Antioxidant Compounds and Health Benefits of Citrus Fruits

A special issue of Antioxidants (ISSN 2076-3921). This special issue belongs to the section "Natural and Synthetic Antioxidants".

Deadline for manuscript submissions: closed (20 February 2023) | Viewed by 42122

Special Issue Editors


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Guest Editor
Departament of Pathology, Center of Biological Sciences, Londrina State University, Londrina, Paraná 86057-970, Brazil
Interests: flavonoids; citrus fruits; oxidative stress; antioxidants; inflammation; infection; pain
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Guest Editor
Biosciences and Biotechnology Postgraduate Program, Carlos Chagas Institute (ICC/Fiocruz/PR), Curitiba, Paraná 81350-010, Brazil
Interests: immunology; tropical diseases; public health; parasitology; schistosomiasis

Special Issue Information

Dear Colleagues,

Citrus fruits are rich in several nutrients, including flavonoids and vitamin C. The biological properties of their constituents include antioxidant, anti-inflammatory, and analgesic actions, as well as microbicidal effects, among others. Research related to the therapeutic potential of their constituents has grown substantially in recent years. Major advances involving the mechanisms of action of these compounds have provided a better understanding of their biological effects. For example, many flavonoids can inhibit the activation of the pro-inflammatory transcription factor nuclear factor κB (NFκB), as well as inducing the activation of the antioxidant, anti-inflammatory, and analgesic nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. However, unravelling new potential mechanisms by which citrus fruit-derived compounds may modulate pathological conditions will contribute to bringing new knowledge on their properties and therapeutic applicability. In this sense, this Special Issue is intended to form a compilation of papers regarding novel advances in the pharmacological properties of citrus fruit-derived compounds covering, but not restricted to, inflammatory, infectious, and neurological diseases. We welcome the submission of studies including reviews, original research, and clinical trials.

Prof. Dr. Sergio Borghi
Prof. Dr. ‪Wander R. Pavanelli
Guest Editors

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Keywords

  • citrus fruits
  • flavonoids
  • antioxidants
  • oxidative stress
  • inflammation
  • infection
  • pain

Published Papers (10 papers)

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Editorial

Jump to: Research, Review

5 pages, 239 KiB  
Editorial
Antioxidant Compounds and Health Benefits of Citrus Fruits
by Sergio Marques Borghi and Wander Rogério Pavanelli
Antioxidants 2023, 12(8), 1526; https://doi.org/10.3390/antiox12081526 - 30 Jul 2023
Cited by 2 | Viewed by 1850
Abstract
Recent evidence emanating from epidemiological prospective studies shows that increased intakes of antioxidant-rich fruits, vegetables, and legumes are associated with a lower risk of developing chronic oxidative stress-related diseases like cardiovascular diseases and cancer, as well as with a lower risk of cardiovascular, [...] Read more.
Recent evidence emanating from epidemiological prospective studies shows that increased intakes of antioxidant-rich fruits, vegetables, and legumes are associated with a lower risk of developing chronic oxidative stress-related diseases like cardiovascular diseases and cancer, as well as with a lower risk of cardiovascular, cancer, and all-cause mortality rates [...] Full article
(This article belongs to the Special Issue Antioxidant Compounds and Health Benefits of Citrus Fruits)

Research

Jump to: Editorial, Review

17 pages, 8407 KiB  
Article
Pharmacologic Comparison of High-Dose Hesperetin and Quercetin on MDCK II Cell Viability, Tight Junction Integrity, and Cell Shape
by Mio Nakashima, Natsuko Goda, Takeshi Tenno, Ayaka Kotake, Yuko Inotsume, Minako Amaya and Hidekazu Hiroaki
Antioxidants 2023, 12(4), 952; https://doi.org/10.3390/antiox12040952 - 18 Apr 2023
Cited by 2 | Viewed by 2592
Abstract
The modulation of tight junction (TJ) integrity with small molecules is important for drug delivery. High-dose baicalin (BLI), baicalein (BLE), quercetin (QUE), and hesperetin (HST) have been shown to open TJs in Madin-Darby canine kidney (MDCK) II cells, but the mechanisms for HST [...] Read more.
The modulation of tight junction (TJ) integrity with small molecules is important for drug delivery. High-dose baicalin (BLI), baicalein (BLE), quercetin (QUE), and hesperetin (HST) have been shown to open TJs in Madin-Darby canine kidney (MDCK) II cells, but the mechanisms for HST and QUE remain unclear. In this study, we compared the effects of HST and QUE on cell proliferation, morphological changes, and TJ integrity. HST and QUE were found to have opposing effects on the MDCK II cell viability, promotion, and suppression, respectively. Only QUE, but not HST, induced a morphological change in MDCK II into a slenderer cell shape. Both HST and QUE downregulated the subcellular localization of claudin (CLD)-2. However, only QUE, but not HST, downregulated CLD-2 expression. Conversely, only HST was shown to directly bind to the first PDZ domain of ZO-1, a key molecule to promote TJ biogenesis. The TGFβ pathway partially contributed to the HST-induced cell proliferation, since SB431541 ameliorated the effect. In contrast, the MEK pathway was not involved by both the flavonoids, since U0126 did not revert their TJ-opening effect. The results offer insight for using HST or QUE as naturally occurring absorption enhancers through the paracellular route. Full article
(This article belongs to the Special Issue Antioxidant Compounds and Health Benefits of Citrus Fruits)
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12 pages, 2233 KiB  
Article
Spatial Distribution and Antioxidant Activity of Extracts from Citrus Fruits
by María García-Nicolás, Carlos A. Ledesma-Escobar and Feliciano Priego-Capote
Antioxidants 2023, 12(4), 781; https://doi.org/10.3390/antiox12040781 - 23 Mar 2023
Cited by 7 | Viewed by 1981
Abstract
Citrus fruits are recommended components of the human diet because of their enriched composition in bioactive compounds and health benefits. Among their notable components are phenols, with a special emphasis on flavonoids, limonoids, and carboxylic acids. In this research, we have carried out [...] Read more.
Citrus fruits are recommended components of the human diet because of their enriched composition in bioactive compounds and health benefits. Among their notable components are phenols, with a special emphasis on flavonoids, limonoids, and carboxylic acids. In this research, we have carried out a spatial metabolomics analysis for the characterization of these bioactive families in three citrus fruits, namely, lemons, limes, and mandarins. Sampling was undertaken, for which the juices and three fruit tissues, namely, albedo, flavedo, and segments, were analyzed. This characterization allowed for the determination of 49 bioactive compounds in all the samples. The composition of the different extracts was correlated with the antioxidant capacity measured by the DPPH radical scavenging activity and β-carotene bleaching assays. Flavonoids, found in the albedo and flavedo at higher concentrations, were the main components responsible for DPPH radical scavenging activity. On the other hand, the combined action of flavonoids and limonoids contributed to explaining the antioxidant activity measured by the β-carotene bleaching assay. Generally, the antioxidant capacity of juices was lower than that estimated for extracts from citrus tissues. Full article
(This article belongs to the Special Issue Antioxidant Compounds and Health Benefits of Citrus Fruits)
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14 pages, 1406 KiB  
Article
Skin Improvement with Antioxidant Effect of Yuja (Citrus junos) Peel Fractions: Wrinkles, Moisturizing, and Whitening
by Young Yun Jung, In Jin Ha, Mina Lee and Kwang Seok Ahn
Antioxidants 2023, 12(1), 51; https://doi.org/10.3390/antiox12010051 - 26 Dec 2022
Cited by 7 | Viewed by 2981
Abstract
Yuja (Citrus junos) has been cultivated and used for food and medicinal purposes in China and Korea. Its antioxidant, anti-wrinkle, moisturizing, and whitening effects were evaluated in HaCaT, HDF, and B16F10 cells. UVB has been known to cause cellular stress and [...] Read more.
Yuja (Citrus junos) has been cultivated and used for food and medicinal purposes in China and Korea. Its antioxidant, anti-wrinkle, moisturizing, and whitening effects were evaluated in HaCaT, HDF, and B16F10 cells. UVB has been known to cause cellular stress and the production of reactive oxygen species (ROS). Ambivalence of oxidative stress has been reported; however, excessive levels of ROS contribute to skin aging through the loss of elasticity and collagen fibers of connective tissue in the dermis. Skin aging is one of the biological processes that is affected by various factors, including UVB. Pro-Collagen I and hyaluronic acid contents were measured in UVB-irradiated HaCaT and HDF cells to evaluate the anti-wrinkle and moisturizing effects of Yuja-peel (YJP) fractions in -EA (ethyl acetate), -Hex (hexane), and -BuOH (butanol). The expression of matrix metalloproteinases (MMPs) involved in collagen degradation was confirmed to be inhibited by YJP fractions at both the protein and mRNA levels. Filaggrin and serine palmitoyltransferase (SPT), which are moisturizing factors, were induced by YJP fractions. B16F10 cells were treated with α-MSH to induce hyperpigmentation, and then the whitening efficacy of YJP fractions was verified by observing a decrease in melanin content. Overall, our results contribute to the development of various novel skin-improving cosmetics and pharmaceuticals with YJP fractions as active ingredients. Full article
(This article belongs to the Special Issue Antioxidant Compounds and Health Benefits of Citrus Fruits)
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23 pages, 2326 KiB  
Article
Comparing Metabolomic and Essential Oil Fingerprints of Citrus australasica F. Muell (Finger Lime) Varieties and Their In Vitro Antioxidant Activity
by Emily Cioni, Chiara Migone, Roberta Ascrizzi, Beatrice Muscatello, Marinella De Leo, Anna Maria Piras, Ylenia Zambito, Guido Flamini and Luisa Pistelli
Antioxidants 2022, 11(10), 2047; https://doi.org/10.3390/antiox11102047 - 18 Oct 2022
Cited by 6 | Viewed by 1799
Abstract
Comparative chemical analyses among peel and pulp essential oils (EOs) and methanolic extracts of four Citrus australasica varieties (Red, Collette, Pink Ice, and Yellow Sunshine), and the hybrid Faustrime, were performed using GC-MS and UHPLC-DAD-HR-Orbitrap/ESI-MS. Peel and pulp extracts were also analysed [...] Read more.
Comparative chemical analyses among peel and pulp essential oils (EOs) and methanolic extracts of four Citrus australasica varieties (Red, Collette, Pink Ice, and Yellow Sunshine), and the hybrid Faustrime, were performed using GC-MS and UHPLC-DAD-HR-Orbitrap/ESI-MS. Peel and pulp extracts were also analysed for their in vitro antioxidant activity on a Balb/3T3 clone A31 mouse embryo fibroblast cell line. The results of peel and pulp EOs were mainly characterised by monoterpenes and sesquiterpenes, respectively. All peels displayed a higher total phenol content (TPC) than pulps, and consequently a greater antioxidant activity. Collette peels and Pink Ice pulps showed the highest amount of identified flavonoids (e.g., luteolin, isosakuranetin, and poncirin derivatives). Collette and Red peels were rich in anthocyanins (delphinidin and petunidin glycosides), exhibiting the maximum protective activity against induced oxidative damage. In conclusion, finger lime fruits are good sources of health-promoting phytocomplexes, with the Red, Collette, and Pink Ice varieties being the most promising. Full article
(This article belongs to the Special Issue Antioxidant Compounds and Health Benefits of Citrus Fruits)
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12 pages, 989 KiB  
Article
Variations of Bioactive Phytochemicals and Antioxidant Capacity of Navel Orange Peel in Response to Different Drying Methods
by Chunling Lai, Yan Liang, Linyan Zhang, Jiangjiang Huang, Kumaravel Kaliaperumal, Yueming Jiang and Jun Zhang
Antioxidants 2022, 11(8), 1543; https://doi.org/10.3390/antiox11081543 - 09 Aug 2022
Cited by 7 | Viewed by 1947
Abstract
The effects of five different drying methods, namely, freeze drying (FD), shade drying (SD), hot-air oven drying at 50 °C (OD50), 70 °C (OD70), and microwave drying (MD) on the bioactive phytochemicals and antioxidant capacity of navel orange peel were assessed and comprehensively [...] Read more.
The effects of five different drying methods, namely, freeze drying (FD), shade drying (SD), hot-air oven drying at 50 °C (OD50), 70 °C (OD70), and microwave drying (MD) on the bioactive phytochemicals and antioxidant capacity of navel orange peel were assessed and comprehensively discussed in detail. Compared with other drying methods, MD-treated peel contained the lowest total phenolic content (TPC) and total flavonoid content (TFC). The peel subjected to OD70 treatment was superior in TPC relative to other treatments and the highest TFC was found in the peels treated with FD. HPLC analysis identified thirteen flavonoids involving three flavanone glycosides (FGs) and ten polymethoxyflavones (PMFs) in navel orange peel and revealed that PMFs in peel were stable under all these drying methods, whereas the three major FGs (narirutin, hesperidin, and didymin) in peel significantly degraded in response to MD treatment. The peels subjected to OD50/OD70 treatments had the most potent antioxidant capacity when compared to other drying methods. Furthermore, Pearson’s correlation analysis was performed. The results revealed here allow us to recommend the use of OD50 or OD70 for the drying of orange peel, both of which help the maintenance of bioactive compounds in the peel and improve its antioxidant capacity. Full article
(This article belongs to the Special Issue Antioxidant Compounds and Health Benefits of Citrus Fruits)
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18 pages, 4002 KiB  
Article
The Flavonoid Hesperidin Methyl Chalcone Targets Cytokines and Oxidative Stress to Reduce Diclofenac-Induced Acute Renal Injury: Contribution of the Nrf2 Redox-Sensitive Pathway
by Allan J. C. Bussmann, Tiago H. Zaninelli, Telma Saraiva-Santos, Victor Fattori, Carla F. S. Guazelli, Mariana M. Bertozzi, Ketlem C. Andrade, Camila R. Ferraz, Doumit Camilios-Neto, Antônio M. B. Casella, Rubia Casagrande, Sergio M. Borghi and Waldiceu A. Verri, Jr.
Antioxidants 2022, 11(7), 1261; https://doi.org/10.3390/antiox11071261 - 27 Jun 2022
Cited by 9 | Viewed by 3241
Abstract
Hesperidin is derived from citrus fruits among other plants. Hesperidin was methylated to increase its solubility, generating hesperidin methyl chalcone (HMC), an emerging flavonoid that possess anti-inflammatory and antioxidant properties. The nuclear factor erythroid 2-related factor 2 (Nrf2) is a powerful regulator of [...] Read more.
Hesperidin is derived from citrus fruits among other plants. Hesperidin was methylated to increase its solubility, generating hesperidin methyl chalcone (HMC), an emerging flavonoid that possess anti-inflammatory and antioxidant properties. The nuclear factor erythroid 2-related factor 2 (Nrf2) is a powerful regulator of cellular resistance to oxidant products. Previous data evidenced HMC can activate Nrf2 signaling, providing antioxidant protection against diverse pathological conditions. However, its effects on kidney damage caused by non-steroidal anti-inflammatory drugs (NSAIDs) have not been evaluated so far. Mice received a nephrotoxic dose of diclofenac (200 mg/kg) orally followed by intra-peritoneal (i.p.) administration of HMC (0.03–3 mg/kg) or vehicle. Plasmatic levels of urea, creatinine, oxidative stress, and cytokines were assessed. Regarding the kidneys, oxidative parameters, cytokine production, kidney swelling, urine NGAL, histopathology, and Nrf2 mRNA expression and downstream targets were evaluated. HMC dose-dependently targeted diclofenac systemic alterations by decreasing urea and creatinine levels, and lipid peroxidation, as well as IL-6, IFN-γ, and IL-33 production, and restored antioxidant properties in plasma samples. In kidney samples, HMC re-established antioxidant defenses, inhibited lipid peroxidation and pro-inflammatory cytokines and upregulated IL-10, reduced kidney swelling, urine NGAL, and histopathological alterations. Additionally, HMC induced mRNA expression of Nrf2 and its downstream effectors HO-1 and Nqo1, as well as reduced the levels of Keap1 protein detected in renal tissue. The present data demonstrate HMC is a potential compound for the treatment of acute renal damage caused by diclofenac, a routinely prescribed non-steroidal anti-inflammatory drug. Full article
(This article belongs to the Special Issue Antioxidant Compounds and Health Benefits of Citrus Fruits)
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Review

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27 pages, 3842 KiB  
Review
Naringenin and Hesperidin as Promising Alternatives for Prevention and Co-Adjuvant Therapy for Breast Cancer
by Maria Beatriz Madureira, Virginia Marcia Concato, Ellen Mayara Souza Cruz, Juliana Maria Bitencourt de Morais, Fabricio Seidy Ribeiro Inoue, Natália Concimo Santos, Manoela Daniele Gonçalves, Milena Cremer de Souza, Thalita Basso Scandolara, Mariane Fontana Mezoni, Murilo Galvani, Fábio Rodrigues Ferreira Seiva, Carolina Panis, Milena Menegazzo Miranda-Sapla and Wander Rogério Pavanelli
Antioxidants 2023, 12(3), 586; https://doi.org/10.3390/antiox12030586 - 27 Feb 2023
Cited by 12 | Viewed by 4079
Abstract
Citrus (genus Citrus L.) fruits are essential sources of bioactive compounds with antioxidant properties, such as flavonoids. These polyphenolic compounds are divided into subclasses, in which flavanones are the most prominent. Among them, naringenin and hesperidin are emerging compounds with anticancer potential, especially [...] Read more.
Citrus (genus Citrus L.) fruits are essential sources of bioactive compounds with antioxidant properties, such as flavonoids. These polyphenolic compounds are divided into subclasses, in which flavanones are the most prominent. Among them, naringenin and hesperidin are emerging compounds with anticancer potential, especially for breast cancer (BC). Several mechanisms have been proposed, including the modulation of epigenetics, estrogen signaling, induction of cell death via regulation of apoptotic signaling pathways, and inhibition of tumor invasion and metastasis. However, this information is sparse in the literature and needs to be brought together to provide an overview of how naringenin and hesperidin can serve as therapeutic tools for drug development and as a successful co-adjuvant strategy against BC. This review detailed such mechanisms in this context and highlighted how naringenin and hesperidin could interfere in BC carcinogenesis and be helpful as potential alternative therapeutic sources for breast cancer treatment. Full article
(This article belongs to the Special Issue Antioxidant Compounds and Health Benefits of Citrus Fruits)
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18 pages, 3128 KiB  
Review
Influence of the Neuroprotective Properties of Quercetin on Regeneration and Functional Recovery of the Nervous System
by Simone Ortiz Moura Fideles, Adriana de Cássia Ortiz, Daniela Vieira Buchaim, Eliana de Souza Bastos Mazuqueli Pereira, Maria Júlia Bento Martins Parreira, Jéssica de Oliveira Rossi, Marcelo Rodrigues da Cunha, Alexandre Teixeira de Souza, Wendel Cleber Soares and Rogerio Leone Buchaim
Antioxidants 2023, 12(1), 149; https://doi.org/10.3390/antiox12010149 - 07 Jan 2023
Cited by 11 | Viewed by 2915
Abstract
Quercetin is a dietary flavonoid present in vegetables, fruits, and beverages, such as onions, apples, broccoli, berries, citrus fruits, tea, and red wine. Flavonoids have antioxidant and anti-inflammatory effects, acting in the prevention of several diseases. Quercetin also has neuroprotective properties and may [...] Read more.
Quercetin is a dietary flavonoid present in vegetables, fruits, and beverages, such as onions, apples, broccoli, berries, citrus fruits, tea, and red wine. Flavonoids have antioxidant and anti-inflammatory effects, acting in the prevention of several diseases. Quercetin also has neuroprotective properties and may exert a beneficial effect on nervous tissue. In this literature review, we compiled in vivo studies that investigated the effect of quercetin on regeneration and functional recovery of the central and peripheral nervous system. In spinal cord injuries (SCI), quercetin administration favored axonal regeneration and recovery of locomotor capacity, significantly improving electrophysiological parameters. Quercetin reduced edema, neutrophil infiltration, cystic cavity formation, reactive oxygen species production, and pro-inflammatory cytokine synthesis, while favoring an increase in levels of anti-inflammatory cytokines, minimizing tissue damage in SCI models. In addition, the association of quercetin with mesenchymal stromal cells transplantation had a synergistic neuroprotective effect on spinal cord injury. Similarly, in sciatic nerve injuries, quercetin favored and accelerated sensory and motor recovery, reducing muscle atrophy. In these models, quercetin significantly inhibited oxidative stress and cell apoptosis, favoring Schwann cell proliferation and nerve fiber remyelination, thus promoting a significant increase in the number and diameter of myelinated fibers. Although there is still a lack of clinical research, in vivo studies have shown that quercetin contributed to the recovery of neurological functions, exerting a beneficial effect on the regeneration of the central and peripheral nervous system. Full article
(This article belongs to the Special Issue Antioxidant Compounds and Health Benefits of Citrus Fruits)
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27 pages, 4018 KiB  
Review
Bioactive Compounds of Citrus Fruits: A Review of Composition and Health Benefits of Carotenoids, Flavonoids, Limonoids, and Terpenes
by Ramesh Kumar Saini, Arina Ranjit, Kavita Sharma, Parchuri Prasad, Xiaomin Shang, Karekal Girinur Mallikarjuna Gowda and Young-Soo Keum
Antioxidants 2022, 11(2), 239; https://doi.org/10.3390/antiox11020239 - 26 Jan 2022
Cited by 117 | Viewed by 16658
Abstract
The increased consumption of fruits, vegetables, and whole grains contributes to the reduced risk of many diseases related to metabolic syndrome, including neurodegenerative diseases, cardiovascular disease (CVD), diabetes, and cancer. Citrus, the genus Citrus L., is one of the most important fruit crops, [...] Read more.
The increased consumption of fruits, vegetables, and whole grains contributes to the reduced risk of many diseases related to metabolic syndrome, including neurodegenerative diseases, cardiovascular disease (CVD), diabetes, and cancer. Citrus, the genus Citrus L., is one of the most important fruit crops, rich in carotenoids, flavonoids, terpenes, limonoids, and many other bioactive compounds of nutritional and nutraceutical value. Moreover, polymethoxylated flavones (PMFs), a unique class of bioactive flavonoids, abundantly occur in citrus fruits. In addition, citrus essential oil, rich in limonoids and terpenes, is an economically important product due to its potent antioxidant, antimicrobial, and flavoring properties. Mechanistic, observational, and intervention studies have demonstrated the health benefits of citrus bioactives in minimizing the risk of metabolic syndrome. This review provides a comprehensive view of the composition of carotenoids, flavonoids, terpenes, and limonoids of citrus fruits and their associated health benefits. Full article
(This article belongs to the Special Issue Antioxidant Compounds and Health Benefits of Citrus Fruits)
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