Atmospheric particulate matter (PM) is an important cause of skin damage, and an increasing number of studies have been conducted to discover safe, natural materials that can alleviate the oxidative stress and inflammation caused by PM. It has been previously shown that the extract of Ecklonia cava Kjellman, a perennial brown macroalga, can alleviate oxidative stress in epidermal keratinocytes exposed to PM less than 10 microns in diameter (PM10). The present study was undertaken to further examine the anti-inflammatory effects of E. cava extract and its major polyphenolic constituent, dieckol. HaCaT keratinocytes were exposed to PM10 in the presence or absence of E. cava extract or dieckol and analyzed for their viability, prostaglandin E₂ (PGE₂) release, and gene expression of cyclooxygenase (COX)-1, COX-2, microsomal prostaglandin E₂ synthase (mPGES)-1, mPGES-2, and cytosolic prostaglandin E₂ synthase (cPGES). PM10 treatment decreased cell viability and increased the production of PGE₂, and these changes were partially abrogated by E. cava extract. E. cava extract also attenuated the expression of COX-1, COX-2, and mPGES-2 stimulated by PM10. Dieckol attenuated PGE₂ production and the gene expression of COX-1, COX-2, and mPGES-1 stimulated by PM10. This study demonstrates that E. cava extract and dieckol alleviate airborne PM10-induced PGE₂ production in keratinocytes through the inhibition of gene expression of COX-1, COX-2, mPGES-1, and/or mPGES-2. Thus, E. cava extract and dieckol are potentially useful natural cosmetic ingredients for counteracting the pro-inflammatory effects of airborne PM.

Airborne particulate matter with a size of 10 μm or less (PM₁₀) can cause oxidative damages and inflammatory reactions in the skin. This study was conducted to discover natural products that are potentially useful in protecting the skin from PM₁₀. Among the hot water extracts of a total of 23 medicinal plants, Siegesbeckiae Herba extract (SHE), which showed the strongest protective effect against PM₁₀ cytotoxicity, was selected, and its mechanism of action and active constituents were explored. SHE ameliorated PM₁₀-induced cell death, lactate dehydrogenase (LDH) release, lipid peroxidation, and reactive oxygen species (ROS) production in HaCaT cells. SHE decreased the expression of KEAP1, a negative regulator of NRF2, and increased the expression of NRF2 target genes, such as HMOX1 and NQO1. SHE selectively induced the enzymes involved in the synthesis of GSH (GCL-c and GCL-m), the regeneration of GSH (GSR and G6PDH), and GSH conjugation of xenobiotics (GSTκ1), rather than the enzymes that directly scavenge ROS (SOD1, CAT, and GPX1). SHE increased the cellular content of GSH and mitigated the oxidation of GSH to GSSG caused by PM₁₀ exposure. Of the solvent fractions of SHE, the n-butyl alcohol (BA) fraction ameliorated cell death in both the absence and presence of PM₁₀. The BA fraction contained a high amount of chlorogenic acid. Chlorogenic acid reduced PM₁₀-induced cell death, LDH release, and ROS production. This study suggests that SHE protects cells from PM₁₀ toxicity by increasing the cellular antioxidant capacity and that chlorogenic acid may be an active phytochemical of SHE.

The purpose of this study is to identify amino acid derivatives with potent anti-eumelanogenic activity. First, we compared the effects of twenty different amidated amino acids on tyrosinase (TYR)-mediated dopachrome formation in vitro and melanin content in dark-pigmented human melanoma MNT-1 cells. The results showed that only L-cysteinamide inhibited TYR-mediated dopachrome formation in vitro and reduced the melanin content of cells. Next, the antimelanogenic effect of L-cysteinamide was compared to those of other thiol compounds (L-cysteine, N-acetyl L-cysteine, glutathione, L-cysteine ethyl ester, N-acetyl L-cysteinamide, and cysteamine) and positive controls with known antimelanogenic effects (kojic acid and β-arbutin). The results showed the unique properties of L-cysteinamide, which effectively reduces melanin content without causing cytotoxicity. L-Cysteinamide did not affect the mRNA and protein levels of TYR, tyrosinase-related protein 1, and dopachrome tautomerase in MNT-1 cells. L-Cysteinamide exhibited similar properties in normal human epidermal melanocytes (HEMs). Experiments using mushroom TYR suggest that L-cysteinamide at certain concentrations can inhibit eumelanin synthesis through a dual mechanism by inhibiting TYR-catalyzed dopaquinone synthesis and by diverting the synthesized dopaquinone to the formation of DOPA-cysteinamide conjugates rather than dopachrome. Finally, L-cysteinamide was shown to increase pheomelanin content while decreasing eumelanin and total melanin contents in MNT-1 cells. This study suggests that L-cysteinamide has an optimal structure that can effectively and safely inhibit eumelanin synthesis in MNT-1 cells and HEMs, and will be useful in controlling skin hyperpigmentation.

Air pollution causes oxidative stress that leads to inflammatory diseases and premature aging of the skin. The purpose of this study was to examine the antioxidant effect of Korean propolis on oxidative stress in human epidermal HaCaT keratinocytes exposed to particulate matter with a diameter of less than 10 μm (PM₁₀). The total ethanol extract of propolis was solvent-fractionated with water and methylene chloride to divide into a hydrophilic fraction and a lipophilic fraction. The lipophilic fraction of propolis was slightly more cytotoxic, and the hydrophilic fraction was much less cytotoxic than the total extract. The hydrophilic fraction did not affect the viability of cells exposed to PM₁₀, but the total propolis extract and the lipophilic fraction aggravated the toxicity of PM₁₀. The total extract and hydrophilic fraction inhibited PM₁₀-induced ROS production and lipid peroxidation in a concentration-dependent manner, whereas the lipophilic fraction did not show such effects. High-performance liquid chromatography with photodiode array detection (HPLC-DAD) analysis showed that the hydrophilic fraction contained phenylpropanoids, such as caffeic acid, p-coumaric acid, and ferulic acid, whereas the lipophilic faction contained caffeic acid phenethyl ester (CAPE). The former three compounds inhibited PM₁₀-induced ROS production, lipid peroxidation, and/or glutathione oxidation, and ferulic acid was the most effective among them, but CAPE exhibited cytotoxicity and aggravated the toxicity of PM₁₀. This study suggests that Korean propolis, when properly purified, has the potential to be used as a cosmetic material that helps to alleviate the skin toxicity of air pollutants.

The total melanin synthesis in the skin depends on various melanogenic factors, including the number of viable melanocytes, the level of melanogenic enzymes per cell, and the reaction rate of the enzymes. The purpose of this study is to examine the effects of L-cysteine (L-Cys), L-ascorbic acid (L-AA), and their derivatives on the tyrosinase (TYR) activity and autoxidation of L-3,4-dihydroxyphenylalanine (L-DOPA) in vitro and the viability and melanin synthesis of B16/F10 cells under different conditions. L-Cysteinamide (C-NH₂), glutathione (GSH), L-Cys, L-AA, and N-acetyl L-cysteine (NAC) inhibited the catalytic activity of TYR in vitro. L-AA, C-NH₂, L-ascorbic acid 2-O-glucoside (AAG), and 3-O-ethyl L-ascorbic acid (EAA) inhibited the autoxidation of L-DOPA in vitro. L-DOPA exhibited cytotoxicity at 0.1 mM and higher concentrations, whereas L-tyrosine (L-Tyr) did not affect cell viability up to 3 mM. L-AA, magnesium L-ascorbyl 2-phosphate (MAP), and L-Cys attenuated the cell death induced by L-DOPA. C-NH₂ decreased the intracellular melanin level at the basal state, whereas L-AA, MAP, and AAG conversely increased it. C-NH₂ reduced the number of darkly pigmented cells via in situ L-DOPA staining, whereas L-AA, MAP, GSH, and AAG increased it. C-NH₂ decreased the intracellular melanin level at the alpha-melanocyte-stimulating hormone (α-MSH)-stimulated state, while NAC and GSH increased it. L-AA and C-NH₂ decreased the intracellular melanin level at the L-Tyr-stimulated state, but NAC and GSH increased it. L-Ascorbyl tetraisopalmitate (ATI) showed no or minor effects in most experiments. This study suggests that L-AA can either promote or inhibit the different melanogenic factors, and C-NH₂ can inhibit the multiple melanogenic factors consistently. This study highlights the multifaceted properties of L-Cys, L-AA, and their derivatives that can direct their therapeutic applications in hyperpigmentation, hypopigmentation, or both disorders.

Metal chelators are used for various industrial and medical purposes based on their physicochemical properties and biological activities. In biological systems, copper ions bind to certain enzymes as cofactors to confer catalytic activity or bind to specific proteins for safe storage and transport. However, unbound free copper ions can catalyze the production of reactive oxygen species (ROS), causing oxidative stress and cell death. The present study aims to identify amino acids with copper chelation activities that might mitigate oxidative stress and toxicity in skin cells exposed to copper ions. A total of 20 free amino acids and 20 amidated amino acids were compared for their copper chelation activities in vitro and the cytoprotective effects in cultured HaCaT keratinocytes exposed to CuSO₄. Among the free amino acids, cysteine showed the highest copper chelation activity, followed by histidine and glutamic acid. Among the amidated amino acids, cysteinamide showed the highest copper chelation activity, followed by histidinamide and aspartic acid. CuSO₄ (0.4–1.0 mM) caused cell death in a concentration-dependent manner. Among the free and amidated amino acids (1.0 mM), only histidine and histidinamide prevented the HaCaT cell death induced by CuSO₄ (1.0 mM). Cysteine and cysteinamide had no cytoprotective effects despite their potent copper-chelating activities. EDTA and GHK-Cu, which were used as reference compounds, had no cytoprotective effects either. Histidine and histidinamide suppressed the CuSO₄-induced ROS production, glutathione oxidation, lipid peroxidation, and protein carbonylation in HaCaT cells, whereas cysteine and cysteinamide had no such effects. Bovine serum albumin (BSA) showed copper-chelating activity at 0.5–1.0 mM (34–68 mg mL⁻¹). Histidine, histidinamide, and BSA at 0.5–1.0 mM enhanced the viability of cells exposed to CuCl₂ or CuSO₄ (0.5 mM or 1.0 mM) whereas cysteine and cysteinamide had no such effects. The results of this study suggest that histidine and histidinamide have more advantageous properties than cysteine and cysteinamide in terms of alleviating copper ion-induced toxic effects in the skin.