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Reactive Oxygen Species in Skin Repair, Regeneration, Aging, Inflammation, and Skin Cancer

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A special issue of Antioxidants (ISSN 2076-3921). This special issue belongs to the section "ROS, RNS and RSS".

Deadline for manuscript submissions: closed (30 September 2022) | Viewed by 42661

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Special Issue Editor

Dr. Jürgen Eberle

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Guest Editor

Department of Dermatology, Venerology and Allergology, Skin Cancer Center Charité, Charité-Universitätsmedizin Berlin, University Medical Center Charité, 10117 Berlin, Germany
Interests: skin cancer; melanoma; cutaneous squamous cell carcinoma (cSCC); cutaneous T-cell lymphoma (CTCL); apoptosis regulation; signaling; protein kinases, new treatment strategies; reactive oxygen species (ROS)

Special Issue Information

Dear Colleagues,

Reactive oxygen species play important roles in multiple conditions concerning skin physiology and homeostasis, for example, skin repair, regeneration, aging, circadian rhythms, inflammation, defense against bacteria, and development of skin cancer, as well as in Photodynamic therapy (PDT) and other skin cancer therapies. The human skin is exposed to damaging agents such as chemicals and UV light, which can increase ROS and cause oxidative stress when ROS production goes beyond their clearance. Intracellular ROS may derive from mitochondria, NADPH oxidase (NOX) enzymes, Rho GTPases or nitric oxide synthase (NOS). Redox processes mediated by ROS have a strong impact on cellular signaling, differentiation, proliferation, apoptosis and migration. This may result in skin aging as well as in pathogenic effects such as DNA damage, gene mutation, chronic inflammation and skin cancer. Chronic inflammation and cancer development appear particularly related, as associated with uncontrolled cell proliferation, angiogenesis, genomic instability and chemotherapy resistance. Nevertheless, the exact roles of ROS in skin cancer have not been exhaustively elucidated. Thus, on one hand, antioxidative strategies appear to be promising for certain pathogenic situations. On the other hand, PDT and other therapeutic strategies have shown strong relation to the induction of ROS. In particular, ROS often appeared as the critical step for induction of apoptosis in different types of skin cancer cells. In this Special Issue, we thus aim to dissect the pathogenic and possible therapeutic effects of ROS in the skin.

Dr. Jürgen Eberle
Guest Editor

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Keywords

skin homeostasis
skin signaling
reactive oxygen species (ROS)
skin cancer (melanoma, cutaneous squamous cell carcinoma, cutaneous T-cell lymphoma)

Published Papers (14 papers)

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Research

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25 pages, 7054 KiB

Open AccessArticle

Heme Oxygenase-1 Expression in Dendritic Cells Contributes to Protective Immunity against Herpes Simplex Virus Skin Infection

by Eduardo I. Tognarelli, Luisa F. Duarte, Mónica A. Farías, Felipe A. Cancino, Nicolás Corrales, Francisco J. Ibáñez, Claudia A. Riedel, Susan M. Bueno, Alexis M. Kalergis and Pablo A. González

Antioxidants 2023, 12(6), 1170; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox12061170 - 29 May 2023

Viewed by 1655

Abstract

Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) infections are highly prevalent in the human population and produce mild to life-threatening diseases. These viruses interfere with the function and viability of dendritic cells (DCs), which are professional antigen-presenting cells that initiate and regulate the host’s antiviral immune responses. Heme oxygenase-1 (HO-1) is an inducible host enzyme with reported antiviral activity against HSVs in epithelial cells and neurons. Here, we sought to assess whether HO-1 modulates the function and viability of DCs upon infection with HSV-1 or HSV-2. We found that the stimulation of HO-1 expression in HSV-inoculated DCs significantly recovered the viability of these cells and hampered viral egress. Furthermore, HSV-infected DCs stimulated to express HO-1 promoted the expression of anti-inflammatory molecules, such as PDL-1 and IL-10, and the activation of virus-specific CD4⁺ T cells with regulatory (Treg), Th17 and Treg/Th17 phenotypes. Moreover, HSV-infected DCs stimulated to express HO-1 and then transferred into mice, promoted the activation of virus-specific T cells and improved the outcome of HSV-1 skin infection. These findings suggest that stimulation of HO-1 expression in DCs limits the deleterious effects of HSVs over these cells and induces a favorable virus-specific immune response in the skin against HSV-1. Full article

(This article belongs to the Special Issue Reactive Oxygen Species in Skin Repair, Regeneration, Aging, Inflammation, and Skin Cancer)

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13 pages, 2145 KiB

Open AccessArticle

Dual Role of DUOX1-Derived Reactive Oxygen Species in Melanoma

by Irene Pardo-Sánchez, Sofía Ibañez-Molero, Diana García-Moreno and Victoriano Mulero

Antioxidants 2023, 12(3), 708; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox12030708 - 13 Mar 2023

Cited by 1 | Viewed by 1656

Abstract

Melanoma is the most serious type of skin cancer. Inflammation and oxidative stress play an essential role in the development of several types of cancer, including melanoma. Although oxidative stress promotes tumor growth, once cells escape from the primary tumor, they are subjected to a more hostile environment, with higher levels of oxidative stress typically killing most cancer cells. As Dual Oxidase 1 (DUOX1) is a major producer of reactive oxygen species (ROS) in epithelia, we used allotransplantation and autochthonous melanoma models in zebrafish together with in silico analysis of the occurrence and relevance of DUOX1 expression of the skin cutaneous melanoma (SKCM) cohort of The Cancer Genome Atlas (TCGA) to address the role of this enzyme in the aggressiveness of melanoma cells in vivo. It was found that high transcript levels of the gene encoding DUOX1 were associated with the poor prognosis of patients in the early-stage melanoma of TCGA cohort. However, DUOX1 transcript levels were not found to be associated to the prognosis of late-stage SKCM patients. In addition, the transcript level of DUOX1 in metastatic SKCM was lower than in primary SKCM. Using zebrafish primary melanoma and allotransplantation models, we interrogated the role of DUOX1 in vivo. Our results confirmed a dual role of DUOX1, which restrains melanoma proliferation but promotes metastasis. As this effect is only observed in immunocompromised individuals, the immune system appears to be able to counteract this elevated metastatic potential of DUOX1-deficient melanomas. Full article

(This article belongs to the Special Issue Reactive Oxygen Species in Skin Repair, Regeneration, Aging, Inflammation, and Skin Cancer)

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20 pages, 9026 KiB

Open AccessArticle

Enzyme-Digested Edible Bird’s Nest (EBND) Prevents UV and Arid Environment-Induced Cellular Oxidative Stress, Cell Death and DNA Damage in Human Skin Keratinocytes and Three-Dimensional Epithelium Equivalents

by Dongliang Wang, Naohiro Shimamura, Mai Mochizuki, Taka Nakahara, Katsuhisa Sunada and Li Xiao

Antioxidants 2023, 12(3), 609; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox12030609 - 01 Mar 2023

Cited by 2 | Viewed by 1644

Abstract

The aim of this study is to investigate the repressive effects of enzyme-digested edible bird’s nest (EBND) on the combination of arid environment and UV-induced intracellular oxidative stress, cell death, DNA double-strand breaks (DSBs) and inflammatory responses in human HaCaT keratinocytes and three-dimensional (3D) epithelium equivalents. An oxygen radical antioxidant capacity assay showed that EBND exhibited excellent peroxyl radical scavenging activity and significantly increased cellular antioxidant capacity in HaCaT cells. When EBND was administered to HaCaT cells and 3D epitheliums, it exhibited significant preventive effects on air-drying and UVA (Dry-UVA)-induced cell death and apoptosis. Dry-UVA markedly induced intracellular reactive oxygen species (ROS) generation in HaCaT cells and 3D epitheliums as quantified by CellROX^® Green/Orange reagents. Once HaCaT cells and 3D epitheliums were pretreated with EBND, Dry-UVA-induced intracellular ROS were significantly reduced. The results from anti-γ-H2A.X antibody-based immunostaining showed that EBND significantly inhibited Dry-UVA-induced DSBs in HaCaT keratinocytes. Compared with sialic acid, EBND showed significantly better protection for both keratinocytes and 3D epitheliums against Dry-UVA-induced injuries. ELISA showed that EBND significantly suppressed UVB-induced IL-6 and TNF-α secretion. In conclusion, EBND could decrease arid environments and UV-induced harmful effects and inflammatory responses in human keratinocytes and 3D epithelium equivalents partially through its antioxidant capacity. Full article

(This article belongs to the Special Issue Reactive Oxygen Species in Skin Repair, Regeneration, Aging, Inflammation, and Skin Cancer)

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16 pages, 5821 KiB

Open AccessArticle

OR2AT4, an Ectopic Olfactory Receptor, Suppresses Oxidative Stress-Induced Senescence in Human Keratinocytes

by Ji-Sun Kim, Ha Lim Lee, Ji Hyun Jeong, Ye Eun Yoon, In-Ryeong Lee, Ji Min Kim, Chunyan Wu and Sung-Joon Lee

Antioxidants 2022, 11(11), 2180; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11112180 - 03 Nov 2022

Cited by 5 | Viewed by 2549

Abstract

Olfactory receptors (ORs) are the largest protein superfamily in mammals. Certain ORs are ectopically expressed in extranasal tissues and regulate cell type-specific signal transduction pathways. OR2AT4 is ectopically expressed in skin cells and promotes wound healing and hair growth. As the capacities of wound healing and hair growth decline with aging, we investigated the role of OR2AT4 in the aging and senescence of human keratinocytes. OR2AT4 was functionally expressed in human keratinocytes (HaCaT) and exhibited co-expression with G-protein-coupled receptor signaling components, G_olfα and adenylate cyclase 3. The OR2AT4 ligand sandalore modulates the intracellular calcium, inositol phosphate, and cyclic adenosine monophosphate (cAMP) levels. The increased calcium level induced by sandalore was attenuated in cells with OR2AT4 knockdown. OR2AT4 activation by sandalore inhibited the senescent cell phenotypes and restored cell proliferation and Ki-67 expression. Sandalore also inhibited the expression of senescence-associated β-galactosidase and increased p21 expression in senescent HaCaT cells in response to hydrogen peroxide. Additionally, sandalore activated the CaMKKβ/AMPK/mTORC1/autophagy signaling axis and promoted autophagy. OR2AT4 knockdown attenuated the increased in the intracellular calcium level, cell proliferation, and AMPK phosphorylation induced by sandalore. These findings demonstrate that the effects of sandalore are mediated by OR2AT4 activation. Our findings suggest that OR2AT4 may be a novel therapeutic target for anti-aging and anti-senescence in human keratinocytes. Full article

(This article belongs to the Special Issue Reactive Oxygen Species in Skin Repair, Regeneration, Aging, Inflammation, and Skin Cancer)

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20 pages, 2650 KiB

Open AccessArticle

Signaling Pathways Associated with Chronic Wound Progression: A Systems Biology Approach

by Proma Basu and Manuela Martins-Green

Antioxidants 2022, 11(8), 1506; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11081506 - 31 Jul 2022

Cited by 9 | Viewed by 2130

Abstract

Previously we have shown that several oxidative stress-driven pathways in cutaneous chronic wounds are dysregulated in the first 48 h post-wounding. Here, we performed an RNASeq analysis of tissues collected up to day 20 after wounding, when we have determined full chronicity is established. Weighted Gene Correlation Network Analysis was performed in R segregating the genes into 14 modules. Genes in the modules significantly correlated (p < 0.05) to early and full chronicity were used for pathway analysis using pathfindR. In early chronicity, we observed enrichment of several pathways. Dysregulation of Ephrin/Eph signaling leads to growth cone collapse and impairs neuronal regeneration. Adra2b and Adra2a overexpression in early and full chronicity, respectively, decreased cAMP production and impaired re-epithelialization and granulation tissue formation. Several pathways involving a Smooth-muscle-actin (Acta1) were also enriched with Acta1 overexpression contributing to impaired angiogenesis. During full chronicity, the ‘JAK-STAT’ pathway was suppressed undermining host defenses against infection. Wnt signaling was also suppressed, impairing re-epithelialization and granulation tissue formation. Biomarkers of cancer such as overexpression of SDC1 and constitutive activation of ErbB2/HER2 were also identified. In conclusion, we show that during progression to full chronicity, numerous signaling pathways are dysregulated, including some related to carcinogenesis, suggesting that chronic wounds behave much like cancer. Experimental verification in vivo could identify candidates for treatment of chronic wounds. Full article

(This article belongs to the Special Issue Reactive Oxygen Species in Skin Repair, Regeneration, Aging, Inflammation, and Skin Cancer)

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14 pages, 4379 KiB

Open AccessArticle

5G Electromagnetic Radiation Attenuates Skin Melanogenesis In Vitro by Suppressing ROS Generation

by Kyuri Kim, Young Seung Lee, Nam Kim, Hyung-Do Choi and Kyung-Min Lim

Antioxidants 2022, 11(8), 1449; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11081449 - 26 Jul 2022

Cited by 4 | Viewed by 3127

Abstract

Recently, the impacts of 5G electromagnetic radiation (EMR) with 28 GHz on human health have been attracting public attention with the advent of 5G wireless communication. Here, we report that 5G (28 GHz) EMR can attenuate the skin pigmentation in murine melanoma cells (B16F10) and a 3D pigmented human epidermis model (Melanoderm™). B16 cells were exposed to 5G (28 GHz) with or without α-MSH for 4 h per day. Interestingly, 5G attenuated α-MSH-induced melanin synthesis. Fontana–Masson staining confirmed that the dendritic formation of α-MSH stimulated B16 cells was diminished by 5G exposure. To confirm the anti-melanogenic effect of 5G EMR, MelanoDerm™ was irradiated with 5G at a power intensity of 10 W/m² for 4 h a day for 16 days and melanin distribution was detected with Fontana–Masson staining, which supported the anti-melanogenic effect of 5G EMR. Consistently, 5G EMR suppressed α-MSH induced upregulation of melanogenic enzymes; tyrosinase, TRP-1, and TRP-2. Of note, 5G EMR attenuated ROS production stimulated by α-MSH and H₂O₂, suggesting that 5G EMR may dissipate ROS generation, which is pivotal for the melanin synthesis. Collectively, we demonstrated that 5G EMR can attenuate skin pigmentation by attenuating ROS generation. Full article

(This article belongs to the Special Issue Reactive Oxygen Species in Skin Repair, Regeneration, Aging, Inflammation, and Skin Cancer)

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18 pages, 3503 KiB

Open AccessArticle

Inhibition of Cell Proliferation and Cell Viability by Sinecatechins in Cutaneous SCC Cells Is Related to an Imbalance of ROS and Loss of Mitochondrial Membrane Potential

by Jiaqi Zhu, Bernd Gillissen, Dieu Linh Dang Tran, Stefanie May, Claas Ulrich, Eggert Stockfleth and Jürgen Eberle

Antioxidants 2022, 11(7), 1416; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11071416 - 21 Jul 2022

Cited by 1 | Viewed by 2794

Abstract

The term sinecatechins designates an extract containing a high percentage of catechins obtained from green tea, which is commercially registered as Veregen or Polyphenon E (PE) and may be considered for treatment of cutaneous squamous cell carcinoma (cSCC) and actinic keratosis (AK). As shown here, treatment of four cSCC cell lines with 200 µg/mL of PE resulted in strong, dose-dependent decrease in cell proliferation (20–30%) as well as strongly decreased cell viability (4–21% of controls, 48 h). Effects correlated with loss of mitochondrial membrane potential, whereas early apoptosis was less pronounced. At the protein level, some activation of caspase-3 and enhanced expression of the CDK inhibitor p21 were found. Loss of MMP and induced cell death were, however, largely independent of caspases and of the proapoptotic Bcl-2 proteins Bax and Bak, suggesting that sinecatechins induce also non-apoptotic, alternative cell death pathways, in addition to apoptosis. Reactive oxygen species (ROS) were downregulated in response to PE at 4 h, followed by an increase at 24 h. The contributory role of initially reduced ROS was supported by the antioxidant N-acetyl cysteine, which in combination with PE further enhanced the negative effects on cell viability. Thus, sinecatechins inhibited cell proliferation and viability of cSCC cells, which could suggest the use of PE for AK treatment. The mechanisms appear as linked to an imbalance of ROS levels. Full article

(This article belongs to the Special Issue Reactive Oxygen Species in Skin Repair, Regeneration, Aging, Inflammation, and Skin Cancer)

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24 pages, 3095 KiB

Open AccessArticle

Antioxidative Role of Hygrophila erecta (Brum. F.) Hochr. on UV-Induced Photoaging of Dermal Fibroblasts and Melanoma Cells

by Su Jin Lee, Ji Eun Kim, Yun Ju Choi, You Jeong Jin, Yu Jeong Roh, A Yun Seol, Hee Jin Song, So Hae Park, Md. Salah Uddin, Sang Woo Lee and Dae Youn Hwang

Antioxidants 2022, 11(7), 1317; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11071317 - 02 Jul 2022

Cited by 7 | Viewed by 2468

Abstract

Antioxidants are an important strategy for treating photoaging because excessive reactive oxygen species (ROS) are produced during UV irradiation. The therapeutic effects of methanol extracts of Hygrophila erecta (Brum. F.) Hochr. (MEH) against UV-induced photoaging were examined by monitoring the changes in the antioxidant defense system, apoptosis, extracellular matrix (ECM) modulation, inflammatory response, and melanin synthesis in normal human dermal fibroblast (NHDF) cells and melanoma B16F1 cells. Four bioactive compounds, including 4-methoxycinnamic acid, 4-methoxybenzoic acid, methyl linoleate, and asterriquinone C-1, were detected in MEH, while the DPPH free radical scavenging activity was IC₅₀ = 7.6769 µg/mL. UV-induced an increase in the intracellular ROS generation, NO concentration, SOD activity and expression, and Nrf2 expression were prevented with the MEH treatment. Significant decreases in the number of apoptotic cells, the ratio of Bax/Bcl-2, and cleaved Cas-3/Cas-3 were observed in MEH-treated NHDF cells. The MEH treatment induced the significant prevention of ECM disruption and suppressed the COX-2-induced iNOS mediated pathway, expression of inflammatory cytokines, and inflammasome activation. Finally, the expression of the melanin synthesis-involved genes and tyrosinase activity decreased significantly in the

α

-melanocyte-stimulating hormone (MSH)-stimulated B16F1 cells after the MEH treatment. MEH may have an antioxidative role against UV-induced photoaging by suppressing ROS-induced cellular damage. Full article

(This article belongs to the Special Issue Reactive Oxygen Species in Skin Repair, Regeneration, Aging, Inflammation, and Skin Cancer)

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17 pages, 1696 KiB

Open AccessArticle

Skin Care Product Rich in Antioxidants and Anti-Inflammatory Natural Compounds Reduces Itching and Inflammation in the Skin of Atopic Dermatitis Patients

by Yu Zhang, Nina Heinemann, Franziska Rademacher, Maxim E. Darvin, Christian Raab, Cornelia M. Keck, Henning Vollert, Joachim W. Fluhr, Regine Gläser, Jürgen Harder and Martina C. Meinke

Antioxidants 2022, 11(6), 1071; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11061071 - 28 May 2022

Cited by 9 | Viewed by 3192

Abstract

The atopic dermatitis (AD) complex pathogenesis mechanism reveals marked changes of certain signaling factors as well as some morphological alterations in the epidermis. Reduced resilience against environmental factors and oxidative stress often makes the treatment with corticosteroids or tacrolismus ointments indispensable. In view of the correlation between oxidative stress and AD pathological factors, antioxidants can be incorporated into AD management strategies. This study investigates a curly kale, apple and green tea-containing natural extract rich in antioxidants for its effects on signaling inflammatory molecules and skin barrier enhancement in human epidermal keratinocytes- (NHEKs) based cell assays. Furthermore, the skin penetration on porcine ears was measured ex vivo using Raman micro spectroscopy. Finally, in a double-blind half-side, placebo-controlled clinical study, the effects of a formulation containing this extract were analyzed for the influence of lesion severity, epidermal barrier function, and pruritus in mild to moderately AD patients. Summarizing our results: The extract reduces expression of inflammatory cytokines in keratinocytes and increases barrier-related molecules. The verum formulation with a very high antioxidant capacity used in AD patients with mild to moderate lesions reduces itching, local SCORAD, and improves barrier function and the hydration of skin lesions. Full article

(This article belongs to the Special Issue Reactive Oxygen Species in Skin Repair, Regeneration, Aging, Inflammation, and Skin Cancer)

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16 pages, 3223 KiB

Open AccessArticle

Pholiota nameko Polysaccharides Protect against Ultraviolet A-Induced Photoaging by Regulating Matrix Metalloproteinases in Human Dermal Fibroblasts

by His Lin, Kuan-Chen Cheng, Jer-An Lin, Liang-Po Hsieh, Chun-Hsu Chou, Yu-Ying Wang, Ping-Shan Lai, Po-Cheng Chu and Chang-Wei Hsieh

Antioxidants 2022, 11(4), 739; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11040739 - 08 Apr 2022

Cited by 4 | Viewed by 2544

Abstract

Ultraviolet-A (UVA) exposure is a major cause of skin aging and can induce oxidative damage and accelerate skin wrinkling. Many natural polysaccharides exhibit a UV protective effect. In research on Pholiota nameko polysaccharides (PNPs), a natural macromolecular polysaccharide (4.4–333.487 kDa), studies have shown that PNPs can significantly decrease elastase activity to protect against UVA-induced aging in Hs68 human dermal fibroblasts. Cellular experiments in the present study indicated that PNPs can protect against UVA-induced oxidative damage in Hs68 cells by inhibiting the production of reactive oxygen species. Furthermore, PNPs significantly attenuated UVA-induced cell aging by decreasing the protein expression of matrix metalloproteinase 1, 3, and 9. Pretreatment of Hs68 cells with PNP-40, PNP-60, and PNP-80 before UVA irradiation increased protein expression of tissue inhibitor metalloproteinase 1 by 41%, 42%, and 56% relative to untreated cells. In conclusion, this study demonstrates that PNPs are a natural resource with potentially beneficial effects in protecting against UVA-induced skin aging. Full article

(This article belongs to the Special Issue Reactive Oxygen Species in Skin Repair, Regeneration, Aging, Inflammation, and Skin Cancer)

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19 pages, 2552 KiB

Open AccessArticle

Improvement of Damage in Human Dermal Fibroblasts by 3,5,7-Trimethoxyflavone from Black Ginger (Kaempferia parviflora)

by Sullim Lee, Taesu Jang, Ki Hyun Kim and Ki Sung Kang

Antioxidants 2022, 11(2), 425; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11020425 - 19 Feb 2022

Cited by 11 | Viewed by 3528

Abstract

Reactive oxygen species (ROS) are generated during intrinsic (chronological aging) and extrinsic (photoaging) skin aging. Therefore, antioxidants that inhibit ROS production may be involved in delaying skin aging. In this study, we investigated the potential effects of compounds isolated from black ginger, Kaempferia parviflora, a traditional medicinal plant, on normal human dermal fibroblasts in the context of inflammation and oxidative stress. The isolated compounds were structurally characterized as 5-hydroxy-7-methoxyflavone (1), 3,7-dimethoxy-5-hydroxyflavone (2), 5-hydroxy-3,7,3,4-tetramethoxyflavone (3), 7,4-dimethylapigenin (4), 3,7,4-trimethylkaempferol (5), and 3,5,7-trimethoxyflavone (6), using nuclear magnetic resonance spectroscopy (NMR) and liquid chromatography–mass spectrometry (LC/MS) analyses. These flavonoids were first evaluated for their ability to suppress extracellular matrix degradation in normal human dermal fibroblasts. Of these, 3,5,7-trimethoxyflavone (6) significantly inhibited the tumor necrosis factor (TNF)-α-induced high expression and secretion of matrix metalloproteinase (MMP)-1 by cells. We further found that 3,5,7-trimethoxyflavone suppressed the excessive increase in ROS, mitogen-activated protein kinases (MAPKs), Akt, and cyclooxygenase-2 (COX-2)and increased heme oxygenase (HO)-1 expression. The expression of pro-inflammatory cytokines, including interleukin (IL)-1β, IL-6, and IL-8, was also suppressed by 3,5,7-trimethoxyflavone (6). Taken together, our results indicate that 3,5,7-trimethoxyflavone (6) isolated from K. parviflora is a potential candidate for ameliorating skin damage. Full article

(This article belongs to the Special Issue Reactive Oxygen Species in Skin Repair, Regeneration, Aging, Inflammation, and Skin Cancer)

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Review

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26 pages, 1505 KiB

Open AccessReview

ANTIAGE-DB: A Database and Server for the Prediction of Anti-Aging Compounds Targeting Elastase, Hyaluronidase, and Tyrosinase

by Christina D. Papaemmanouil, Jorge Peña-García, Antonio Jesús Banegas-Luna, Androniki D. Kostagianni, Ioannis P. Gerothanassis, Horacio Pérez-Sánchez and Andreas G. Tzakos

Antioxidants 2022, 11(11), 2268; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11112268 - 17 Nov 2022

Cited by 8 | Viewed by 6640

Abstract

Natural products bear a multivariate biochemical profile with antioxidant, anti-inflammatory, antibacterial, and antitumoral properties. Along with their natural sources, they have been widely used both as anti-aging and anti-melanogenic agents due to their effective contribution in the elimination of reactive oxygen species (ROS) caused by oxidative stress. Their anti-aging activity is mainly related to their capacity of inhibiting enzymes like Human Neutrophil Elastase (HNE), Hyaluronidase (Hyal) and Tyrosinase (Tyr). Herein, we accumulated literature information (covering the period 1965–2020) on the inhibitory activity of natural products and their natural sources towards these enzymes. To navigate this information, we developed a database and server termed ANTIAGE-DB that allows the prediction of the anti-aging potential of target compounds. The server operates in two axes. First a comparison of compounds by shape similarity can be performed against our curated database of natural products whose inhibitory potential has been established in the literature. In addition, inverse virtual screening can be performed for a chosen molecule against the three targeted enzymes. The server is open access, and a detailed report with the prediction results is emailed to the user. ANTIAGE-DB could enable researchers to explore the chemical space of natural based products, but is not limited to, as anti-aging compounds and can predict their anti-aging potential. ANTIAGE-DB is accessed online. Full article

(This article belongs to the Special Issue Reactive Oxygen Species in Skin Repair, Regeneration, Aging, Inflammation, and Skin Cancer)

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31 pages, 4510 KiB

Open AccessReview

Carotenoids in Human Skin In Vivo: Antioxidant and Photo-Protectant Role against External and Internal Stressors

by Maxim E. Darvin, Jürgen Lademann, Jörg von Hagen, Silke B. Lohan, Harald Kolmar, Martina C. Meinke and Sora Jung

Antioxidants 2022, 11(8), 1451; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11081451 - 26 Jul 2022

Cited by 26 | Viewed by 3790

Abstract

The antioxidant system of the human body plays a crucial role in maintaining redox homeostasis and has an important protective function. Carotenoids have pronounced antioxidant properties in the neutralization of free radicals. In human skin, carotenoids have a high concentration in the stratum corneum (SC)—the horny outermost layer of the epidermis, where they accumulate within lipid lamellae. Resonance Raman spectroscopy and diffuse reflectance spectroscopy are optical methods that are used to non-invasively determine the carotenoid concentration in the human SC in vivo. It was shown by electron paramagnetic resonance spectroscopy that carotenoids support the entire antioxidant status of the human SC in vivo by neutralizing free radicals and thus, counteracting the development of oxidative stress. This review is devoted to assembling the kinetics of the carotenoids in the human SC in vivo using non-invasive optical and spectroscopic methods. Factors contributing to the changes of the carotenoid concentration in the human SC and their influence on the antioxidant status of the SC in vivo are summarized. The effect of chemotherapy on the carotenoid concentration of the SC in cancer patients is presented. A potential antioxidant-based pathomechanism of chemotherapy-induced hand-foot syndrome and a method to reduce its frequency and severity are discussed. Full article

(This article belongs to the Special Issue Reactive Oxygen Species in Skin Repair, Regeneration, Aging, Inflammation, and Skin Cancer)

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Other

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17 pages, 4778 KiB

Open AccessSystematic Review

Anti-Inflammatory, Antioxidant, and Skin Regenerative Potential of Secondary Metabolites from Plants of the Brassicaceae Family: A Systematic Review of In Vitro and In Vivo Preclinical Evidence (Biological Activities Brassicaceae Skin Diseases)

by Patricia da Silva Mattosinhos, Mariáurea Matias Sarandy, Rômulo Dias Novaes, Debora Esposito and Reggiani Vilela Gonçalves

Antioxidants 2022, 11(7), 1346; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11071346 - 10 Jul 2022

Cited by 10 | Viewed by 2915

Abstract

The Brassicaceae family constitutes some of the most well-studied natural products in the world, due to their anti-inflammatory, anti-oxidative, and pro-regenerative properties as well as their ubiquitous distribution across the world. To evaluate the potential efficacy of the Brassicaceae family in the treatment of inflammatory skin disorders and wounds, based on preclinical evidence from in vivo and in vitro studies. This systematic review was performed according to the PRISMA guidelines, using a structured search on the PubMed-Medline, Scopus, and Web of Science platforms. The studies included were those that used murine models and in vitro studies to investigate the effect of Brassicaceae on skin disorders. Bias analysis and methodological quality assessments were examined through SYRCLE’s RoB tool. Brassicaceae have shown positive impacts on inflammatory regulation of the skin, accelerating the wound healing process, and inhibiting the development of edema. The studies showed that the Brassicaceae family has antioxidant activity and effects on the modulation of cyclooxygenase 2 and the nuclear factor kappa β (NFκβ) pathway. The secondary metabolites present in Brassicas are polyphenols (68.75%; n = 11), terpenes/carotenoids (31.25%; n = 5), and glycosylates (25%; n = 4), which are responsible for their anti-inflammatory, healing, and antioxidant effects. In addition, the current evidence is reliable because the bias analysis showed a low risk of bias. Our review indicates that compounds derived from Brassicaceae present exceptional potential to treat inflammatory skin diseases and accelerate cutaneous wound healing. We hope that our critical analysis can help to expedite clinical research and to reduce methodological bias, thereby improving the quality of evidence in future research. The registration number on the Prospero platform is CRD42021262953. Full article

(This article belongs to the Special Issue Reactive Oxygen Species in Skin Repair, Regeneration, Aging, Inflammation, and Skin Cancer)

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Reactive Oxygen Species in Skin Repair, Regeneration, Aging, Inflammation, and Skin Cancer

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