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Natural Antioxidants: Multiple Mechanisms for Skin Protection

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A special issue of Antioxidants (ISSN 2076-3921). This special issue belongs to the section "Health Outcomes of Antioxidants and Oxidative Stress".

Deadline for manuscript submissions: closed (1 December 2023) | Viewed by 23754

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Dr. Hang Ma

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Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, USA
Interests: bioactive natural products; nutraceuticals and cosmeceuticals; ferroptosis; senescence
Special Issues, Collections and Topics in MDPI journals

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Dear Colleagues,

Human skin is the largest organ, covering the body and protecting us against environmental insults. Although it is a robust defensive system, the skin can be susceptible to both internal stress (e.g., oxidation, glycation, and inflammation) and external stimuli, including mechanical damage, ultraviolet (UV) radiation, toxic chemicals, and the invasion of microorganisms. These factors can collectively undermine the structural integrity and biological functions of the skin, which leads to skin aging and other undesired conditions. To ameliorate these insults to the skin, natural antioxidants (e.g., phytochemicals from medicinal plants and functional foods, as well as their synthetic derivatives) have been used as treatments for dermatological maladies and/or active ingredients for cosmetic products. The skin protective effects of natural antioxidants are supported by numerous published preclinical studies (with in vitro and in vivo experimental models). However, only a paucity of human clinical trials has reported the efficacy of natural products’ skin protection. This is, at least partially, attributed to the lack of understanding of natural antioxidants’ mechanisms of action (MOA) at the molecular level. In recent decades, mechanistic studies on the skin protection of natural antioxidants have been greatly promoted by various advanced biophysical and biochemical technologies, which enabled researchers in this field to address research challenges with novel approaches. For instance, sophisticated methods, such as ‘multi-omics’, including genomics, epigenomics, proteomics, lipidomics, metabolomics, and microbiomics, are adopted to provide an integrated perspective to power investigation across multiple levels of biology.

Herein, this Special Issue (SI), entitled Natural Antioxidants: Multiple Mechanisms for Skin Protection, aims to provide a platform for researchers to showcase their studies in fields related to skin protection by natural antioxidants. This SI includes (but is not limited to) the following research topics: (1) evaluations of natural antioxidants’ skin protective effects; (2) the investigation of mechanisms of action; (3) the development of natural antioxidants and their derivatives as new cosmeceutical ingredients; (4) the applications of ‘multi-omics’ approaches; and (5) the discovery of the molecular target(s) of action. Studies in this SI can be published in the format of a research article, review, perspective, and short communication.

Dr. Hang Ma
Guest Editor

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Keywords

natural products
mechanism(s) of action
multi-omics approaches
target identification
dermatological treatment
skin protection
inflammation
skin cancers
skin aging
cosmeceuticals

Published Papers (10 papers)

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Research

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17 pages, 8020 KiB

Open AccessArticle

Bipiperidinyl Derivatives of Cannabidiol Enhance Its Antiproliferative Effects in Melanoma Cells

by Peihong Lyu, Huifang Li, Junzhao Wan, Ying Chen, Zhen Zhang, Panpan Wu, Yinsheng Wan, Navindra P. Seeram, Jean Christopher Chamcheu, Chang Liu and Hang Ma

Antioxidants 2024, 13(4), 478; https://doi.org/10.3390/antiox13040478 - 17 Apr 2024

Viewed by 316

Abstract

Cannabis and its major cannabinoid cannabidiol (CBD) are reported to exhibit anticancer activity against skin tumors. However, the cytotoxic effects of other minor cannabinoids and synthetic CBD derivatives in melanoma are not fully elucidated. Herein, the antiproliferative activity of a panel of phytocannabinoids was screened against murine (B16F10) and human (A375) melanoma cells. CBD was the most cytotoxic natural cannabinoid with respective IC₅₀ of 28.6 and 51.6 μM. Further assessment of the cytotoxicity of synthetic CBD derivatives in B16F10 cells identified two bipiperidinyl group-bearing derivatives (22 and 34) with enhanced cytotoxicity (IC₅₀ = 3.1 and 8.5 μM, respectively). Furthermore, several cell death assays including flow cytometric (for apoptosis and ferroptosis) and lactate dehydrogenase (for pyroptosis) assays were used to characterize the antiproliferative activity of CBD and its bipiperidinyl derivatives. The augmented cytotoxicity of 22 and 34 in B16F10 cells was attributed to their capacity to promote apoptosis (as evidenced by increased apoptotic population). Taken together, this study supports the notion that CBD and its derivatives are promising lead compounds for cannabinoid-based interventions for melanoma management. Full article

(This article belongs to the Special Issue Natural Antioxidants: Multiple Mechanisms for Skin Protection)

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17 pages, 3562 KiB

Open AccessArticle

Laricitrin 3-Rutinoside from Ginkgo biloba Fruits Prevents Damage in TNF-α-Stimulated Normal Human Dermal Fibroblasts

by Sullim Lee, Yea Jung Choi, Chen Huo, Akida Alishir, Ki Sung Kang, Il-Ho Park, Taesu Jang and Ki Hyun Kim

Antioxidants 2023, 12(7), 1432; https://doi.org/10.3390/antiox12071432 - 15 Jul 2023

Cited by 1 | Viewed by 1653

Abstract

Human skin comprises the epidermis and dermis, which perform interactive functional activities with each other in order to maintain the skin’s tensile strength. In particular, the dermal layer is crucial for skin protection. However, skin aging destroys collagen and elastin fibers, causing wrinkles, pigments, and sagging. Skin aging-related factors, such as tumor necrosis factor-α (TNF-α), promote the generation of intercellular reactive oxygen species (ROS). These are known to stimulate the hypersecretion of matrix metalloproteinase-1 (MMP-1), which degrades collagen and inhibits collagen synthesis. In this study, as part of our ongoing discovery of natural products, we investigated potential natural products derived from ginkgo fruit (Ginkgo biloba fruit) with protective effects against TNF-α-induced skin aging. Phytochemical investigation of the MeOH extract of G. biloba fruits, aided by liquid chromatography–mass spectrometry, led to the isolation of 14 compounds (1–14) from the n-butanol-soluble fraction. These were structurally determined to be: (E)-coniferin (1), syringin (2), 4-hydroxybenzoic acid 4-O-β-D-glucopyranoside (3), vanillic acid 4-O-β-D-glucopyranoside (4), glucosyringic acid (5), (E)-ferulic acid 4-O-β-D-glucoside (6), (E)-sinapic acid 4-O-β-D-glucopyranoside (7), ginkgotoxin-5-glucoside (8), ginkgopanoside (9), (Z)-4-coumaric acid 4-O-β-D-glucopyranoside (10), (1′R,2′S,5′R,8′S,2′Z,4′E)-dihydrophaseic acid 3’-O-β-D-glucopyranoside (11), eucomic acid (12), rutin (13), and laricitrin 3-rutinoside (L3R) (14). Biological evaluation of the isolated compounds for their effects on intracellular ROS generation showed that, of these 14 compounds, L3R (14) inhibited TNF-α-stimulated ROS generation (p < 0.001 at 100 μM). Inhibition of ROS generation by L3R led to the suppression of MMP-1 secretion and protection against collagen degradation. The inhibitory effect of L3R was mediated by the inhibition of extracellular signal regulated kinase (ERK) phosphorylation. Furthermore, L3R diminished the secretion of pro-inflammatory cytokines interleukin 6 (IL-6) and interleukin 8 (IL-8). Based on these experimental results, L3R is a potential bioactive natural product that can be used to protect against skin damage, including aging, in cosmetics and pharmaceuticals. Full article

(This article belongs to the Special Issue Natural Antioxidants: Multiple Mechanisms for Skin Protection)

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20 pages, 3104 KiB

Open AccessArticle

Hydroxypropyl-β-Cyclodextrin-Based Helichrysum italicum Extracts: Antioxidant and Cosmeceutical Activity and Biocompatibility

by Lejsa Jakupović, Ivana Bačić, Jasna Jablan, Eva Marguí, Marijan Marijan, Suzana Inić, Laura Nižić Nodilo, Anita Hafner and Marijana Zovko Končić

Antioxidants 2023, 12(4), 855; https://doi.org/10.3390/antiox12040855 - 01 Apr 2023

Cited by 3 | Viewed by 1891

Abstract

Two Helichrysum italicum extracts, OPT-1 (rich in phenolic acids) and OPT-2 (rich in total phenols and flavonoids), were prepared using hydroxypropyl-β-cyclodextrin (HP-β-CD)-assisted extraction. The prepared extracts were rich in phenolic compounds, including flavonoids and phenolic acids. GC-MS analysis of the extracts identified neryl acetate, neo-intermedeol, β-selinene, γ-curcumene, italidione I, and nerol as the main volatile components of the extracts, as well as plant sterols, γ-sitosterol, campesterol, and stigmasterol. The antioxidant (DPPH radical scavenging, reducing power, and a carotene linoleic acid assay) and cosmeceutical (anti-hyaluronidase, anti-tyrosinase, anti-lipoxygenase, ovalbumin anti-coagulation, and a UV-absorption assay) activity of the extracts in most of the assays was better than the activity of the applied positive controls. Especially low were the IC₅₀ values of the extracts in the anti-hyaluronidase (14.31 ± 0.29 μL extract/mL and 19.82 ± 1.53 μL extract/mL for OPT-1 and OPT-2, respectively) and the anti-lipoxygenase (0.96 ± 0.11 μL extract/mL and 1.07 ± 0.01 μL extract/mL for OPT-1 and OPT-2, respectively) assays. The extracts were non-toxic to HaCaT cells in concentrations of up to 62.5 µL extract/mL assuring their status as excellent candidates for cosmeceutical product development appropriate for direct use in cosmetic products without solvent evaporation. Full article

(This article belongs to the Special Issue Natural Antioxidants: Multiple Mechanisms for Skin Protection)

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18 pages, 5543 KiB

Open AccessArticle

Protopanaxadiol-Enriched Rice Extracts Suppressed Oxidative and Melanogenic Activities in Melan-a Cells

by Chaiwat Monmai, Jin-Suk Kim, Karantharat Promyot and So-Hyeon Baek

Antioxidants 2023, 12(1), 166; https://doi.org/10.3390/antiox12010166 - 10 Jan 2023

Cited by 3 | Viewed by 1447

Abstract

Concerns about hyperpigmentation and skin appearance have led to increasing research into the prevention and altering of skin pigmentation. Natural compounds may be of interest in the search for skin-lightening actives. Protopanaxadiol (PPD), a gut microbiome-induced ginseng metabolite, has been reported to have anti-melanogenic effects. This study aimed to evaluate the antioxidative and anti-melanogenic effects of PPD-enriched rice seed extracts on melan-a cells. The antioxidant and cytotoxicity activities of the extracts were investigated in melan-a cells before measuring their responses to melanogenic activities. The extracts significantly enhanced the antioxidant potency compared with normal rice seed extract. PPD-enriched rice seed extracts (i) significantly downregulated microphthalmia-associated transcription factor, which led to a reduction in tyrosinase and tyrosinase-related protein-1 and -2, (ii) decrease in the cellular tyrosinase activity and melanin content, (iii) reduction in the number of melanin-containing cells, (iv) promotion of melanogenesis downregulators, phosphorylation of extracellular signal-regulated kinase 1/2 and protein kinase B, and (v) downregulation of the phosphorylated p38 mitogen-activated protein kinase and melanin synthesis. These results indicate the feasibility of PPD-enriched rice seed extracts as a novel agent for suppressing melanogenesis and controlling hyperpigmentation. Full article

(This article belongs to the Special Issue Natural Antioxidants: Multiple Mechanisms for Skin Protection)

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15 pages, 1519 KiB

Open AccessArticle

Jasminum sambac Cell Extract as Antioxidant Booster against Skin Aging

by Sara Ceccacci, Adriana De Lucia, Assunta Tortora, Antonio Colantuono, Gennaro Carotenuto, Annalisa Tito and Maria Chiara Monti

Antioxidants 2022, 11(12), 2409; https://doi.org/10.3390/antiox11122409 - 06 Dec 2022

Viewed by 2490

Abstract

Oxidative stress plays a major role in the skin aging process through the reactive oxygen species production and advanced glycation end products (AGEs) formation. Antioxidant ingredients are therefore needed in the skin care market and the use of molecules coming from plant cell cultures provide a unique opportunity. In this paper, the features of an hydroethanolic extract obtained by Jasminum sambac cells (JasHEx) were explored. The antioxidant and anti-AGE properties were investigated by a multidisciplinary approach combining mass spectrometric and bio-informatic in vitro and ex vivo experiments. JasHEx contains phenolic acid derivatives, lignans and triterpenes and it was found to reduce cytosolic reactive oxygen species production in keratinocytes exposed to exogenous stress. It also showed the ability to reduce AGE formation and to increase the collagen type I production in extracellular matrix. Data demonstrated that JasHEx antioxidant properties were related to its free radical scavenging and metal chelating activities and to the activation of the Nrf2/ARE pathway. This can well explain JasHEx anti-inflammatory activity related to the decrease in NO levels in LPS-stimulated macrophages. Thus, JasHEx can be considered a powerful antioxidant booster against oxidative stress-induced skin aging. Full article

(This article belongs to the Special Issue Natural Antioxidants: Multiple Mechanisms for Skin Protection)

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11 pages, 3764 KiB

Open AccessArticle

Antioxidant, Anti-Inflammation and Antiaging Activities of Artocarpus altilis Methanolic Extract on Urban Particulate Matter-Induced HaCaT Keratinocytes Damage

by Chun-Yin Yang, Cheng-Chang Pan, Chih-Hua Tseng and Feng-Lin Yen

Antioxidants 2022, 11(11), 2304; https://doi.org/10.3390/antiox11112304 - 21 Nov 2022

Cited by 5 | Viewed by 2498

Abstract

Particulate matter (PM) is one of the reasons that exacerbate skin diseases. Impaired barrier function is a common symptom in skin diseases, including atopic dermatitis, eczema and psoriasis. Herbal extracts rich in antioxidants are thought to provide excellent pharmacological activities; however, the anti-pollution activity of Artocarpus altilis extract (AAM) has not been investigated yet. The present study demonstrated that 5 μg/mL of AAM was considered to be a safe dose for further experiments without cytotoxicity. Next, we evaluated the anti-pollution activity of AAM through the PM-induced keratinocytes damage cell model. The results showed that AAM could reduce PM-induced overproduction of intracellular ROS and the final product of lipid peroxidation, 4-hydroxynonenal (4HNE). In addition, AAM not only reduced the inflammatory protein expressions, including tumor necrosis factor α (TNFα), TNF receptor 1 (TNFR1) and cyclooxygenase-2 (COX-2), but also balanced the aging protein ratio of matrix metalloproteinase (MMPs) and tissue inhibitors of metalloproteases (TIMPs) through downregulating the phosphorylation of mitogen-activated protein kinase (MAPK) signaling. For skin barrier protection, AAM could repair PM-induced barrier function proteins damage, including filaggrin, loricrin and aquaporin 3 for providing anti-aging bioactivity. In conclusion, AAM has the potential to be developed as an anti-pollution active ingredient for topical skin products to prevent skin oxidation, inflammation and aging, and restore the skin barrier function. Full article

(This article belongs to the Special Issue Natural Antioxidants: Multiple Mechanisms for Skin Protection)

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15 pages, 2409 KiB

Open AccessArticle

Prinsepiae Nux Extract Activates NRF2 Activity and Protects UVB-Induced Damage in Keratinocyte

by Shih-Han Wang, Yi-Siao Chen, Kuei-Hung Lai, Chung-Kuang Lu, Hsun-Shuo Chang, Ho-Cheng Wu, Feng-Lin Yen, Lo-Yun Chen, Jin-Ching Lee and Chia-Hung Yen

Antioxidants 2022, 11(9), 1755; https://doi.org/10.3390/antiox11091755 - 05 Sep 2022

Cited by 7 | Viewed by 2243

Abstract

Ultraviolet B (UVB) is one of the most important environmental factors that cause extrinsic aging through increasing intracellular reactive oxygen species (ROS) production in the skin. Due to its protective roles against oxidative stress, nuclear factor erythroid-2-related factor (NRF2) has been traditionally considered as a target for skin aging prevention. Here, we identified the extract of Prinsepiae Nux, a top-grade drug listed in Shen Nong Ben Cao Jing, as a potent NRF2 activator by high-throughput screening. A bioassay-guided fractionation experiment revealed that NRF2-activating components were concentrated in the 90% methanol (MP) fraction. MP fraction significantly increased the expression of NRF2 and HO-1 protein and upregulated HO-1 and NQO1 mRNA expression in HaCaT cells. Moreover, MP fraction pre-treatment dramatically reversed UVB-induced depletion of NRF2 and HO-1, accumulation of intracellular ROS, NF-κB activation, and the upregulation of pro-inflammatory genes. Finally, the qualitative analysis using UPLC-tandem mass spectroscopy revealed the most abundant ion peak in MP fraction was identified as α-linolenic acid, which was further proved to activate NRF2 signaling. Altogether, the molecular evidence suggested that MP fraction has the potential to be an excellent source for the discovery of natural medicine to treat/prevent UVB-induced skin damage. Full article

(This article belongs to the Special Issue Natural Antioxidants: Multiple Mechanisms for Skin Protection)

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Review

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18 pages, 5711 KiB

Open AccessReview

Antioxidant Effects of Catechins (EGCG), Andrographolide, and Curcuminoids Compounds for Skin Protection, Cosmetics, and Dermatological Uses: An Update

by Gatien Messire, Raphaël Serreau and Sabine Berteina-Raboin

Antioxidants 2023, 12(7), 1317; https://doi.org/10.3390/antiox12071317 - 21 Jun 2023

Cited by 3 | Viewed by 2863

Abstract

Here we have chosen to highlight the main natural molecules extracted from Camellia sinensis, Andrographis paniculata, and Curcuma longa that may possess antioxidant activities of interest for skin protection. The molecules involved in the antioxidant process are, respectively, catechins derivatives, in particular, EGCG, andrographolide, and its derivatives, as well as various curcuminoids. These plants are generally used as beverages for Camellia sinensis (tea tree), as dietary supplements, or as spices. The molecules they contain are known for their diverse therapeutic activities, including anti-inflammatory, antimicrobial, anti-cancer, antidiabetic, and dermatological treatment. Their common antioxidant activities and therapeutic applications are widely documented, but their use in cosmetics is more recent. We will see that the use of pharmacomodulated derivatives, the addition of co-antioxidants, and the use of various formulations enable better skin penetration and greater ingredient stability. In this review, we will endeavor to compile the cosmetic uses of these natural molecules of interest and the various structural modulations reported with the aim of improving their bioavailability as well as establishing their different mechanisms of action. Full article

(This article belongs to the Special Issue Natural Antioxidants: Multiple Mechanisms for Skin Protection)

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17 pages, 2128 KiB

Open AccessReview

Acetyl Zingerone: A Photostable Multifunctional Skincare Ingredient That Combats Features of Intrinsic and Extrinsic Skin Aging

by Thomas A. Meyer, William R. Swindell and Ratan K. Chaudhuri

Antioxidants 2023, 12(6), 1168; https://doi.org/10.3390/antiox12061168 - 29 May 2023

Cited by 3 | Viewed by 2819

Abstract

The cumulative damage skin sustains from exposure to environmental stressors throughout life exerts significant effects on skin aging and cancer development. One of the main ways by which environmental stressors mediate their effects within skin is through induction of reactive oxygen species (ROS). In this review, we chronicle the multiple properties by which acetyl zingerone (AZ) as a skincare ingredient can benefit skin (1) by helping manage overproduction of ROS through multiple routes as an antioxidant, physical quencher and selective chelator, (2) by fortifying protection after UV exposure ends to prevent the type of epidermal DNA damage that correlates with development of skin cancer, (3) by modulating matrisome activity and nurturing the integrity of the extracellular matrix (ECM) within the dermis and (4) through its proficient ability to neutralize singlet oxygen, by stabilizing the ascorbic acid precursor tetrahexyldecyl ascorbate (THDC) in the dermal microenvironment. This activity improves THDC bioavailability and may blunt pro-inflammatory effects of THDC, such as activation of type I interferon signaling. Moreover, AZ is photostable and can sustain its properties during UV exposure, in contrast to α-tocopherol. All these properties of AZ translate into measurable clinical benefits to improve the visual appearance of photoaged facial skin and to strengthen the skin’s own defenses against sun damage. Full article

(This article belongs to the Special Issue Natural Antioxidants: Multiple Mechanisms for Skin Protection)

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20 pages, 831 KiB

Open AccessReview

Rosmarinus officinalis and Skin: Antioxidant Activity and Possible Therapeutical Role in Cutaneous Diseases

by Federica Li Pomi, Vincenzo Papa, Francesco Borgia, Mario Vaccaro, Alessandro Allegra, Nicola Cicero and Sebastiano Gangemi

Antioxidants 2023, 12(3), 680; https://doi.org/10.3390/antiox12030680 - 09 Mar 2023

Cited by 15 | Viewed by 4083

Abstract

The rosemary plant, Rosmarinus officinalis L., one of the main members of the Lamiaceae family, is currently one of the most promising herbal medicines due to its pharmaceutical properties. This research aimed to evaluate the antioxidant role of Rosmarinus officinalis and its bioactive compounds on the skin, with a focus on the newly emerging molecular mechanisms involved, providing extensive scientific evidence of its anti-inflammatory, antimicrobial, wound-healing and anticancer activity in dermatological practice. The search was conducted on articles concerning in vitro and in vivo studies in both animals and humans. The results obtained confirm the antioxidant role of R. officinalis. This assumption derives the possibility of using R. officinalis or its bioactive elements for the treatment of inflammatory and infectious skin pathologies. However, although the use of rosemary in the treatment of skin diseases represents a fascinating line of research, future perspectives still require large and controlled clinical trials in order to definitively elucidate the real impact of this plant and its components in clinical practice. Full article

(This article belongs to the Special Issue Natural Antioxidants: Multiple Mechanisms for Skin Protection)

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