extraction, Biological Activity and Practical Applications—2nd Edition)

15 pages, 2348 KiB

Open AccessArticle

1,3-Butanediol Administration Increases β-Hydroxybutyrate Plasma Levels and Affects Redox Homeostasis, Endoplasmic Reticulum Stress, and Adipokine Production in Rat Gonadal Adipose Tissue

by Giuliana Panico, Gianluca Fasciolo, Vincenzo Migliaccio, Rita De Matteis, Lillà Lionetti, Gaetana Napolitano, Claudio Agnisola, Paola Venditti and Assunta Lombardi

Antioxidants 2023, 12(7), 1471; https://doi.org/10.3390/antiox12071471 - 22 Jul 2023

Cited by 1 | Viewed by 1837

Abstract

Ketone bodies (KBs) are an alternative energy source under starvation and play multiple roles as signaling molecules regulating energy and metabolic homeostasis. The mechanism by which KBs influence visceral white adipose tissue physiology is only partially known, and our study aimed to shed [...] Read more.

Ketone bodies (KBs) are an alternative energy source under starvation and play multiple roles as signaling molecules regulating energy and metabolic homeostasis. The mechanism by which KBs influence visceral white adipose tissue physiology is only partially known, and our study aimed to shed light on the effects they exert on such tissue. To this aim, we administered 1,3-butanediol (BD) to rats since it rapidly enhances β-hydroxybutyrate serum levels, and we evaluated the effect it induces within 3 h or after 14 days of treatment. After 14 days of treatment, rats showed a decrease in body weight gain, energy intake, gonadal-WAT (gWAT) weight, and adipocyte size compared to the control. BD exerted a pronounced antioxidant effect and directed redox homeostasis toward reductive stress, already evident within 3 h after its administration. BD lowered tissue ROS levels and oxidative damage to lipids and proteins and enhanced tissue soluble and enzymatic antioxidant capacity as well as nuclear erythroid factor-2 protein levels. BD also reduced specific mitochondrial maximal oxidative capacity and induced endoplasmic reticulum stress as well as interrelated processes, leading to changes in the level of adipokines/cytokines involved in inflammation, macrophage infiltration into gWAT, adipocyte differentiation, and lipolysis. Full article

(This article belongs to the Special Issue The 10th Anniversary of Antioxidants: Past, Present and Future)

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Graphical abstract

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Effect of BD treatment on (D) β-OHB serum levels, detected after 3 h from BD i.p administration (BD 3 h) and after 14 days of oral administration (BD 14 d). Values represent the mean ± SE of 10 different animals. * p < 0.0001. Full article ">Figure 2
Effect of 14 days BD administration on gWAT morphology and lipolysis. (A) shows a representative histological analysis of gWAT from control (C) and BD-treated rats (BD 14 d). Below is the enlargement (100×) of the framed areas. Note the presence of capillaries (arrow) and infiltrating (inflammatory) cells/macrophages (arrowhead) around the adipocytes in BD 14 d-compared to C-gWAT. Hematoxylin and Eosin staining. (B) represents Basal and isoprotenerol-stimulated lipolysis. Values represent the mean ± ES of 8 different animals * p < 0.05, ** p < 0.01. Full article ">Figure 3
Effect of BD on gWAT redox homeostasis. Total ROS (A), lipid hydroperoxides (B), protein oxidative damage (C), and tissue soluble antioxidant capacity (D). Values are means ± SEM of 8 different rats. * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001. Enzymatic antioxidant capacity (E). Representative Western Blot of Superoxide dismutase-2 (SOD-2), catalase (CAT), peroxiredoxin-3 (PRDX-3), and Nuclear factor erythroid-related factor 2 (Nrf2) (E). GAPDH was used as loading control (25 μg of protein/rat/lane). Histograms represent the quantification of data. Data were normalized to the value obtained for control animals, set as 100. Values represent the mean ± SEM of 6 different rats or 3 rats in the case of PRDX-3. Full article ">Figure 4
Effect of BD on gWAT levels of proteins linked to ER and cellular stress involved in ER stress and UPRER response detected. Representative Western blots of GRP78/BiP, Calnexin and TnF-α (A), and total and phosphorylated (ser 78) levels of eIF2α (B) were performed in gWAT lysate. GAPDH was used as loading control (25 μg of protein/rat/lane). Histograms represent the quantification of data. Data were normalized to the value obtained for control animals, set as 100. Values represent the mean ± SEM of 6 different rats. * p < 0.05, ** p < 0.01, *** p < 0.0001. Full article ">Figure 5
Effect of BD on gWAT mitochondrial respiratory complexes abundance and cytochrome oxidase activity. (A) shows representative Western Blots of specific subunits of the five mitochondrial respiratory complexes, namely CI-NDUF88, CII-SDHB, CIII-UQCRC2, CIV-MTCO1, and CV-ATP VA. GAPDH was used as loading control (25 μg of protein/rat/lane). Histograms represent the quantification of data. Data were normalized to the value obtained for control animals, set as 100. Values represent the mean ± SEM of 6 different rats. (B,C) show Cytochrome oxidase/complex IV activity reported as nmoles O/min mg tissue proteins (B) or normalized for Complex IV levels and expressed in arbitrary units (C). * p < 0.05, ** p < 0.01, *** p < 0,001, **** p < 0.0001. Values represent the mean ± SEM of 8 different rats. Full article ">Figure 6
Effect of administration of BD for 14 days on gWAT adipokines profiles. Representative adipokine profile detected in gWAT from C and BD 14 d rats, by an adipokine protein array (A). The arrowheads indicate signals with significant changes. Magnifications of the spot of proteins whose intensity resulted statistically different are reported in (B). Histograms represent the quantification of relative levels of adipokines with observable changes (C). The values represent the mean ± SEM of 3 different samples, each one obtained by a pool of two different animals. Data were normalized to the value obtained for control animals, set as 100. * p < 0.05, ** p < 0.01. Full article ">

13 pages, 675 KiB

Open AccessArticle

Oxidative Stress and Performance after Training in Professional Soccer (European Football) Players

by Michele Abate, Raffaello Pellegrino, Angelo Di Iorio and Vincenzo Salini

Antioxidants 2023, 12(7), 1470; https://doi.org/10.3390/antiox12071470 - 22 Jul 2023

Viewed by 1219

Abstract

Vitamins, hormones, free radicals, and antioxidant substances significantly influence athletic performance. The aim of this study was to evaluate whether these biological mediators changed during the season and if this was associated with the rate of improvement in performance after training, assessed by [...] Read more.

Vitamins, hormones, free radicals, and antioxidant substances significantly influence athletic performance. The aim of this study was to evaluate whether these biological mediators changed during the season and if this was associated with the rate of improvement in performance after training, assessed by means of a standardized test. Professional male soccer players took part in the study. Two evaluations were performed: the first in the pre-season period and the second at the mid-point of the official season, after about 6 months of intensive training and weekly matches. Blood levels of vitamins D, B12, and folic acid, testosterone and cortisol, free radicals, and antioxidant substances were measured. Two hours after breakfast, a Yo-Yo test was performed. The relationships between the biological mediators and the rate of improvement after training (i.e., the increase in meters run in the Yo-Yo test between the pre-season and mid-season periods) were evaluated by means of a linear mixed models analysis. Results: Eighty-two paired tests were performed. The athletes showed better performance after training, with an increase in the meters run of about 20%. No significant relationships between the vitamin and hormone values and the gain in the performance test were observed. Plasmatic levels of free radicals increased significantly, as did the blood antioxidant potential. An indirect relationship between oxidative stress and the improvement in performance was observed (free radicals β ± SE: = −0.33 ± 0.10; p-value = 0.001), with lower levels of oxidative stress being associated with higher levels of performance in the Yo-Yo test. Monitoring the measures of oxidative stress could be a useful additional tool for coaches in training and/or recovery programs tailored to each player. Full article

(This article belongs to the Special Issue Exercise-Induced Antioxidant Response and Oxidative Stress)

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22 pages, 2309 KiB

Open AccessReview

Biosynthesis, Deficiency, and Supplementation of Coenzyme Q

by Carmine Staiano, Laura García-Corzo, David Mantle, Nadia Turton, Lauren E. Millichap, Gloria Brea-Calvo and Iain Hargreaves

Antioxidants 2023, 12(7), 1469; https://doi.org/10.3390/antiox12071469 - 21 Jul 2023

Cited by 2 | Viewed by 3807

Abstract

Originally identified as a key component of the mitochondrial respiratory chain, Coenzyme Q (CoQ or CoQ₁₀ for human tissues) has recently been revealed to be essential for many different redox processes, not only in the mitochondria, but elsewhere within other cellular membrane [...] Read more.

Originally identified as a key component of the mitochondrial respiratory chain, Coenzyme Q (CoQ or CoQ₁₀ for human tissues) has recently been revealed to be essential for many different redox processes, not only in the mitochondria, but elsewhere within other cellular membrane types. Cells rely on endogenous CoQ biosynthesis, and defects in this still-not-completely understood pathway result in primary CoQ deficiencies, a group of conditions biochemically characterised by decreased tissue CoQ levels, which in turn are linked to functional defects. Secondary CoQ deficiencies may result from a wide variety of cellular dysfunctions not directly linked to primary synthesis. In this article, we review the current knowledge on CoQ biosynthesis, the defects leading to diminished CoQ₁₀ levels in human tissues and their associated clinical manifestations. Full article

(This article belongs to the Special Issue The Ubiquitous and Multifaceted Coenzyme Q)

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Figure 1
CoQ biosynthesis pathway. A compendium of the reactions carried out to synthesize CoQ in bacteria (enzymes in green), yeast (enzymes in orange), plants (enzymes in pink), and mammals (enzymes in purple) is depicted including the name of the proteins involved. Proteins whose functions are still unknown are indicated separately. For simplicity, only some proteins involved in the 4HB biosynthesis in mammals have been indicated. For an extensive revision on 4HB biosynthesis, see Fernández-del-Río and Clarke, 2021 [<a href="#B21-antioxidants-12-01469" class="html-bibr">21</a>]. PAH, phenylalanine hydrolase; TAT, tyrosine aminotransferase; AADAT, mitochondrial alpha-aminoadipate aminotransferase; ALDH3A1, aldehyde dehydrogenase 3A1; HPDL, hydroxyphenylpyruvate dioxygenase-like [<a href="#B22-antioxidants-12-01469" class="html-bibr">22</a>]; simbols ? and ?? indicate enzyme/s still not identified. Full article ">Figure 2
Statin associated side effects. SAMS—Statin associated muscle symptoms; HFpEF—Heart failure with preserved ejection fraction; BBB—Blood–brain barrier. Full article ">Figure 3
CoQ10 transport across the blood–brain barrier under normal conditions. SR-B1: Scavenger receptor B1; LRP-1: Low Density Lipoprotein related protein-1; RAGE: Receptor Advanced Glycation End-products; P-gp: P-glycoprotein transporter. Although P-gp has been shown to mediate CoQ10 transport in other cell lines, it does not participate in its movement across the BBB [<a href="#B147-antioxidants-12-01469" class="html-bibr">147</a>]. Full article ">

17 pages, 2078 KiB

Open AccessArticle

Micromolar Dihydroartemisinin Concentrations Elicit Lipoperoxidation in Plasmodium falciparum-Infected Erythrocytes

by Oleksii Skorokhod, Elena Valente, Giorgia Mandili, Daniela Ulliers and Evelin Schwarzer

Antioxidants 2023, 12(7), 1468; https://doi.org/10.3390/antiox12071468 - 21 Jul 2023

Cited by 3 | Viewed by 1469

Abstract

Malaria is still the most important parasitic infectious disease. Numerous substances are known to have antimalarial activity; among them, artemisinin is the most widely used one, and artemisinin-based combination therapy (ACT) is recommended for the treatment of Plasmodium falciparum (P.f.) malaria. Antitumor, immunomodulatory, [...] Read more.

Malaria is still the most important parasitic infectious disease. Numerous substances are known to have antimalarial activity; among them, artemisinin is the most widely used one, and artemisinin-based combination therapy (ACT) is recommended for the treatment of Plasmodium falciparum (P.f.) malaria. Antitumor, immunomodulatory, and other therapeutic applications of artemisinin are under extensive study. Several different mechanisms of action were proposed for dihydroartemisinin (DHA), the active metabolite of artemisinin, such as eliciting oxidative stress in target cells. The goal of this study is to monitor the generation of reactive oxygen species (ROS) and lipid peroxidation product 4-hydroxynonenal (4-HNE) by DHA in P.f.-infected human erythrocytes. Checking ROS and 4-HNE-protein adducts kinetics along the maturation of the parasite, we detected the highest level of 4-HNE in ring forms of P.f. due to DHA treatment. Low micromolar concentrations of DHA quickly induced levels of 4-HNE-adducts which are supposed to be damaging. Mass spectrometry identified the P.f. protein cysteine proteinase falcipain-1 as being heavily modified by 4-HNE, and plausibly, 4-HNE conjugation with vital P.f. proteins might contribute to DHA-elicited parasite death. In conclusion, significant 4-HNE accumulation was detectable after DHA treatment, though, at concentrations well above pharmacologically effective ranges in malaria treatment, but at concentrations described for antitumor activity. Thus, lipid peroxidation with consequent 4-HNE conjugation of functionally relevant proteins might be considered as a uniform mechanism for how DHA potentiates antimalarials’ action in ACT and controls the progression of tumors. Full article

(This article belongs to the Section Aberrant Oxidation of Biomolecules)

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Graphical abstract
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Common DHA effects on ring-stage P.f.-infected RBC. (A) The chemical structure of DHA is shown with oxygen atoms in red, including the functional endoperoxide group (National Center for Biotechnology Information. PubChem Compound Summary for CID 540327, Dihydroartemisinin, <a href="https://pubchem.ncbi.nlm.nih.gov/compound/Dihydroartemisinin" target="_blank">https://pubchem.ncbi.nlm.nih.gov/compound/Dihydroartemisinin</a>, accessed on 30 May 2023). (B) Morphological damage and growth delay of P.f. parasites were assessed in synchronous in vitro cultures of asexual stages of parasites grown in erythrocytes and treated at the ring stage (time 0) with 0, 10, and 100 nM DHA for 6 and 24 h. Microscopic images taken after Diff-Quik®-stained smears show damaged and shrunken parasite forms after DHA treatment. Images were acquired using an inverted microscope Leica DM IRB (Leica Microsystems, Wetzlar, Germany) equipped with a 100× oil planar apochromatic objective with 1.32 numerical aperture and a Leica camera DFC 420 C. Leica DFC software (version 3.3.1) was applied. Full article ">Figure 2
Inhibition of parasite growth by DHA. Synchronized P. falciparum cultures were treated at the ring stage (12–16 h after reinfection, grey columns) and the trophozoite stage (26–30 h after reinfection, black columns) with 0–10,000 nM DHA. Parasite growth was assessed at 6 h after the start of DHA exposure by flow cytometry after cell staining with ethidium bromide (EtBr). Mean fluorescence intensities (MFIs) are shown as mean ± SE of 3–5 independent experiments performed with erythrocytes of different donors. The significance of differences vs. untreated control cultures (0 µM DHA) is indicated by * for p < 0.01 and ** for p < 0.05. Full article ">Figure 3
Damage of ring-stage P. falciparum and decrease in multiplication rate by DHA. (A) Synchronized P. falciparum cultures were treated at the ring stage (12–16 h after reinfection) with 0–1000 nM DHA (time 0; T = 0) and examined for parasitemia at 24 h after DHA supplementation (T = 24) by manual microscopic inspection of Diff-Quik®-stained smears. Parasites with irregular shapes (distorted, broken, pyknotic, and fragmented forms) were counted as damaged (black columns) separately from infected erythrocytes harboring normally shaped viable parasites (gray columns). (B) The multiplication rate was determined for P.f., which were treated at the ring stage with DHA and calculated as the ratio of parasitemias of viable parasites after and before reinfection of freshly added erythrocytes. The parasitemia before reinfection was adjusted by supplementation with fresh non-infected erythrocytes at a schizont parasitemia of 4.93 ± 0.6% in the case of not DHA-treated synchronous control cultures (DHA 0 nM). Parasite cultures pre-treated with 1–1000 nM DHA at the ring stage were identically supplemented with fresh erythrocytes prior to reinfection, even though alive schizont parasitemias were lower due to DHA treatment as compared to untreated control culture. Parasitemia after reinfection was counted 9 h after adding non-infected donor erythrocyte suspension. (C) The absence of DHA-elicited hemolysis is shown as a normalized hemolysis rate. Free hemoglobin was quantified in culture supernatant after 6 h of DHA treatment. Supernatant hemoglobin was referred to as total hemoglobin in the RBC suspension to obtain the hemolysis rate. These rates were normalized by referring any measured value to the hemolysis rate assessed in respective untreated cultures with erythrocytes from the same donor. Means ± SE are shown for independent cultures with RBCs from 3 different donors. The significances of differences between treated (0–1000 nM DHA) and untreated control cultures (0 nM DHA) are indicated by * for p < 0.05 for damaged parasites, § for p < 0.05 for total parasitemia (viable plus damaged parasites), and # for p < 0.05 for multiplication rate of parasites. Full article ">Figure 4
ROS production by DHA in infected erythrocytes. Synchronized P. falciparum cultures were adjusted to 10% parasitemia and treated with 0–10 µM DHA at the ring stage (12–16 h after reinfection). Where present, 100 µM NAC was added 30 min prior to DHA to the parasites culture. In parallel, an otherwise untreated culture was incubated with pro-oxidant xanthine/xanthine oxidase as a positive control for ROS production. Cells were stained with the ROS-sensitive fluorescent probes DCF-DA (A) and DHE (B) at 3 h after pre-incubation with DHA. The probe was separately assessed in non-infected (white columns) and infected (grey/black columns) erythrocytes distinguished by ethidium bromide using flow cytometry. The mean fluorescence intensity (MFI) of labeled cells was normalized by setting the MFI of corresponding non-infected, not-DHA-treated erythrocytes as 1. Means ± SE for 3–5 erythrocyte donors are plotted. The significance of the differences vs. untreated control cultures (0 µM DHA) is indicated by * for p < 0.01 and ** for p < 0.05. The significance of difference between 10 µM DHA-treated P.f. cultures pretreated with NAC or not is indicated by §. Full article ">Figure 5
Slow increase in 4-HNE conjugate formation in infected erythrocytes by DHA. Synchronized P.f. cultures were treated at the ring stage (12–16 h after reinfection, A,B) and the trophozoite stage (26–30 h after reinfection, C,D) with 0–1000 nM DHA for 3–24 h. 4-HNE-conjugate formation was assessed in intact infected (A,C) and non-infected erythrocytes from the same cultures (B,D) using flow cytometry at indicated time points after DHA addition at time 0 and expressed as MFI normalized to isotype control. Means ± SE are presented for independent cultures from 4 RBC donors (A,B) and 3 RBC donors (C,D). The significance of differences between DHA-treated and non-treated cultures (A–D) at the same time point is indicated by * for p < 0.05. The significance of differences between untreated cultures (concentration 0, white columns) at different time points and the starting point of observation (time 0) is indicated by § for p < 0.05. Full article ">

16 pages, 1885 KiB

Open AccessArticle

Evaluation of the Antioxidant and Anti-Lipoxygenase Activity of Berberis vulgaris L. Leaves, Fruits, and Stem and Their LC MS/MS Polyphenolic Profile

by Anna Och, Marta Olech, Kamil Bąk, Sebastian Kanak, Anna Cwener, Marek Cieśla and Renata Nowak

Antioxidants 2023, 12(7), 1467; https://doi.org/10.3390/antiox12071467 - 21 Jul 2023

Cited by 4 | Viewed by 1697

Abstract

Berberis vulgaris L. is currently widely studied for its antioxidant and chemopreventive properties, especially with regard to the beneficial properties of its fruits. Although the bark and roots have been well known and used in traditional medicine since ancient times, little is known [...] Read more.

Berberis vulgaris L. is currently widely studied for its antioxidant and chemopreventive properties, especially with regard to the beneficial properties of its fruits. Although the bark and roots have been well known and used in traditional medicine since ancient times, little is known about the other parts of this plant. The aim of the research was to determine the antioxidant and LOX inhibitory activity effects of extracts obtained from the leaves, fruits, and stems. Another aim of the work was to carry out the quantitative and qualitative analysis of phenolic acids, flavonoid aglycones, and flavonoid glycosides. The extracts were obtained with the use of ASE (accelerated solvent extraction). The total content of polyphenols was determined and was found to vary depending on the organ, with the highest amount of polyphenols found in the leaf extracts. The free radical scavenging activity of the extracts was determined spectrophotometrically in relation to the DPPH (2,2-diphenyl-1-picrylhydrazyl) radical, with results ranging from 63.9 mgTE/g for the leaves to 65.2 mgTE/g for the stem. Antioxidant activity was also assessed using the ABTS test. The lowest value was recorded for the barberry fruit (117.9 mg TE/g), and the highest level was found for the barberry leaves (140.5 mgTE/g). The oxygen radical absorbance capacity test (ORAC) showed the lowest value for the stem (167.7 mgTE/g) and the highest level for the leaves (267.8 mgTE/g). The range of the percentage inhibition of LOX was determined as well. The percentage inhibition of the enzyme was positively correlated with the sum of the flavonoids, TPC, TFC, and the content of selected flavonoids. Phenolic acids, flavonoid aglycones, and flavonoid glycosides were determined qualitatively and quantitatively in individual parts of Berberis vulgaris L. The content of phenolic acids, flavonoid aglycones, and flavonoid glycosides was determined with the LC-MS/MS method. The following phenolic acids were quantitatively and qualitatively identified in individual parts of Berberis vulgaris L.: gallic acid, 3-caffeoylquinic acid, protocatechuic acid, 5-caffeoylquinic acid, 4-caffeoylquinic acid, and caffeic acid. The flavonoid glycosides determined were: eleutheroside E, Eriodictyol-7-glucopyranoside, rutin, hyperoside, isoquercitin, luteoloside, narcissoside, naringenin-7-glucoside, isorhamnetin-3-glucoside, afzeline, and quercitrin. Flavonoid aglycones such as catechin, luteolin, quercetin, and eriodictyol were also determined qualitatively and quantitatively. Full article

(This article belongs to the Section Natural and Synthetic Antioxidants)

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21 pages, 1709 KiB

Open AccessReview

Aldehyde Dehydrogenase and Aldo-Keto Reductase Enzymes: Basic Concepts and Emerging Roles in Diabetic Retinopathy

by Burak Mugdat Karan, Karis Little, Josy Augustine, Alan W. Stitt and Tim M. Curtis

Antioxidants 2023, 12(7), 1466; https://doi.org/10.3390/antiox12071466 - 21 Jul 2023

Cited by 2 | Viewed by 2492

Abstract

Diabetic retinopathy (DR) is a complication of diabetes mellitus that can lead to vision loss and blindness. It is driven by various biochemical processes and molecular mechanisms, including lipid peroxidation and disrupted aldehyde metabolism, which contributes to retinal tissue damage and the progression [...] Read more.

Diabetic retinopathy (DR) is a complication of diabetes mellitus that can lead to vision loss and blindness. It is driven by various biochemical processes and molecular mechanisms, including lipid peroxidation and disrupted aldehyde metabolism, which contributes to retinal tissue damage and the progression of the disease. The elimination and processing of aldehydes in the retina rely on the crucial role played by aldehyde dehydrogenase (ALDH) and aldo-keto reductase (AKR) enzymes. This review article investigates the impact of oxidative stress, lipid-derived aldehydes, and advanced lipoxidation end products (ALEs) on the advancement of DR. It also provides an overview of the ALDH and AKR enzymes expressed in the retina, emphasizing their growing importance in DR. Understanding the relationship between aldehyde metabolism and DR could guide innovative therapeutic strategies to protect the retina and preserve vision in diabetic patients. This review, therefore, also explores various approaches, such as gene therapy and pharmacological compounds that have the potential to augment the expression and activity of ALDH and AKR enzymes, underscoring their potential as effective treatment options for DR. Full article

(This article belongs to the Special Issue Retinal Diseases Associated with Oxidative Stress: Advances in Pathophysiology and Therapeutic Approaches)

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Figure 1
Mechanisms of neurovascular unit dysfunction in DR. Under normal conditions, the neurovascular unit (NVU) comprises vascular endothelial cells, pericytes, glial cells, microglia, and neurons, which work together to maintain neurovascular coupling and the integrity of the inner blood-retinal barrier (iBRB). In diabetes, the NVU is disrupted through several mechanisms. Müller cells, crucial for supporting retinal neurons, undergo gliosis and exhibit a pro-inflammatory state. Additionally, they experience impaired regulation of glutamate and potassium levels in the extracellular space. These changes disrupt neurovascular coupling, compromise iBRB integrity, and lead to neuronal apoptosis. In parallel, microglia become pro-inflammatory and contribute to neurovascular degeneration. Increased oxidative stress and inflammation result in pericyte cell death and compromised tight junctions at the iBRB. The breakdown of iBRB leads to hemorrhage and leakage from blood vessels, facilitating the infiltration of pro-inflammatory cells from the circulation. Full article ">Figure 2
Pathways of Oxidative Stress in DR. Retinal hyperglycemia triggers multiple mechanisms that culminate in oxidative stress, as described from left to right in the figure. Dysregulated autophagy disrupts retinal antioxidant mechanisms, leading to an imbalance between the production of ROS and antioxidant activity. Hyperglycemia further enhances ROS production and affects various metabolic pathways in the retina, including the polyol pathway, hexosamine pathway, formation of advanced glycation end products (AGEs), and the protein kinase C (PKC) pathway. These pathways promote oxidative stress, and elevated levels of ROS, in turn, further activating these pathways, creating a detrimental cycle of oxidative stress in DR. Additionally, hyperglycemia contributes to mitochondrial dysfunction and endoplasmic reticulum (ER) stress, which perpetuate oxidative stress in the retina. The high levels of oxidative stress result in increased lipid peroxidation, inflammation, and apoptosis of retinal cells, which are characteristic features of DR. Full article ">

54 pages, 5917 KiB

Open AccessReview

Oxidative Stress: A Suitable Therapeutic Target for Optic Nerve Diseases?

by Francesco Buonfiglio, Elsa Wilma Böhm, Norbert Pfeiffer and Adrian Gericke

Antioxidants 2023, 12(7), 1465; https://doi.org/10.3390/antiox12071465 - 20 Jul 2023

Cited by 12 | Viewed by 2967

Abstract

Optic nerve disorders encompass a wide spectrum of conditions characterized by the loss of retinal ganglion cells (RGCs) and subsequent degeneration of the optic nerve. The etiology of these disorders can vary significantly, but emerging research highlights the crucial role of oxidative stress, [...] Read more.

Optic nerve disorders encompass a wide spectrum of conditions characterized by the loss of retinal ganglion cells (RGCs) and subsequent degeneration of the optic nerve. The etiology of these disorders can vary significantly, but emerging research highlights the crucial role of oxidative stress, an imbalance in the redox status characterized by an excess of reactive oxygen species (ROS), in driving cell death through apoptosis, autophagy, and inflammation. This review provides an overview of ROS-related processes underlying four extensively studied optic nerve diseases: glaucoma, Leber’s hereditary optic neuropathy (LHON), anterior ischemic optic neuropathy (AION), and optic neuritis (ON). Furthermore, we present preclinical findings on antioxidants, with the objective of evaluating the potential therapeutic benefits of targeting oxidative stress in the treatment of optic neuropathies. Full article

(This article belongs to the Special Issue Oxidative-Stress in Human Diseases—2nd Edition)

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Figure 1
Prevalence (per 100,000) in some of the most frequent optic neuropathies. LHON: Leber’s hereditary optic neuropathy; ON: optic neuritis; NA-AION: nonarteritic anterior ischemic optic neuropathy; A-AION: arteritic anterior ischemic optic neuropathy; GCA: giant cell arteritis. * We used a y-axis break in consideration of the remarkably higher prevalence of glaucoma compared to all other optic nerve disorders. ** LHON prevalence in case of incomplete penetrance is meaningfully higher than in complete penetrance due to the high frequency of the variant mutant carriers. Full article ">Figure 2
Anatomy and perfusion of the visual pathway. LGN: lateral geniculate nucleus. Full article ">Figure 3
Model representing the ROS impact on the retina and on the optic nerve. ROS: reactive oxidative species; NOX2: NADPH oxidase type 2; XO: xanthine oxidase; eNOS: endothelial nitric oxide synthase; RGC: retinal ganglion cell; RNFL: retinal nerve fiber layer; RPE: retinal pigment epithelium; BM: Brunch’s membrane. Up arrows mean increase or upregulation. Full article ">Figure 4
Anatomic overview of aqueous humor outflow, with focus on the drainage system through the trabecular meshwork and the Schlemm’s canal to the superficial veins. Full article ">Figure 5
Model of etiopathogenesis in glaucomatous optic neuropathies. AH: aqueous humor; TM: trabecular meshwork; TMC: trabecular meshwork cell; ONH: optic nerve head; OPA1: optic atrophy 1 gene; TNF-α: tumor necrosis factor alpha; NF-kB: nuclear factor “kappa-light-chain-enhancer” of activated B-cells; ATP: adenosintriphosphat; RGC: retinal ganglion cell; oxLDL: oxidized low density lipoprotein; AGE: advanced glycation end product; pJNK: c-Jun N-terminal kinase; pERK: extracellular-signal-regulated kinase. Full article ">Figure 6
Role of calcium and reactive oxygen species in the interplay between ER and mitochondria. ER: endoplasmic reticulum; PERK: protein kinase RNA-like ER kinase; ATF: activating transcription factor; IRE-1: inositol-requiring protein 1; CHOP: CCAAT-enhancer-binding protein homologous protein; eIF2α: eukaryotic initiation factor 2α; sXBP1: spliced X-box binding protein-1; TNFR-2: tumor necrosis factor alpha receptor 2; ASK-1: apoptosis signal-regulating kinase 1; JNK: c-Jun N-terminal kinase; ERAD: ER-associated degradation; NF-kB: nuclear factor “kappa-light-chain-enhancer” of activated B-cells. Up arrows mean increase or upregulation. Down arrows mean decrease. Full article ">Figure 7
Direct and indirect effect of idebenone on the mitochondrial oxidative metabolism. COQ10: cofactor Q 10; Cyt c: cytochrome c; GSH: glutathione; SOD: superoxide dismutase; GPX: glutathione peroxidase; NQO1: NAD(P)H quinone oxidoreductase 1; NOX2: nicotinamide adenine dinucleotide phosphate oxidase 2; Nrf2: nuclear factor erythroid-derived 2-related factor 2. Full article ">Figure 8
Model of LHON pathogenesis. NAD: nicotinamide dinucleotide; ETC: electron transport chain; ATP: adenosine triphosphate; cyt c: cytochrome c; Bid: BH3 interacting-domain death agonist; Apaf-1: apoptotic protease-activating factor 1; PTP: permeability transition pore. Full article ">

37 pages, 11146 KiB

Open AccessReview

Quinones as Neuroprotective Agents

by Ángel Cores, Noelia Carmona-Zafra, José Clerigué, Mercedes Villacampa and J. Carlos Menéndez

Antioxidants 2023, 12(7), 1464; https://doi.org/10.3390/antiox12071464 - 20 Jul 2023

Cited by 17 | Viewed by 4488

Abstract

Quinones can in principle be viewed as a double-edged sword in the treatment of neurodegenerative diseases, since they are often cytoprotective but can also be cytotoxic due to covalent and redox modification of biomolecules. Nevertheless, low doses of moderately electrophilic quinones are generally [...] Read more.

Quinones can in principle be viewed as a double-edged sword in the treatment of neurodegenerative diseases, since they are often cytoprotective but can also be cytotoxic due to covalent and redox modification of biomolecules. Nevertheless, low doses of moderately electrophilic quinones are generally cytoprotective, mainly due to their ability to activate the Keap1/Nrf2 pathway and thus induce the expression of detoxifying enzymes. Some natural quinones have relevant roles in important physiological processes. One of them is coenzyme Q₁₀, which takes part in the oxidative phosphorylation processes involved in cell energy production, as a proton and electron carrier in the mitochondrial respiratory chain, and shows neuroprotective effects relevant to Alzheimer’s and Parkinson’s diseases. Additional neuroprotective quinones that can be regarded as coenzyme Q₁₀ analogues are idobenone, mitoquinone and plastoquinone. Other endogenous quinones with neuroprotective activities include tocopherol-derived quinones, most notably vatiquinone, and vitamin K. A final group of non-endogenous quinones with neuroprotective activity is discussed, comprising embelin, APX-3330, cannabinoid-derived quinones, asterriquinones and other indolylquinones, pyrroloquinolinequinone and its analogues, geldanamycin and its analogues, rifampicin quinone, memoquin and a number of hybrid structures combining quinones with amino acids, cholinesterase inhibitors and non-steroidal anti-inflammatory drugs. Full article

(This article belongs to the Special Issue Oxidative Stress and Nrf2 in Neuroprotection)

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22 pages, 3242 KiB

Open AccessArticle

Protective Effects of Polyphenol-Rich Extracts against Neurotoxicity Elicited by Paraquat or Rotenone in Cellular Models of Parkinson’s Disease

by Mitali A. Tambe, Aurélie de Rus Jacquet, Katherine E. Strathearn, Jennifer A. Hensel, Bryce D. Colón, Aswathy Chandran, Gad G. Yousef, Mary H. Grace, Mario G. Ferruzzi, Qingli Wu, James E. Simon, Mary Ann Lila and Jean-Christophe Rochet

Antioxidants 2023, 12(7), 1463; https://doi.org/10.3390/antiox12071463 - 20 Jul 2023

Cited by 5 | Viewed by 1717

Abstract

Parkinson’s disease (PD) is a neurodegenerative disorder involving motor symptoms caused by a loss of dopaminergic neurons in the substantia nigra region of the brain. Epidemiological evidence suggests that anthocyanin (ANC) intake is associated with a low risk of PD. Previously, we reported [...] Read more.

Parkinson’s disease (PD) is a neurodegenerative disorder involving motor symptoms caused by a loss of dopaminergic neurons in the substantia nigra region of the brain. Epidemiological evidence suggests that anthocyanin (ANC) intake is associated with a low risk of PD. Previously, we reported that extracts enriched with ANC and proanthocyanidins (PAC) suppressed dopaminergic neuron death elicited by the PD-related toxin rotenone in a primary midbrain culture model. Here, we characterized botanical extracts enriched with a mixed profile of polyphenols, as well as a set of purified polyphenolic standards, in terms of their ability to mitigate dopaminergic cell death in midbrain cultures exposed to another PD-related toxicant, paraquat (PQ), and we examined underlying neuroprotective mechanisms. Extracts prepared from blueberries, black currants, grape seeds, grape skin, mulberries, and plums, as well as several ANC, were found to rescue dopaminergic neuron loss in PQ-treated cultures. Comparison of a subset of ANC-rich extracts for the ability to mitigate neurotoxicity elicited by PQ versus rotenone revealed that a hibiscus or plum extract was only neuroprotective in cultures exposed to rotenone or PQ, respectively. Several extracts or compounds with the ability to protect against PQ neurotoxicity increased the activity of the antioxidant transcription factor Nrf2 in cultured astrocytes, and PQ-induced dopaminergic cell death was attenuated in Nrf2-expressing midbrain cultures. In other studies, we found that extracts prepared from hibiscus, grape skin, or purple basil (but not plums) rescued defects in O₂ consumption in neuronal cells treated with rotenone. Collectively, these findings suggest that extracts enriched with certain combinations of ANC, PAC, stilbenes, and other polyphenols could potentially slow neurodegeneration in the brains of individuals exposed to PQ or rotenone by activating cellular antioxidant mechanisms and/or alleviating mitochondrial dysfunction. Full article

(This article belongs to the Special Issue Dietary Polyphenols and Neuroprotection II)

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22 pages, 6944 KiB

Open AccessArticle

High-Intensity Exercise Promotes Deleterious Cardiovascular Remodeling in a High-Cardiovascular-Risk Model: A Role for Oxidative Stress

by Aline Meza-Ramos, Anna Alcarraz, Marta Lazo-Rodriguez, Gemma Sangüesa, Elisenda Banon-Maneus, Jordi Rovira, Maria Jose Ramirez-Bajo, Marta Sitges, Lluís Mont, Pedro Ventura-Aguiar, Montserrat Batlle and Eduard Guasch

Antioxidants 2023, 12(7), 1462; https://doi.org/10.3390/antiox12071462 - 20 Jul 2023

Viewed by 1650

Abstract

Although the benefits of moderate exercise in patients at high cardiovascular risk are well established, the effects of strenuous exercise remain unknown. We aimed to study the impact of strenuous exercise in a very high cardiovascular risk model. Nephrectomized aged Zucker obese rats [...] Read more.

Although the benefits of moderate exercise in patients at high cardiovascular risk are well established, the effects of strenuous exercise remain unknown. We aimed to study the impact of strenuous exercise in a very high cardiovascular risk model. Nephrectomized aged Zucker obese rats were trained at a moderate (MOD) or high (INT) intensity or were kept sedentary (SED) for 10 weeks. Subsequently, echocardiography and ex vivo vascular reactivity assays were performed, and blood, aortas, perivascular adipose tissue (PVAT), and left ventricles (LVs) were harvested. An improved risk profile consisting of decreased body weight and improved response to a glucose tolerance test was noted in the trained groups. Vascular reactivity experiments in the descending thoracic aorta demonstrated increased endothelial NO release in the MOD group but not in the INT group, compared with SED; the free radical scavenger TEMPOL improved endothelial function in INT rats to a similar level as MOD. An imbalance in the expression of oxidative stress-related genes toward a pro-oxidant environment was observed in the PVAT of INT rats. In the heart, INT training promoted eccentric hypertrophy and a mild reduction in ejection fraction. Obesity was associated with LV fibrosis and a transition toward β-myosin heavy chain and the N2Ba titin isoform. Exercise reverted the myosin imbalance, but only MOD reduced the predominance of the N2Ba titin isoform. In conclusion, moderate exercise yields the most intense cardiovascular benefits in a high-cardiovascular-risk animal model, while intense training partially reverts them. Full article

(This article belongs to the Special Issue Exercise-Induced Antioxidant Response and Oxidative Stress)

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20 pages, 4195 KiB

Open AccessArticle

Pepper Fruit Extracts Show Anti-Proliferative Activity against Tumor Cells Altering Their NADPH-Generating Dehydrogenase and Catalase Profiles

by Marta Rodríguez-Ruiz, María C. Ramos, María J. Campos, Inmaculada Díaz-Sánchez, Bastien Cautain, Thomas A. Mackenzie, Francisca Vicente, Francisco J. Corpas and José M. Palma

Antioxidants 2023, 12(7), 1461; https://doi.org/10.3390/antiox12071461 - 20 Jul 2023

Cited by 2 | Viewed by 2585

Abstract

Cancer is considered one of the main causes of human death worldwide, being characterized by an alteration of the oxidative metabolism. Many natural compounds from plant origin with anti-tumor attributes have been described. Among them, capsaicin, which is the molecule responsible for the [...] Read more.

Cancer is considered one of the main causes of human death worldwide, being characterized by an alteration of the oxidative metabolism. Many natural compounds from plant origin with anti-tumor attributes have been described. Among them, capsaicin, which is the molecule responsible for the pungency in hot pepper fruits, has been reported to show antioxidant, anti-inflammatory, and analgesic activities, as well as anti-proliferative properties against cancer. Thus, in this work, the potential anti-proliferative activity of pepper (Capsicum annuum L.) fruits from diverse varieties with different capsaicin contents (California < Piquillo < Padrón < Alegría riojana) against several tumor cell lines (lung, melanoma, hepatoma, colon, breast, pancreas, and prostate) has been investigated. The results showed that the capsaicin content in pepper fruits did not correspond with their anti-proliferative activity against tumor cell lines. By contrast, the greatest activity was promoted by the pepper tissues which contained the lowest capsaicin amount. This indicates that other compounds different from capsaicin have this anti-tumor potentiality in pepper fruits. Based on this, green fruits from the Alegría riojana variety, which has negligible capsaicin levels, was used to study the effect on the oxidative and redox metabolism of tumor cell lines from liver (Hep-G2) and pancreas (MIA PaCa-2). Different parameters from both lines treated with crude pepper fruit extracts were determined including protein nitration and protein S-nitrosation (two post-translational modifications (PTMs) promoted by nitric oxide), the antioxidant capacity, as well as the activity of the antioxidant enzymes superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPX), among others. In addition, the activity of the NADPH-generating enzymes glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase (6PGDH), and NADP-isocitrate dehydrogenase (NADP-ICDH) was followed. Our data revealed that the treatment of both cell lines with pepper fruit extracts altered their antioxidant capacity, enhanced their catalase activity, and considerably reduced the activity of the NADPH-generating enzymes. As a consequence, less H₂O₂ and NADPH seem to be available to cells, thus avoiding cell proliferation and possibly triggering cell death in both cell lines. Full article

(This article belongs to the Special Issue Application of Antioxidants and Bioactive Compounds in Food from Agriculture to Health Benefits, 2nd Edition)

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Plant materials and pepper varieties used in this work, and their capsaicin content. (A) Different parts of a representative pepper fruit. (B) Phenotype of fruits from the four varieties at two ripening stages: immature green and ripe red. Whereas California-Melchor is a sweet pepper fruit type, Piquillo Padrón and Alegría riojana contain different capsaicin levels with the sequence Piquillo <<< Padrón < Alegría riojana. (C) Content of total capsaicin levels in placenta and pericarp from fruits of the four pepper varieties at two ripening stages. Placenta tissue was processed once seeds were discarded. Data are the means ± SEM of three replicates determined from five fruits of the four varieties and at the two ripening stages. Different letters after each value indicate that differences were statistically significant (one-way Anova and Tukey test, p < 0.05). FW, fresh weight. Figure designed from data provided in Palma et al. [<a href="#B51-antioxidants-12-01461" class="html-bibr">51</a>]. Full article ">Figure 2
Antiproliferative activity and capsaicin content of crude extracts from fruits of four pepper varieties against seven tumor cell lines. The antiproliferative activity is expressed as % of dead cells after the treatment, and capsaicin content as μg/g fresh weight (FW), determined in the samples of pepper fruits used in the assays. Plant materials assayed in this experiment and their corresponding codes include pericarp (PE) and placenta (PL) from green (g) and red (r) pepper fruits from the varieties California (C), Piquillo (Pi), Padrón (P), and Alegría riojana (AR). The cell lines used corresponded to tumors from lung (A549), melanoma (A2058), hepatoma (Hep-G2), colon (HT-29), breast (MCF-7), pancreas (MIA PaCa-2), and prostate (PC-3). The plot shown is representative of three independent experiments. Color code of each graph is provided in the legend on the right. Full article ">Figure 3
IC50 and level of the tumor marker ERK 1/2 from Hep-G2 and MIA PaCa-2 tumor cell lines after the incubation with crude pepper fruit extracts from the Alegría riojana variety. IC50 was defined as the amount of pepper fruit that reduced by 50% the cell viability. (A) IC50 in Hep-G2 cells. (B) IC50 in MIA PaCa-2 cells. The plots shown are representative of the three independent experiments performed. Each symbol at the assayed concentrations, either triangles, squares or circles, represents a replicate. Grey symbols denote outlier values once the regression curve is adjusted to all data. Square brackets in the two plots denote the IC50 for each cell line. Full article ">Figure 4
Level of the tumor marker ERK 1/2 from Hep-G2 and MIA PaCa-2 tumor cell lines after the incubation with crude pepper fruit extracts from the Alegría riojana variety. (A) Detection of the tumor marker ERK 1/2 (related protein-serine/threonine kinases 1 and 2) in Hep-G2 and MIA PaCa-2 cells that were untreated (C) and treated (T) with crude extracts from pepper fruits. Polypeptides were separated by SDS-PAGE in 4–20% precast polyacrylamide gels, and blotting assays were performed using a monoclonal antibody against ERK1/2 proteins (dilution 1:1000). Molecular weight markers are indicated on the left. (B) Densitograms of the ERK 1/2 bands detected after the blotting assay, where arbitrary units (in parentheses) were assigned to each tumor marker band by the use of the program ImageJ. The blotting image shown is representative of the three independent experiments performed. Full article ">Figure 5
Detection of tyrosine (NO2-Tyr, panel (A)) and tryptophan (NO2-Trp, panel (B)) nitrated polypeptides from Hep-G2 and MIA PaCa-2 tumor cell lines after the incubation with crude pepper fruit extracts from the Alegría riojana variety. Polypeptides were separated by SDS-PAGE in 4–20% precast polyacrylamide gels, and blotting assays were performed using a polyclonal antibody against nitro-tyrosine (NO2-Tyr, dilution 1:500), and a monoclonal antibody against nitro-tryptophan (NO2-Trp, dilution 1:1000). C, untreated cells. T, treated cells. PHY, Polypeptide from Hep-G2 cells with nitrated Tyr (Y). PMY, Polypeptide from MIA PaCa-2 cells with nitrated Tyr (Y). PHW, Polypeptide from Hep-G2 cells with nitrated Trp (W). PMT, Polypeptide from MIA PaCa-2 cells with nitrated Trp (W). Molecular weight markers (Mw) are indicated on both sides of the panel. The blotting shown is representative of three independent experiments. Full article ">Figure 6
Detection of S-nitrosated (SNO-Cys, panel (A)) and glutathionylated (panel (B)) polypeptides from Hep-G2 and MIA PaCa-2 tumor cell lines after the incubation with crude pepper fruit extracts from the Alegría riojana variety. Polypeptides were separated by SDS-PAGE in 4–20% precast polyacrylamide gels and blotting assays were performed using a polyclonal antibody against S-nitrosocysteine (SNO-Cys, dilution 1:500), and a polyclonal antibody against glutathione (anti-GSH, dilution 1:1000). C, untreated cells. T, treated cells. PHC, Polypeptide from Hep-G2 cells with nitrosated Cys (C). PMC, Polypeptide from MIA PaCa-2 cells with nitrated nitrosated Cys (C). PHG, Polypeptide from Hep-G2 cells Glutathionylated. PMG, Polypeptide from MIA PaCa-2 cells Glutathionylated. Molecular weight markers (Mw) are indicated on both sides of the panel. The blotting shown is representative of the three independent experiments. Full article ">Figure 7
Total antioxidant activity and catalase activity from Hep-G2 and MIA PaCa-2 tumor cell lines after the incubation with crude pepper fruit extracts from the Alegría riojana variety. (A) Total antioxidant activity expressed as ascorbate equivalents. (B) Catalase activity. Data are expressed as the means of at least nine measurements from three independent experiments ± SEM. Asterisks denote significant differences in comparisons of treated cells to untreated (control) ones at p < 0.05 (Student t-test). Full article ">Figure 8
Superoxide dismutase (SOD) isoenzymes from Hep-G2 and MIA PaCa-2 tumor cell lines after the incubation with crude pepper fruit extracts from the Alegría riojana variety. Proteins (20 μg, see <a href="#sec2dot4-antioxidants-12-01461" class="html-sec">Section 2.4</a>) were separated using non-denaturing PAGE in 10% polyacrylamide gels, and activity was detected in gels through the specific NBT staining method. C, untreated cells. T, cells treated with pepper fruit crude extracts. The zymogram shown is representative of the three experiments performed. Full article ">Figure 9
Activity of NADPH-generating enzymes from Hep-G2 and MIA PaCa-2 tumor cell lines after the incubation with crude pepper fruit extracts from the Alegría riojana variety. (A) Glucose-6-phosphate dehydrogenase (G6PDH). (B) 6-Phosphogluconate dehydrogenase (6PGDH). (C) NADP-dependent isocitrate dehydrogenase (NADP-ICDH). Data are expressed as the means of at least nine measurements from three independent experiments ± SEM. Asterisks denote significant differences in comparisons of treated cells to untreated (control) ones at a p < 0.05 (Student t-test). Full article ">Figure 10
Proposed model of the effect of crude extracts from pepper fruits on the antioxidant and redox metabolism of tumor cells. As a consequence of the treatment with pepper extracts, an increase of catalase activity and a decline of the NADPH-generation enzymes occurs, thus provoking lower H2O2 levels and limited NADPH availability. Under these circumstances, cell proliferation is arrested and cell death may be triggered. CAT, catalase. SOD, superoxide dismutase. GPX, glutathione peroxidase. GSH, reduced glutathione. GSSG, oxidized glutathione. GR, glutathione reductase. G6PDH, glucose-6-phosphate dehydrogenase. 6PGDH, 6-phosphogluconate dehydrogensase. ICDH, isocitrate dehydrogenase. G6P, glucose-6-phosphate. 6PG, 6-phosphogluconate. Ru5P, ribulose-5-phosphate. αKG, α-ketoglutarate. In blue ink are the enzymatic systems studied in this work. Full article ">

27 pages, 4088 KiB

Open AccessReview

Alzheimer’s Disease and Green Tea: Epigallocatechin-3-Gallate as a Modulator of Inflammation and Oxidative Stress

by Víctor Valverde-Salazar, Daniel Ruiz-Gabarre and Vega García-Escudero

Antioxidants 2023, 12(7), 1460; https://doi.org/10.3390/antiox12071460 - 20 Jul 2023

Cited by 11 | Viewed by 3745

Abstract

Alzheimer’s disease (AD) is the most common cause of dementia, characterised by a marked decline of both memory and cognition, along with pathophysiological hallmarks including amyloid beta peptide (Aβ) accumulation, tau protein hyperphosphorylation, neuronal loss and inflammation in the brain. Additionally, oxidative stress [...] Read more.

Alzheimer’s disease (AD) is the most common cause of dementia, characterised by a marked decline of both memory and cognition, along with pathophysiological hallmarks including amyloid beta peptide (Aβ) accumulation, tau protein hyperphosphorylation, neuronal loss and inflammation in the brain. Additionally, oxidative stress caused by an imbalance between free radicals and antioxidants is considered one of the main risk factors for AD, since it can result in protein, lipid and nucleic acid damage and exacerbate Aβ and tau pathology. To date, there is a lack of successful pharmacological approaches to cure or even ameliorate the terrible impact of this disease. Due to this, dietary compounds with antioxidative and anti-inflammatory properties acquire special relevance as potential therapeutic agents. In this context, green tea, and its main bioactive compound, epigallocatechin-3-gallate (EGCG), have been targeted as a plausible option for the modulation of AD. Specifically, EGCG acts as an antioxidant by regulating inflammatory processes involved in neurodegeneration such as ferroptosis and microglia-induced cytotoxicity and by inducing signalling pathways related to neuronal survival. Furthermore, it reduces tau hyperphosphorylation and aggregation and promotes the non-amyloidogenic route of APP processing, thus preventing the formation of Aβ and its subsequent accumulation. Taken together, these results suggest that EGCG may be a suitable candidate in the search for potential therapeutic compounds for neurodegenerative disorders involving inflammation and oxidative stress, including Alzheimer’s disease. Full article

(This article belongs to the Special Issue Oxidative Stress in Alzheimer's Disease)

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Amyloid β and tau pathology in Alzheimer’s disease. The main hallmarks of an AD brain are the accumulation of extracellular amyloid-β senile plates (1), the accumulation of intracellular neurofibrillary tangles of tau (2) and neuronal death (3). The areas in which these three features coexist are called neuritic plates (4). Amyloid precursor protein (APP) processing can take place through the amyloidogenic pathway (A), being cleaved by β-secretase (BACE), generating the sAPPβ and CTFβ fragments. The latter is subsequently processed by γ-secretase, generating Aβ42 and Aβ40, which induce amyloid β pathology in an AD brain (5) that ultimately affects neuronal homeostasis and induces cell death (6). On the contrary, in the non-amyloidogenic pathway (B), APP is cleaved by α- and γ-secretases, generating CTFα and sAPPα fragments that exert a neuroprotective function because a diminished APP conversion to Aβ and sAPPα inhibits BACE (7). On the other hand, tau is a microtubule-associated protein that establishes their structure. Post-translational modifications of tau, including phosphorylation, induce the detachment of tau and microtubule destabilization (8) and lead to tau aggregation (9). The accumulation of tau protein causes a failure of neuronal homeostasis whose final consequence is neuronal death (10). Full article ">Figure 2
Oxidative stress in Alzheimer’s disease. There is an increase in oxidative stress in an AD brain, which induces hyperphosphorylated tau (1) and amyloid-β (2) accumulation, mitochondrial dysfunction (3) and inflammation (4). At the same time, these processes also induce oxidative stress, generating a vicious cycle. Mitochondrial dysfunction is related to Aβ accumulation and, at the same time, Aβ is able to impair mitochondrial function (5). The accumulation of Aβ also induces tau hyperphosphorylation (6), which provokes mitochondrial dysfunction (7). Either Aβ (8) or tau (9) accumulation induce inflammation, which, in the same way, favours the accumulation of Aβ and tau. The accumulation of metals is one of the main causes of ROS increasement (10) in an AD brain and it also favours Aβ pathology (11) and inflammation processes (12). All these features together induce the loss of neuronal connections and the reduction in neurons shown in an AD brain (13). Ferroptosis is increased in an AD brain due to increased levels of iron, ferririn and transferrin and diminished ferroporter and GPX4 (14) that causes neuron necroptotic death and subsequent inflammation (15). EGCG is able to block oxidative stress (16) and, thanks to its chelating activity, it counteracts the accumulation of heavy metals (17) and ferroptosis (18), protecting the brain from all these harmful effects. Full article ">Figure 3
Antioxidant activity of EGCG. The antioxidant compound EGCG binds to antioxidant regulatory elements (ARE), inducing the expression of stress response genes (1) such as haem oxygenase (2) and glutathione-S-transferase (3) enzymes, counteracting oxidative stress processes (4). Additionally, EGCG enhances the activity of SOD and catalase (5), which reduce oxidative stress (4). Thanks to its hydroxyl groups, EGCG harbours chelating properties (6) that exert antioxidant activity, promoting neuroprotective effects (7). Also, EGCG can inhibit the production of ROS/RNS and 3-Hydroxykynurenine effect due to this antioxidant capacity (8), avoiding oxidative stress (9). Full article ">Figure 4
Effect of metal chelation mediated by EGCG in Alzheimer’s pathology. In an AD brain, iron accumulation promotes amyloidogenic processing (1), increasing Aβ40/Aβ42 levels (2), leading to the accumulation of Aβ (3). Moreover, brain iron accumulation produces an increase in tau hyperphosphorylation (4) that results in microtubule destabilization and the accumulation of tau protein (5). As a consequence, iron produces neurodegeneration (6). The metal chelator activity of EGCG (6) inhibits iron accumulation in the brain (7), therefore diminishing the accumulation of Aβ (8) and tau protein (9). Moreover, EGCG can directly potentiate the expression of p21 (10) and p27 (11), while diminishing the expression of cyclin D1 (12) and pRB (13), abolishing cell cycle re-entry (14). On the other hand, EGCG can promote the activation of HIF-1α (15), inducing the expression of cell survival genes (16). EGCG promotes the production of SAPPα (17) and the non-amyloidogenic processing of APP (18), generating neuroprotection effects (19). Full article ">Figure 5
Modulation of PKC-mediated pathways by EGCG in Alzheimer’s disease. EGCG can induce the activation of PKC pathways (1), specifically the isoform PKCζ (2) that enhances long-term memory (3), PKCα (4) that results in an increase in memory function (5) and PKCε (6) that activates BDNF factor (7), promoting synaptogenesis (8), neuronal survival (9), Ca2+ liberation (10) and changes of synaptic structures (11), altogether promoting neuroprotection (12). The generation of Aβ produces Aβ plaques (13), promoting neurodegeneration processes (14). Aβ also inhibits the PKC pathway (15) and RACK (16), whose receptors are required to activate PKC (17), and blocks BDNF (18). Moreover, the isoforms PKCα and PKCε activate α-secretase (19), promoting the generation of sAPPα (20) that inhibits Aβ production (21). PKCε activates ECE1 (22), which degrades Aβ (21). The activation of the PKC pathway inhibits GSK3β (23), which is involved in tau hyperphosphorylation (24) that finally leads to neurodegeneration processes (14). EGCG produces the reduction in protein Bax (25) and promotes the degradation of protein Bad (26) through the proteasomal system (27). Full article ">Figure 6
Modulation of MAPK pathway by EGCG in Alzheimer’s disease. Upon oxidative stress, EGCG induces antioxidant defences with the activation of the Keap1/Nrf2/ARE pathway (1) and increases ERK1/2 (2), promoting cell survival (3) and neuroprotective effects (4). Conversely, EGCG inhibits the ERK (5), p38 (6) and JNK (7) pathways whose effects contribute to mitochondrial disfunction and altered dynamics (8), induce tau protein hyperphosphorylation and aggregation (9) and increase apoptosis (10) and inflammation (11), leading to cell death (12). Therefore, EGCG can avoid this cell death (13). Full article ">Figure 7
Modulation of PI3K/Akt pathway mediated by EGCG. Akt/protein kinase B (PKB) is activated by Phosphatidyl Inositol 3 Kinase (PI3K) (1), which catalyses the conversion of phosphatidyl inositol (4,5) biphosphate (PIP2) into phosphatidyl inositol (3,4,5) triphosphate (PIP3), a process that is reversed by phosphatidylinositol (3,4,5)-triphosphate 3-phosphatase (PTEM) (2). PIP3 also recruits phosphoinositide-dependent kinase 1 (PDK1) to the plasma membrane, activating Akt (3). Akt phosphorylates glycogen synthase kinase 3 (GSK3), inhibiting its function (4). Active GSK3 is able to phosphorylate Mcl-1 (5), which is targeted for proteasomal degradation (6), liberating Bax and Bak proapoptotic factors (7). This causes the permeabilization of the mitochondrial outer membrane, releasing cytochrome c (Cyt C) (8) that attaches to Apaf-1, generating the apoptosome (9), leading to the activation of caspase 3 (10) that induces apoptosis (11). GSK3 also phosphorylates tau, inducing its aggregation and subsequent neurodegeneration (12). EGCG can ultimately increase PI3K and Akt activity (13) and inhibit PTEM in the presence of ROS (14), inhibiting apoptosis (15), phospho-Tau aggregation (16) and, therefore, generating neuroprotection. Full article ">

16 pages, 21608 KiB

Open AccessArticle

Pharmacological and Genetic Suppression of VDAC1 Alleviates the Development of Mitochondrial Dysfunction in Endothelial and Fibroblast Cell Cultures upon Hyperglycemic Conditions

by Konstantin N. Belosludtsev, Dmitriy A. Serov, Anna I. Ilzorkina, Vlada S. Starinets, Mikhail V. Dubinin, Eugeny Yu. Talanov, Maxim N. Karagyaur, Alexandra L. Primak and Natalia V. Belosludtseva

Antioxidants 2023, 12(7), 1459; https://doi.org/10.3390/antiox12071459 - 20 Jul 2023

Cited by 3 | Viewed by 2011

Abstract

Prolonged hyperglycemia related to diabetes and its complications leads to multiple cellular disorders, the central one being the dysfunction of mitochondria. Voltage-dependent anion channels (VDAC) of the outer mitochondrial membrane control the metabolic, ionic, and energy cross-talk between mitochondria and the rest of [...] Read more.

Prolonged hyperglycemia related to diabetes and its complications leads to multiple cellular disorders, the central one being the dysfunction of mitochondria. Voltage-dependent anion channels (VDAC) of the outer mitochondrial membrane control the metabolic, ionic, and energy cross-talk between mitochondria and the rest of the cell and serve as the master regulators of mitochondrial functions. Here, we have investigated the effect of pharmacological suppression of VDAC1 by the newly developed inhibitor of its oligomerization, VBIT-4, in the primary culture of mouse lung endotheliocytes and downregulated expression of VDAC1 in human skin fibroblasts on the progression of mitochondrial dysfunction upon hyperglycemic stress. The cells were grown in high-glucose media (30 mM) for 36 h. In response to hyperglycemia, the mRNA level of VDAC1 increased in endotheliocytes and decreased in human skin fibroblasts. Hyperglycemia induced overproduction of mitochondrial ROS, an increase in the susceptibility of the organelles to mitochondrial permeability transition (MPT) pore opening and a drop in mitochondrial membrane potential, which was accompanied by a decrease in cell viability in both cultures. Treatment of endotheliocytes with 5 µM VBIT-4 abolished the hyperglycemia-induced increase in susceptibility to spontaneous opening of the MPT pore and ROS generation in mitochondria. Silencing of VDAC1 expression in human skin fibroblasts exposed to high glucose led to a less pronounced manifestation of all the signs of damage to mitochondria. Our data identify a mitochondria-related response to pharmacological and genetic suppression of VDAC activity in vascular cells in hyperglycemia and suggest the potential therapeutic value of targeting these channels for the treatment of diabetic vasculopathies. Full article

(This article belongs to the Special Issue Oxidative Stress in Metabolic Disease)

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11 pages, 1175 KiB

Open AccessArticle

Beneficial Effects of Olive Oil Enriched with Lycopene on the Plasma Antioxidant and Anti-Inflammatory Profile of Hypercholesterolemic Patients

by Jesus Roman Martínez Álvarez, Ana Belen Lopez Jaen, Monica Cavia-Saiz, Pilar Muñiz and Victoria Valls-Belles

Antioxidants 2023, 12(7), 1458; https://doi.org/10.3390/antiox12071458 - 20 Jul 2023

Cited by 1 | Viewed by 1806

Abstract

Olive oil and lycopene are foods that have potent antioxidant activity. The objective was to determine the effects of consumption of olive oil enriched with lycopene on oxidative stress biomarkers in hypercholesterolemic subjects. We examined the effects of oil enriched with lycopene extract [...] Read more.

Olive oil and lycopene are foods that have potent antioxidant activity. The objective was to determine the effects of consumption of olive oil enriched with lycopene on oxidative stress biomarkers in hypercholesterolemic subjects. We examined the effects of oil enriched with lycopene extract daily intake during 1 month on plasma antioxidant capacity, lipids profile (triacylgycerols, total cholesterol, cHDL; cLDL, ox-LDL), biomarkers of oxidative stress, and inflammatory markers related with atherosclerosis risk (C-reactive protein (CRP), IL-6; sDC4L) in subjects hypercholesteremics (cholesterol > 220 mg/dL). In the group consuming olive oil-lycopene, significant increases (p < 0.05) in the levels of plasma lycopene concentration (0.146 ± 0.03 versus 0.202 ± 0.04 (µmol/L)), α-carotene (0.166 ± 0.064 versus 0.238 ± 0.07) and in β-carotene (0.493 ± 0.187 versus 0.713 ± 0.221) were observed. These results are linked with the increases of plasma antioxidants and decreases biomarkers of oxidative stress (carbonyl groups, malondialdehyde and 8-hydroxy-deoxiguanosine) observed in hypercholesterolemic group. In relation to lipid profile, a significant decrease was observed in the levels of ox-LDL (781 ± 302 versus 494 ± 200), remaining unchanged the levels of TG, cholesterol, HDL and LDL-c. Regarding inflammatory biomarkers, the levels of CRP and IL-6 decreased significantly. The positive results obtained in this study support the use of olive oil enriched with lycopene to reduce the risk of coronary disease. Full article

(This article belongs to the Special Issue Olive Antioxidants: Extraction, Biological Activity and Practical Applications—2nd Edition)

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(A)—Lycopene, α-carotene, β-carotene and cryptoxanthin levels in the plasma of patients with hypercholesterolemia, at the basal time (initial value) and after 30 days of diet supplementation with lycopene-olive oil (A) and olive oil (B). Values are means ± SD. Different alphabetical letters indicate significant differences (p < 0.005). * Indicates that significant different (p < 0.05) between initial value and 1 month. Full article ">Figure 2
Blood lipid profile levels in plasma of patients with hypercholesterolemic, at basal time (initial value) and after 30 days of diet supplementation with lycopene-olive oil (A) and olive oil (B). TG = triglycerides; HDL = high-density lipoprotein; LDL: low-density lipoprotein; LDLox: LDL oxidized low-density protein. Values are means ± SD. * Indicate that after 1 month the means are significantly different (p < 0.05) when compared to initial time values. Full article ">Figure 3
Biomarkers of oxidative stress (MDA, Carbonyl groups, and 8OHdG) levels in plasma of patients with hypercholesterolemic, at basal time (initial value) and after 1 month of diet supplementation with lycopene-olive oil and olive oil. Values are means ± SD. * Indicate that means values after 1 month are significantly different (p < 0.05) when compared to initial time baseline. Full article ">Figure 3 Cont.
Biomarkers of oxidative stress (MDA, Carbonyl groups, and 8OHdG) levels in plasma of patients with hypercholesterolemic, at basal time (initial value) and after 1 month of diet supplementation with lycopene-olive oil and olive oil. Values are means ± SD. * Indicate that means values after 1 month are significantly different (p < 0.05) when compared to initial time baseline. Full article ">

19 pages, 568 KiB

Open AccessArticle

Contribution of Saccharomyces and Non-Saccharomyces Yeasts on the Volatile and Phenolic Profiles of Rosehip Mead

by Alexandra-Costina Avîrvarei, Carmen Rodica Pop, Elena Mudura, Floricuța Ranga, Simona-Codruța Hegheș, Emese Gal, Haifeng Zhao, Anca Corina Fărcaș, Maria Simona Chiș and Teodora Emilia Coldea

Antioxidants 2023, 12(7), 1457; https://doi.org/10.3390/antiox12071457 - 19 Jul 2023

Cited by 4 | Viewed by 1670

Abstract

The resurgence of mead, a honey-based fermented beverage, is attributed to the increasing consumption of fermented foods and beverages, driven by its distinct flavors and perceived health benefits. This study investigates the influence of different yeast strains, namely Saccharomyces cerevisiae var. bayanus, [...] Read more.

The resurgence of mead, a honey-based fermented beverage, is attributed to the increasing consumption of fermented foods and beverages, driven by its distinct flavors and perceived health benefits. This study investigates the influence of different yeast strains, namely Saccharomyces cerevisiae var. bayanus, and Torulaspora delbrueckii, on the volatile and phenolic compounds of these beverages. Analytical techniques, including HPLC-DAD and GS/MS, were employed to analyze the chemical composition of the beverages. ANOVA analysis of variance was conducted to assess differences in the volatile and phenolic compounds. The findings reveal that yeast selection significantly impacts the chemical profiles of the beverages. Saccharomyces cerevisiae fermentation preserves rosehip-specific flavonoids and phenolic acids. Sequential fermentation with Torulaspora delbrueckii demonstrated proficiency in generating esters, contributing to fruity and floral aromas in the beverages. This study investigates the importance of yeast selection in shaping the chemical composition of rosehip mead, providing insights into the distinct characteristics conferred by different yeast strains. By optimizing yeast selection and fermentation techniques, the overall quality and diversity of these beverages can be enhanced. Full article

(This article belongs to the Special Issue Plant Materials and Their Antioxidant Potential)

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15 pages, 1071 KiB

Open AccessReview

Apples and Apple By-Products: Antioxidant Properties and Food Applications

by Umme Asma, Ksenia Morozova, Giovanna Ferrentino and Matteo Scampicchio

Antioxidants 2023, 12(7), 1456; https://doi.org/10.3390/antiox12071456 - 19 Jul 2023

Cited by 14 | Viewed by 6478

Abstract

In recent years, there has been a growing interest in utilizing natural antioxidants as alternatives to synthetic additives in food products. Apples and apple by-products have gained attention as a potential source of natural antioxidants due to their rich phenolic content. However, the [...] Read more.

In recent years, there has been a growing interest in utilizing natural antioxidants as alternatives to synthetic additives in food products. Apples and apple by-products have gained attention as a potential source of natural antioxidants due to their rich phenolic content. However, the extraction techniques applied for the recovery of phenolic compounds need to be chosen carefully. Studies show that ultrasound-assisted extraction is the most promising technique. High yields of phenolic compounds with antioxidant properties have been obtained by applying ultrasound on both apples and their by-products. Promising results have also been reported for green technologies such as supercritical fluid extraction, especially when a co-solvent is used. Once extracted, recent studies also indicate the feasibility of using these compounds in food products and packaging materials. The present review aims to provide a comprehensive overview of the antioxidant properties of apples and apple by-products, their extraction techniques, and potential applications in food products because of their antioxidant or nutritional properties. The findings reported here highlight the proper utilization of apples and their by-products in food to reduce the detrimental effect on the environment and provide a positive impact on the economy. Full article

(This article belongs to the Section Extraction and Industrial Applications of Antioxidants)

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18 pages, 3194 KiB

Open AccessArticle

Effect of Brewing Conditions on Antioxidant Properties of Ginkgo biloba Leaves Infusion

by Patrycja Biernacka, Katarzyna Felisiak, Iwona Adamska, Marek Śnieg and Cezary Podsiadło

Antioxidants 2023, 12(7), 1455; https://doi.org/10.3390/antiox12071455 - 19 Jul 2023

Cited by 1 | Viewed by 1670

Abstract

Due to the growing awareness of the importance of healthy eating in society, there is an increasing interest in the use of herbs and low-processed, natural products. Ginkgo biloba is a raw material with a high pro-health potential, which is related to the [...] Read more.

Due to the growing awareness of the importance of healthy eating in society, there is an increasing interest in the use of herbs and low-processed, natural products. Ginkgo biloba is a raw material with a high pro-health potential, which is related to the high content of antioxidant compounds. The aim of the study was to determine the relationship between the antioxidant activity of Ginkgo biloba leaf infusions and the weighted amount of leaves and brewing time. In addition, a sensory analysis of the infusions obtained was carried out. The innovation is to determine the migration of micro- and macroelements to the infusion prepared from Ginkgo biloba depending on the leaves’ weight used and the brewing time. The research showed the dependence of the antioxidant activity of the infusions and the migration of microelements on the size of the dried material and the brewing time. In the publication, the main factors influencing the quality of infusions were analysed, their mutual correlations were determined, and combinations showing the highest antioxidant activity and, at the same time, the highest sensory acceptability were selected. Full article

(This article belongs to the Special Issue Phenolics as Antioxidant Agents II)

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Changes in the pH of various weights in relation to the length of brewing the infusion. Full article ">Figure 2
Changes in the acidity [g/L] of various weights in relation to the length of brewing the infusion. Full article ">Figure 3
PCA biplot based on the first two principal component axes for antioxidant activity, acidity and soluble dry matter (A) and distribution of the 20 test samples based on the first two components derived from principal constituent analysis (B). Full article ">Figure 4
Hierarchical method of agglomeration of clusters of the tested samples in relation to the antioxidant activity (total polyphenol content of the water (W) and methanol (M) fractions, DPPH, FRAP of the water (W) and methanol (M) fractions and TEAC of the water (W) and methanol (M) fractions). Cluster analysis is expressed in Euclidean distance [binding distance/maximum distance × 100]. Full article ">Figure 5
HPLC profile of infusions from dried Ginkgo biloba leaves in selected samples ((A)—samples with 2.5 g weight—S, brewing time 10, 15 and 60 min; (B)—samples with 5.0 g weight—M, brewing time 10, 15 and 60 min; (C)—samples with 7.5 g weight—L, brewing time 10, 15 and 60 min). All samples were determined—(1) chlorogenic acid; (2) epicatechin; (3) catechin; (4) coumarin; and (5) apigenin—with detection at 280 nm. Full article ">Figure 6
Comparing colour, smell, flavour and overall acceptability of samples X—the smallest weight (A), S—small weight (B), M—medium weight (C) and L—large weight (D). Full article ">Figure 7
Sensory profile of smell and flavour of samples X—the smallest weight (A), S—small weight (B), M—medium weight (C) and L—large weight (D) for attributes such as herbal, acrid, sweet, bitter and sour. For the clarity of the graphs, the scale has been limited to six. Full article ">

22 pages, 3622 KiB

Open AccessArticle

Interactions between Angiotensin Type-1 Antagonists, Statins, and ROCK Inhibitors in a Rat Model of L-DOPA-Induced Dyskinesia

by Andrea Lopez-Lopez, Rita Valenzuela, Ana Isabel Rodriguez-Perez, María J. Guerra, Jose Luis Labandeira-Garcia and Ana Muñoz

Antioxidants 2023, 12(7), 1454; https://doi.org/10.3390/antiox12071454 - 19 Jul 2023

Cited by 3 | Viewed by 1803

Abstract

Statins have been proposed for L-DOPA-induced dyskinesia (LID) treatment. Statin anti-dyskinetic effects were related to the inhibition of the Ras-ERK pathway. However, the mechanisms responsible for the anti-LID effect are unclear. Changes in cholesterol homeostasis and oxidative stress- and inflammation-related mechanisms such as [...] Read more.

Statins have been proposed for L-DOPA-induced dyskinesia (LID) treatment. Statin anti-dyskinetic effects were related to the inhibition of the Ras-ERK pathway. However, the mechanisms responsible for the anti-LID effect are unclear. Changes in cholesterol homeostasis and oxidative stress- and inflammation-related mechanisms such as angiotensin II and Rho-kinase (ROCK) inhibition may be involved. The nigra and striatum of dyskinetic rats showed increased levels of cholesterol, ROCK, and the inflammatory marker IL-1β, which were reduced by the angiotensin type-1 receptor (AT1) antagonist candesartan, simvastatin, and the ROCK inhibitor fasudil. As observed for LID, angiotensin II-induced, via AT1, increased levels of cholesterol and ROCK in the rat nigra and striatum. In cultured dopaminergic neurons, angiotensin II increased cholesterol biosynthesis and cholesterol efflux without changes in cholesterol uptake. In astrocytes, angiotensin induced an increase in cholesterol uptake, decrease in biosynthesis, and no change in cholesterol efflux, suggesting a neuronal accumulation of cholesterol that is reduced via transfer to astrocytes. Our data suggest mutual interactions between angiotensin/AT1, cholesterol, and ROCK pathways in LID, which are attenuated by the corresponding inhibitors. Interestingly, these three drugs have also been suggested as neuroprotective treatments against Parkinson’s disease. Therefore, they may reduce dyskinesia and the progression of the disease using common mechanisms. Full article

(This article belongs to the Special Issue The Role of the Renin–Angiotensin System in Oxidative-Stress-Related Mechanisms in Neurodegenerative Diseases)

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Experimental design of the in vivo experiments. Groups of rats and mice and time-course of experiments: lesions, behavioral tests, treatments, and sample analysis. Abbreviations: Amph, amphetamine; Ang II, angiotensin II; MFB, medial forebrain bundle; TH, tyrosine hydroxylase. Full article ">Figure 2
A maximal lesion (i.e., lack of TH-immunoreactivity) can be observed by immunohistochemistry in the right substantia nigra (A) and right striatum (B) relative to the non-lesioned side (left side) or through Western blot analysis comparing the control side and the lesioned side (6-OHDA); (E) Nigral areas squared in A were magnified in (C,D). Abbreviations: SN, substantia nigra compacta; ST, striatum; TH, tyrosine hydroxylase. Scale bars: 600 µm (A,B); 100 µm (C,D). Full article ">Figure 3
Effect of simvastatin on the development of L-DOPA-induced dyskinesia. Rats co-treated with the HMGCR inhibitor, simvastatin (15 mg/kg, orally), and L-DOPA (6 mg/kg; white circles) for 3 weeks showed a significant reduction in the development of AIMs relative to control rats treated with vehicle and L-DOPA (dark circles). This decrease was observed in the AIMs total score (A) and in the different components: axial (B), limb (C), and orolingual (D). Total AIMs score (A) was estimated as the addition of limb (C), orolingual (D), and axial (B) components. Values are expressed as means ± SEM. Two-way ANOVA for repeated measures and Holm–Sidak post hoc test, *, p < 0.05. AIMs, abnormal involuntary movements. Full article ">Figure 4
Effect of simvastatin on the therapeutic effect of L-DOPA assessed via the cylinder test and turning behavior (A,B) and the effect of simvastatin and the co-treatment of simvastatin and the ROCK inhibitor fasudil in L-DOPA-primed rats (C). (A) Spontaneous forelimb use in the cylinder test revealed that simvastatin administration did not reduce the ability of L-DOPA to improve forelimb akinesia, showing a similar number of touches performed with the left paw in animals treated with simvastatin and L-DOPA (LD + simv; violet bars) than in those treated with vehicle and L-DOPA (LD; green bars). (B) Total contralateral turns in 90 min showed that simvastatin did not reduce contralateral rotation. (C) In rats with previously established L-DOPA-induced dyskinesia (L-DOPA-primed rats, treated with L-DOPA 6 mg/kg for 3 weeks), treatment with oral simvastatin (15 mg/kg; white circles) and L-DOPA did not induce any significant difference in AIMs score with respect to control rats treated with vehicle and L-DOPA (dark circles). Co-treatment with simvastatin and fasudil (10 or 20 mg/kg) did not induce any significant improvement in dyskinetic behavior. In A and B, data are means ± SEM. * p < 0.05, significant differences relative to baseline levels, off L-DOPA, Student t-test. In (C), two-way ANOVA for repeated measures and Holm–Sidak post hoc test, * p < 0.05. AIMs, abnormal involuntary movements. Full article ">Figure 5
Effect of L-DOPA-induced dyskinesia and simvastatin on HMGCR, ROCK, and interleukin-1β. Dyskinetic rats chronically treated with L-DOPA 6 mg/kg (6-OHDA + LD, green bars) showed a significant increase in cholesterol levels (A,F) and in HMGCR protein levels (B,G), relative to 6-OHDA-lesioned rats (6-OHDA, orange bars) in the substantia nigra (A,B) and striatum (F,G). Moreover, dyskinetic animals showed a significant increase in ROCK protein levels (C,H), ROCK activity (D,I), and interleukin-1β (IL-1β) protein expression (E,J) in both regions. The inhibition of cholesterol biosynthesis by simvastatin (6-OHDA + LD + simv, blue bars) reduces dyskinesia, ROCK levels (C,H), ROCK activity (D,I), and IL-1β levels (E,J) in the striatum and substantia nigra. Data are means ± SEM. The results were normalized to the values of 6-OHDA-lesioned rats treated with vehicle. * p < 0.05, significant differences relative to 6-OHDA-lesioned rats; # p < 0.05 significant differences relative to L-DOPA-treated rats. One-way ANOVA and Holm–Sidak post hoc tests were used. Full article ">Figure 6
Effects of ROCK inhibitors and AT1 receptor blockers in the cholesterol biosynthesis marker HMGCR. The increase in HMGCR protein levels induced by dyskinesia (6-OHDA + LD, green bars) is reduced via the co-administration of L-DOPA and the ROCK inhibitor fasudil, (6-OHDA + LD + fasudil, blue bars) in the substantia nigra (A) and the striatum (C). Co-treatment with L-DOPA and the AT1 receptor antagonist candesartan (6-OHDA + LD + candesartan, blue bars) also produces a significant reduction in HMGCR protein levels induced through dyskinesia in the substantia nigra (B) and the striatum (D). The results were normalized to the values of 6-OHDA-lesioned animals treated with saline. Data are mean ± standard error of the mean (SEM); * p < 0.05, significant differences relative to 6-OHDA-lesioned rats; $ p < 0.05 significant differences relative to L-DOPA-treated rats. One-way ANOVA and Holm–Sidak post hoc test were used. Full article ">Figure 7
Effects of angiotensin, AT1 inhibition or AT1 or AT2 receptor deletion, and ROCK inhibition on cholesterol levels. Rats treated with an intraventricular injection of Angiotensin II (Ang II, pink bars) showed significantly higher levels of cholesterol in both substantia nigra (A) and striatum (B) compared to control saline-injected rats (green bars). The administration of the AT1 receptor antagonist candesartan (orange bars) induced a significant reduction in cholesterol levels in both regions (C,D). Moreover, AT1 KO mice (AT1KO, purple bars) showed significantly lower cholesterol levels than WT mice in the substantia nigra (E) and striatum (F), while AT2 KO mice (AT2KO, violet bars) showed significantly higher cholesterol content than in WT mice (G,H) in both regions. ROCK inhibition by fasudil (yellow bars) also induced a significant reduction in cholesterol levels in the nigra (I) and striatum (J). The results were normalized to the values of control animals treated with saline or WT mice. Data are mean ± standard error of the mean (SEM). * p < 0.05 compared to control (Student’s t-test). Full article ">Figure 8
Effects of angiotensin, AT1 inhibition, or AT1 or AT2 receptor deletion on ROCK expression. Rats treated with intraventricular angiotensin II (Ang II, pink bars) showed a significant increase in ROCK protein expression levels in the substantia nigra (A) and striatum (B) relative to control rats injected with saline (green bars). However, treatment with the AT1 antagonist candesartan (orange bars) showed a significant reduction in ROCK levels in the substantia nigra (C) and the striatum (D). Consistent with this, AT1 KO mice (AT1KO, purple bars) showed a significant decrease in ROCK levels in comparison with control WT mice in both regions (E,F). The results were normalized to the values of control animals treated with saline or WT mice. Data are mean ± standard error of the mean (SEM). * p < 0.05 compared to control (Student’s t-test). Full article ">Figure 9
Effect of angiotensin treatment on N27 dopaminergic neuron culture. The treatment of N27 dopaminergic cell line with angiotensin II (Ang II) for 24 h produced an increase in the mRNA (A) and protein expression (D) of cholesterol biosynthesis enzyme HMGCR, an increase in cholesterol in efflux-related molecule ABCA1 (B,E), and no changes in cholesterol uptake-related molecule LDL receptor (LDLR) expression (C,F). Data are mean ± standard error of the mean (SEM). * p < 0.05 compared to control (Student’s t-test). HMGCR, 3-hydroxy-3-methylglutaryl CoA reductase; ABCA1, ATP-binding cassette transporter-1. Full article ">Figure 10
Effect of angiotensin treatment on C6 astroglial culture. Treatment of C6 astroglial cell line with angiotensin II (Ang II) for 24 h produced an increase in mRNA (A) and protein (D) cholesterol uptake-related molecule LDL receptor (LDLR) expression, a decrease in cholesterol biosynthesis enzyme HMGCR (B,E), and no changes in cholesterol efflux-related molecule ABCA1 (C,F). Data are mean ± standard error of the mean (SEM). * p < 0.05 compared to control (Student’s t-test). HMGCR, 3-hydroxy-3-methylglutaryl CoA reductase; ABCA1, ATP-binding cassette transporter-1. Full article ">

34 pages, 2091 KiB

Open AccessReview

A Review of the Changes Produced by Extrusion Cooking on the Bioactive Compounds from Vegetal Sources

by Silvia Mironeasa, Ionica Coţovanu, Costel Mironeasa and Mădălina Ungureanu-Iuga

Antioxidants 2023, 12(7), 1453; https://doi.org/10.3390/antiox12071453 - 19 Jul 2023

Cited by 6 | Viewed by 2010

Abstract

The demand for healthy ready-to-eat foods like snacks is increasing. Physical modification of vegetal food matrices through extrusion generates significant changes in the chemical composition of the final product. There is a great variety of food matrices that can be used in extrusion, [...] Read more.

The demand for healthy ready-to-eat foods like snacks is increasing. Physical modification of vegetal food matrices through extrusion generates significant changes in the chemical composition of the final product. There is a great variety of food matrices that can be used in extrusion, most of them being based on cereals, legumes, fruits, vegetables, or seeds. The aim of this review was to summarize the main effects of the extrusion process on the bioactive compounds content, namely phenolics, terpenes, vitamins, minerals, and fibers of vegetal mixes, as well as on their biological activity. The literature reported contradictory results regarding the changes in bioactive compounds after extrusion, mainly due to the differences in the processing conditions, chemical composition, physicochemical properties, and nutritional value of the extruded material and quantification methods. The thermolabile phenolics and vitamins were negatively affected by extrusion, while the fiber content was proved to be enhanced. Further research is needed regarding the interactions between bioactive components during extrusion, as well as a more detailed analysis of the impact of extrusion on the terpenes since there are few papers dealing with this aspect. Full article

(This article belongs to the Special Issue Impact of Processing on Antioxidant Rich Foods - 2nd Edition)

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31 pages, 1438 KiB

Open AccessReview

Exploring the Potential of Bee-Derived Antioxidants for Maintaining Oral Hygiene and Dental Health: A Comprehensive Review

by Poonam Choudhary, Surya Tushir, Manju Bala, Sanjula Sharma, Manjeet Kaur Sangha, Heena Rani, Nileshwari Raju Yewle, Parminder Kumar, Diksha Singla, Deepak Chandran, Manoj Kumar and Mohamed Mekhemar

Antioxidants 2023, 12(7), 1452; https://doi.org/10.3390/antiox12071452 - 19 Jul 2023

Cited by 3 | Viewed by 3434

Abstract

Honey bee products comprise various compounds, including honey, propolis, royal jelly, bee pollen, bee wax and bee venom, which have long been recognized for their pharmacological and health-promoting benefits. Scientists have discovered that periodontal disorders stem from dental biofilm, an inflammatory response to [...] Read more.

Honey bee products comprise various compounds, including honey, propolis, royal jelly, bee pollen, bee wax and bee venom, which have long been recognized for their pharmacological and health-promoting benefits. Scientists have discovered that periodontal disorders stem from dental biofilm, an inflammatory response to bacterial overgrowth produced by dysbiosis in the oral microbiome. The bee products have been investigated for their role in prevention of oral diseases, which are attributed to a myriad of biologically active compounds including flavonoids (pinocembrin, catechin, caffeic acid phenethyl ester (CAPE) and galangin), phenolic acids (hydroxybenzoic acid, hydroxycinnamic acid, p-coumaric, ellagic, caffeic and ferulic acids) and terpenoids. This review aims to update the current understanding of role of selected bee products, namely, honey, propolis and royal jelly, in preventing oral diseases as well as their potential biological activities and mechanism of action in relation to oral health have been discussed. Furthermore, the safety of incorporation of bee products is also critically discussed. To summarize, bee products could potentially serve as a therapy option for people suffering from a variety of oral disorders. Full article

(This article belongs to the Special Issue Antioxidant Activity of Honey Bee Products)

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22 pages, 4826 KiB

Open AccessArticle

24-Epibrassinolide Facilitates Adventitious Root Formation by Coordinating Cell-Wall Polyamine Oxidase- and Plasma Membrane Respiratory Burst Oxidase Homologue-Derived Reactive Oxygen Species in Capsicum annuum L.

by Zhengyang Wen, Zhifeng Chen, Xinyan Liu, Jingbo Sun, Feng Zhang, Mengxia Zhang and Chunjuan Dong

Antioxidants 2023, 12(7), 1451; https://doi.org/10.3390/antiox12071451 - 19 Jul 2023

Cited by 1 | Viewed by 1447

Abstract

Adventitious root (AR) formation is a critical process in cutting propagation of horticultural plants. Brassinosteroids (BRs) have been shown to regulate AR formation in several plant species; however, little is known about their exact effects on pepper AR formation, and the downstream signaling [...] Read more.

Adventitious root (AR) formation is a critical process in cutting propagation of horticultural plants. Brassinosteroids (BRs) have been shown to regulate AR formation in several plant species; however, little is known about their exact effects on pepper AR formation, and the downstream signaling of BRs also remains elusive. In this study, we showed that treatment of 24-Epibrassinolide (EBL, an active BR) at the concentrations of 20–100 nM promoted AR formation in pepper (Capsicum annuum). Furthermore, we investigated the roles of apoplastic reactive oxygen species (ROS), including hydrogen peroxide (H₂O₂) and superoxide radical (O₂^•−), in EBL-promoted AR formation, by using physiological, histochemical, bioinformatic, and biochemical approaches. EBL promoted AR formation by modulating cell-wall-located polyamine oxidase (PAO)-dependent H₂O₂ production and respiratory burst oxidase homologue (RBOH)-dependent O₂^•− production, respectively. Screening of CaPAO and CaRBOH gene families combined with gene expression analysis suggested that EBL-promoted AR formation correlated with the upregulation of CaPAO1, CaRBOH2, CaRBOH5, and CaRBOH6 in the AR zone. Transient expression analysis confirmed that CaPAO1 was able to produce H₂O₂, and CaRBOH2, CaRBOH5, and CaRBOH6 were capable of producing O₂^•−. The silencing of CaPAO1, CaRBOH2, CaRBOH5, and CaRBOH6 in pepper decreased the ROS accumulation and abolished the EBL-induced AR formation. Overall, these results uncover one of the regulatory pathways for BR-regulated AR formation, and extend our knowledge of the functions of BRs and of the BRs-ROS crosstalk in plant development. Full article

(This article belongs to the Special Issue ROS Homeostasis during Plant Growth and Development)

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