Anti-melanogenic Activity Research Articles

Design, Synthesis, and Anti-Melanogenic Activity of 2-Mercaptomethylbenzo[d]imidazole Derivatives Serving as Tyrosinase Inhibitors: An In Silico, In Vitro, and In Vivo Exploration.

2-Mercaptomethylbenzo[d]imidazole (2-MMBI) derivatives were designed and synthesized as tyrosinase (TYR) chelators using 2-mercaptomethylimidazole scaffolds. Seven of the ten 2-MMBI derivatives exhibited stronger inhibition of mushroom TYR activity than kojic acid. Their ability to chelate copper ions was demonstrated through experiments using the copper chelator pyrocatechol violet and assays measuring TYR activity in the presence or absence of exogenous CuSO4. The inhibition mechanisms of derivatives 1, 3, 8, and 9, which showed excellent TYR inhibitory activity, were elucidated through kinetic studies and supported by the docking simulation results. Derivatives 3, 7, 8, and 10 significantly inhibited cellular TYR activity and melanin production in B16F10 cells in a dose-dependent manner, with stronger potency than kojic acid. Furthermore, in situ, derivatives 7 and 10 showed stronger inhibitory effects on B16F10 cell TYR activity than kojic acid. Six derivatives, including 8, showed highly potent depigmentation in zebrafish larvae, outpacing kojic acid even at 200-670 times lower concentrations. Additionally, all derivatives could scavenge for reactive oxygen species without causing cytotoxicity in epidermal cells. These results suggested that 2-MMBI derivatives are promising anti-melanogenic agents.

Anti-Melanogenic Effects of a Polysaccharide Isolated from Undaria pinnatifida Sporophyll Extracts.

Undaria pinnatifida is a temperate brown alga known to exert free radical-scavenging and anti-inflammatory effects. In this study, we investigated the skin-whitening effects of U. pinnatifida sporophyll extracts (UPEs) in α-melanocyte-stimulating hormone (α-MSH)-stimulated B16F10 melanoma cells. The crude polysaccharide fraction (UPF) was obtained via ethanol precipitation. Four polysaccharide fractions (UPF1-4) were isolated and purified using ion-exchange column chromatography, and their anti-melanogenic activity was evaluated. UPF3 exhibited the highest anti-melanogenic activity, showing the highest sulfate (39.79%), fucose (143 μg/mg), and galactose (208 μg/mg) contents. UPF3 significantly inhibited intracellular tyrosinase activity in B16F10 cells. We also evaluated the melanogenic signaling pathway to determine the mechanism of action of UPF3 in melanongenesis. UPF3 reduced the expression of tyrosinase-related protein-1 (TRP-1), tyrosinase-related protein-2 (TRP-2), and tyrosinase, which play important roles in melanin production. Therefore, UPF3 has high potential for use in skin-whitening functional pharmaceuticals and cosmetics.

Lokāt (Eriobotrya japonica; family: Rosaceae): Nutritional and Medicinal Properties, in the Light of Unani Medicine and Scientific Studies

Eriobotrya japonica Lind. (Family: Rosaceae) named as loquat, is a subtropical fruit, which is well known medicinal plant cultivated in Japan and China. Various parts, like leaves, peels and fruits have been shown to possess various useful health benefits. In Unani medicine, it is vastly utilized in many illnesses, like fevers, nausea, de-arranged sanguinous humour (diseases due to morbidity of blood), indigestion, liver diseases, vomiting, dysentery, wounds, inflammations etc. Loquat plant contains many active constituents, such as glycosides, flavonoids, polyphenolic compounds, tannin etc. and nutritional and mineral compounds like, carotenoids, vitamins, starch, amino acids, sugar and others. According to various pharmacological studies it is found that the plant has many biological effects like antitussive, anti-melanogenic, anti-diabetic, anti-inflammatory, antimicrobial, kidney protective, hepatoprotective and hypolipidemic activity. This review aims to shed light on the therapeutic applications of loquat based on both traditional Unani literature and scientific studies conducted on different parts of the plant.

The influence of spatial distribution and transcriptional regulation of secondary metabolites on the bioactivities of Adenophora triphylla (Japanese lady bell)

The distribution of secondary metabolites in plant tissues plays a crucial role in determining their pharmacological properties. In this study, we investigated the dynamics of the bioactive compounds in Adenophora triphylla, a medicinal herb with diverse therapeutic applications.The anti-inflammatory properties of the EtOAc fraction from the aerial part extract (A_ EtF) exhibited an IC50 value of 27.2 ± 2.3 μg/mL, significantly surpassing that of the EtOAc fraction from the root extract (R_EtF) with an IC50 of 38.9 ± 2.9 μg/mL. Similarly, the anti-melanogenic activity of A_EtF (IC50 = 68.9 ± 2.3 μg/mL) outperformed that of R_EtF (IC50 = 90.0 ± 5.5 μg/mL). Analysis of the distinct chemical profiles of these tissues using UPLC-ESI-Q-TOF-MS revealed that the distribution of secondary metabolites contributes to the observed variations in pharmacological properties between the aerial parts and roots. Transcriptome analysis further elucidated spatially regulated genes associated with secondary metabolism, highlighting the role of AbtYABBYs as potential regulators of phenylpropanoid biosynthesis. To validate their function, these genes were transiently expressed in tobacco leaves via agro-infiltration, confirming their role in modulating polyphenolic compound biosynthesis. Our findings underscore the importance of understanding spatial gene expression patterns for harnessing the complete pharmacological potential of medicinal plants. This study provides valuable insights into the spatial regulation of secondary metabolism and lays the groundwork for targeted manipulation of plant bioactivity for therapeutic and industrial applications.

Photobiomodulation Using 830 nm Lighting-Emitting Diode Inhibits Melanogenesis via FOXO3a in Human Melanocyte.

Photobiomodulation (PBM) using 830 nm light-emitting diode (LED) benefits tissue regeneration, wound healing and neural stimulation. However, there is not much exploration of its effect on melanocytes and exvivo skin model. This study aims to investigate the mechanism behind the anti-melanogenic activity of 830 nm LED and provides evidence for its activity in human exvivo skin model. Our results showed that 830 nm LED at fluences ranging from 5 to 20 J/cm2 inhibited melanosome maturation and reduced melanin content, tyrosinase activity and melanogenesis-related proteins. 830 nm LED inhibited the phosphorylation of AKT and its downstream FOXO3a, leading to nuclear translocation of FOXO3a. Furthermore, FOXO3a knockdown and AKT activator like SC79 could reverse the melanogenesis inhibition phenotype induced by 830 nm LED. In human exvivo skin model, Fontana-Masson staining revealed a decrease in epidermal basal pigmentation after 830 nm LED irradiation. Taken together, 830 nm LED demonstrated the anti-melanogenic activity via FOXO3a.

Genetic Variation Affects the Anti-Melanogenic Efficacy of Platycodon grandiflorus Flowers

This study investigated the utilization of by-products from Platycodon grandiflorus and the role of genetic diversity in their anti-melanogenic properties, focusing on the purple-flower (PF) and white-flower (WF) varieties. Our results show that the WF variety exhibited significantly higher anti-melanogenic activity, attributed to higher concentrations of key saponins such as platycodin D3 and platycodin D. These saponins demonstrated strong tyrosinase inhibitory effects as confirmed by molecular docking analysis. Further, the WF variety showed increased expression of genes involved in saponin biosynthesis, highlighting the role of genetic diversity in determining phytochemical composition and pharmacological efficacy. The superior anti-melanogenic activity of WF suggests its potential as a valuable ingredient in the cosmetic industry for skin-whitening products. Our findings emphasize the importance of utilizing by-products and selecting specific genotypes to enhance the quality and efficacy of plant-derived products. Future research should explore the full spectrum of bioactive compounds in P. grandiflorus, investigate sustainable extraction methods, and conduct clinical trials to validate the safety and effectiveness of these compounds in cosmetic and therapeutic applications.

Potential Wound Healing and Anti-Melanogenic Activities in Skin Cells of Aralia elata (Miq.) Seem. Flower Essential Oil and Its Chemical Composition.

Aralia elata (Miq.) Seem. (AES; family Araliaceae) is a medicinal plant and has been reported to have various bioactivities, including anticancer and hepatotoxicity protective activities. However, no studies have investigated the biological activities of AES or its extracts on skin. To address this, we aimed to explore the effect of AES-flower-derived absolute-type essential oil (AESFEO) on skin-related biological activities, especially skin wound healing and whitening-related responses in skin cells (human-derived keratinocytes [HaCaT cells] and melanocytes [B16BL6 cells]) and to identify the components of AESFEO. Cell biological activities were analyzed using WST and BrdU incorporation assays, ELISA, or by immunoblotting. In HaCaT cells, AESFEO promoted proliferation, type IV collagen production, and enhanced the phosphorylations of Erk1/2, p38 MAPK, JNK, and Akt. In B16BL6 cells, AESFEO reduced serum-induced proliferation, α-MSH-stimulated increases in melanin synthesis and tyrosinase activity, and α-MSH-induced increases in MITF, tyrosinase, TRP-1, and TRP-2 expressions. In addition, AESFEO inhibited the phosphorylation of Erk1/2, p38 MAPK, and JNK in α-MSH-stimulated B16BL6 cells. Eighteen compounds were identified in AESFEO by GC/MS. These results suggest that AESFEO has beneficial effects on keratinocyte activities related to skin wound healing and melanocyte activities related to inhibition of skin pigmentation. AESFEO may serve as a useful natural substance for developing agents that facilitate skin wound healing and inhibit melanogenesis.

Epidermal and Blood Vessel Barrier Functions of Glucosylceramides and Digalactosyldiacylglycerols Isolated from Yellow Strawberry Guava

Strawberry guava is the fruit of Psidium littorale, which grows in tropical regions. Few studies have examined the hydrophobic compounds and biological activities of this fruit. Therefore, we purified lipophilic compounds of strawberry guava and examined their effects on epidermal and blood vessel barrier functions as well as their anti-melanogenic activity. Lipophilic compounds were isolated by silica gel column chromatography followed by reversed-phase HPLC with MeOH from an EtOH extract of the fruit. Isolated compounds were identified by comparing NMR and MS spectra with those of reference values. The effects of these compounds on epidermal barrier function were evaluated by measuring transepidermal water loss (TEWL) using reconstructed human epidermal keratinocytes (RHEKs). Blood vessel barrier function was examined using dye permeability through human umbilical vein endothelial cell (HUVEC) layers. Anti-melanogenic activity was assessed by theophylline-induced melanogenesis in B16 melanoma cells. We isolated six glucosylceramides (GlcCers) and three digalactosyldiacylglycerols (DGDGs). Only GlcCer[t18:1(8Z)/23:0] significantly lowered TEWL in RHEKs, while GlcCer[t18:1(8Z)/24:0] induced a slight reduction. Regarding the permeability of the HUVEC layer, GlcCer[d18:2(4E,8Z)/16:0] and DGDG (1,2-dilinolenoyl-3-digalactosylglycerol) significantly suppressed dye permeability and this effect was accompanied by the expression of VE-cadherin, which facilitates cell-to-cell adhesion. GlcCers and DGDGs did not exhibit anti-melanogenic activity. Therefore, strawberry guava containing specific GlcCers and DGDGs may promote epidermal and blood vessel barrier functions.

Anti-Melanogenic Activity of Ethanolic Extract from Garcinia atroviridis Fruits Using In Vitro Experiments, Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation.

Melanin, the pigment responsible for human skin color, increases susceptibility to UV radiation, leading to excessive melanin production and hyperpigmentation disorders. This study investigated the ethanolic extract of Garcinia atroviridis fruits for its phenolic and flavonoid contents, antioxidant activity, and impact on melanogenesis pathways using qRT-PCR and Western blot analysis. Utilizing network pharmacology, molecular docking, and dynamics simulations, researchers explored G. atroviridis fruit extract's active compounds, targets, and pharmacological effects on hyperpigmentation. G. atroviridis fruit extract exhibited antioxidant properties, scavenging DPPH• and ABTS•+ radicals radicals and chelating copper. It inhibited cellular tyrosinase activity and melanin content in stimulated B16F10 cells, downregulating TYR, TRP-1, phosphorylated CREB, CREB, and MITF proteins along with transcription levels of MITF, TYR, and TRP-2. LC-MS analysis identified thirty-three metabolites, with seventeen compounds selected for further investigation. Network pharmacology revealed 41 hyperpigmentation-associated genes and identified significant GO terms and KEGG pathways, including cancer-related pathways. Kaempferol-3-O-α-L-rhamnoside exhibited high binding affinity against MAPK3/ERK1, potentially regulating melanogenesis by inhibiting tyrosinase activity. Stable ligand-protein interactions in molecular dynamics simulations supported these findings. Overall, this study suggests that the ethanolic extract of G. atroviridis fruits possesses significant antioxidant, tyrosinase inhibitory, and anti-melanogenic properties mediated through key molecular targets and pathways.

The Potency of Adenostemma platyphyllum as Antimelanogenic Agent: In-vitro and In-silico Studies

Melanin is a crucial amino acid in determining human skin and hair pigmentation. Excessive melanin production can lead to hyperpigmentation and darkening of the skin. This study aims to assess the capability of Adenostemma platyphyllum as a tyrosinase enzyme inhibitor. It predicts its anti-melanogenic activity through molecular docking with proteins involved in the melanogenesis process. The in-vitro approach was conducted by determining the tyrosinase enzyme inhibition capacity, while the in-silico approach involved ligand binding to target proteins from melanogenesis pathways. The highest tyrosinase inhibition capacity was observed in the ethanol extract, with values of 9.74 Kojic Acid Equivalent (KAE)/g extract (L-tyrosine) and 17.91 (KAE)/g extract (L-DOPA). Molecular docking analysis showed that the binding of eriodictyol 7-O-sophoroside (ΔG = -9.7 kcal/mol) has the best energy affinity for the PKC-β protein, genistein (ΔG = -7.5 kcal/mol) for the tyrosinase-related protein-1 (TYRP1) protein, eriodictyol 7-O-sophoroside (ΔG = -10.2 kcal/mol) for the cGMP protein, vincosamide (ΔG = -7.2 kcal/mol) for the microphthalmia-associated transcription factor (MITF) protein, and dicaffeoylquinic acid (ΔG = -7.4 kcal/mol) for the β-catenin protein. Based on a comparison of in-vitro and in-silico studies, melanogenesis inhibition is more potent in the PKC-β and cGMP pathways than direct tyrosinase inhibition because they exhibit lower binding energy.

Discovery of Novel Diesters Incorporating Kojic Acid With NSAIDs and Palmitic Acid as Dual Inhibitor of Melanogenesis and Inflammation

Our study focuses on creating hybrid compounds and assessing their suitability for use in skincare products. The synergistic combination of Kojic acid, NSAIDs, and Palmitic acid proved to be an effective approach in inhibiting melanin production, making it a promising solution for individuals with hyperpigmentation concerns with Kojic acid (KA) Ibuprofen monoester (IBUM) and Ibuprofen-Kojic acid-Palmitic acid diester (IBUD) exhibiting a potential tyrosinase (38 % and 49 % inhibition at 200 µM) and anti-melanogenesis activity (77 % and 79 % inhibition at 100 µM). Furthermore, these compounds exhibited potent anti-inflammatory effects, Kojic acid-Diclofenac monoester (DICM) and Diclofenac-Kojic acid-Palmitic acid diester (DICD) offering potential benefits for inflammation by lowering the paw volume. A stability study under chemical conditions and enzymatic conditions was also performed, wherein DICM and DICD showed a better half-life of 515, 593 h under chemical stability and 6.3, 7.5 h under enzymatic stability studies respectively. The diester hybrids IBUD, DICD, Naproxen-Kojic acid-Palmitic acid diester (NAPD) showed a better permeation and penetration profiles compared to their parent drugs. In-vitro cell line studies were conducted to assess the safety and efficacy of these hybrid esters, with promising results. The dual inhibitor demonstrated minimal cytotoxicity and remarkable anti-melanogenic and anti-inflammatory activities, showing its potential as a versatile agent in addressing both melanogenesis and inflammation.

Anti-Melanogenic Activity of Undecylprodigiosin, a Red Pigment Isolated from a Marine Streptomyces sp. SNA-077.

Bioassay and HPLC-UV guided fractionations of the crude extract of marine-derived Streptomyces sp. SNA-077 have led to the isolation of a red pigment, undecylprodigiosin (1). The chemical structure of undecylprodigiosin (1) was revealed by the interpretation of NMR and mass spectroscopic (MS) data. Further, anti-melanogenic effects of undecylprodigiosin (1) were investigated. First, the melanin contents of undecylprodigiosin (1)-treated B16 cells were evaluated. Furthermore, undecylprodigiosin (1) significantly inhibited the key enzymes involved in melanogenesis, including tyrosinase, tyrosinase related protein-1 (TYRP-1), and dopachrome tautomerase (DCT). The mRNA and protein expression levels of Microphthalmia-associated transcriptian factor (MiTF), a critical transcription factor for tyrosinase gene expression, were also suppressed by undecylprodigiosin (1) treatment in B16 analyses. Collectively, our results suggest for the first time that undecylprodigiosin (1), a potent component isolated from an extract of marine Streptomyces sp. SNA-077, critically exerts the anti-melanogenic ability for melanin synthesis.

Development and evaluation of high permeability liposomes for improving anti-melanogenic activity of taxus chinensis fruit polysaccharide

Taxus chinensis var. mairei fruit polysaccharide (TMFP) is a natural resource with effective hypoglycemic and anti-tumor properties. However, its impact on melanogenesis remains largely unexploited. This study explores the anti-melanogenic activity of TMFP using in vitro and in vivo models. It was found that TMFP can safely and effectively eliminate melanin and inhibit tyrosinase activity without cytotoxicity. More specifically, the inhibitory effect of TMFP on melanin synthesis was verified in zebrafish embryos. In addition, nine formulations of TMFP-Liposomes were prepared to improve drug transdermal absorption, and TMFP-Liposome E was determined as the optimal formulation after characterization and transdermal comparison experiments. Most importantly, in vivo skin whitening experiments gave that TMFP-Liposome E has better skin whitening activity than control, model, blank liposomes, TMFP aqueous, and arbutin groups. The cell viability and animal safety tests confirmed the good biosafety of TMFP-Liposome E. Overall, this research suggests that TMFP may serve as a potential therapeutic agent for skin diseases and a potent whitening agent for cosmetic use. TMFP-Liposome E may enhance the therapeutic effect of melanin through improved transdermal absorption.

Comparative Study of the Effects of Curcuminoids and Tetrahydrocurcuminoids on Melanogenesis: Role of the Methoxy Groups

Curcuminoids are naturally occurring yellow-colored compounds that, when hydrogenated to remove their conjugated double bond, become colorless and are referred to as tetrahydrocurcuminoids. Curcuminoids consist of pure curcumin (PC) in major amounts and demethoxycurcumin (DC) and bisdemethoxycurcumin (BDC) in minor amounts. Tetrahydrocurcuminoids similarly consist mainly of tetrahydrocurcumin (THC), along with minor amounts of tetrahydrodemethoxycurcumin (THDC) and tetrahydrobisdemethoxycurcumin (THBDC). Previous studies have shown the inhibitory effects of PC, DC, and BDC on melanin production, but there are contradictory findings about THC. In addition, there are currently no reports on the effects of THDC and THBDC on melanogenesis. Our previous report described that, in contrast to PC, which suppressed melanin production, THC stimulated melanin production in B16F10 and MNT-1 cells; this effect was ascribed to the loss of the conjugated heptadiene moiety of PC. However, whether this finding can be generalized to the two curcumin derivatives (DC and BDC), such that THDC and THBDC might also stimulate melanogenesis, has not been addressed. Herein, a comparative study of six curcumin derivatives (PC, DC, BDC, THC, THDC, and THBDC) was undertaken to identify their effects on melanogenesis with the goal of elucidating the structure–activity relationships (SARs) focused on assessing the two regions of the parent curcumins’ structure: (i) the hydrogenation of the two double bonds bridging the phenyl rings to the β-diketone moiety, and (ii) the effect of the ortho-methoxy substituent (-OCH3) on the two phenyl rings. To determine the direct effects of the six compounds, antioxidant activity and tyrosinase activity were assessed in cell-free systems before cellular experiments utilizing the B16F10 mouse melanoma cells, MNT-1 human melanoma cells, and primary cells. Evaluations were made on cytotoxicity, melanin concentration, and cellular tyrosinase activity. The results showed that BDC inhibited melanogenesis in B16F10 and MNT-1 cells. However, it was ineffective in primary human melanocytes, while THBDC continued to exhibit anti-melanogenic capacity in normal human melanocytes. Moreover, these findings provide a novel perspective into the role of the methoxy groups of PC on the biological effects of melanogenesis and also confirm that the removal of the conjugated double bonds abolishes the anti-melanogenic capacity of PC and DC only, but not BDC, as THBDC maintained anti-melanogenic activity that was greater than BDC. However, the outcome is contingent upon the specific kind of cell involved. To the best of our knowledge, this work presents novel findings indicating that the anti-melanogenic capacity of the colored BDC is not only intact but enhanced after its hydrogenation as observed in THBDC. The findings show potential for using colorless THBDC as a pharmacological candidate to diminish the increased pigmentation characteristic of skin hyperpigmentation disorders. Future pharmacological therapeutics that incorporate pure THBDC or THBDC-enriched extracts, which retain both a colorless appearance and potent anti-melanogenic activity, can be applied to compounds for anti-melanoma therapeutics where the demand for nontoxic novel molecules is desired for established efficacies.

Comparative Teratogenic and Skin whitening effect of Herbal extract Glycyrrhiza glabra and Citrus sineus on Zebrafish (Danio rerio)

Objective: To determine acute toxicity and Synergistic effect of the anti-melanogenic activity of methanolic extract Glycyrrhiza glabra and Citrus sineus on zebrafish. Materials and method: Fish embryo toxicity (FET) was studied as per OECD guidelines 236. The LC50 and maximum non-lethal concentration of both the extracts were calculated. The images of zebrafish larvae exposed to different concentrations of methanolic extracts and their combination were taken by using labomed digital microscope. The skin whitening effect of extract was studied by measuring integrated density of images by using imageJ software Result: LC50 Value and maximum non-lethal concentration of methanolic extracts of Glycyrrhiza glabra and Citrus sineus were found to be 56.23ppm and 34.7ppm respectively. The result revealed significant reduction in percentage hatchability (p < 0.0014 for glycyrrhiza glabra and p<0.0011 for Citrus sinenus), dose dependant increased in percentage mortality and different developmental morphological abnormalities in zebrafish embryos exposed to the methanolic extracts Glycyrrhiza glabra and Citrus sineus. The synergistic effect of herbal extracts was found to be more effective in reducing the melanin content. Conclusion: Very High concentration of Glycyrrhiza glabra and Citrus Sineus showed teratogenic effect in zebrafish embryoes. However, based on OECD aquatic toxicity classification, both the extracts were found to be safe. Our study also revealed synergestic skin whitening effect of both the extracts in zebrafish larvae which might be due to reduction of melatonin content by these extracts.

Melanosomal localization is required for GIF-2115/2250 to inhibit melanogenesis in B16F10 melanoma cells.

Tyrosinase inhibitors suppress melanogenesis in melanocytes. During a screening for tyrosinase inhibitors, however, we noticed some discrepancies in inhibitory efficacies between melanocytes and invitro assays. The compound (S)-N-{3-[4-(dimethylamino)phenyl]propyl}-N-methyl-indan-1-amine (GIF-2115) exerts antioxidative stress activity upon accumulation in late endosomes and lysosomes. GIF-2115 was also identified as a potent antimelanogenic reagent in B16F10 mouse melanoma cells. GIF-2115 inhibited the activity of mushroom tyrosinase and the lysates of B16F10 cells. However, structure-activity relationship studies indicated that GIF-2238, which lacks the benzene ring in the aminoindan structure of GIF-2115, inhibited tyrosinase activity invitro but did not inhibit melanogenesis in B16F10 cells. The aim of the present study is to show the importance of the intracellular distribution of tyrosinase inhibitors in exerting their antimelanogenic activity in melanocytes. The intracellular distribution of compounds was monitored by linking with the fluorescent group of 7-nitro-2,1,3-benzoxadiazole (NBD). To mislocalize GIF-2115 to mitochondria, the mitochondria-preferring fluoroprobe ATTO565 was used. We reconfirmed the localization of GIF-2250 (GIF-2115-NBD) not only to matured but also to early-stage melanosomes. Although GIF-2286 (GIF-2238-NBD) maintained tyrosinase inhibitory activity, it did not show specific intracellular localization. Moreover, when GIF-2115 was linked with ATTO565, the resultant compound GIF-2265 did not inhibit melanogenesis in B16F10 cells, despite its strong tyrosinase inhibitory activity. These results suggest that melanosomal localization is essential for the antimelanogenic activity of GIF-2115, and GIF-2115 derivatives may be new guides for drugs to endosomes and lysosomes as well as melanosomes.

The Antimelanogenic Activity of the Extract of Heukharang Lettuce (Lactuca sativa L.) Leaf

Heukharang (Lactuca sativa L.), the artificially developed lettuce cultivar for enhancement of lactucin content, exhibits antioxidant activities and sleep-promoting effects. However, potential of Heukharang as a raw material for the skin-whitening agent has not been investigated yet. This study evaluated the effects of Heukharang extract (HHE) on α-melanocyte-stimulating hormone (α-MSH)-induced melanogenesis in vitro and in vivo models. Our findings revealed that HHE (25–100 μg/mL) effectively inhibited α-MSH-induced melanin synthesis in both 2D and 3D cell culture environments without compromising the viability of the B16F10 murine melanoma cell line. Furthermore, HHE suppressed intracellular tyrosinase activity, along with both gene and protein expression of tyrosinase (TYR) and tyrosinase-related protein (TRP)-1 and TRP-2. HHE downregulated the mRNA level of microphthalmia-associated transcription factor (MITF) and the phosphorylation of cAMP response element-binding (CREB) protein. The antimelanogenic activity of HHE (50 and 100 μg/mL) was also confirmed using a zebrafish embryo model, highlighting its efficacy in inhibiting α-MSH-induced melanogenesis through the downregulating CREB/MITF/TYR signaling pathways. Moreover, our study demonstrated that a corresponding amount of lactucin (5–20 μM) to the HHE inhibited and regulated melanogenesis. These results collectively suggest that HHE, enriched with lactucin, holds promise as a potential skin-whitening agent for nutricosmetic industries.

Ginsenoside Rf in wild ginseng adventitious roots extract inhibits melanogenesis via cAMP/PKA and NO/cGMP signalling pathways in α-melanocyte-stimulating hormone-stimulated B16F10 mouse melanoma cells and zebrafish

The scarcity of more effective wild ginseng has severely limited its use, culturing of adventitious roots from wild ginseng were its good substitute. In this study, we found ginsenoside Rf as the special component in adventitious roots extract significantly decreased melanin levels and tyrosinase activity in B16F10 cells and zebrafish, and suppressed the expression of microphthalmia-associated transcription factor and melanogenic enzymes in B16F10 cells. Notably, Rf treatment of B16F10 cells led to reduced cell levels of adenosine cyclic 3′, 5′-monophosphate (cAMP), nitric oxide (NO), and guanoside cyclic 3′, 5′-monophosphate (cGMP), and reduced activities of adenylate cyclase (AC), protein kinase A (PKA), guanylate cyclase (GC), and protein kinase G (PKG), which suggest Rf anti-melanogenic activity potentially involved inhibition of AC/cAMP/PKA and NO/GC/cGMP/PKG signalling pathway. This work provides experimental basis for skin-lightening effect of wild ginseng adventitious roots and their functional part.

Antioxidant and Antimelanogenic Activities of Lactobacillus kunkeei NCHBL-003 Isolated from Honeybees.

Excessive reactive oxygen species production can detrimentally impact skin cell physiology, resulting in cell growth arrest, melanogenesis, and aging. Recent clinical studies have found that lactic acid bacteria have a special effect directly or indirectly on skin organs, but the exact mechanism has not been elucidated. In this study, we investigated the mechanisms underlying the antioxidant protective effect and the inhibitory effect on melanin synthesis of Lactobacillus kunkeei culture supernatant (CSK), isolated from Apis mellifera Linnaeus (the Western honeybee). CSK exhibited notable efficacy in promoting cell migration and wound healing under oxidative stress, surpassing the performance of other strains. CSK pretreatment significantly upregulated the expression of Nrf2/HO-1 (nuclear factor erythroid 2-related factor 2/heme oxygenase-1), a key player in cellular defenses against oxidative stress, relative to the control H2O2-treated cells. The DCF-DA (dichloro-dihydro-fluorescein diacetate) assay results confirmed that CSK's ability to enhance Nrf2 and HO-1 expression aligns with its robust ability to remove H2O2-induced reactive oxygen species. Furthermore, CSK upregulated MAPK (mitogen-activated protein kinase) phosphorylation, an upstream signal for HO-1 expression, and MAPK inhibitors compromised the wound-healing effect of CSK. Additionally, CSK exhibited inhibitory effects on melanin synthesis, downregulating melanogenesis-related genes in B16F10 cells. Thus, the present study demonstrated that CSK exhibited antioxidant effects by activating the Nrf2/HO-1 pathway through MAPK phosphorylation, thereby restoring cell migration and demonstrating inhibitory effects on melanin production. These findings emphasize the antioxidant and antimelanogenic potential of CSK, suggesting its potential use as a therapeutic agent, promoting wound healing, and as an active ingredient in skin-lightening cosmetics.

Marine resources compound with melanogenic regulatory properties: Especially seagrass, seaweed, and marine sponges as an anti-melanogenic activity

Tyrosinase is a rate-limiting enzyme that is essential for the synthesis of melanin and controls pigmentation in the skin. The most common strategy in cosmeceutical products for skin lightening is the suppression of tyrosinase. Marine substances contain a variety of unique chemical compounds that have the potential to develop into new bioactive compounds as future medications for skin hyperpigmentation therapy. In this review, we summarize 55 compounds from marine resources that have been identified as active in inhibiting tyrosinase enzyme activity from research studies published up to April 2023. Those substances are classified to be very strong, strong, and moderate inhibit tyrosinase activity and melanin biosynthesis. Based on the IC50 value, there are 12 compounds that act as potential anti-melanogenic agents. 7-phloroeckol isolated from Ecklonia cava has the highest tyrosinase enzyme inhibitory activity with an IC50 value of 0.85 μM, while Arenarol isolated from Dysidea arenaria has the most active properties in reducing the synthesis of melanin with an IC50 value of <3 μM on B16 melanoma cells. We propose to present a new perspective on the discovery of metabolites from seagrasses, seaweeds, and marine sponges that can be applied as lead compounds in developing medications for anti-hyperpigmentation therapy through this review.