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Background: Ginseng has been used as a traditional medicine and functional cosmetic ingredients for many years. Recent studies have focused on the potential biological effects of the ginseng berry and its ingredients. (+)-Syringaresinol (SYR) is enriched in ginseng berry and its beneficial effects on the skin have been recently reported. However, little is known about the its effects on the wound healing process of skin. Methods: Here, we evaluated the skin wound healing effect of (+)-SYR using the human fibroblast Hs68 cell and ex vivo pig and human skin tissue model. Scratch wound test and hydrogen peroxide (HPO) induce chemical wound model were employed. Results: (+)-SYR promoted the migration and proliferation of Hs68 cells without significant cytotoxicity at the tested concentrations. Especially, in ex vivo pig and human skin tissue, HPO-induced chemical wound was recovered almost completely by (+)-SYR. In line with the finding in Hs68, the protein expression levels of TGF-β and PCNA, a proliferation marker were increased, demonstrating the beneficial effects of (+)-SYR on skin wound repair. Conclusion: Collectively, we demonstrated that (+)-SYR from ginseng berry, can enhance the wound healing effect by accelerating cell proliferation and skin regeneration, suggesting the potential utility of (+)-SYR for skin wound repair.

Ginseng has been utilized for centuries in both the medicinal and cosmetic realms. Recent studies have actively investigated the biological activity of ginseng berry and its constituents. (+)-Syringaresinol [(+)-SYR], an active component of ginseng berry, has been demonstrated to have beneficial effects on the skin, but its potential impact on skin pigmentation has not been fully explored. Here, the antioxidant and anti-pigmentary activity of (+)-SYR were evaluated in B16F10 murine melanoma cells and in an artificial human pigmented skin model, Melanoderm™. A real-time PCR, Western blotting, immunofluorescence staining, and histochemistry staining were conducted to confirm the effects of (+)-SYR on pigmentation. (+)-SYR reduced melanogenesis and dendrite elongation in α-melanocyte-stimulating hormone (α-MSH)-primed B16F10 cells with low cytotoxicity. (+)-SYR suppressed the expression of melanogenic genes, namely tyrosinase (TYR), tyrosinase-related protein 1 (TRP-1), and tyrosinase-related protein 2 (TRP-2). Notably, (+)-SYR attenuated α-MSH-induced cytosolic and mitochondrial reactive oxygen species (ROS) generation, which was attributable at least in part to the suppression of NADPH oxidase-4 (NOX 4) expression. Finally, the brightening activities of (+)-SYR were verified using Melanoderm™, underscoring the potential of ginseng berry and (+)-SYR as functional ingredients in skin-brightening cosmetics.

Natural language processing (NLP) technology has recently used to predict substance properties based on their Simplified Molecular-Input Line-Entry System (SMILES). We aimed to develop a model predicting human skin sensitizers by integrating text features derived from SMILES with in vitro test outcomes. The dataset on SMILES, physicochemical properties, in vitro tests (DPRA, KeratinoSensTM, h-CLAT, and SENS-IS assays), and human potency categories for 122 substances sourced from the Cosmetics Europe database. The ChemBERTa model was employed to analyze the SMILES of substances. The last hidden layer embedding of ChemBERTa was tested with other features. Given the modest dataset size, we trained five XGBoost models using subsets of the training data, and subsequently employed bagging to create the final model. Notably, the features computed from SMILES played a pivotal role in the model for distinguishing sensitizers and non-sensitizers. The final model demonstrated a classification accuracy of 80% and an AUC-ROC of 0.82, effectively discriminating sensitizers from non-sensitizers. Furthermore, the model exhibited an accuracy of 82% and an AUC-ROC of 0.82 in classifying strong and weak sensitizers. In summary, we demonstrated that the integration of NLP of SMILES with in vitro test results can enhance the prediction of health hazard associated with chemicals.

Background & Aims: Histamine in the stomach traditionally is considered to regulate acid secretion but also has been reported to participate in macrophage differentiation, which plays an important role in tissue homeostasis. Therefore, this study aimed to uncover the precise role of histamine in mediating macrophage differentiation and in maintaining stomach homeostasis. Methods: Here, we expand on this role using histidine decarboxylase knockout (Hdc-/-) mice with hypertrophic gastropathy. In-depth in vivo studies were performed in Hdc-/- mice, germ-free Hdc-/- mice, and bone-marrow–transplanted Hdc-/- mice. The stomach macrophage populations and function were characterized by flow cytometry. To identify stomach macrophages and find the new macrophage population, we performed single-cell RNA sequencing analysis on Hdc+/+ and Hdc-/- stomach tissues. Results: Single-cell RNA sequencing and flow cytometry of the stomach cells of Hdc-/- mice showed alterations in the ratios of 3 distinct tissue macrophage populations (F4/80+Il1bhigh, F4/80+CD93+, and F4/80-MHC class IIhighCD74high). Tissue macrophages of the stomachs of Hdc-/- mice showed impaired phagocytic activity, increasing the bacterial burden of the stomach and attenuating hypertrophic gastropathy in germ-free Hdc-/- mice. The transplantation of bone marrow cells of Hdc+/+ mice to Hdc-/- mice recovered the normal differentiation of stomach macrophages and relieved the hypertrophic gastropathy of Hdc-/- mice. Conclusions: This study showed the importance of histamine signaling in tissue macrophage differentiation and maintenance of gastric homeostasis through the suppression of bacterial overgrowth in the stomach.

The pathophysiological mechanism of venous thrombosis associated with Vibrio vulnificus infection remains largely unknown. In this work, the authors investigate this association, focusing on effects of the pore-forming MARTX toxin of V. vulnificus on red blood cells, and the utilisation of a rat venous thrombosis model.

Canine atopic dermatitis (CAD) is a genetically predisposed inflammatory pruritic skin disease. The available treatments for CAD have several adverse effects and vary in efficacy, indicating the need for the development of improved treatments. In this study, we aimed to elucidate the therapeutic effects of allogeneic and xenogeneic exosomes on CAD. Six laboratory beagle dogs with CAD were randomly assigned to three treatment groups: control, canine exosome (cExos), or human exosome (hExos) groups. Dogs in the cExos and hExos groups were intravenously administered 1.5 mL of cExos (5 × 1010) and hExos (7.5 × 1011) solutions, respectively, while those in the control group were administered 1.5 mL of normal saline three times per week for 4 weeks. Skin lesion score and transepidermal water loss decreased in cExos and hExos groups compared with those in the control group. The exosome treatments decreased the serum levels of inflammatory cytokines (interferon-γ, interleukin-2, interleukin-4, interleukin-12, interleukin-13, and interleukin-31) but increased those of anti-inflammatory cytokines (interleukin-10 and transforming growth factor-β), indicating the immunomodulatory effect of exosomes. Skin microbiome analysis revealed that the exosome treatments alleviated skin bacterial dysbiosis. These results suggest that allogeneic and xenogeneic exosome therapy may alleviate CAD in dogs.

Abstract This study proposes using microalgae‐containing carbohydrate bioactives, an Euglena gracilis‐derived extracellular microvesicle (EMVEG) system, for enhanced skin regeneration. The critical deformation ratio, 1.67, during cell extrusion enables the authors to tune the particle size of the EMVEG at ≈1 µm, thus satisfying the encapsulation yield of β‐1,3‐glucan and the cellular delivery performance. In vitro 5‐bromo‐2'‐deoxyuridine and cell scratch assays reveal that the EMVEG promotes the proliferation and migration of skin cells, thereby increasing both collagen synthesis and the expressions of proliferation‐associated proteins. An ex vivo wound‐healing test using both artificial and porcine skin reveals that similar to that seen using β‐1,3‐glucan, the EMVEG can substantially increase the cell population, expressing the proliferation‐related protein, termed proliferating cell nuclear antigen. These results demonstrate that the EMVEG system shows considerable potential in the field of skin regeneration. This technique is expected to design new types of extracellular vesicles that are applicable for skin regeneration in the pharmaceutical and cosmetic industries.

Abstract Formaldehyde is a colorless, pungent, highly reactive, and toxic environmental pollutant used in various industries and products. Inhaled formaldehyde is a human and animal carcinogen that causes genotoxicity, such as reactive oxygen species formation and DNA damage. This study aimed to identify the toxic effects of inhaled formaldehyde through an integrated toxicogenomic approach utilizing database information. Microarray datasets (GSE7002 and GSE23179) were collected from the Gene Expression Omnibus database, and differentially expressed genes were identified. The network analyses led to the construction of the respiratory system-related biological network associated with formaldehyde exposure, and six upregulated hub genes (AREG, CXCL2, HMOX1, PLAUR, PTGS2, and TIMP1) were identified. The expression levels of these genes were verified via qRT-PCR in 3D reconstructed human airway tissues exposed to aerosolized formaldehyde. Furthermore, NRARP was newly found as a potential gene associated with the respiratory and carcinogenic effects of formaldehyde by comparison with human in vivo and in vitro formaldehyde-exposure data. This study improves the understanding of the toxic mechanism of formaldehyde and suggests a more applicable analytic pipeline for predicting the toxic effects of inhaled toxicants.

Abstract Background Expanding biomedical application of anatase titanium dioxide (TiO2) nanoparticles (NPs) is raising the public concern on its potential health hazards. Here, we demonstrated that TiO2 NPs can increase phosphatidylserine (PS) exposure and procoagulant activity of red blood cells (RBCs), which may contribute to thrombosis. Results We conducted in vitro studies using RBCs freshly isolated from healthy male volunteers. TiO2 NPs exposure (≦ 25 μg/mL) induced PS exposure and microvesicles (MV) generation accompanied by morphological changes of RBCs. While ROS generation was not observed following the exposure to TiO2 NPs, intracellular calcium increased and caspase-3 was activated, which up-regulated scramblase activity, leading to PS exposure. RBCs exposed to TiO2 NPs could increase procoagulant activity as measured by accelerated thrombin generation, and enhancement of RBC-endothelial cells adhesion and RBC-RBC aggregation. Confirming the procoagulant activation of RBC in vitro, exposure to TiO2 NPs (2 mg/kg intravenously injection) in rats increased thrombus formation in the venous thrombosis model. Conclusion Collectively, these results suggest that anatase TiO2 NPs may harbor prothrombotic risks by promoting the procoagulant activity of RBCs, which needs attention for its biomedical application.

Background: Global pharmaceutical companies in Korea argue that the development of innovative drugs should be recognized as a social contribution, yet it has been countered by various stakeholders. The need to distinguish between philanthropic activities and Corporate Social Responsibility (CSR) of pharmaceutical companies and reaching consensus in the Korean context has been raised. We sought to evaluate the CSR status of Korean pharmaceutical companies and collect the stakeholders’ opinions to define philanthropic activities and CSR related to pharmaceutical companies in Korea.Methods: We conducted a literature review on the definition of CSR of pharmaceutical companies, and the CSR activities of the domestic pharmaceutical companies were compared with those of global pharmaceutical companies operating in Korea. The opinions of stakeholder groups (patient advocate groups, consumer organizations, and domestic/global pharmaceutical companies) were collected using focus group interviews (FGI) and written surveys.Results: Literature review suggested that CSR is categorized as “must do” (economic and legal responsibilities), “ought to do” (ethical responsibilities), and “can do” (philanthropic responsibilities), whereas contributions beyond the economic, legal, or ethical responsibilities can be defined as “can do” (philanthropic responsibilities). Domestic pharmaceutical companies simply adopted systems for ethical and ESG (Environmental, Social, and Governance) management, which are at the “ought to do” level (ethical responsibility), whereas the headquarters of these global pharmaceutical companies established the CSR team and systematically reported on the CSR activity, including ESG management reports, which is at the “ought to do” level and further moving to the “can do” level, but the Korean branch rarely has CSR teams, and the CSR activities in Korea were also insufficient. At the FGI, the global pharmaceutical companies argued that CSR activities, such as innovative drug development, should be recognized as similar to philanthropic activities, yet stakeholders besides them suggested that those activities are “can do” rather than being philanthropic.Discussion: We found that the pharmaceutical companies in Korea are attempting to achieve the “ought to do” level (ethical responsibilities) while complying with the “must do” level (legal and economic responsibilities) yet not philanthropic activities. A social consensus regarding the philanthropic responsibilities of pharmaceutical companies in Korea was not reached.

The opportunistic human pathogen Staphylococcus aureus can evade antibiotics by acquiring antibiotic resistance genes or by entering into a non-growing dormant state. Moreover, the particular circumstances of a specific infection site, such as acidity or anaerobicity, often weaken antibiotic potency. Decreased bacterial susceptibility combined with diminished antibiotic potency is responsible for high failure rates when treating S. aureus infections. Here, we report that the membrane-active antimicrobial agent nTZDpa does not only exhibit enhanced antibiotic activity against multidrug-resistant Gram-positive pathogens in acidic pH, but also retains antimicrobial potency under anaerobic conditions. This agent completely eradicated highly antibiotic-tolerant cells and biofilms formed by methicillin-resistant S. aureus at pH 5.5 at concentrations at which it was not potent at pH 7.4. Furthermore, nTZDpa was more potent at synergistically potentiating gentamicin killing against antibiotic-tolerant MRSA cells at low pH than at high pH. All-atom molecular dynamics simulations combined with membrane-permeabilization assays revealed that the neutral form of nTZDpa, which contains carboxylic acid, is more effective than the deprotonated form at penetrating the bacterial membrane and plays an essential role in membrane activity. An acidic pH increases the proportion of the neutrally charged nTZDpa, which results in antimicrobial enhancement. Our results provide key insights into rational design of pH-sensitive membrane-active antimicrobials and antibiotic adjuvants that are effective in an infection environment. These findings demonstrate that nTZDpa is a promising lead compound for developing new therapeutics against hard-to-cure infections caused by drug-resistant and -tolerant S. aureus.

Flavonoids enhance the self-renewal and differentiation potential of mesenchymal stem cells (MSCs) and have therapeutic activities, including regenerative, anti-oxidative, and anti-inflammatory effects. Recent studies have revealed that MSC-derived extracellular vesicles (MSC-EVs) have therapeutic effects on tissue regeneration and inflammation. To facilitate further research on the therapeutic potential of MSC-EVs derived from flavonoid-treated MSCs, we surveyed the production of EVs and their therapeutic applications in wound regeneration. MSCs treated with flavonoids enhanced EV production twofold compared with naïve MSCs. EVs produced by MSCs treated with flavonoids (Fla-EVs) displayed significant anti-inflammatory and wound-healing effects in vitro. The wound-healing capacity of EVs was mediated by the upregulation of mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling. Interestingly, the protein level of p-ERK under inhibition of MEK signals was maintained in Fla-EV-treated fibroblasts, suggesting that Fla-EVs have a higher therapeutic potential than naïve MSC-EVs (Cont-EVs) in wound healing. Moreover, the in vivo wound closure effect of the Fla-EVs showed significant improvement compared with that of the flavonoid-only treatment group and the Cont-EVs. This study provides a strategy for the efficient production of EVs with superior therapeutic potential using flavonoids.

Background: Ginseng extracts and ginseng-fermented products are widely used as functional cosmetic ingredients for their whitening and antiwrinkle effects. Recently, increasing attention has been given to bioactive metabolites isolated from endophytic fungi. However, little is known about the bioactive metabolites of the fungi associated with Panax ginseng Meyer. Methods: An endophytic fungus, Penicillium sp. SNF123 was isolated from the root of P. ginseng, from which acremonidin E was purified. Acremonidin E was tested on melanin synthesis in the murine melanoma cell line B16F10, in the human melanoma cell line MNT-1, and in a pigmented 3D-human skin model, Melanoderm. Results: Acremonidin E reduced melanogenesis in α-melanocyte-stimulating hormone (α-MSH)-stimulated B16F10 cells with minimal cytotoxicity. qRT–PCR analysis demonstrated that acremonidin E downregulated melanogenic genes, including tyrosinase and tyrosinase-related protein 1 (TRP-1), while their enzymatic activities were unaffected. The antimelanogenic effects of acremonidin E were further confirmed in MNT-1 and a pigmented 3D human epidermal skin model, Melanoderm. Immunohistological examination of the Melanoderm further confirmed the regression of both melanin synthesis and melanocyte activation in the treated tissue. Conclusion: This study demonstrates that acremonidin E, a bioactive metabolite derived from a fungal endophyte of P. ginseng, can inhibit melanin synthesis by downregulating tyrosinase, illuminating the potential utility of microorganisms associated with P. ginseng for cosmetic ingredients.

The growing concerns regarding the adverse biological effects of radiofrequency electromagnetic fields (RF-EMFs), which are generated by common electronic devices, on the human brain led us to investigate their impact on Alzheimer’s disease (AD). We aimed to establish the effects of RF-EMF on the expression of molecular markers associated with amyloid precursor protein (APP), cell death, and clonogenic survival in HT22 and APP-overexpressing 7w-PSML cells. We compared the effects of RF-EMF at a high specific absorption rate (SAR) level with the neuronal-cell-death-inducing effects of ionizing radiation (IR). RF-EMF exposure (8 W/kg SAR) promoted the protein expression of ADAM10 (α-secretase) in the HT22 cells (p < 0.05) and downregulated the APP mRNA level in the 7w-PSML cells (p < 0.01). In contrast, IR (10 Gy) significantly reduced the APP and a disintegrin and metalloproteinase 10 (ADAM10) levels without altering their respective mRNA levels in these cells. Interestingly, IR exposure significantly upregulated BACE1 (β-secretase) at both the protein and mRNA levels, suggesting adverse effects in AD. IR induced cell death and reduced clonogenic survival in both cell lines. Although RF-EMF (high SAR level) influenced APP processing, it did not induce any deleterious change in either cell line. Thus, further studies are necessary to clarify the influence of RF-EMF on AD.

Background: We aimed to evaluate the influence of cold airflow from the air conditioner on skin barrier function and filaggrin degradation products (FDPs) in children with atopic deramtitis (AD). Methods: In a case-control study, 28 children with AD and 12 normal children without AD were exposed to one of two air conditioner modes (conventional or wind-free) for 2 h. Skin temperature, transepidermal water loss (TEWL), and skin pH were measured on right cheek and forearm at pre- and post-exposure time points. We also measured filaggrin and FDPs from the volar surface of the forearm. Results: In AD patients, skin temperature on the forearm decreased after exposure to the conventional and wind-free modes (P

Context Research interest in monoamine oxidase (MAO) as a promising drug target for neurodegenerative diseases has a long history. However, efforts to develop MAO inhibitors (MAOIs) from marine sources have been limited, despite the increasing number of interesting marine natural products. Objective To review the potential of marine natural products as MAOIs source, including their activities and selectivity on MAO. Methods Public databases such as SciFinder, MarinLit and PubMed were systematically searched from 1991 until Dec 2019. MAO and MAOI were the key terms searched combined with marine natural products and marine. Results Six classes of marine natural products with good selectivity between the two MAO subtypes were organized with their selectivity and sources. Conclusions This is the first review to investigate the potential of marine natural products as MAOIs source. Despite the small number of known MAOIs from marine sources, marine natural products are potential leads for the further development of MAOI drugs with novel chemical frames and good selectivity.

Biocides are widely used in everyday life, and accordingly, human exposure to them is inevitable. Especially, the inhalational exposure of humans to biocides and resultant respiratory toxicity are gaining public interest due to the recent catastrophe associated with humidifier disinfectants. Aerosolized chemicals are subject to gravitational deposition and chemical degradation. Therefore, the characterization of the disposition of aerosols is essential to estimate the inhalational exposure to biocides. Here, we compared the disposition of aerosols of one of the commonly used biocide classes, isothiazolinone-based biocides, BIT, MIT, and OIT. An acrylic chamber (40 cm × 40 cm × 50 cm) was created to simulate the indoor environment, and a vacuum pump was used to create airflow (1 LPM). Biocides were sprayed from a vertical nebulizer placed on the ceiling of the chamber, and the distribution of particle sizes and volume was measured using the Optical Particle Sizer (OPS) 3330 device. During and after the aerosol spraying, airborne biocides and those deposited on the surface of the chamber were sampled to measure the deposition using LC-MS/MS. As a result, the broad particle size distribution was observed ranging from 0.3 to 8 μm during the nebulization. The inhalable particle faction (>2 μm) of the isothiazolinones was 32–67.9% in number but 1.2 to 6.4% in volume. Most of the aerosolized biocides were deposited on the chamber’s surface while only a minimal portion was airborne (

Cleaners such as dishwashing liquids contain various chemicals that cause skin damage. Alkaline agents used in cleaners alter the lipid composition of the skin and damage the skin barrier. However, little is known about the effects of acids used in cleaners on the skin. Here, we investigated the effects of acidic pH on the skin and evaluated the skin irritation of acids commonly used in cleaners with a 3D-reconstructed human epidermis model, KeraSkinTM, according to OECD TG439. First, to examine the effects of acidic pH, we evaluated the skin irritation of citrate buffers (0.1 M, McIlvaine buffer) prepared in a wide pH range (pH 1.5–6.0). Surprisingly, cell viability was not significantly affected even at pH 1.5, reflecting that the acidity alone may not be sufficient to induce skin irritation. Even after longer exposure (180 min), the cell viability was not reduced below 50%, a cutoff to determine an irritant. To examine the effect of the anionic part, several organic acids used in cleaners (citric acid, glycolic acid, lactic acid, malic acid, and succinic acid) were examined. These organic acids also failed to reduce viability at 0.1 M. However, at 1 M, most of the acids tested, except lactic acid, were determined to be skin irritants. Histology further supported the skin irritancy of acids at 1 M. Similarly, inorganic acids (hydrogen bromide, hydrogen chloride, nitric acid, and sulfuric acid) were determined to be irritants only at 1 M. In the case of alkaline agents, pH and concentrations were also important factors to determine the skin irritancy, although the epidermal structure and lipids were more damaged than acids. Collectively, we demonstrated that both the pH and concentration are important factors for the skin irritancy of acids, shedding an important insight into the mechanism of skin irritation.

Background: Various therapeutic modalities have been implemented for wart treatment, with limited efficacy. Recently, resistant warts treated using quadrivalent human papilloma virus (HPV) vaccine have been reported, although original articles on the efficacy of quadrivalent HPV vaccine on warts are rare. Objective: We performed the present study to evaluate the efficacy of quadrivalent HPV vaccine in the treatment of multiple warts. Methods: We retrospectively reviewed 30 patients from our centers. Patient demographics, clinical features such as duration of disease, number and location of lesions, therapeutic response, and adverse reactions were assessed. Results: Regarding therapeutic response, 14 patients (46.67%) showed “Complete response”, 5 (16.67%) showed “Partial response”, and 11 (36.67%) showed “No response”. There were no statistically significant differences in sex, age, disease duration, and lesion number and location between the three groups divided by treatment response. No severe adverse events after quadrivalent HPV vaccination were noted. Conclusion: The advantage of quadrivalent HPV vaccine in the treatment of warts is that it is more convenient and less painful. HPV vaccine might be a good alternative to conventional destructive methods for incompetent cases such as those including multiple warts, dangerous lesion locations, and uncooperative patients.

Abstract Background Silver nanoparticles (AgNP) are widely used in medical practices owing to their distinct antibacterial, antiviral and anticancer activities. However, with increasing use of AgNP, concerns over its potential toxicity are also escalating. Here, we demonstrated the potential thrombotic effect of AgNP which was mediated by the procoagulant activity of red blood cells (RBCs). Results In freshly isolated human RBCs, AgNP, but not silver microparticles (AgMP), elicited morphological changes, phosphatidylserine (PS) exposure and microvesicles (MV) generation, the key indicators of procoagulant activity in RBCs at concentration ranges (≤ 100 μg/mL) that were free of significant hemolysis. In line with this, AgNP potentiated thrombin generation and adherence of RBCs to endothelial cells, while AgMP did not. Oxidative stress, intracellular calcium increase and ATP depletion were found to underlie the procoagulant effects of AgNP, which led to altered activity of membrane aminophospholipid translocases. These in vitro findings were well reproduced in rat in vivo, where intravenously exposure to AgNP promoted venous thrombosis significantly. Of note, RBCs isolated from cancer patients, who inherently convey the risk of thrombogenesis, were more sensitive to the procoagulant effects of AgNP. In addition, AgNP significantly potentiated the procoagulant effects of a chemotherapeutic drug, paclitaxel. Conclusion Collectively, these results suggest that AgNP may have prothrombotic risks by promoting procoagulant activity of RBCs and caution shall be taken for its use in the population sensitive to thrombosis like cancer patients.

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.

1,2-Benzisothiazolin-3-one (BIT) is a commonly used organic biocide containing an isothiazolone ring. However, it may have adverse effects on human health and its risk needs to be properly evaluated. Dermal exposure is the main route of BIT exposure, and co-exposed substances may affect its absorption. The dermal permeation profile of BIT has not been well-studied. This study aimed to investigate the dermal permeation profiles of BIT with or without cosmetic use. Dermal permeation profiles of BIT were investigated after infinite- (100 μg/cm2), or a finite-dose (10 μg/cm2) application with or without cosmetics using a minipig skin and Strat-M®, an artificial membrane. A cream, lotion, and essence (namely, face serum) were pre-treated as representative cosmetics on minipig skin for 30 min, with BIT treatment afterward. After the treatment, BIT left on the skin surface was collected by cotton swabbing, BIT in the stratum corneum, by sequential tape stripping, and BIT retained in the remaining skin was extracted after cutting the skin into pieces before LC-MS/MS analysis. When an infinite dose was applied, permeation coefficients (Kp, cm/h) for minipig skin and Strat-M® were 2.63 × 10−3 and 19.94 × 10−3, respectively, reflecting that skin permeation was seven to eight times higher in Strat-M® than in the minipig skin. BIT, in the presence of cosmetics, rapidly permeated the skin, while the amount in the stratum corneum and skin deposit was reduced. We performed a risk assessment of dermally applied BIT in the absence or presence of cosmetics by calculating the skin absorption rate at 10 h based on the toxicological data from several references. The risk level was higher in the presence of essence as compared to lotion, which was higher than cream, which was higher than the control (non-treated). However, all of the margins of safety values obtained were greater than 100, suggesting that BIT is safe for use in dermally exposed consumer products. We believe that this research contributes to a greater understanding of the risk assessment of isothiazolinone biocides.

The tricyclic quinazoline alkaloid deoxyvasicinone (DOV, 1) was isolated from a marine-derived Streptomyces sp. CNQ-617, and its anti-melanogenic effects were investigated. Deoxyvasicinone was shown to decrease the melanin content of B16F10 and MNT-1 cells that have been stimulated by α-melanocyte-stimulating hormone (α-MSH). In addition, microscopic images of the cells showed that deoxyvasicinone attenuated melanocyte activation. Although, deoxyvasicinone did not directly inhibit tyrosinase (TYR) enzymatic activity, real-time PCR showed that it inhibited the mRNA expression of TYR, tyrosinase-related protein 1 (TRP-1), and tyrosinase-related protein 2 (TRP-2). In the artificial 3D pigmented skin model MelanodermTM, deoxyvasicinone brightened the skin significantly, as confirmed by histological examination. In conclusion, this study demonstrated that the marine microbial natural product deoxyvascinone has an anti-melanogenic effect through downregulation of melanogenic enzymes.

Background: Patients tend to apply topical medications less frequently, in improper amounts. Not only frequency but also application amount may influence treatment outcome. However, studies on relationship between application amount and objective treatment outcome have rarely been conducted. Objective: To assess efficacy of topical agent according to application amount in adult patients, using the finger-tip unit method. Methods: The efficacy of 0.1% topical tacrolimus in adult patients with localised atopic dermatitis was assessed using EASI, TIS, IGA, and PGA scores at baseline, follow-up. Adherence in amount was evaluated after 2 weeks of treatment using the ratio of the actual amount applied to the expected amount applied (A/E). Results: Twenty-seven patients (20.93%) used topical tacrolimus in proper amounts (A/E: 0.8–1.2). However, 86 patients (66.67%) underused topical tacrolimus; 16 (12.40%) patients overused topical tacrolimus. Decreases in EASI scores between baseline and 2 weeks of follow-up in each group (under-amount, proper amount, over-amount) were 1.64, 4.65 and 4.21, respectively. Treatment efficacy increased in accordance with application amount. Further, TIS, IGA, PGA, VAS for Itch and DLQI scores improved concomitantly, exhibiting similar tendencies. Conclusion: Application amount of topical agent is important in increasing treatment efficacy in adult patients with atopic dermatitis.

Since the animal test ban on cosmetics in the EU in 2013, alternative in vitro safety tests have been actively researched to replace in vivo animal tests. For the development and evaluation of a new test method, reference chemicals with quality in vivo data are essential to assess the predictive capacity and applicability domain. Here, we compiled a reference chemical database (ChemSkin DB) for the development and evaluation of new in vitro skin irritation tests. The first candidates were selected from 317 chemicals (source data n = 1567) searched from the literature from the last 20 years, including previous validation study reports, ECETOC, and published papers. Chemicals showing inconsistent classification or those that were commercially unavailable, difficult or dangerous to handle, prohibitively expensive, or without quality in vivo or in vitro data were removed, leaving a total of 100 chemicals. Supporting references, in vivo Draize scores, UN GHS/EU CLP classifications and commercial sources were compiled. Test results produced by the approved methods of OECD Test No. 439 were included and compared using the classification table, scatter plot, and Pearson correlation analysis to identify the false predictions and differences between in vitro skin irritation tests. These results may provide an insight into the future development of new in vitro skin irritation tests.

Animal models are used for preclinical toxicity studies, and the need for in vitro alternative methods has been strongly raised. Our study aims to elucidate the potential mechanism of change in EGR1 expression under situations of toxic injury and to develop an Egr1 promoter–luciferase gene reporter assay for an in vitro alternative method for toxicity prediction in drug discovery. We first found an increase in early growth response-1 (EGR1) mRNA/protein expressions in the liver and kidney of cisplatin-treated injured rats. Additionally, the EGR1 protein level was also elevated under situations of ocular injury after sodium lauryl sulfate (SLS) eye drops. These in vivo observations on injury-related EGR1 induction were confirmed by in vitro studies, where human corneal epithelial cells were treated with representative irritants (SLS and benzalkonium chloride) and 17 chemicals having different UN GHS irritant categories. Additionally, our results suggest the involvement of ERK, JNK, p38 MAPK pathways in EGR1 elevation in response to gamma-butyrolactone-induced injury. As EGR1 is considered to be a pivotal factor in proliferation and regeneration, siRNA-mediated knockdown of Egr1 promoted cytotoxic potential through a delay of injury-related recovery. More importantly, the elevation of promoter activities was observed by various irritants in cells transfected with Egr1 promoter-reporter vector. In conclusion, Egr1 can be a potential biomarker in a promoter-reporter system to improve the accuracy of in vitro predictions for ocular irritation.

Hyper-activated melanocytes are the major cause of skin hyper-pigmentary disorders, such as freckles and melasma. Increasing efforts have been made to search for materials with depigmenting activity to develop functional cosmetics. As a result, numerous materials have been reported to have depigmenting activity but some of them are known to cause unwanted side effects. Consequently, anti-pigmentary natural compounds without concern of toxicity are in great demand. Virtually all sorts of natural sources have been investigated to find anti-pigmentary natural compounds. This review summarizes recently reported anti-pigmentary natural compounds and their mode of action from the ocean, plants, and bacteria.

With the rapid growth of the wireless communication industry, humans are extensively exposed to electromagnetic fields (EMF) comprised of radiofrequency (RF). The skin is considered the primary target of EMFs given its outermost location. Recent evidence suggests that extremely low frequency (ELF)-EMF can improve the efficacy of DNA repair in human cell-lines. However, the effects of EMF-RF on DNA damage remain unknown. Here, we investigated the impact of EMF-long term evolution (LTE, 1.762 GHz, 8 W/kg) irradiation on DNA double-strand break (DSB) using the murine melanoma cell line B16 and the human keratinocyte cell line HaCaT. EMF-LTE exposure alone did not affect cell viability or induce apoptosis or necrosis. In addition, DNA DSB damage, as determined by the neutral comet assay, was not induced by EMF-LTE irradiation. Of note, EMF-LTE exposure can attenuate the DNA DSB damage induced by physical and chemical DNA damaging agents (such as ionizing radiation (IR, 10 Gy) in HaCaT and B16 cells and bleomycin (BLM, 3 μM) in HaCaT cells and a human melanoma cell line MNT-1), suggesting that EMF-LTE promotes the repair of DNA DSB damage. The protective effect of EMF-LTE against DNA damage was further confirmed by attenuation of the DNA damage marker γ-H2AX after exposure to EMF-LTE in HaCaT and B16 cells. Most importantly, irradiation of EMF-LTE (1.76 GHz, 6 W/kg, 8 h/day) on mice in vivo for 4 weeks reduced the γ-H2AX level in the skin tissue, further supporting the protective effects of EMF-LTE against DNA DSB damage. Furthermore, p53, the master tumor-suppressor gene, was commonly upregulated by EMF-LTE irradiation in B16 and HaCaT cells. This finding suggests that p53 plays a role in the protective effect of EMF-LTE against DNA DSBs. Collectively, these results demonstrated that EMF-LTE might have a protective effect against DNA DSB damage in the skin, although further studies are necessary to understand its impact on human health.

Abstract Increased filaggrin expression was found to be correlated with severity scores in chronic spontaneous urticaria (CSU); however, the role of filaggrin breakdown products (FBPs) in CSU has not been studied. We collected stratum corneum (SC) specimens from the volar forearms of 10 CSU patients, 10 AD patients, and 10 healthy normal controls (NCs) and measured contents of FBPs (pyrrolidone carboxylic acid [PCA] and urocanic acid [UCA]) using UPLC-MS/MS, transepidermal water loss (TEWL) and epidermal pH. Compared to NCs, cis-UCA level was increased in CSU lesions (P

Objective This study attempted to identify altered metabolism and pathways related to non-Hodgkin’s lymphoma (NHL) and myeloma patients. Materials and Methods In this retrospective study, we collected plasma samples from 11 patients-6 healthy controls with no evidence of any blood cancers and 5 patients with either multiple myeloma (n=3) or NHL (n=2) during the preliminary study period. Samples were analyzed using quadrupole time-of-flight liquid chromatography mass spectrometry (LC-MS). Significant features generated after statistical analyses were used for metabolomics and pathway analysis. Results Data after false discovery rate (FDR) adjustment at q=0.05 of features showed 136 for positive and 350 significant features for negative ionization mode in NHL patients as well as 262 for positive and 98 features for negative ionization mode in myeloma patients. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis determined that pathways such as steroid hormone biosynthesis, ABC transporters, and arginine and proline metabolism were affected in NHL patients. In myeloma patients, pyrimidine metabolism, carbon metabolism, and bile secretion pathways were potentially affected by the disease. Conclusion The results have shown tremendous differences in the metabolites of healthy individuals compared to myeloma and lymphoma patients. Validation through quantitative metabolomics is encouraged, especially for the metabolites with significantly expression in blood cancer patients.

Curcuma longa (C. longa) has been the subject of intensive research for pleiotropic therapeutic potential. However, except for curcumin, the biological activities of other active ingredients of C. longa are not well known. Here, we demonstrated that C. longa extract significantly attenuated shear stress-induced platelet aggregation and cyclocurcumin exhibited the most potent activity (IC50 of 6.33 ± 3.29 μM). Cyclocurcumin potently inhibited shear stress-induced platelet activation, primarily through modulating the initial step, vWF – platelets GP Ib interaction. Moreover, cyclocurcumin effectively inhibited thrombus formation, without influencing platelet cell viability or blood clotting time. Collectively, we demonstrated that cyclocurcumin might be a promising therapeutic agent for the treatment or prevention of thrombotic diseases.

Isothiazolinone (IT) biocides are potent antibacterial substances commonly used as preservatives or disinfectants, and 2-n-Octyl-4-isothiazolin-3-one (OIT; octhilinone) is a common IT biocide that is present in leather products, glue, paints, and cleaning products. Although humans are exposed to OIT through personal and industrial use, the potentially deleterious effects of OIT on human health are still unknown. To investigate the effects of OIT on the vascular system, which is continuously exposed to xenobiotics through systemic circulation, we treated brain endothelial cells with OIT. OIT treatment significantly activated caspase-3-mediated apoptosis and reduced the bioenergetic function of mitochondria in a bEnd.3 cell-based in vitro blood–brain barrier (BBB) model. Interestingly, OIT significantly altered the thiol redox status, as evidenced by reduced glutathione levels and protein S-nitrosylation. The endothelial barrier function of bEnd.3 cells was significantly impaired by OIT treatment. OIT affected mitochondrial dynamics through mitophagy and altered mitochondrial morphology in bEnd.3 cells. N-acetyl cysteine significantly reversed the effects of OIT on the metabolic capacity and endothelial function of bEnd.3 cells. Taken together, we demonstrated that the alteration of the thiol redox status and mitochondrial damage contributed to OIT-induced BBB dysfunction, and we hope that our findings will improve our understanding of the potential hazardous health effects of IT biocides.

The skin epidermis is the outermost epithelial tissue that protects the body from the external environment [...]

Biocides are commonly used as spray- or trigger-type formulations, thus dermal and respiratory exposure to biocide aerosol is unavoidable. However, little is known about the impact of aerosolization on the local toxicity of biocides on the skin or the airway. We compared the local toxicity of biocides after direct or aerosol exposure on reconstructed human skin epidermis and upper airway models. Three biocides, 1,2-benzisothiazol-3(2H)-one (BIT), 2-phenoxyethanol (PE), and 2-phenylphenol (OPP), most widely used in the market were selected. When the biocide was treated in aerosols, toxicity to the skin epidermis and upper airway tissue became significantly attenuated compared with the direct application as determined by the higher tissue viabilities. This was further confirmed in histological examination, wherein the tissue damages were less pronounced. LC-MS/MS and GC/MS analysis revealed that concentrations of biocides decreased during aerosolization. Importantly, the toxicity of biocides treated in 3 μm (median mass aerodynamic diameter (MMAD)) aerosols was stronger than that of 5 μm aerosol, suggesting that the aerosol particle size may affect biocide toxicity. Collectively, we demonstrated that aerosolization could affect the local toxicity of biocides on the skin epidermis and the upper airway.

Since the European Union (EU) announced their animal testing ban in 2013, all animal experiments related to cosmetics have been prohibited, creating a demand for alternatives to animal experiments for skin studies. Here, we investigated whether an ex vivo live porcine skin model can be employed to study the safety and skin barrier-improving effects of hydroxyacids widely used in cosmetics for keratolytic peels. Glycolic acid (1–10%), salicylic acid (0.2–2%), and lactobionic acid (1.2–12%) were used as representative substances for α-hydroxyacid (AHA), β-hydroxyacid (BHA), and polyhydroxyacid (PHA), respectively. When hydroxyacids were applied at high concentrations on the porcine skin every other day for 6 days, tissue viability was reduced to 50–80%, suggesting that the toxicity of cosmetic ingredients can be evaluated with this model. Based on tissue viability, the treatment scheme was changed to a single exposure for 20 min. The protective effects of a single exposure of hydroxyacids on skin barrier function were evaluated by examining rhodamine permeability and epidermal structural components of barrier function using immunohistochemistry (IHC) and immunofluorescence (IF) staining. Lactobionic acid (PHAs) improved skin barrier function most compared to other AHAs and BHAs. Most importantly, trans-epidermal water loss (TEWL), an important functional marker of skin barrier function, could be measured with this model, which confirmed the significant skin barrier-protective effects of PHAs. Collectively, we demonstrated that the ex vivo live full-thickness porcine skin model can be an excellent alternative to animal experiments for skin studies on the safety and efficacy of cosmetic ingredients.

Lycii Fructus is a traditional medicine used to prevent liver and kidney diseases, which commonly derives from Lycium chinense and Lycium barbarum. Here, the extracts and ethyl acetate-soluble fractions of L. chinense fruits exhibited better hepatoprotective effects than those of L. barbarum, which was likely due to differences in their composition. Therefore, GC-MS and HPLC analyses were conducted to characterize the metabolite differences between L. chinense and L. barbarum. Based on amino acid (AA) and phenolic acid (PA) profiling, 24 AAs and 9 PAs were identified in the two species. Moreover, each species exhibited unique and readily distinguishable AA and PA star graphic patterns. HPLC analysis elucidated composition differences between the ethyl acetate-soluble layers of the two compounds. Further, NMR analysis identified their chemical structures as 4-(2-formyl-5-(hydroxymethyl)-1H-pyrrol-1-yl)butanoic acid and p-coumaric acid. The higher content of 4-(2-formyl-5-(hydroxymethyl)-1H-pyrrol-1-yl)butanoic acid was detected in L. chinense, whereas the content of p-coumaric acid was higher in L. barbarum. Therefore, the differences in the relative contents of these two secondary metabolites in the ethyl acetate-soluble layer of Lycii Fructus could be a good marker to discriminate between L. chinense and L. barbarum.

With the rapid growth of wireless communication devices, the influences of electromagnetic fields (EMF) on human health are gathering increasing attention. Since the skin is the largest organ of the body and is located at the outermost layer, it is considered a major target for the health effects of EMF. Skin pigmentation represents one of the most frequent symptoms caused by various non-ionizing radiations, including ultraviolet radiation, blue light, infrared, and extremely low frequency (ELF). Here, we investigated the effects of EMFs with long-term evolution (LTE, 1.762 GHz) and 5G (28 GHz) bandwidth on skin pigmentation in vitro. Murine and Human melanoma cells (B16F10 and MNT-1) were exposed to either LTE or 5G for 4 h per day, which is considered the upper bound of average smartphone use time. It was shown that neither LTE nor 5G exposure induced significant effects on cell viability or pigmentation. The dendrites of MNT-1 were neither lengthened nor regressed after EMF exposure. Skin pigmentation effects of EMFs were further examined in the human keratinocyte cell line (MNT-1-HaCaT) co-culture system, which confirmed the absence of significant hyper-pigmentation effects of LTE and 5G EMFs. Lastly, MelanoDerm™, a 3D pigmented human epidermis model, was irradiated with LTE (1.762 GHz) or 5G (28 GHz), and image analysis and special staining were performed. No changes in the brightness of MelanoDerm™ tissues were observed in LTE- or 5G-exposed tissues, except for only minimal changes in the size of melanocytes. Collectively, these results imply that exposure to LTE and 5G EMFs may not affect melanin synthesis or skin pigmentation under normal smartphone use condition.

Objectives Korea’s Act on the Registration and Evaluation of Chemicals (K-REACH) was enacted for the protection of human health and the environment in 2015. Considering that about 2000 new substances are introduced annually across the globe, the extent of animal testing requirement could be overwhelming unless regulators and companies work proactively to institute and enforce global best practices to replace, reduce or refine animal use. In this review, the way to reduce the animal use for K-REACH is discussed. Methods Background of the enforcement of the K-REACH and its details was reviewed along with the papers and regulatory documents regarding the limitation of animal experiments and its alternatives in order to discuss the regulatory adoption of alternative tests. Results Depending on the tonnage of the chemical used, the data required ranges from acute and other short-term studies for a single exposure route to testing via multiple exposure routes and costly, longer-term studies such as a full two-generation reproducibility toxicity. The European Registration, Evaluation, Authorization and Restriction of Chemicals regulation provides for mandatory sharing of vertebrate test data to avoid unnecessary duplication of animal use and test costs, and obligation to revise data requirements and test guidelines “as soon as possible” after relevant, validated replacement, reduction or refinement (3R) methods become available. Furthermore, the Organization for Economic Cooperation and Development actively accepts alternative animal tests and 3R to chemical toxicity tests. Conclusions Alternative tests which are more ethical and efficient than animal experiments should be widely used to assess the toxicity of chemicals for K-REACH registration. The relevant regulatory agencies will have to make efforts to actively adopt and uptake new alternative tests and 3R to K-REACH.

Antiplatelet agents are important in the pharmacotherapeutic regime for many cardiovascular diseases, including thrombotic disorders. However, bleeding, the most serious adverse effect associated with current antiplatelet therapy, has led to many efforts to discover novel anti-platelet drugs without bleeding issues. Of note, shear stress-induced platelet aggregation (SIPA) is a promising target to overcome bleeding since SIPA happens only in pathological conditions. Accordingly, this study was carried out to discover antiplatelet agents selectively targeting SIPA. By screening various herbal extracts, Paeonia suffruticosa and its major bioactive constituent, paeoniflorin, were identified to have significant inhibitory effects against shear-induced aggregation in human platelets. The effects of paeoniflorin on intraplatelet calcium levels, platelet degranulation, and integrin activation in high shear stress conditions were evaluated by a range of in vitro experiments using human platelets. The inhibitory effect of paeoniflorin was determined to be highly selective against SIPA, through modulating von Willebrand Factor (vWF)-platelet glycoprotein Ib (GP Ib) interaction. The effects of paeoniflorin on platelet functions under high shear stress were confirmed in the ex vivo SIPA models in rats, showing the good accordance with the anti-SIPA effects on human platelets. Treatment with paeoniflorin significantly prevented arterial thrombosis in vivo from the dose of 10 mg/kg without prolonging bleeding time or blood clotting time in rats. Collectively, our results demonstrated that paeoniflorin can be a novel anti-platelet agent selectively targeting SIPA with an improved safety profile.

The main function of the skin is to protect the body from the external environment. The barrier function of the skin is mainly provided by the stratum corneum, which consists of corneocytes bound with the corneodesmosomes and lamellar lipids. Skin barrier proteins like loricrin and filaggrin also contribute to the skin barrier function. In various skin diseases, skin barrier dysfunction is a common symptom, and skin irritants like detergents or surfactants could also perturb skin barrier function. Many efforts have been made to develop strategies to improve skin barrier function. Here, we investigated whether the microfluidized lysates of Lactobacillus rhamnosus (LR), one of the most widely used probiotic species for various health benefits, may improve the skin barrier function in a reconstructed human epidermis, Keraskin™. Application of LR lysate on Keraskin™ increased the expression of tight junction proteins; claudin 1 and occludin as determined by immunofluorescence analysis, and skin barrier proteins; loricrin and filaggrin as determined by immunohistochemistry and immunofluorescence analysis and qPCR. Also, the cytotoxicity of a skin irritant, sodium lauryl sulfate (SLS), was alleviated by the pretreatment of LR lysate. The skin barrier protective effects of LR lysate could be further demonstrated by the attenuation of SLS-enhanced dye-penetration. LR lysate also attenuated the destruction of desmosomes after SLS treatment. Collectively, we demonstrated that LR lysate has protective effects on the skin barrier, which could expand the utility of probiotics to skin-moisturization ingredients.

A single herb can contain multiple constituents with diverse bioactivities. We found that the extract of Citrus unshiu peel (CUP), induced abnormal vasoconstriction responses on the freshly isolated rat aortic rings in vitro. CUP stimulated the vasoconstriction alone, and it suppressed the phenylephrine-stimulated vasoconstriction. We studied the reasons behind this abnormal vasoconstriction pattern. Major constituents of CUP were determined and evaluated for their vaso-activities. Notably, synephrine, a contractile agonist, and nobiletin, newly identified to have anti-contractile activity co-existed in CUP. Synephrine and nobiletin competitively blocked or activated the same contractile targets resulting in contradicting and abnormal vasoconstriction responses. Accordingly, the vasoconstriction pattern varies significantly depending on the relative contents of synephrine and nobiletin in CUP. Interestingly, this response pattern could be observed with another plant extract, Acorus gramineus Sol. Collectively, we demonstrated that active ingredients with contradicting bioactivities could co-exist in a single plant extract, interact and produce abnormal response patterns in bioassay, which would give an important insight into the interpretation of unusual activity patterns induced by plant extracts.

Intensive study of the organic extract of the marine-derived bacterium Saccharomonospora sp. CNQ-490 has yielded three new α-pyrones, saccharomonopyrones A–C (1–3). The chemical structures of these compounds were assigned from the interpretation of 1D, 2D NMR and mass spectrometry data. Saccharomonopyrone A (1) is the first α-pyrone microbial natural product bearing the ethyl-butyl ether chain in the molecule, while saccharomonopyrones B and C possess unusual 3-methyl and a 6-alkyl side-chain within a 3,4,5,6-tetrasubstituted α-pyrone moiety. Saccharomonopyrone A exhibited weak antioxidant activity using a cation radical scavenging activity assay with an IC50 value of 140 μM.