Antioxidants

28 pages, 6562 KiB

Open AccessReview

Current Status and Future Perspectives on Therapeutic Potential of Apigenin: Focus on Metabolic-Syndrome-Dependent Organ Dysfunction

by Waqas Alam, Carmine Rocca, Haroon Khan, Yaseen Hussain, Michael Aschner, Anna De Bartolo, Nicola Amodio, Tommaso Angelone and Wai San Cheang

Antioxidants 2021, 10(10), 1643; https://doi.org/10.3390/antiox10101643 - 19 Oct 2021

Cited by 15 | Viewed by 4505

Abstract

Metabolic syndrome and its associated disorders such as obesity, insulin resistance, atherosclerosis and type 2 diabetes mellitus are globally prevalent. Different molecules showing therapeutic potential are currently available for the management of metabolic syndrome, although their efficacy has often been compromised by their [...] Read more.

Metabolic syndrome and its associated disorders such as obesity, insulin resistance, atherosclerosis and type 2 diabetes mellitus are globally prevalent. Different molecules showing therapeutic potential are currently available for the management of metabolic syndrome, although their efficacy has often been compromised by their poor bioavailability and side effects. Studies have been carried out on medicinal plant extracts for the treatment and prevention of metabolic syndrome. In this regard, isolated pure compounds have shown promising efficacy for the management of metabolic syndrome, both in preclinical and clinical settings. Apigenin, a natural bioactive flavonoid widely present in medicinal plants, functional foods, vegetables and fruits, exerts protective effects in models of neurological disorders and cardiovascular diseases and most of these effects are attributed to its antioxidant action. Various preclinical and clinical studies carried out so far show a protective effect of apigenin against metabolic syndrome. Herein, we provide a comprehensive review on both in vitro and in vivo evidence related to the promising antioxidant role of apigenin in cardioprotection, neuroprotection and renoprotection, and to its beneficial action in metabolic-syndrome-dependent organ dysfunction. We also provide evidence on the potential of apigenin in the prevention and/or treatment of metabolic syndrome, analysing the potential and limitation of its therapeutic use. Full article

(This article belongs to the Special Issue Dietary Antioxidants and Chronic Diseases)

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18 pages, 1447 KiB

Open AccessArticle

Insights into the Phytochemical and Multifunctional Biological Profile of Spices from the Genus Piper

by Simon Vlad Luca, Katarzyna Gaweł-Bęben, Marcelina Strzępek-Gomółka, Karolina Czech, Adriana Trifan, Gokhan Zengin, Izabela Korona-Glowniak, Mirjana Minceva, Jürg Gertsch and Krystyna Skalicka-Woźniak

Antioxidants 2021, 10(10), 1642; https://doi.org/10.3390/antiox10101642 - 19 Oct 2021

Cited by 9 | Viewed by 3208

Abstract

Piper spices represent an inexhaustible reservoir of bioactive compounds that may act as drug leads in natural product research. The aim of this study was to investigate a series of methanolic fruit extracts obtained from P. nigrum (black, green, white and red), P. [...] Read more.

Piper spices represent an inexhaustible reservoir of bioactive compounds that may act as drug leads in natural product research. The aim of this study was to investigate a series of methanolic fruit extracts obtained from P. nigrum (black, green, white and red), P. longum and P. retrofractum in comparative phytochemical and multi-directional biological (antimicrobial, antioxidant, anti-enzymatic and anti-melanogenic) assays. The metabolite profiling revealed the presence of 17 piperamides, with a total content of 247.75–591.42 mg piperine equivalents/g. Among the 22 tested microorganism strains, Piper spices were significantly active (MIC < 0.1 mg/mL) against the anaerobes Actinomyces israelii and Fusobacterium nucleatum. The antioxidant and anti-enzymatic activities were evidenced in DPPH (10.64–82.44 mg TE/g) and ABTS (14.20–77.60 mg TE/g) radical scavenging, CUPRAC (39.94–140.52 mg TE/g), FRAP (16.05–77.00 mg TE/g), chelating (0–34.80 mg EDTAE/g), anti-acetylcholinesterase (0–2.27 mg GALAE/g), anti-butyrylcholinesterase (0.60–3.11 mg GALAE/g), anti-amylase (0.62–1.11 mmol ACAE/g) and anti-glucosidase (0–1.22 mmol ACAE/g) assays. Several Piper extracts (10 μg/mL) inhibited both melanin synthesis (to 32.05–60.65% of αMSH+ cells) and release (38.06–45.78% of αMSH+ cells) in αMSH-stimulated B16F10 cells, partly explained by their tyrosinase inhibitory properties. Our study uncovers differences between Piper spices and sheds light on their potential use as nutraceuticals or cosmeceuticals for the management of different diseases linked to bacterial infections, Alzheimer’s dementia, type 2 diabetes mellitus or hyperpigmentation. Full article

(This article belongs to the Special Issue Natural Products: Biological-, Antioxidant Properties and Health Effects)

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29 pages, 13514 KiB

Open AccessArticle

Highly Potent, Selective, and Competitive Indole-Based MAO-B Inhibitors Protect PC12 Cells against 6-Hydroxydopamine- and Rotenone-Induced Oxidative Stress

by Mohamed H. Elsherbeny, Jushin Kim, Noha A. Gouda, Lizaveta Gotina, Jungsook Cho, Ae Nim Pae, Kyeong Lee, Ki Duk Park, Ahmed Elkamhawy and Eun Joo Roh

Antioxidants 2021, 10(10), 1641; https://doi.org/10.3390/antiox10101641 - 19 Oct 2021

Cited by 13 | Viewed by 2460

Abstract

Monoamine oxidase B (MAO-B) is responsible for dopamine metabolism and plays a key role in oxidative stress by changing the redox state of neuronal and glial cells. To date, no disease-modifying therapy for Parkinson’s disease (PD) has been identified. However, MAO-B inhibitors have [...] Read more.

Monoamine oxidase B (MAO-B) is responsible for dopamine metabolism and plays a key role in oxidative stress by changing the redox state of neuronal and glial cells. To date, no disease-modifying therapy for Parkinson’s disease (PD) has been identified. However, MAO-B inhibitors have emerged as a viable therapeutic strategy for PD patients. Herein, a novel series of indole-based small molecules was synthesized as new MAO-B inhibitors with the potential to counteract the induced oxidative stress in PC12 cells. At a single dose concentration of 10 µM, 10 compounds out of 30 were able to inhibit MAO-B with more than 50%. Among them, compounds 7b, 8a, 8b, and 8e showed 84.1, 99.3, 99.4, and 89.6% inhibition over MAO-B and IC₅₀ values of 0.33, 0.02, 0.03, and 0.45 µM, respectively. When compared to the modest selectivity index of rasagiline (II, a well-known MAO-B inhibitor, SI > 50), compounds 7b, 8a, 8b and 8e showed remarkable selectivity indices (SI > 305, 3649, 3278, and 220, respectively). A further kinetic study displayed a competitive mode of action for 8a and 8b over MAO-B with Ki values of 10.34 and 6.63 nM. Molecular docking studies of the enzyme-inhibitor binding complexes in MAO-B revealed that free NH and substituted indole derivatives share a common favorable binding mode: H-bonding with a crucial water “anchor” and Tyr326. Whereas in MAO-A the compounds failed to form favorable interactions, which explained their high selectivity. In addition, compounds 7b, 8a, 8b, and 8e exhibited safe neurotoxicity profiles in PC12 cells and partially reversed 6-hydroxydopamine- and rotenone-induced cell death. Accordingly, we report compounds 7b, 8a, 8b, and 8e as novel promising leads that could be further exploited for their multi-targeted role in the development of a new oxidative stress-related PD therapy. Full article

(This article belongs to the Special Issue Oxidative Stress and Neurodegenerative Disorders II)

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16 pages, 2391 KiB

Open AccessArticle

Protective Effects of Lignin-Carbohydrate Complexes from Wheat Stalk against Bisphenol a Neurotoxicity in Zebrafish via Oxidative Stress

by Jie Gu, Min Guo, Liping Zheng, Xiaogang Yin, Linjun Zhou, Deling Fan, Lili Shi, Caoxing Huang and Guixiang Ji

Antioxidants 2021, 10(10), 1640; https://doi.org/10.3390/antiox10101640 - 18 Oct 2021

Cited by 11 | Viewed by 1967

Abstract

Lignin-carbohydrate complexes (LCCs) from different lignocellulosic biomass have shown biological qualities as antioxidant and immunostimulant. By contrast, the application of LCCs as protectant against neurotoxicity caused by different compounds is scarce. In this work, two kinds of LCCs with carbohydrate-rich and lignin-rich fractions [...] Read more.

Lignin-carbohydrate complexes (LCCs) from different lignocellulosic biomass have shown biological qualities as antioxidant and immunostimulant. By contrast, the application of LCCs as protectant against neurotoxicity caused by different compounds is scarce. In this work, two kinds of LCCs with carbohydrate-rich and lignin-rich fractions were obtained from wheat stalk and used to protect against BPA-neurotoxicity in zebrafish. The results showed that BPA at a concentration of 500 µg/L results in neurotoxicity, including significant behavioral inhibition, and prevents the expression of central nervous system proteins in transgenic zebrafish models (Tg (HuC-GFP)). When the zebrafish was treated by LCCs, the reactive oxygen species of zebrafish decreased significantly with the change of antioxidant enzymes and lipid peroxidation, which was due to the LCCs’ ability to suppress the mRNA expression level of key genes related to nerves. This is essential in view of the neurotoxicity of BPA through oxidative stress. In addition, BPA exposure had negative effects on the exercise behavior, the catalase (CAT) and superoxide dismutase (SOD) activity, and the larval development and gene expression of zebrafish larvae, and LCC preparations could recover these negative effects by reducing oxidative stress. In zebrafish treated with BPA, carbohydrate-rich LCCs showed stronger antioxidant activity than lignin-rich LCCs, showing their potential as a neuroprotective agents. Full article

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17 pages, 2802 KiB

Open AccessArticle

Calystegia soldanella Extract Exerts Anti-Oxidative and Anti-Inflammatory Effects via the Regulation of the NF-κB/Nrf-2 Pathways in Mouse Macrophages

by Taekil Eom, In-Hye Kim, Hyung-Joo Kim, YounHee Choi and Taek-Jeong Nam

Antioxidants 2021, 10(10), 1639; https://doi.org/10.3390/antiox10101639 - 18 Oct 2021

Cited by 3 | Viewed by 2069

Abstract

Plant polyphenols are widely used to treat various inflammatory diseases, owing to their ability to suppress reactive oxygen species production and the expression of inflammatory cytokines. Herein, we investigated phenolic compounds from Calystegia soldanella using UPLC Q-TOF MS/MS and their antioxidative and anti-inflammatory [...] Read more.

Plant polyphenols are widely used to treat various inflammatory diseases, owing to their ability to suppress reactive oxygen species production and the expression of inflammatory cytokines. Herein, we investigated phenolic compounds from Calystegia soldanella using UPLC Q-TOF MS/MS and their antioxidative and anti-inflammatory activities were analyzed. The C. soldanella ethyl acetate fraction (CsEF) had the strongest antioxidative activity, given its high polyphenol compound content. It also exhibited anti-inflammatory effects, inhibiting the production of inflammatory cytokines such as NO, PGE2, IL-1β, IL-6, and TNF-α in LPS-stimulated mouse macrophages. CsEF activated the nuclear transcription factor Nrf-2, thereby upregulating antioxidant enzymes such as HO-1 and NQO-1 and inhibiting NF-κB expression, which in turn, suppressed the expression of COX-2, iNOS, and inflammatory cytokines, ultimately exerting anti-inflammatory effects. Further, UPLC-Q-TOF-MS/MS was used to analyze the polyphenol compound contents in CsEF. The quercetin glycosides isoquercitrin and quercitrin were the primary flavonoid compounds, while the caffeic acid derivatives, chlorogenic acid and dicaffeoylquinic acid, were the primary phenolic acids. Thus, C. soldanella, which had only a limited use thus far as a medicinal plant, may serve as a natural medicinal resource for treating inflammatory diseases. Full article

(This article belongs to the Special Issue Dietary Bioactives and Their Metabolites as Modulators of Oxidative Stress and Inflammation)

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20 pages, 4105 KiB

Open AccessArticle

Quercus acuta Thunb. (Fagaceae) and Its Component, Isoquercitrin, Inhibit HSV-1 Replication by Suppressing Virus-Induced ROS Production and NF-κB Activation

by Buyun Kim, Young Soo Kim, Youn-Hwan Hwang, Hye Jin Yang, Wei Li, Eun-Bin Kwon, Tae In Kim, Younghoon Go and Jang-Gi Choi

Antioxidants 2021, 10(10), 1638; https://doi.org/10.3390/antiox10101638 - 18 Oct 2021

Cited by 11 | Viewed by 2388

Abstract

HSV-1 is a neurotropic virus that replicates lytically during acute infection and establishes latency in peripheral neurons. Currently, the clinically approved compounds for the prevention of HSV-1 infection include acyclovir and penciclovir; however, long-term use of the drug is associated with serious side [...] Read more.

HSV-1 is a neurotropic virus that replicates lytically during acute infection and establishes latency in peripheral neurons. Currently, the clinically approved compounds for the prevention of HSV-1 infection include acyclovir and penciclovir; however, long-term use of the drug is associated with serious side effects, and drug-resistant strains often appear. Therefore, it is important to find a safe and novel antiviral agent for HSV-1 infection. Quercus acuta Thunb. (Fagaceae) (QA) is widely distributed as an ornamental and dietary plant in Korea, Taiwan, China, and Japan. Thus far, the effects of QA extract and its active ingredients are known to have antioxidant, antibacterial, and anti-inflammatory activity, but studies of possible antiviral effects have not been reported. We studied the antiviral effects and molecular mechanism of QA after HSV-1 infection at the cellular level. We confirmed that QA suppresses ROS expression after HSV-1 infection and also suppresses inflammatory cytokine expression through inhibition of NF-кB activity. In addition, we found that QA increases the phosphorylation activity of IRF3 through induction of TBK1 activity during HSV-1 infection. QA exhibits an antiviral effect, and we confirmed through UPLC-DAD-mass spectrometer (MS)/MS analysis that it contains five main components: catechin, chlorogenic acid, fraxin, isoquercitrin, and taxifolin. Of these, isoquercitrin was confirmed to exhibit an antiviral effect on SK-N-SH cells through ICP27 inhibition. Overall, our results suggest that QA is a novel inhibitor with antiviral effects against HSV-1 infection and may be used specifically to prevent and treat of herpes simplex virus encephalitis infection. Full article

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

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16 pages, 2322 KiB

Open AccessArticle

Effect of Deep Frying of Potatoes and Tofu on Thermo-Oxidative Changes of Cold Pressed Rapeseed Oil, Cold Pressed High Oleic Rapeseed Oil and Palm Olein

by Małgorzata Wroniak, Marianna Raczyk, Bartosz Kruszewski, Edyta Symoniuk and Dominika Dach

Antioxidants 2021, 10(10), 1637; https://doi.org/10.3390/antiox10101637 - 18 Oct 2021

Cited by 14 | Viewed by 3339

Abstract

One of the commonly used food preparation methods is frying. Fried food is admired by consumers due to its unique taste and texture. Deep frying is a process of dipping food in oil at high temperature, usually 170–190 °C, and it requires a [...] Read more.

One of the commonly used food preparation methods is frying. Fried food is admired by consumers due to its unique taste and texture. Deep frying is a process of dipping food in oil at high temperature, usually 170–190 °C, and it requires a relatively short time. The aim of this study was to analyze the thermo-oxidative changes occurring during the deep frying of products such as potatoes and tofu in cold pressed rapeseed oils and palm olein. Cold pressed rapeseed oil from hulled seeds (RO), cold pressed high oleic rapeseed oil from hulled seeds (HORO), and palm olein (PO) (for purposes of comparison) were used. Characterization of fresh oils (after purchase) and oils after 6, 12, and 18 h of deep frying process of a starch product (potatoes) and a protein product (tofu) was performed. The quality of oils was analyzed by determining peroxide value, acid value, p-anisidine value, content of carotenoid and chlorophyll pigments, polar compounds, smoke point, color (CIE L*a*b*), fatty acids content and profile, calculation of lipid nutritional quality indicators, and oxidative stability index (Rancimat). Cold pressed high oleic rapeseed oil was more stable during deep frying compared to cold pressed rapeseed oil, but much less stable than palm olein. In addition, more thermo-oxidative changes occurred in the tested oils when deep frying the starch product (potatoes) compared to the deep frying of the protein product (tofu). Full article

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

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14 pages, 2541 KiB

Open AccessArticle

Physiological Functions of Thiol Peroxidases (Gpx1 and Prdx2) during Xenopus laevis Embryonic Development

by Hongchan Lee, Na Young Lee, Youni Kim, Hong-Seok Choi, Tayaba Ismail, Hong-Yeoul Ryu, Dong-Hyung Cho, Zae Young Ryoo, Dong-Seok Lee, Taeg Kyu Kwon, Tae Joo Park, Taejoon Kwon and Hyun-Shik Lee

Antioxidants 2021, 10(10), 1636; https://doi.org/10.3390/antiox10101636 - 17 Oct 2021

Viewed by 2434

Abstract

Glutathione peroxidase 1 (Gpx1) and peroxiredoxin 2 (Prdx2) belong to the thiol peroxidase family of antioxidants, and have been studied for their antioxidant functions and roles in cancers. However, the physiological significance of Gpx1 and Prdx2 during vertebrate embryogenesis are lacking. Currently, we [...] Read more.

Glutathione peroxidase 1 (Gpx1) and peroxiredoxin 2 (Prdx2) belong to the thiol peroxidase family of antioxidants, and have been studied for their antioxidant functions and roles in cancers. However, the physiological significance of Gpx1 and Prdx2 during vertebrate embryogenesis are lacking. Currently, we investigated the functional roles of Gpx1 and Prdx2 during vertebrate embryogenesis using Xenopus laevis as a vertebrate model. Our investigations revealed the zygotic nature of gpx1 having its localization in the eye region of developing embryos, whereas prdx2 exhibited a maternal nature and were localized in embryonic ventral blood islands. Furthermore, the gpx1-morphants exhibited malformed eyes with incompletely detached lenses. However, the depletion of prdx2 has not established its involvement with embryogenesis. A molecular analysis of gpx1-depleted embryos revealed the perturbed expression of a cryba1-lens-specific marker and also exhibited reactive oxygen species (ROS) accumulation in the eye regions of gpx1-morphants. Additionally, transcriptomics analysis of gpx1-knockout embryos demonstrated the involvement of Wnt, cadherin, and integrin signaling pathways in the development of malformed eyes. Conclusively, our findings indicate the association of gpx1 with a complex network of embryonic developmental pathways and ROS responses, but detailed investigation is a prerequisite in order to pinpoint the mechanistic details of these interactions. Full article

(This article belongs to the Special Issue Physiological and Pathological Significance of Peroxiredoxins)

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17 pages, 2172 KiB

Open AccessArticle

Superoxide Production by the Red Tide-Producing Chattonella marina Complex (Raphidophyceae) Correlates with Toxicity to Aquacultured Fishes

by Tomoyuki Shikata, Koki Yuasa, Saho Kitatsuji, Setsuko Sakamoto, Kazuki Akita, Yuichiro Fujinami, Yoshitaka Nishiyama, Toshihisa Kotake, Ryusuke Tanaka and Yasuhiro Yamasaki

Antioxidants 2021, 10(10), 1635; https://doi.org/10.3390/antiox10101635 - 17 Oct 2021

Cited by 9 | Viewed by 2155

Abstract

The marine raphidophyte Chattonella marina complex forms red tides, causing heavy mortalities of aquacultured fishes in temperate coastal waters worldwide. The mechanism for Chattonella fish mortality remains unresolved. Although several toxic chemicals have been proposed as responsible for fish mortality, the cause is [...] Read more.

The marine raphidophyte Chattonella marina complex forms red tides, causing heavy mortalities of aquacultured fishes in temperate coastal waters worldwide. The mechanism for Chattonella fish mortality remains unresolved. Although several toxic chemicals have been proposed as responsible for fish mortality, the cause is still unclear. In this study, we performed toxicity bioassays with red sea bream and yellowtail. We also measured biological parameters potentially related to ichthyotoxicity, such as cell size, superoxide (O₂^•−) production, and compositions of fatty acids and sugars, in up to eight Chattonella strains to investigate possible correlations with toxicity. There were significant differences in moribundity rates of fish and in all biological parameters among strains. One strain displayed no ichthyotoxicity even at high cell densities. Strains were categorized into three groups based on cell length, but this classification did not significantly correlate with ichthyotoxicity. O₂^•− production differed by a factor of more than 13 between strains at the late exponential growth phase. O₂^•− production was significantly correlated with ichthyotoxicity. Differences in fatty acid and sugar contents were not related to ichthyotoxicity. Our study supports the hypothesis that superoxide can directly or indirectly play an important role in the Chattonella-related mortality of aquacultured fishes. Full article

(This article belongs to the Special Issue Oxidative Stress in Marine Environment)

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16 pages, 2428 KiB

Open AccessArticle

Comprehensive Analysis of Secondary Metabolites in the Extracts from Different Lily Bulbs and Their Antioxidant Ability

by Yu-Chao Tang, Yi-Jie Liu, Guo-Ren He, Yu-Wei Cao, Meng-Meng Bi, Meng Song, Pan-Pan Yang, Lei-Feng Xu and Jun Ming

Antioxidants 2021, 10(10), 1634; https://doi.org/10.3390/antiox10101634 - 17 Oct 2021

Cited by 47 | Viewed by 5406

Abstract

The genus Lilium contains more than 100 wild species and numerous hybrid varieties. Some species of them have been used as medicine and food since ancient times. However, the research on the active components and the medical properties of lilies has only focused [...] Read more.

The genus Lilium contains more than 100 wild species and numerous hybrid varieties. Some species of them have been used as medicine and food since ancient times. However, the research on the active components and the medical properties of lilies has only focused on a few species. In this study, the total phenolic acid content (TPC), total flavonoid content (TFC), and antioxidant capacity of 22 representative lilies were systematically investigated. The results showed that the TPC, TFC and antioxidant activity were highly variable among different lilies, but they were significantly positively correlated. Hierarchical cluster analysis indicated that L. henryi and L. regale were arranged in one group characterized by the highest TPC, TFC and antioxidant capacity, followed by Oriental hybrids and Trumpet and Oriental hybrids. The traditional edible and medicinal lilies were clustered in low TPC, TFC and antioxidant capacity group. A total of 577 secondary metabolites, including 201 flavonoids, 153 phenolic acids, were identified in the five species with great differences in antioxidant capacity by extensive targeted metabonomics. Differentially accumulated metabolites (DAMs) analysis reviewed that the DAMs were mainly enriched in secondary metabolic pathways such as isoflavonoid, folate, flavonoid, flavone, flavonol, phenylpropanoid, isoquinoline alkaloid biosynthesis, nicotinate and nicotinamide metabolism and so on. Correlation analysis identified that 64 metabolites were significantly positively correlated with antioxidant capacity (r ≥ 0.9 and p < 0.0001). These results suggested that the genus Lilium has great biodiversity in bioactive components. The data obtained greatly expand our knowledge of the bioactive constituents of Lilium spp. Additionally, it also highlights the potential application of Lilium plants as antioxidants, functional ingredients, cosmetic products and nutraceuticals. Full article

(This article belongs to the Special Issue New Insights into Phytochemical Antioxidants in Food)

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13 pages, 1680 KiB

Open AccessArticle

Anti-Sarcopenic Obesity Effects of Lonicera caerulea Extract in High-Fat Diet-Fed Mice

by You-Suk Lee, Eun-Jung Park, Sung-Min Kim, Jong-Yeon Kim and Hae-Jeung Lee

Antioxidants 2021, 10(10), 1633; https://doi.org/10.3390/antiox10101633 - 17 Oct 2021

Cited by 8 | Viewed by 3791

Abstract

Sarcopenic obesity is a combination of sarcopenia and obesity. Although several herbal extracts showed improvement on sarcopenia and obesity, respectively, there are few studies on sarcopenic obesity. Lonicera caerulea (honeysuckle berry, HB) can ameliorate metabolic disorders including obesity. However, its effects on sarcopenic [...] Read more.

Sarcopenic obesity is a combination of sarcopenia and obesity. Although several herbal extracts showed improvement on sarcopenia and obesity, respectively, there are few studies on sarcopenic obesity. Lonicera caerulea (honeysuckle berry, HB) can ameliorate metabolic disorders including obesity. However, its effects on sarcopenic obesity have not been reported yet. Thus, the aim of this study was to investigate whether HB extract might have any beneficial effects on sarcopenic obesity in high-fat diet-induced mice. Forty-eight mice were classified into six groups and treated for eight weeks: (1) NC, normal diet control; (2) HC, high-fat diet control; (3) PC, high-fat diet with orlistat; (4) HB100, high-fat diet with HB extract at 100 mg/kg; (5) HB200, high-fat diet with HB extract at 200 mg/kg; and (6) HB400, high-fat diet with HB extract at 400 mg/kg. Body weight, fat accumulation, muscle mass, muscle strength, and mRNA expression of muscle atrophy were monitored. Compared with the HC group, HB administration showed anti-obesity properties. It reduced body weight gain and modulated serum biochemical parameters and tissue antioxidant enzymes. HB also increased muscle strength and muscle mass of hind legs. In addition, it decreased mRNA expression levels of Atrogin1 and MuRF1 as markers of muscle atrophy but increased PGC1α and SIRT1 as markers of muscle growth. These results suggest that HB might be effective in preventing sarcopenia associated with obesity. Full article

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17 pages, 3597 KiB

Open AccessArticle

The Recovery of Cognitive and Affective Deficiencies Linked with Chronic Osteoarthritis Pain and Implicated Pathways by Slow-Releasing Hydrogen Sulfide Treatment

by Gerard Batallé, Xue Bai, Enric Pouso-Vázquez, Gerard Roch, Laura Rodríguez and Olga Pol

Antioxidants 2021, 10(10), 1632; https://doi.org/10.3390/antiox10101632 - 16 Oct 2021

Cited by 12 | Viewed by 2534

Abstract

Chronic osteoarthritis pain is accompanied by several comorbidities whose treatment has not been completely resolved. The anti-inflammatory, analgesic, and antidepressant effects of slow-releasing hydrogen sulfide (H₂S) donors during osteoarthritic pain have been shown, but their actions in the accompanying memory impairment [...] Read more.

Chronic osteoarthritis pain is accompanied by several comorbidities whose treatment has not been completely resolved. The anti-inflammatory, analgesic, and antidepressant effects of slow-releasing hydrogen sulfide (H₂S) donors during osteoarthritic pain have been shown, but their actions in the accompanying memory impairment and anxious-like behaviors have not yet been demonstrated. Using female mice with chronic osteoarthritic pain, the effects of natural, diallyl disulfide (DADS) or synthetic, morpholin-4-ium 4-methoxyphenyl(morpholino) phosphinodithioate dichloromethane complex (GYY4137) slow-releasing H₂S donors, on associated cognitive and grip strength deficits and anxiodepressive-like behaviors, were assessed. Their effects on specific brain areas implicated in the modulation of pain and emotional responses were also determined. Results demonstrated an improvement in memory and grip strength deficits, as well as in the anxious-like behaviors associated with chronic pain in GYY4137 and/or DADS treated mice. The painkiller and antidepressant properties of both treatments were also established. Treatment with DADS and/or GYY4137 inhibited: oxidative stress in the amygdala; phosphoinositide 3-kinase overexpression in the amygdala, periaqueductal gray matter, and anterior cingulate cortex; protein kinase B activation in the amygdala and infralimbic cortex; up-regulation of inducible nitric oxide synthase in the amygdala, periaqueductal gray matter and infralimbic cortex and apoptotic responses in the amygdala. These results might explain the recovery of memory and grip strength and the inhibition of allodynia and associated anxiodepressive-like behaviors by these treatments. In conclusion, this study revealed new properties of slow-releasing H₂S donors in cognitive impairment and affective disorders linked with chronic osteoarthritis pain and their effects on the central nervous system. Full article

(This article belongs to the Special Issue Antioxidants in Chronic Pain II)

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18 pages, 929 KiB

Open AccessReview

Protein Persulfidation in Plants: Function and Mechanism

by Peng Wang, Hua Fang, Rong Gao and Weibiao Liao

Antioxidants 2021, 10(10), 1631; https://doi.org/10.3390/antiox10101631 - 16 Oct 2021

Cited by 10 | Viewed by 2524

Abstract

As an endogenous gaseous transmitter, the function of hydrogen sulfide (H₂S) has been extensively studied in plants. Once synthesized, H₂S may be involved in almost all life processes of plants. Among them, a key route for H₂S [...] Read more.

As an endogenous gaseous transmitter, the function of hydrogen sulfide (H₂S) has been extensively studied in plants. Once synthesized, H₂S may be involved in almost all life processes of plants. Among them, a key route for H₂S bioactivity occurs via protein persulfidation, in which process oxidizes cysteine thiol (R-SH) groups into persulfide (R-SSH) groups. This process is thought to underpin a myriad of cellular processes in plants linked to growth, development, stress responses, and phytohormone signaling. Multiple lines of emerging evidence suggest that this redox-based reversible post-translational modification can not only serve as a protective mechanism for H₂S in oxidative stress, but also control a variety of biochemical processes through the allosteric effect of proteins. Here, we collate emerging evidence showing that H₂S-mediated persulfidation modification involves some important biochemical processes such as growth and development, oxidative stress, phytohormone and autophagy. Additionally, the interaction between persulfidation and S-nitrosylation is also discussed. In this work, we provide beneficial clues for further exploration of the molecular mechanism and function of protein persulfidation in plants in the future. Full article

(This article belongs to the Special Issue Plant and Human Sulfur Biology)

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18 pages, 1437 KiB

Open AccessReview

Identification and Recovery of Valuable Bioactive Compounds from Potato Peels: A Comprehensive Review

by Beatriz Rodríguez-Martínez, Beatriz Gullón and Remedios Yáñez

Antioxidants 2021, 10(10), 1630; https://doi.org/10.3390/antiox10101630 - 16 Oct 2021

Cited by 26 | Viewed by 5790

Abstract

Nowadays, the potato is one of the most cultivated and consumed food crops in the world and, in recent years, its production has experienced a sharp increase. Its industrial processing generates several by-products that are wasted and cause economic and environmental problems. Among [...] Read more.

Nowadays, the potato is one of the most cultivated and consumed food crops in the world and, in recent years, its production has experienced a sharp increase. Its industrial processing generates several by-products that are wasted and cause economic and environmental problems. Among them, potato peel stands out, representing up to 10% of the total potato residues obtained in the processing. On the other hand, these wastes, in addition to presenting antioxidant compounds, are rich in interesting chemical compounds of great value in a biorefinery model. This review summarizes the main compounds present in potato skins as well as the most used and innovative extraction methods employed for their isolation, with special emphasis on the fractions with biological activities. In addition, a sustainable biorefinery proposal focused on obtaining high added-value products with potential applications in the pharmaceutical, food, nutraceutical, or cosmetic industries is included. Full article

(This article belongs to the Special Issue Advances in Natural Antioxidants for Food Improvement)

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20 pages, 4175 KiB

Open AccessArticle

Anticancer Potential of Lipophilic Constituents of Eleven Shellfish Species Commonly Consumed in Korea

by Juhyun Shin, Min-Ho Song, Ji-Woo Yu, Eun-Young Ko, Xiaomin Shang, Jae-Wook Oh, Young-Soo Keum and Ramesh Kumar Saini

Antioxidants 2021, 10(10), 1629; https://doi.org/10.3390/antiox10101629 - 15 Oct 2021

Cited by 4 | Viewed by 2537

Abstract

The present study was aimed to investigate the composition and contents and the major lipophilic compounds, including the sterols, fatty acids, and tocols of shellfish species. Moreover, to explore the antitumor activity of these lipophilic constituents, their cytotoxicity potentials were determined against five [...] Read more.

The present study was aimed to investigate the composition and contents and the major lipophilic compounds, including the sterols, fatty acids, and tocols of shellfish species. Moreover, to explore the antitumor activity of these lipophilic constituents, their cytotoxicity potentials were determined against five different human cancer cells, including colon carcinoma (HCT116), epithelial melanoma (A2058), glioblastoma multiforme (T98G), lung carcinoma (A549), and adenocarcinoma (HeLa). The results show a significant variation in the contents and composition of lipophilic constituents among the studied species. The highest omega-3 (n-3) polyunsaturated fatty acids (PUFAs) were recorded from arrow squid and pacific oysters, accounting for 53.2% and 53.0% of their total fatty acids, respectively. However, the highest cholesterol content was also recorded in arrow squid (154.4 mg/100 g; 92.6% of total sterols). In contrast, in the Japanese littleneck, Yesso scallop, and common orient clam, cholesterol was just 17.1%, 18.3%, and 18.9% of total sterols, respectively, making them the richest source of non-cholesterol sterols (NCS). Lipids extracted from shellfish species showed ABTS^+•- and DPPH^•-scavenging activities. In the cytotoxicity analysis, lipids extracted from the Argentine red shrimp showed the highest cytotoxicity against glioblastoma multiforme T98G cells, with an IC₅₀ value of 12.3 µg/mL. The composition and cytotoxicity data reported herein may help explore the nutritional and anticancer potentials of shellfish species. Full article

(This article belongs to the Special Issue Natural Products: Biological-, Antioxidant Properties and Health Effects)

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46 pages, 2005 KiB

Open AccessReview

Anti-Oxidative, Anti-Inflammatory and Anti-Apoptotic Effects of Flavonols: Targeting Nrf2, NF-κB and p53 Pathways in Neurodegeneration

by Maja Jazvinšćak Jembrek, Nada Oršolić, Lucija Mandić, Anja Sadžak and Suzana Šegota

Antioxidants 2021, 10(10), 1628; https://doi.org/10.3390/antiox10101628 - 15 Oct 2021

Cited by 28 | Viewed by 4284

Abstract

Neurodegenerative diseases are one of the leading causes of disability and death worldwide. Intracellular transduction pathways that end in the activation of specific transcription factors are highly implicated in the onset and progression of pathological changes related to neurodegeneration, of which those related [...] Read more.

Neurodegenerative diseases are one of the leading causes of disability and death worldwide. Intracellular transduction pathways that end in the activation of specific transcription factors are highly implicated in the onset and progression of pathological changes related to neurodegeneration, of which those related to oxidative stress (OS) and neuroinflammation are particularly important. Here, we provide a brief overview of the key concepts related to OS- and neuroinflammation-mediated neuropathological changes in neurodegeneration, together with the role of transcription factors nuclear factor erythroid 2–related factor 2 (Nrf2) and nuclear factor-κB (NF-κB). This review is focused on the transcription factor p53 that coordinates the cellular response to diverse genotoxic stimuli, determining neuronal death or survival. As current pharmacological options in the treatment of neurodegenerative disease are only symptomatic, many research efforts are aimed at uncovering efficient disease-modifying agents. Natural polyphenolic compounds demonstrate powerful anti-oxidative, anti-inflammatory and anti-apoptotic effects, partially acting as modulators of signaling pathways. Herein, we review the current understanding of the therapeutic potential and limitations of flavonols in neuroprotection, with emphasis on their anti-oxidative, anti-inflammatory and anti-apoptotic effects along the Nrf2, NF-κB and p53 pathways. A better understanding of cellular and molecular mechanisms of their action may pave the way toward new treatments. Full article

(This article belongs to the Special Issue Oxidative Stress, Neuroinflammation and Neurodegeneration)

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23 pages, 654 KiB

Open AccessReview

Omega−3 Polyunsaturated Fatty Acids (PUFAs): Emerging Plant and Microbial Sources, Oxidative Stability, Bioavailability, and Health Benefits—A Review

by Ramesh Kumar Saini, Parchuri Prasad, Reddampalli Venkataramareddy Sreedhar, Kamatham Akhilender Naidu, Xiaomin Shang and Young-Soo Keum

Antioxidants 2021, 10(10), 1627; https://doi.org/10.3390/antiox10101627 - 15 Oct 2021

Cited by 106 | Viewed by 10301

Abstract

The omega−3 (n−3) polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic (DHA) acid are well known to protect against numerous metabolic disorders. In view of the alarming increase in the incidence of chronic diseases, consumer interest and demand are rapidly increasing for [...] Read more.

The omega−3 (n−3) polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic (DHA) acid are well known to protect against numerous metabolic disorders. In view of the alarming increase in the incidence of chronic diseases, consumer interest and demand are rapidly increasing for natural dietary sources of n−3 PUFAs. Among the plant sources, seed oils from chia (Salvia hispanica), flax (Linum usitatissimum), and garden cress (Lepidium sativum) are now widely considered to increase α-linolenic acid (ALA) in the diet. Moreover, seed oil of Echium plantagineum, Buglossoides arvensis, and Ribes sp. are widely explored as a source of stearidonic acid (SDA), a more effective source than is ALA for increasing the EPA and DHA status in the body. Further, the oil from microalgae and thraustochytrids can also directly supply EPA and DHA. Thus, these microbial sources are currently used for the commercial production of vegan EPA and DHA. Considering the nutritional and commercial importance of n−3 PUFAs, this review critically discusses the nutritional aspects of commercially exploited sources of n−3 PUFAs from plants, microalgae, macroalgae, and thraustochytrids. Moreover, we discuss issues related to oxidative stability and bioavailability of n−3 PUFAs and future prospects in these areas. Full article

(This article belongs to the Special Issue Antioxidants in Foods II)

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12 pages, 3275 KiB

Open AccessArticle

Cimicifugae Rhizoma Extract Attenuates Oxidative Stress and Airway Inflammation via the Upregulation of Nrf2/HO-1/NQO1 and Downregulation of NF-κB Phosphorylation in Ovalbumin-Induced Asthma

by Je-Oh Lim, Kwang Hoon Song, Ik Soo Lee, Se-Jin Lee, Woong-Il Kim, So-Won Pak, In-Sik Shin and Taesoo Kim

Antioxidants 2021, 10(10), 1626; https://doi.org/10.3390/antiox10101626 - 15 Oct 2021

Cited by 24 | Viewed by 2428

Abstract

Cimicifugae Rhizoma has been used as a medicinal herb for fever, pain, and inflammation in East Asia. We conducted this study because the effect of Cimicifugae Rhizoma extract (CRE) on allergic asthma has not yet been evaluated. To induce allergic airway inflammation, we [...] Read more.

Cimicifugae Rhizoma has been used as a medicinal herb for fever, pain, and inflammation in East Asia. We conducted this study because the effect of Cimicifugae Rhizoma extract (CRE) on allergic asthma has not yet been evaluated. To induce allergic airway inflammation, we intraperitoneally injected ovalbumin (OVA) mixed with aluminum hydroxide into mice twice at intervals of 2 weeks (Days 0 and 14) and then inhaled them thrice with 1% OVA solution using a nebulizer (Days 21 to 23). CRE (30 and 100 mg/kg) was administered orally daily for 6 days (Days 18 to 23). The mice showed remarkable reduction in allergic inflammation at 100 mg/kg of CRE, as evidenced by decreased inflammatory cell counts, pro-inflammatory cytokine levels, OVA-specific immunoglobulin E level, airway hyperresponsiveness, and production of mucus. Additionally, these effects were involved with the enhancement of heme oxygenase-1 (HO-1), NAD(P)H: quinone oxidoreductase (NQO1), and nuclear factor erythroid 2-related factor 2 (Nrf2) expression and reduction of nuclear factor-κB (NF-κB) phosphorylation and matrix metalloproteinase-9 expression. Our findings indicated that CRE effectively protected against OVA-induced inflammation and oxidative stress via upregulation of the Nrf2/HO-1/NQO1 signaling and downregulation of NF-κB phosphorylation in asthma caused by OVA. Full article

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15 pages, 1742 KiB

Open AccessArticle

Taxifolin as a Promising Ingredient of Cosmetics for Adult Skin

by Iwona Micek, Joanna Nawrot, Agnieszka Seraszek-Jaros, Dorota Jenerowicz, Grzegorz Schroeder, Tomasz Spiżewski, Adela Suchan, Mariola Pawlaczyk and Justyna Gornowicz-Porowska

Antioxidants 2021, 10(10), 1625; https://doi.org/10.3390/antiox10101625 - 15 Oct 2021

Cited by 13 | Viewed by 2712

Abstract

Active substances, effective in the reduction in or delay of skin changes caused by aging occurring in natural compounds, are desirable. Taxifolin (TXF), a flavonoid of strong antioxidant activity found in the plant Stizolophus balsamita (S. balsamita), has been tested for [...] Read more.

Active substances, effective in the reduction in or delay of skin changes caused by aging occurring in natural compounds, are desirable. Taxifolin (TXF), a flavonoid of strong antioxidant activity found in the plant Stizolophus balsamita (S. balsamita), has been tested for its biological effects on adult human skin. The aim of the study was to investigate the effects of two creams: 3% S. balsamita extract and 3% TXF on the function of adult skin. In total, 97 Caucasian women with clinical signs of skin aging were investigated. The biophysical and biomechanical skin parameters were measured before and after applying the creams, using Colorimeter CL400, Mexameter MX16, Skin-pH-Meter PH900, Skin-Thermometer ST 500, Glossymeter GL200, and Cutiscan SC100. Patch tests were performed with the investigated products to assess their potential irritant properties. The percutaneous penetration of creams was examined with the use of electrospray ionization mass spectrometry (ESI-MS) and confocal Raman spectroscopy. The 3% S. balsamita extract cream reduced hyperpigmentation, erythema, and elevated pH. All the tested preparations were proven to be nonirritant. A higher penetration rate was revealed for the 3% TXF cream than for the 3% S. balsamita extract cream. A total of 3% TXF cream improved skin viscoelasticity. The obtained results suggested that S. balsamita extract and TXF may be considered as ingredients of skincare products for adults. Full article

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22 pages, 8307 KiB

Open AccessArticle

Histochrome Attenuates Myocardial Ischemia-Reperfusion Injury by Inhibiting Ferroptosis-Induced Cardiomyocyte Death

by Ji-Won Hwang, Jae-Hyun Park, Bong-Woo Park, Hyeok Kim, Jin-Ju Kim, Woo-Sup Sim, Natalia P. Mishchenko, Sergey A. Fedoreyev, Elena A. Vasileva, Kiwon Ban, Hun-Jun Park and Sang-Hong Baek

Antioxidants 2021, 10(10), 1624; https://doi.org/10.3390/antiox10101624 - 15 Oct 2021

Cited by 38 | Viewed by 3905

Abstract

Reactive oxygen species (ROS) and intracellular iron levels are critical modulators of lipid peroxidation that trigger iron-dependent non-apoptotic ferroptosis in myocardial ischemia-reperfusion (I/R) injury. Histochrome (HC), with a potent antioxidant moiety and iron-chelating capacity, is now available in clinical practice. However, limited data [...] Read more.

Reactive oxygen species (ROS) and intracellular iron levels are critical modulators of lipid peroxidation that trigger iron-dependent non-apoptotic ferroptosis in myocardial ischemia-reperfusion (I/R) injury. Histochrome (HC), with a potent antioxidant moiety and iron-chelating capacity, is now available in clinical practice. However, limited data are available about the protective effects of HC on ferroptotic cell death in myocardial I/R injury. In this study, we investigated whether the intravenous administration of HC (1 mg/kg) prior to reperfusion could decrease myocardial damage by reducing ferroptosis. Rats undergoing 60 min of ischemia and reperfusion were randomly divided into three groups as follows: (1) Sham, (2) I/R control, and (3) I/R + HC. Serial echocardiography up to four weeks after I/R injury showed that intravenous injection of HC significantly improved cardiac function compared to the I/R controls. In addition, the hearts of rats who received intravenous injection of HC exhibited significantly lower cardiac fibrosis and higher capillary density. HC treatment decreased intracellular and mitochondrial ROS levels by upregulating the expression of nuclear factor erythroid 2-related factor (Nrf2) and its downstream genes. HC also inhibited erastin- and RSL3-induced ferroptosis in rat neonatal cardiomyocytes by maintaining the intracellular glutathione level and through upregulated activity of glutathione peroxidase 4. These findings suggest that early intervention with HC before reperfusion rescued myocardium from I/R injury by preventing ferroptotic cell death. Therefore, HC is a promising therapeutic option to provide secondary cardioprotection in patients who undergo coronary reperfusion therapy. Full article

(This article belongs to the Special Issue Natural Antioxidant in Cardiovascular and Cerebrovascular Diseases)

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18 pages, 2703 KiB

Open AccessArticle

Influence of Redox Imbalances on the Transposition of Insertion Sequences in Deinococcus geothermalis

by Qianying Ye, Chanjae Lee, Eunjung Shin and Sung-Jae Lee

Antioxidants 2021, 10(10), 1623; https://doi.org/10.3390/antiox10101623 - 15 Oct 2021

Cited by 5 | Viewed by 1678

Abstract

The transposition of insertion sequence elements was evaluated among different Deinococcus geothermalis lineages, including the wild-type, a cystine importer-disrupted mutant, a complemented strain, and a cystine importer-overexpressed strain. Cellular growth reached early exponential growth at OD₆₀₀ 2.0 and late exponential growth at [...] Read more.

The transposition of insertion sequence elements was evaluated among different Deinococcus geothermalis lineages, including the wild-type, a cystine importer-disrupted mutant, a complemented strain, and a cystine importer-overexpressed strain. Cellular growth reached early exponential growth at OD₆₀₀ 2.0 and late exponential growth at OD₆₀₀ 4.0. Exposing the cells to hydrogen peroxide (80–100 mM) resulted in the transposition of insertion sequences (ISs) in genes associated with the carotenoid biosynthesis pathway. Particularly, ISDge7 (an IS5 family member) and ISDge5 (an IS701 family member) from the cystine importer-disrupted mutant were transposed into phytoene desaturase (dgeo_0524) via replicative transposition. Further, the cystine importer-overexpressed strain Δdgeo_1985R showed transposition of both ISDge2 and ISDge5 elements. In contrast, IS transposition was not detected in the complementary strain. Interestingly, a cystine importer-overexpressing strain exhibited streptomycin resistance, indicating that point mutation occurred in the rpsL (dgeo_1873) gene encoding ribosomal protein S12. qRT-PCR analyses were then conducted to evaluate the expression of oxidative stress response genes, IS elements, and low-molecular-weight thiol compounds such as mycothiol and bacillithiol. Nevertheless, the mechanisms that trigger IS transposition in redox imbalance conditions remain unclear. Here, we report that the active transposition of different IS elements was affected by intracellular redox imbalances caused by cystine importer deficiencies or overexpression. Full article

(This article belongs to the Special Issue Redox Biology in Microorganisms)

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23 pages, 2695 KiB

Open AccessReview

Metabolomics of Chlorophylls and Carotenoids: Analytical Methods and Metabolome-Based Studies

by María Roca and Antonio Pérez-Gálvez

Antioxidants 2021, 10(10), 1622; https://doi.org/10.3390/antiox10101622 - 15 Oct 2021

Cited by 9 | Viewed by 2856

Abstract

Chlorophylls and carotenoids are two families of antioxidants present in daily ingested foods, whose recognition as added-value ingredients runs in parallel with the increasing number of demonstrated functional properties. Both groups include a complex and vast number of compounds, and extraction and analysis [...] Read more.

Chlorophylls and carotenoids are two families of antioxidants present in daily ingested foods, whose recognition as added-value ingredients runs in parallel with the increasing number of demonstrated functional properties. Both groups include a complex and vast number of compounds, and extraction and analysis methods evolved recently to a modern protocol. New methodologies are more potent, precise, and accurate, but their application requires a better understanding of the technical and biological context. Therefore, the present review compiles the basic knowledge and recent advances of the metabolomics of chlorophylls and carotenoids, including the interrelation with the primary metabolism. The study includes material preparation and extraction protocols, the instrumental techniques for the acquisition of spectroscopic and spectrometric properties, the workflows and software tools for data pre-processing and analysis, and the application of mass spectrometry to pigment metabolomics. In addition, the review encompasses a critical description of studies where metabolomics analyses of chlorophylls and carotenoids were developed as an approach to analyzing the effects of biotic and abiotic stressors on living organisms. Full article

(This article belongs to the Special Issue Antioxidant Capacity of Anthocyanins and other Vegetal Pigments: Modern Assisted Extraction Methods and Analysis)

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1 pages, 187 KiB

Open AccessErratum

Erratum: Altomare et al. In-Depth AGE and ALE Profiling of Human Albumin in Heart Failure: Ex Vivo Studies. Antioxidants 2021, 10, 358

by Alessandra Altomare, Giovanna Baron, Marta Balbinot, Alma Martínez Fernández, Alessandro Pedretti, Beatrice Zoanni, Maura Brioschi, Piergiuseppe Agostoni, Marina Carini, Cristina Banfi and Giancarlo Aldini

Antioxidants 2021, 10(10), 1621; https://doi.org/10.3390/antiox10101621 - 15 Oct 2021

Cited by 1 | Viewed by 1018

Abstract

The authors of this paper [...] Full article

18 pages, 38715 KiB

Open AccessArticle

Salvianolic Acid C Protects against Cisplatin-Induced Acute Kidney Injury through Attenuation of Inflammation, Oxidative Stress and Apoptotic Effects and Activation of the CaMKK–AMPK–Sirt1-Associated Signaling Pathway in Mouse Models

by Liang-Hsuan Chien, Chien-Ta Wu, Jeng-Shyan Deng, Wen-Ping Jiang, Wen-Chin Huang and Guan-Jhong Huang

Antioxidants 2021, 10(10), 1620; https://doi.org/10.3390/antiox10101620 - 15 Oct 2021

Cited by 17 | Viewed by 3279

Abstract

Acute kidney injury (AKI) is a sudden reduction in kidney activity and has a high mortality rate. Salvianolic acid C (SAC), one of the main polyphenolic components of Salvia miltiorrhiza, displays significant pharmacologically active effects. An animal model of cisplatin-induced kidney injury [...] Read more.

Acute kidney injury (AKI) is a sudden reduction in kidney activity and has a high mortality rate. Salvianolic acid C (SAC), one of the main polyphenolic components of Salvia miltiorrhiza, displays significant pharmacologically active effects. An animal model of cisplatin-induced kidney injury was used to study the potential of SAC to improve AKI. First, SAC was administered intraperitoneally in mice for 10 consecutive days, and then cisplatin was administered intraperitoneally on day 7 to establish a nephrotoxicity mouse model. SAC mitigated renal histological changes, blood creatinine (CRE) and blood urea nitrogen (BUN) production and the levels of inflammatory mediators in the cisplatin-induced AKI. Furthermore, malondialdehyde (MDA) levels were reduced and glutathione (GSH) was increased after intraperitoneal injection (i.p.) administration of SAC. In addition, based on Western blot data, SAC reduced the expression of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) activation in mouse renal tissues. Finally, SAC diminished the level of TLR-4 expression and enhanced the production of several antioxidative enzymes (superoxidase dismutase (SOD1), glutathione peroxidase (GPx3), catalase, nuclear-factor-erythroid-2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1)), Sirtuin 1 (Sirt1), p-AMP-activated protein kinase (AMPK) and p-Ca²⁺/calmodulin-dependent protein kinase kinase (CaMKK). In addition, Sirt1 inhibition (EX 527) inverted the effect of SAC against cisplatin-induced nephrotoxicity. Collectively, SAC provides a therapeutic target with promising clinical potential after cisplatin treatment by attenuating oxidative stress and inflammation. Full article

(This article belongs to the Special Issue Redox Regulation in Inflammation and Disease)

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10 pages, 1081 KiB

Open AccessArticle

Hydroxytyrosol-Fortified Foods Obtained by Supercritical Fluid Extraction of Olive Oil

by Lucia Bartella, Fabio Mazzotti, Ines Rosita Talarico, Ilaria Santoro and Leonardo Di Donna

Antioxidants 2021, 10(10), 1619; https://doi.org/10.3390/antiox10101619 - 14 Oct 2021

Cited by 6 | Viewed by 1820

Abstract

A new original process has been set-up to obtain hydroxytyrosol-enriched food by means of CO₂ supercritical fluid extraction. The process is based on the direct adsorption of hydroxytyrosol on selected foodstuff (e.g., flour, whole-wheat flour, and sugar) when placed in contact with [...] Read more.

A new original process has been set-up to obtain hydroxytyrosol-enriched food by means of CO₂ supercritical fluid extraction. The process is based on the direct adsorption of hydroxytyrosol on selected foodstuff (e.g., flour, whole-wheat flour, and sugar) when placed in contact with olive oil (which is known to contain this phenol) under controlled temperature and pressure conditions of supercritical CO₂. The transfer of the nutraceutical to the foodstuff was initially evaluated using a fortified olive oil model and was then applied to commercial olive oil and foodstuff. The yield of the hydroxytyrosol transfer was demonstrated to be quantitative. In order to prove the suitability of the final products, hydroxytyrosol-enriched flour was used to prepare a bread roll, which maintained the nutraceutical characteristics after the cooking. Finally, DPPH based experiments were performed to prove the radical scavenging activity of the functionalized foodstuff. Full article

(This article belongs to the Special Issue Fortification of Food Products with Antioxidant-Rich Materials)

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17 pages, 4075 KiB

Open AccessArticle

FRI-1 Is an Anti-Cancer Isoquinolinequinone That Inhibits the Mitochondrial Bioenergetics and Blocks Metabolic Shifts by Redox Disruption in Breast Cancer Cells

by Miguel Córdova-Delgado, Sebastián Fuentes-Retamal, Charlotte Palominos, Camila López-Torres, Daniela Guzmán-Rivera, Oney Ramírez-Rodríguez, Ramiro Araya-Maturana and Félix A. Urra

Antioxidants 2021, 10(10), 1618; https://doi.org/10.3390/antiox10101618 - 14 Oct 2021

Cited by 11 | Viewed by 2530

Abstract

Since breast cancer (BC) cells are dependent on mitochondrial bioenergetics for promoting proliferation, survival, and metastasis, mitochondria highlight as an important target for anticancer drug discovery. FRI-1, methyl 1, 3-dimethyl-5, 8-dioxo-5, 8-dihydro-4-isoquinolinecarboxylate, was previously described as a selective cytotoxic compound on cancer cell [...] Read more.

Since breast cancer (BC) cells are dependent on mitochondrial bioenergetics for promoting proliferation, survival, and metastasis, mitochondria highlight as an important target for anticancer drug discovery. FRI-1, methyl 1, 3-dimethyl-5, 8-dioxo-5, 8-dihydro-4-isoquinolinecarboxylate, was previously described as a selective cytotoxic compound on cancer cell lines, however, details on the mechanism of action remain unknown. In this work, we describe that FRI-1 inhibits mitochondrial bioenergetics, producing apoptosis in MCF7 and MDA-MB-231 BC cell lines. FRI-1 decreases the maximal oxygen consumption rate (OCR), Δψm, NADH, and ATP levels, with a notable increase of mitochondrial reactive oxygen species (ROS) production, promoting AMPK activation with pro-survival effects. Moreover, FRI-1 inhibits the metabolic remodeling to glycolysis induced by oligomycin. In isolated tumoral mitochondria, FRI-1 increases Complex I and III-dependent OCR state 2, and this is sensitive to rotenone and antimycin A inhibitor additions, suggesting a redox cycling event. Remarkably, α-ketoglutarate and lipoic acid supplementation reversed and promoted, respectively, the FRI-1-induced apoptosis, suggesting that mitochondrial redox disruption affects 2-oxoglutarate dehydrogenase (OGDH) activity, and this is involved in their anticancer mechanism. Consistent with this, the combination of FRI-1 and CPI-613, a dual inhibitor of redox-sensible tricarboxylic acid (TCA) cycle enzymes PDH and OGDH, produced extensive BC cell death. Taken together, our results suggest that FRI-1 exhibits anticancer effects through inhibition of mitochondrial bioenergetics by redox disruption in BC cells. Full article

(This article belongs to the Special Issue Mitochondrial Redox Regulations)

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14 pages, 2604 KiB

Open AccessArticle

A Novel Sesquiterpene Lactone Xanthatin-13-(pyrrolidine-2-carboxylic acid) Isolated from Burdock Leaf Up-Regulates Cells’ Oxidative Stress Defense Pathway

by Yanis A. Idres, Didier Tousch, Guillaume Cazals, Aurélien Lebrun, Sarah Naceri, Luc P. R. Bidel and Patrick Poucheret

Antioxidants 2021, 10(10), 1617; https://doi.org/10.3390/antiox10101617 - 14 Oct 2021

Cited by 5 | Viewed by 2349

Abstract

The aim of our study was to identify novel molecules able to induce an adaptative response against oxidative stress during the first stages of metabolic syndrome. A cellular survival in vitro test against H₂O₂-based test was applied after pretreatment [...] Read more.

The aim of our study was to identify novel molecules able to induce an adaptative response against oxidative stress during the first stages of metabolic syndrome. A cellular survival in vitro test against H₂O₂-based test was applied after pretreatment with various natural bitter Asteraceae extracts. This screening revealed potent protection from burdock leaf extract. Using chromatography and LC-MS—RMN, we then isolated and identified an original sesquiterpene lactone bioactive molecule: the Xanthatin-13-(pyrrolidine-2-carboxylic acid) (XPc). A real-time RT-qPCR experiment was carried out on three essential genes involved in oxidative stress protection: GPx, SOD, and G6PD. In presence of XPc, an over-expression of the G6PD gene was recorded, whereas no modification of the two others genes could be observed. A biochemical docking approach demonstrated that XPc had a high probability to directly interact with G6PD at different positions. One of the most probable docking sites corresponds precisely to the binding site of AG1, known to stabilize the G6PD dimeric form and enhance its activity. In conclusion, this novel sesquiterpene lactone XPc might be a promising prophylactic bioactive agent against oxidative stress and inflammation in chronic diseases such as metabolic syndrome or type 2 diabetes. Full article

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31 pages, 2900 KiB

Open AccessReview

Reactive Oxygen Species in Acute Lymphoblastic Leukaemia: Reducing Radicals to Refine Responses

by Abdul Mannan, Zacary P. Germon, Janis Chamberlain, Jonathan R. Sillar, Brett Nixon and Matthew D. Dun

Antioxidants 2021, 10(10), 1616; https://doi.org/10.3390/antiox10101616 - 14 Oct 2021

Cited by 9 | Viewed by 3657

Abstract

Acute lymphoblastic leukaemia (ALL) is the most common cancer diagnosed in children and adolescents. Approximately 70% of patients survive >5-years following diagnosis, however, for those that fail upfront therapies, survival is poor. Reactive oxygen species (ROS) are elevated in a range of cancers [...] Read more.

Acute lymphoblastic leukaemia (ALL) is the most common cancer diagnosed in children and adolescents. Approximately 70% of patients survive >5-years following diagnosis, however, for those that fail upfront therapies, survival is poor. Reactive oxygen species (ROS) are elevated in a range of cancers and are emerging as significant contributors to the leukaemogenesis of ALL. ROS modulate the function of signalling proteins through oxidation of cysteine residues, as well as promote genomic instability by damaging DNA, to promote chemotherapy resistance. Current therapeutic approaches exploit the pro-oxidant intracellular environment of malignant B and T lymphoblasts to cause irreversible DNA damage and cell death, however these strategies impact normal haematopoiesis and lead to long lasting side-effects. Therapies suppressing ROS production, especially those targeting ROS producing enzymes such as the NADPH oxidases (NOXs), are emerging alternatives to treat cancers and may be exploited to improve the ALL treatment. Here, we discuss the roles that ROS play in normal haematopoiesis and in ALL. We explore the molecular mechanisms underpinning overproduction of ROS in ALL, and their roles in disease progression and drug resistance. Finally, we examine strategies to target ROS production, with a specific focus on the NOX enzymes, to improve the treatment of ALL. Full article

(This article belongs to the Special Issue Reactive Oxygen Species (ROS), Haematopoiesis and Leukaemia)

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23 pages, 1972 KiB

Open AccessArticle

Redox-Modulating Capacity and Antineoplastic Activity of Wastewater Obtained from the Distillation of the Essential Oils of Four Bulgarian Oil-Bearing Roses

by Almira Georgieva, Yana Ilieva, Zlatina Kokanova-Nedialkova, Maya Margaritova Zaharieva, Paraskev Nedialkov, Ana Dobreva, Alexander Kroumov, Hristo Najdenski and Milka Mileva

Antioxidants 2021, 10(10), 1615; https://doi.org/10.3390/antiox10101615 - 14 Oct 2021

Cited by 10 | Viewed by 2845

Abstract

The wastewater from the distillation of rose oils is discharged directly into the soil because it has a limited potential for future applications. The aim of the present study was to determine in vitro the chromatographic profile, redox-modulating capacity, and antineoplastic activity of [...] Read more.

The wastewater from the distillation of rose oils is discharged directly into the soil because it has a limited potential for future applications. The aim of the present study was to determine in vitro the chromatographic profile, redox-modulating capacity, and antineoplastic activity of wastewater obtained by distillation of essential oils from the Bulgarian Rosa alba L., Rosa damascena Mill., Rosa gallica L., and Rosa centifolia L. We applied UHPLC-HRMS for chromatographic analysis of rose wastewaters, studied their metal-chelating and Fe(III)-reducing ability, and performed MTT assay for the evaluation of cytotoxic potential against three tumorigenic (HEPG2—hepatocellular adenocarcinoma, A-375—malignant melanoma, A-431—non-melanoma epidermoid squamous skin carcinoma) and one non-tumorigenic human cell lines (HaCaT—immortalized keratinocytes). The median inhibitory concentrations (IC₅₀) were calculated with nonlinear modeling using the MAPLE^® platform. The potential of the wastewaters to induce apoptosis was also examined. Mono-, di-, and acylated glycosides of quercetin and kaempferol, ellagic acid and its derivatives as main chemical components, and gallic acid and its derivatives—such as catechin and epicatechin—were identified. The redox-modulating capacity of the samples (TPTZ test) showed that all four wastewaters exhibited the properties of excellent heavy metal cleaners, but did not exert very strong cytotoxic effects. The lowest IC₅₀ rate was provided in wastewater from R. centifolia (34–35 µg/mL of gallic acid equivalents after a 72 h period for all cell lines). At 24 and 48 hours, the most resistant cell line was HEPG2, followed by HaCaT. After 72 h of exposure, the IC₅₀ values were similar for tumor and normal cells. Still, R. damascena had a selectivity index over 2.0 regarding A-431 non-melanoma skin cancer cells, showing a good toxicological safety profile in addition to moderate activity—IC₅₀ of 35 µg/mL polyphenols. The obtained results related to wastewaters acquired after the distillation of essential oils from the Bulgarian R. alba, R. damascena, R. gallica, and R. centifolia direct our attention to further studies for in-depth elucidation of their application as detoxifying agents under oxidative damage conditions in other experimental datasets. Full article

(This article belongs to the Special Issue Natural Products: Biological-, Antioxidant Properties and Health Effects)

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12 pages, 2306 KiB

Open AccessArticle

Antioxidant Activity and Inhibitory Effect on Nitric Oxide Production of Hydroponic Ginseng Fermented with Lactococcus lactis KC24

by Yerim Chung, Ji-Young Park, Ji-Eun Lee, Kee-Tae Kim and Hyun-Dong Paik

Antioxidants 2021, 10(10), 1614; https://doi.org/10.3390/antiox10101614 - 13 Oct 2021

Cited by 9 | Viewed by 2375

Abstract

Panax ginseng Meyer is used as a medicinal plant. The aim of this study was to ferment hydroponic ginseng with Lactococcus lactis KC24 and confirm its antioxidant activity and inhibitory effect on nitric oxide (NO) production. Flavonoid and phenol contents in fermented ginseng [...] Read more.

Panax ginseng Meyer is used as a medicinal plant. The aim of this study was to ferment hydroponic ginseng with Lactococcus lactis KC24 and confirm its antioxidant activity and inhibitory effect on nitric oxide (NO) production. Flavonoid and phenol contents in fermented ginseng extracts were measured. Antioxidant activity was measured by DPPH, ABTS, reducing power, FRAP and β-carotene assays. Additionally, inhibitory effects on NO production and toxicity of the fermented extract were determined using RAW 264.7 cells. Phenol and flavonoid contents increased as the fermentation time increased, and the contents were higher in hydroponic ginseng than in soil-cultivated ginseng. The DPPH assay revealed that the antioxidant activity of the 24 h fermented extract significantly increased from 32.57% to 41% (p < 0.05). The increase in antioxidant activity may be affected by an increase in phenol and flavonoid contents. At 1 mg/mL solid content, the 24 h fermented hydroponic ginseng extract inhibited NO production from 9.87 ± 0.06 μM to 1.62 ± 0.26 μM. In conclusion, the increase in antioxidant activity affects the inhibition of NO production, suggesting that fermented hydroponic ginseng may be used in the industries of functional food and pharmaceutical industry as a functional material with anti-inflammatory effects. Full article

(This article belongs to the Special Issue Antioxidants and Bioactive Compounds in Fermented Foods)

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Antioxidants, Volume 10, Issue 10 (October 2021) – 142 articles

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