Chalcone is a type of flavonoid compound that is widely biosynthesized in plants. Studies have shown that consuming flavonoids from fruits and vegetables or applying individual ingredients reduces the risk of skin disease. However, the effects of chalcone on melanogenesis and inflammation have not been fully investigated. The aim of this study was to evaluate the anti-melanogenic and anti-inflammatory effects of 2\'-hydroxy-3,4\'-dimethoxychalcone (3,4\'-DMC), 2\'-hydroxy-4,4\'-dimethoxychalcone (4,4\'-DMC), 2\'-hydroxy-3\',4\'-dimethoxychalcone (3\',4\'-DMC), and 2\'-hydroxy-4\',6\'-dimethoxychalcone (4\',6\'-DMC). Among the derivatives of 2\'-hydroxy-4\'-methoxychalcone, 4\',6\'-DMC demonstrated the most potent melanogenesis-inhibitory and anti-inflammatory effects. As evidenced by various biological assays, 4\',6\'-DMC showed no cytotoxicity and notably decreased the expression of tyrosinase, tyrosinase-related protein (TRP)-1, and TRP-2 enzymes. Furthermore, it reduced cellular melanin content and intracellular tyrosinase activity in B16F10 melanoma cells by downregulating microphthalmia-associated transcription factor (MITF), cAMP-dependent protein kinase (PKA), cAMP response element-binding protein (CREB), p38, c-Jun N-terminal kinase (JNK), β-catenin, glycogen synthase kinase-3β (GSK3β), and protein kinase B (AKT) proteins, while upregulating extracellular signal-regulated kinase (ERK) and p-β-catenin. Additionally, treatment with 4\',6\'-DMC significantly mitigated the lipopolysaccharide (LPS)-induced expression of NO, PGE2, inflammatory cytokines, COX-2, and iNOS proteins. Overall, 4\',6\'-DMC treatment notably alleviated LPS-induced damage by reducing nuclear factor kappa B (NF-κB), p38, JNK protein levels, and NF-kB/p65 nuclear translocation. Finally, the topical applicability of 4\',6\'-DMC was evaluated in a preliminary human skin irritation test and no adverse effects were found. These findings suggest that 4\',6\'-DMC may offer new possibilities for use as functional ingredients in cosmeceuticals and ointments.

Petanin, an acylated anthocyanin from the Solanaceae family, shows potential in tyrosinase inhibitory activity and anti-melanogenic effects; however, its mechanism remains unclear. Therefore, to investigate the underlying mechanism of petanin\'s anti-melanogenic effects, the enzyme activity, protein expression and mRNA transcription of melanogenic and related signaling pathways in zebrafish using network pharmacology, molecular docking and molecular dynamics simulation were combined for analysis. The results showed that petanin could inhibit tyrosinase activity and melanogenesis, change the distribution and arrangement of melanocytes and the structure of melanosomes, reduce the activities of catalase (CAT) and peroxidase (POD) and enhance the activity of glutathione reductase (GR). It also up-regulated JNK phosphorylation, inhibited ERK/RSK phosphorylation and down-regulated CREB/MITF-related protein expression and mRNA transcription. These results were consistent with the predictions provided through network pharmacology and molecular docking. Thus, petanin could inhibit the activity of tyrosinase and the expression of tyrosinase by inhibiting and negatively regulating the tyrosinase-related signaling pathway ERK/CREB/MITF through p-JNK. In conclusion, petanin is a good tyrosinase inhibitor and anti-melanin natural compound with significant market prospects in melanogenesis-related diseases and skin whitening cosmetics.

Hyperpigmentation occurs due to irregular secretion of melanin pigment in the skin. This can affect quality of life depending on its severity, so prevention and management are essential. Oats (Avena sativa L.), a grain consumed worldwide, are known to offer improved health benefits upon germination and fermentation. This study is aimed to investigate the protective effects of lactobacilli-fermented sprouted oat extracts on oxidative stress and melanin overproduction in vitro. The anti-melanogenic effect was investigated using melanin content and tyrosinase activity assays in B16F10 cells, as well as a mushroom tyrosinase-based enzyme inhibition assay. The results showed that L. casei-fermented oat extracts were the most effective for reducing melanin formation by reducing the mRNA expression of microphthalmia-associated transcription factor, tyrosinase, and tyrosinase-related protein 2. Furthermore, L. casei fermentation was effective in improving the total phenolic, flavonoid, and avenanthramide A contents of sprouted oat extracts. The results also demonstrated the antioxidant effects of L. casei-fermented sprouted oat extracts in promoting DPPH radical-scavenging activity, superoxide dismutase-like activity, and reduction in reactive oxygen species levels. Overall, the findings indicate that fermented sprouted oat extracts are promising candidates for antioxidant and anti-hyperpigmentation treatments.

Common tyrosinase (TYR) inhibitors used in cosmetics, such as hydroquinone, kojic acid, and arbutin, can cause side effects including erythema, skin peeling, and dryness. Therefore, the development of natural whitening agents that offer excellent permeability, minimal irritation, and high safety has become a primary focus in the field of TYR inhibitors. In this study, we demonstrate that White birch sap (WBS), within a safe concentration range, effectively reduces TYR activity and melanin content in both B16F10 mouse melanoma cells and zebrafish larvae. Importantly, WBS exhibits minimal irritation to neutrophils in fluorescent zebrafish and does not affect the behavior of adult zebrafish. Furthermore, WBS downregulates the gene expression levels of microphthalmia-associated transcription factor, TYR, tyrosinase-related protein-1, and tyrosinase-related protein-2 in B16F10 cells. In conclusion, our research confirms that WBS, a naturally derived substance, offers high safety and mild effects, making it a promising candidate for a skin-whitening agent.

BACKGROUND: The roots and rhizomes of Bergenia purpurascens (Hook. f. et Thomson) Engl., was used as a sunscreen to protect against ultraviolet rays in Tibet of China historically, but its skin whitening constituents and pharmacological effects of this plant remained unknown.
OBJECTIVE: To investigate the anti-melanogenesis effect of B. purpurascens in vitro and in vivo, and then explore the preliminary mechanism.
METHODS: An ultraviolet B (UVB)-induced skin injury model of mice was used to verify the ameliorative effect of B. purpurascens extract (BPE) on ultraviolet damage. Then, alpha-melanocyte stimulating hormone (α-MSH)-induced murine melanoma cell line (B16F10) melanin generation model was further adopted to approval the effects of BPE and its bioactive compound, cuscutin, in vitro. Moreover, α-MSH stimulated melanogenesis model in zebrafish was employed to confirm the anti-pigmentation effect of cuscutin. Then, proteins expressions associated with melanin production were observed using western blotting assay to explore preliminary mechanism.
RESULTS: BPE inhibited UVB-induced mice injury and restored skin barrier function observably in vivo. BPE and cuscutin suppressed the overproduction of melanin in α-MSH induced B16F10 significantly, in which cuscutin exhibited better effect than well-known whitening agent α-arbutin at same 10 μg/mL concentration. Moreover, the pigmentation of zebrafish embryo was decreased by cuscutin. Finally, cuscutin showed significant downregulation of expressions of tyrosinase (TYR) and tyrosinase related protein-1 (TRP-1), TRP-2 and microphthalmia-associated transcription factor (MITF) in the melanogenic signaling pathway.
CONCLUSIONS: B. purpurascens extract and its major bioactive constituent, cuscutin, showed potent anti-melanogenesis and skin-whitening effect by targeting TYR and TRP-2 proteins for the first time, which supported its traditional use.

In this study, we investigated the structural characterization and biological activities of Bletilla striata polysaccharides (BSPs) for their role as antioxidants and anti-melanogenesis agents in skin healthcare protection. Three neutral polysaccharides (BSP-1, BSP-2, and BSP-3) with molecular weights of 269.121 kDa, 57.389 kDa, and 28.153 kDa were extracted and purified. Their structural characteristics were analyzed by ion chromatography, GC-MS, and 1D/2D NMR. The results showed that BSP-1, which constitutes the major part of BSPs, was composed of α-D-Glcp, β-D-Glcp, β-D-Manp, and 2-O-acetyl-β-D-Manp, with the branched-chain accompanied by β-D-Galp and α-D-Glcp. BSP-1, BSP-2, and BSP-3 can enhance the total antioxidant capacity of skin fibroblasts with non-toxicity. Meanwhile, BSP-1, BSP-2, and BSP-3 could significantly inhibit the proliferative activity of melanoma cells. Among them, BSP-1 and BSP-2 showed more significance in anti-melanogenesis, tyrosinase inhibition activity, and cell migration inhibition. BSPs have effective antioxidant capacity and anti-melanogenesis effects, which should be further emphasized and developed as skin protection components.

Our skin is constantly exposed to blue light (BL), which is abundant in sunlight and emitted by digital devices. Prolonged exposure to BL can lead to oxidative stress-induced damages and skin hyperpigmentation. For this study, we used a cell line-based model to examine the protective effects of tocotrienol-rich fraction (TRF) on BL-induced oxidative stress and hyperpigmentation in B16-F1 melanocytes. Alpha-tocopherol (αTP) was used as a comparator. Molecular assays such as cell viability assay, flow cytometry, western blotting, fluorescence imaging, melanin and tyrosinase analysis were performed. Our results showed that TRF effectively suppressed the formation of reactive oxygen species and preserved the mitochondrial membrane potential. Additionally, TRF exhibited anti-apoptotic properties by reducing the activation of the p38 mitogen-activated protein kinase molecule and downregulating the expression of cleaved caspase-3. Moreover, TRF modulated tyrosinase activity, resulting in a lowered rate of melanogenesis and reduced melanin production. In contrast, αTP did not exhibit significant protective effects against skin damages and pigmentation in BL-induced B16-F1 cells. Therefore, this study indicates that TRF may offer superior protective effects over αTP against the effects of BL on melanocytes. These findings demonstrate the potential of TRF as a protective natural ingredient that acts against BL-induced skin damages and hyperpigmentation via its anti-oxidative and anti-melanogenic properties.

Thirty-four phytochemicals were isolated from dry tubers of Bletilla striata Rchb.f. The compounds were classified as bibenzyls 1-14, dihydrophenanthrenes 15, 17, 20, 21, phenanthrenes 16, 18, 19, simple benzoids 22-24, a fatty acid 25, glucosyloxybenzyl 2-isobutylmalates 26-32, and glucosyloxybenzyl cinnamates 33, 34. Compounds 1-4, 7, 8, 11, 12, and 16 inhibited melanogenesis (17.96-55.27%) induced by α-MSH in B16F10 cells at 10-40 μM. However, compounds 9, 10, 17, 18, and 21 exhibited significant cytotoxicity against melanomas, with IC50 values of 12-34 μM. Additionally, compounds 15, 17, 19, 20, 23, 31, and 33 reduced the ROS generation induced by H2O2 in HaCaT cells at 6.25-100 μM. In particular, compounds 15, 19, and 20 strongly inhibited ROS generation, with IC50 values of 2.15-9.48 μM. Consequently, compounds 1-4, 7-12, and 15-21 may be the strongest leads to follow in B. striata extract for further research on the skin disorders, hyperpigmentation, melanoma, and ageing.

BACKGROUND: The flavonoids and polysaccharides in Portulaca oleracea L. (PO) have significant antibacterial and antioxidant effects, which can inhibit common bacteria and remove free radicals in the body. However, there was little research on the use of PO to alleviate hyperpigmentation and photoaging damage.
OBJECTIVE: This study was to investigate the anti-photoaging and whitening activity mechanism of polysaccharide of PO (POP) in vitro and in vivo.
METHODS: In this study, 16 fractions obtained by four enzyme-assisted extraction from PO and their scavenging capabilities against 2,2-diphenyl-1-picrylhydrazyl and hydroxyl radicals were evaluated. Among these fractions, a polysaccharide fraction (VPOP3) showed the strongest biological activity. VPOP3 was characterized by Fourier-transform infrared spectroscopy, molecular weight (MW), and monosaccharide composition analysis, and the protective effect of VPOP3 on photoaging and hyperpigmentation was researched.
RESULTS: VPOP3 is a low-MW acidic heteropolysaccharide with MW mainly distributed around 0.71KDa, arabinose as its main monosaccharide component. VPOP3 reliably reduced the reactive oxygen species levels in cells and zebrafish and the level of lipid peroxidation in zebrafish. In addition, VPOP3 inhibited UVB-induced apoptotic body formation and apoptosis by downregulating caspase-3 and Bax and upregulating Bcl-2 in mitochondrion-mediated signaling pathways. On the other hand, VPOP3 at high concentrations significantly downregulated the expression of microphthalmia-associated transcription factor, tyrosinase (TYR), and TYR-related protein-1 and TYR-related protein-2 in the melanogenic signaling pathway to achieve a whitening effect.
CONCLUSIONS: The above results showed that VPOP3 has superior activities of anti-photoaging and anti-melanogenesis and can be utilized as a safe resource in the manufacture of cosmetics.

Maca is a well-known biennial herb with various physiological properties, such as antioxidant activity and immune response regulation. In this study, the antioxidant, anti-inflammatory, and anti-melanogenic effects of fermented maca root extracts were investigated. The fermentation was carried out using Lactobacillus strains, such as Lactiplantibacillus plantarum subsp. plantarum, Lacticaseibacillus rhamnosus, Lacticaseibacillus casei, and Lactobacillus gasseri. In RAW 264.7 cells, the non-fermented maca root extracts increased the secretion of nitric oxide (NO), an inflammatory mediator, in a dose-dependent manner. In contrast, the fermented extracts showed considerably lower NO secretion than the non-fermented extracts at concentrations of 5% and 10%. This indicates the effective anti-inflammatory effects of fermented maca. The fermented maca root extracts also inhibited tyrosinase activity, melanin synthesis, and melanogenesis by suppressing MITF-related mechanisms. These results show that fermented maca root extracts exhibit higher anti-inflammatory and anti-melanogenesis effects than non-fermented maca root extracts. Thus, maca root extracts fermented using Lactobacillus strains have the potential to be used as an effective cosmeceutical raw material.