Search Results (225)

Ultraviolet (UV) radiation stimulates melanogenesis, leading to various esthetic problems. UV increases oxidative stress and nuclear factor-kappa B (NF-κB), which increase the nucleotide-binding oligomerization domain (NOD) or leucine-rich repeat and pyrin do-main containing 3 (NLRP3) inflammasome. Given that polydeoxyribonucleotides reduce melanogenesis and polynucleotide (PN) has molecular similarity to polydeoxyribonucleotides, we hypothesized that PN can decrease melanogenesis. We compared the anti-melanogenic effect of PN with that of a PN mixture (PNM) that contained other antioxidants, such as glutathione and hyaluronic acid, in UVB-irradiated keratinocytes and animal skin. PN and PNM both decreased oxidative stress, which was evaluated according to the expression of NADPH oxidase (NOX) 1/2/4, the glutathione (GSH):oxidized glutathione (GSSG) ratio, and 8-hydroxy-2′-deoxyguanosine (8-OHdG) in UVB-irradiated keratinocytes. The expression of NLRP3 inflammasome components (NLRP3, ASC, and pro-caspase-1) and IL-18 was increased by UVB radiation and reduced by PN and PNM. When conditioned media from PN or PNM were administered to UVB-radiated keratinocytes, melanogenesis-related signals (MITF, tyrosinase, and tyrosinase-related protein1/2) were decreased. These effects were similar in the UVB-irradiated animal skin. Both PN and PNM decreased melanin accumulation and increased skin lightness in UVB-irradiated skin. The anti-melanogenic effect of PNM was greater than that of PN. In conclusion, PN and PNM decreased melanogenesis by decreasing oxidative stress, NF-κB, and NLRP3 inflammasome activation. Full article

Caffeic acid (CA) is a naturally occurring polyphenol antioxidant found in coffee, tea, fruits, and vegetables, known for its strong antioxidant, anti-inflammatory, and anti-aging properties. However, its cosmetic application is limited because of poor dermal absorption due to its high polarity. This study aimed to evaluate the antioxidant and skin-brightening effects of a novel lipophilic CA derivative, CAD (caffeic acid-3,4-dihydroxyphenylpropanolester). CAD was synthesized by conjugating CA with 3,4-DHPEA, a lipophilic antioxidant derived from olive oil. In both DPPH and ABTS assays, CAD exhibited more potent antioxidant activity than CA. In B16F10 melanoma cells, CAD significantly inhibited melanin production without cytotoxicity at concentrations lower than those required for CA. Cellular assays using DCF-DA staining demonstrated that CAD effectively reduced intracellular ROS levels. Mechanistic studies revealed that CAD inhibited tyrosinase activity and downregulated the expression of TYR, TRP-1, and TRP-2. Additionally, CAD suppressed MITF phosphorylation, along with reduced phosphorylation of ERK and JNK, elucidating its anti-melanogenic mechanism. Importantly, CAD showed dose-dependent skin-brightening effects in the 3D human skin model Melanoderm™, as evidenced by increased lightness and histological evaluation. In conclusion, CAD demonstrates strong potential as a safe and effective antioxidant and skin-brightening agent for cosmetic applications. Full article

Allium genus (Amaryllidaceae) is widely distributed in the Northern hemisphere. Some species, including garlic and onion, have been used since ancient times as both food ingredients and medicinal plants. Many reviews deal with the chemical constituents, particularly the typical sulfur compounds, as well as with Allium pharmacological properties, such as antimicrobial, anti-inflammatory, antioxidant, and cytotoxic activities. The bibliographic search performed in this review is mainly focused on the potential role of Allium species in inhibiting melanogenesis, which has been mainly assessed through the evaluation of the inhibitory properties on tyrosinase, the key enzyme in melanin biosynthesis. Two well established models for identifying potential skin-whitening agents have been used to assess the anti-melanogenic effects of Allium species, the mushroom tyrosinase and the murine melanoma B16 cell line. Here, a literature search from Scopus, Web of Science, and PubMed databases has been performed using the keywords “Allium”, “tyrosinase”, “anti-melanogenic”, and “melanogenesis”, combined by means of Boolean operators. Based on selected inclusion criteria, 32 eligible papers have been selected. The aim of this systematic review is to offer an overview of the species for which the ability to affect melanogenesis has been demonstrated to date, highlighting a new and emerging perspective on the potential therapeutic use of Allium species. The biological properties of isolated pure compounds and the negative outcomes have been also considered. Full article

The rhizomes of Boesenbergia rotunda (fingerroot) and its bioactive compound, panduratin A, exhibit potent anti-inflammatory, antioxidant, and anti-proliferative properties. The aim of this study was to investigate the anti-melanogenic (including anti-tyrosinase) effects of B. rotunda extract and panduratin A in B16F10 melanoma cells induced by UVA radiation. The effects of the compounds on fibroblast proliferation and migration were also assessed by scratch wound healing assays in human primary fibroblasts. The results showed that B. rotunda extract and panduratin A significantly reduced tyrosinase activity and cellular melanogenesis induced by UVA radiation in a dose-dependent manner. The compounds also demonstrated inhibitory effects on fibroblast cell migration and proliferation. These findings suggest that B. rotunda extract may have potential therapeutic effects on skin hyperpigmentation and fibroproliferative skin disorders. Full article

Ergothioneine (EGT), a natural thiol compound with potent antioxidant properties, exhibits diverse biological functions, including anti-inflammatory, neuroprotective, and cardioprotective effects. Despite its promising health and food applications, current production methods, such as mushroom-based liquid fermentation, are hindered by low yields and complex processes. Advances in biosynthetic fermentation, including heterologous expression of key pathway genes and optimization of cultivation conditions, offer promising solutions to these challenges. Recent discoveries, such as the catalytic efficiency of mononuclear non-heme iron enzymes like Egt1 and EgtB, have streamlined EGT biosynthetic pathways, reducing steps and increasing yield. The compound’s active transport via the OCTN1 protein facilitates its distribution across tissues, enhancing its therapeutic efficacy and potential in functional foods. Currently employed as an antioxidant and antimelanogenic agent in aquatic products, EGT holds vast potential for broader applications in food systems. This review explores the advancements in EGT production and biosynthesis while emphasizing its prospects as a safe, versatile, and effective natural ingredient for health and industrial applications. Full article

The 2,4-dihydroxyphenyl group is commonly present in the chemical structures of potent tyrosinase inhibitors. Based on this observation, a series of 6-(substituted phenyl)-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-d]thiazole compounds 1–13 were designed and synthesized as potential tyrosinase inhibitors. Among these, compounds 5 and 9 strongly inhibited mushroom tyrosinase activity. Particularly, compound 9 exhibited nanomolar IC₅₀ values regardless of the substrate used, whereas kojic acid yielded IC₅₀ values of 15.99–26.18 μM. Kinetic studies on mushroom tyrosinase revealed that compounds 5 and 9 competitively inhibited tyrosinase activity, findings further corroborated by in silico docking analysis. In B16F10 cell-based experiments, both compounds effectively inhibited the cellular tyrosinase activity and melanin formation. These inhibitory effects were confirmed through in situ cellular tyrosinase activity assays. Compound 9 exhibited strong antioxidant activity by scavenging radicals, suggesting that its ability to reduce melanin production may be attributed to a combination of its antioxidant and tyrosinase inhibitory properties. Additionally, five compounds, including compound 5, demonstrated effective depigmentation activity in vivo in zebrafish embryos, and their depigmentation efficacy was similar to that of kojic acid, even at concentrations hundreds of times lower. These findings suggest that 6-(substituted phenyl)-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-d]thiazole compounds may be promising anti-melanogenic agents. Full article

Background/Objectives: Flavones, a class of plant-based flavonoids, have demonstrated conflicting anti-melanogenic activities in mouse and human melanocytes. Sinensetin (SNT), a polymethoxyflavone, has shown pro-melanogenic activity in B16F10 mouse melanoma (MM) cells, while eupatilin (EU) and jaceosidin (JAC), two flavones that are structural analogs of SNT, have not been evaluated for their effects on melanogenesis yet. Methods: Herein, the effects of SNT, EU, and JAC on melanogenesis in MNT-1 cells (human melanoma) and HEMn-DP cells (primary human melanocytes) have been examined. The mushroom tyrosinase (TYR) activity was tested in cell-free conditions, followed by examination of the cytotoxicity of the compounds via the Alamar Blue (AB) assay. Cellular melanin production and TYR activity were estimated in MNT-1 cells. The compounds were further examined in primary human melanocytes for melanin production, TYR activity, and protein levels. Results: Our findings show that SNT was a potent inhibitor of TYR activity in a cell-free assay, while EU and JAC had no effect. However, both SNT and EU were shown to exhibit anti-melanogenic activity (that was reversible) in human cells, while JAC was ineffective and cytotoxic. Conclusions: SNT and EU are potential novel candidates for hyperpigmentation treatment without cytotoxicity. Additional studies are warranted to elucidate the signaling mechanisms that govern their anti-melanogenesis action. Future research is necessary to assess the anti-melanogenic effectiveness of SNT/EU using 3D skin tissue equivalents and to select the optimal candidate. Full article

In the present study, we investigated the anti-inflammatory and anti-melanogenic effects of Leuconostoc mesenteroides subsp. DB-21-derived exosomes (DB-21 exosomes), isolated from Camellia japonica flower in lipopolysaccharide (LPS)-induced RAW 264.7 macrophage cells and melanocyte-stimulating hormone (α-MSH)-induced B16F10 melanoma cells. We confirmed that DB-21 exosomes were not toxic to LPS-induced RAW 264.7 macrophage cells and α-MSH-induced B16F10 melanoma cells. Moreover, we confirmed that DB-21 exosomes inhibit the pro-inflammatory cytokines IL-6, IL-1β, TNF-α, PGE₂, and the expression of inflammatory factors iNOS and COX-2. We also found that DB-21 exosomes have a concentration-dependent ability to inhibit melanin, TRP-1, TRP-2, tyrosinase, and MITF, which are factors involved in melanogenesis. Additionally, it inhibits the phosphorylation of Akt and GSK-3β, and MAP kinase pathway proteins such as ERK, JNK, and p38. We confirmed that DB-21 exosomes inhibit melanin synthesis in B16F10 cells through various pathways, and based on previous results, they may be used as a functional cosmetic material with anti-inflammatory and anti-melanogenic activities. Full article

L-Theanine, a natural amino acid found in green tea (Camellia sinensis) leaves, is known for its diverse psychotropic effects. This study aimed to evaluate the inhibitory effect of L-theanine on melanin production and uncover its regulatory mechanism. We evaluated the anti-melanogenic activities of L-theanine in vitro and in vivo. In B16F10 murine melanoma cells induced by α-melanocyte-stimulating hormone, melanin content and intracellular tyrosinase activity were determined, and melanogenesis-related protein expression and signaling pathways were analyzed by Western blotting. Melanin reduction was further assessed using the zebrafish (Danio rerio) test. L-Theanine reduced the intracellular tyrosinase activity and melanin content of B16F10 cells. It also attenuated the expression of melanogenesis-related proteins, such as microphthalmia- associated transcription factor, tyrosinase (TYR), TYR-related protein-1, and dopachrome tautomerase. L-Theanine modulated the protein kinase A (PKA), cAMP responder element binding protein (CREB), phosphorylation of/protein kinase B (Akt), glycogen synthase kinase-3β (GSK-3β), and β-catenin. The antimelanogenic activity of L-theanine (<2 mg/mL) was further confirmed using zebrafish larvae. L-Theanine inhibited melanogenesis by downregulating the PKA/CREB and Akt/GSK-3β/β-catenin signaling pathways. In summary, L-theanine shows potential as a skin-whitening compound, warranting further investigation for its possible applications in cosmetic and pharmaceutical products. Full article

Drug repurposing is a cost-effective and innovative strategy for identifying new therapeutic applications for existing drugs, thereby shortening development timelines and accelerating the availability of treatments. Applying this approach to the development of cosmeceutical ingredients enables the creation of functional compounds with proven safety and efficacy, adding significant value to the cosmetic industry. This study evaluated the potential of rifampicin, a drug widely used for the treatment of tuberculosis and leprosy, as a cosmeceutical agent. The anti-melanogenic effects of rifampicin were assessed in B16F10 melanoma cells, showing no cytotoxicity at concentrations up to 40 µM and a significant reduction in intracellular tyrosinase activity and melanin content. Mechanistically, rifampicin reduced the expression of melanogenic enzymes, including tyrosinase, tyrosinase-related protein (TRP)-1, and TRP-2, via a protein kinase A (PKA)-dependent pathway, leading to the suppression of microphthalmia-associated transcription factor (MITF), which is a key regulator of melanogenesis. Additionally, rifampicin inhibited the p38 signaling pathway but was independent of the PI3K/protein kinase B (Akt) pathway. Furthermore, it decreased Ser9 phosphorylation, enhancing glycogen synthase kinase-3β (GSK-3β) activity, promoted β-catenin phosphorylation, and facilitated β-catenin degradation, collectively contributing to the inhibition of melanin synthesis. To evaluate the topical applicability of rifampicin, primary human skin irritation tests were conducted, and no adverse effects were observed at concentrations of 20 µM and 40 µM. These findings demonstrate that rifampicin inhibits melanogenesis through multiple signaling pathways, including PKA, MAPKs, and GSK-3β/β-catenin. This study highlights the potential of rifampicin to be repurposed as a topical agent for managing hyperpigmentation disorders, offering valuable insights into novel therapeutic strategies for pigmentation-related conditions. Full article

In our previous study, Lentzea sp. JNUCC 0626 was isolated from Hwasun Gotjawal on Jeju Island, and its melanogenic effects were confirmed in B16F10 melanoma cells through the identification of 1-acetyl-β-carboline. In this study, we conducted a comprehensive taxonomic characterization of Lentzea sp. JNUCC 0626, including enzymatic activities, carbohydrate metabolism, growth conditions, and cellular composition. Major fatty acids identified were iso-C16:0, iso-C15:0, and C15:0 anteiso, with polar lipids such as diphosphatidylglycerol, phosphatidylethanolamine, and several unidentified lipids. Ubiquinone Q-9 was determined as the predominant respiratory quinone. Enzymatic activity analysis (API ZYM) showed alkaline phosphatase, esterase (C4), esterase lipase (C8), and leucine arylamidase activities, while carbohydrate metabolism analysis (API 50CHB) indicated acid production from esculin alone. Complete genome sequencing revealed a 10,602,950 bp linear chromosome and a 177,940 bp plasmid. This plasmid encodes essential plasmid-related genes, including a Type IV secretion system and ParA proteins critical for plasmid transfer and stability. These findings suggest that the plasmid in Lentzea sp. JNUCC 0626 could be utilized for developing host–vector systems to facilitate the combinatorial biosynthesis of novel bioactive compounds. Comparative genomic analysis identified Lentzea pudingi CGMCC 4.7319 as the closest relative, but significant genetic divergence (dDDH 46.7%, ANI 88.02%) strongly supports the classification of Lentzea sp. JNUCC 0626 as a novel species. AntiSMASH analysis revealed 34 biosynthetic gene clusters (BGCs), highlighting the strain’s capacity to produce diverse bioactive compounds. Finally, the JNUCC 0626 extract exhibited concentration-dependent NO inhibition in LPS-stimulated RAW 264.7 cells, demonstrating significant anti-inflammatory activity. This suggests that the secondary metabolites inferred from genomic analysis may contribute to these observed bioactivities. Full article

Background/Objectives: Voglibose, an α-glucosidase inhibitor commonly prescribed to manage postprandial hyperglycemia in diabetes mellitus, demonstrates potential for repurposing as an anti-melanogenic agent. This study aims to explore the inhibitory effects of voglibose on melanogenesis and elucidate its molecular mechanisms, highlighting its possible applications in treating hyperpigmentation disorders. Methods: The anti-melanogenic effects of voglibose were investigated using B16F10 melanoma cells. Cell viability, melanin content, and tyrosinase activity were assessed following voglibose treatment. Western blot analysis was performed to examine changes in melanogenic proteins and transcription factors. The role of signaling pathways, including PKA/CREB, MAPK, PI3K/AKT, and GSK3β/β-Catenin, was analyzed. Primary human skin irritation tests were conducted to evaluate the topical safety of voglibose. Results: Voglibose significantly reduced melanin synthesis and tyrosinase activity in B16F10 cells in a dose-dependent manner. Western blot analysis revealed decreased expression of MITF, TRP-1, and TRP-2, indicating the inhibition of melanogenesis. Voglibose modulated key signaling pathways, including the suppression of PKA/CREB, MAPK, and AKT activation, while restoring GSK3β activity to inhibit β-catenin stabilization. Human skin irritation tests confirmed voglibose’s safety for topical application, showing no adverse reactions at 50 and 100 μM concentrations. Conclusions: Voglibose demonstrates anti-melanogenic properties through the modulation of multiple signaling pathways and the inhibition of melanin biosynthesis. Its safety profile and efficacy suggest its potential as a repurposed drug for managing hyperpigmentation and advancing cosmeceutical applications. Full article

Cutaneous melanoma (CM) is an aggressive and metastatic tumor, resulting in high mortality rates. Despite significant advances in therapeutics, the available treatments still require improvements. Thus, purinergic signaling emerged as a potential pathway to cancer therapy due to its involvement in cell communication, proliferation, differentiation, and apoptosis. In addition, due to safety and acceptable clinical tolerability, carotenoids from microalgae have been investigated as adjuvants in anti-melanoma therapy. Then, this work aimed to investigate the in vitro anti-melanogenic effect of carotenoid extract (CA) and total biomass (BM) of the Scenedesmus obliquus microalgae on two cutaneous melanoma cell lines (A375 and B16F10). Cells were cultivated under ideal conditions and treated with 10, 25, 50, and 100 μM of CA or BM for 24 h. The effects of the compounds on viability, oxidant status, and purinergic signaling were verified. The IC50 cell viability results showed that CA and BM decreased B16F10 viability at 24.29 μM and 74.85 μM, respectively and decreased A375 viability at 73.93 μM and 127.80 μM, respectively. Carotenoid treatment for 24 h in B16F10 and A375 cells increased the release of reactive oxygen species compared to the control. In addition, CA and BM isolated or combined with cisplatin chemotherapy (CIS) modulated the purinergic system in B16F10 and A375 cell lines through P2X7, A2AR, CD39, and 5′-nucleotidase. They led to cell apoptosis and immunoregulation by activating A2A receptors and CD73 inhibition. The results disclose that CA and BM from Scenedesmus obliquus exhibit an anti-melanogenic effect, inhibiting melanoma cell growth. Full article

To discover novel anti-melanogenic compounds with tyrosinase inhibitory activity, (Z)-3-benzyl-5-benzylidene-2-thioxothiazolidin-4-one ((Z)-BBTT) analogs 1–12, designed based on the hybrid structure of a β-phenyl-α,β-unsaturated carbonyl motif and a 3-benzyl-2-thioxothiazolidin-4-one scaffold, were synthesized as novel tyrosinase inhibitors. Of the 12 analogs, 2 (6 and 8) showed mushroom tyrosinase inhibitory activity similar to that of kojic acid, a representative tyrosinase inhibitor, and 3 analogs (1–3) exhibited mushroom tyrosinase inhibitory activity that was more potent than that of kojic acid. In particular, analog 3 revealed highly potent inhibition with an IC₅₀ value of 90 nM, which was 214 times lower than that of kojic acid (IC₅₀ value = 19.22 μM). A kinetic study using mushroom tyrosinase and analogs 1–3 and 6 demonstrated that these analogs were competitive inhibitors, which was further supported by in silico studies. Analogs 1 and 3 have strong anti-melanogenic potency in B16F10 mammalian cells owing to their anti-tyrosinase activity without perceptible cytotoxicity in melanoma cells (B16F10) and the main epidermal cells (HaCaT). Moreover, analog 3 exhibited strong antioxidant capacity, scavenging reactive oxygen species, 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) cation radical, and 2,2-diphenyl-1-picrylhydrazyl radical, partially contributing to its anti-melanogenic effect. (Z)-BBTT analogs, including analog 3, may be promising candidates for inhibiting melanin production. Full article

Fifteen compounds (1–15) constructed on a hybrid structure combining a β-phenyl-α,β-unsaturated carbonyl template and a 2-aminothiazol-4(5H)-one scaffold were designed and synthesized as potential novel anti-tyrosinase substances. Two compounds (10 and 15) showed more potent inhibition against mushroom tyrosinase than kojic acid, and the inhibitory activity of 10 (IC₅₀ value: 1.60 μM) was 11 times stronger than that of kojic acid. Lineweaver–Burk plots indicated that these two compounds were competitive inhibitors that bound to the mushroom tyrosinase active site, which was supported by in silico experiments. Compound 10 was an anti-tyrosinase and anti-melanogenic substance in B16F10 cells and was more potent than kojic acid, without cytotoxicity. Compound 15 exhibited the most potent effect on zebrafish larval depigmentation and showed a depigmentation effect comparable to kojic acid, even at a concentration 200 times lower. Compounds 8 and 10 exhibited strong antioxidant capacities, scavenging 2,2-diphenyl-1-picrylhydrazyl, (2,2-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid)⁺ radicals, and reactive oxygen species. Hybrid compounds 10 and 15 are potential therapeutic agents for skin hyperpigmentation disorders. Full article