Investigation of utilization possibilities of natural sources has been an important area for research. Tyrosinase inhibitory activity plays a key role in food and medicine industry. Strawberry tree (Arbutus unedo), a widely distributed plant among Mediterranean countries, possess fruits and leaves with rich bioactive phytochemicals, especially polyphenolic compounds. In this study, we aimed to investigate the antityrosinase activity of the fruit and leaf extracts of the plant, and to determine the phenolic compounds that contribute to the antityrosinase activity. In this regard, we evaluated the effect of solvent composition on the extraction of phenolic compounds from A. unedo and on its antityrosinase activity using a simplex centroid design approach, and used chromatographic and LC-MS/MS techniques. The leaf extracts prepared using EtOH:water (50:50) provided higher TPC (456.39 mg GAE/g extract) and acetone:EtOH:water (33:33:33) provided higher TFC (56.15 mg QE/g extract) values than of fruit extracts. LC-MS/MS analysis revealed 23 phenolic/flavonoid compounds in leaf extracts (L1-8), and major metabolites were detected as quercitrin, quinic acid, catechin, tannic acid, isoquercitrin, gallic acid, and ellagic acid. Among the leaf extracts, L3 (aceton:water, 50:50) exhibited 72.01% tyrosinase inhibition at 500 μg/mL. After fractionation studies guided by antityrosinase activity, its subfraction L3-Fr2 exhibited 40.06% inhibition at 50 μg/mL concentration (IC50: 146 ± 7.75 μg/mL), and catechin (113.19 mg/g), tannic acid (53.14 mg/g), ellagic acid (22.14 mg/g), gallic acid (10.27 mg/g), and epicatechin gallate (8.65 mg/g) were determined as major metabolites. Its subfraction L3-Fr2-sub7 exhibited better antityrosinase activity (IC50: 206.23 ± 9.87 μg/mL), and quantitative analysis results revealed the presence of tannic acid (127.40 mg/g), gallic acid (13.96 mg/g), ellagic acid (7.66 mg/g), quercetin-3-O-glucuronide (5.06 mg/g), and quinic acid (3.2 mg/g) as major metabolites, and correlation analysis showed that ellagic acid and quinic acid were positively correlated with antityrosinase activity.

Based on the fact that substances with a β-phenyl-α,β-unsaturated carbonyl (PUSC) motif confer strong tyrosinase inhibitory activity, benzylidene-3-methyl-2-thioxothiazolidin-4-one (BMTTZD) analogs 1-8 were prepared as potential tyrosinase inhibitors. Four analogs (1-3 and 5) inhibited mushroom tyrosinase strongly. Especially, analog 3 showed an inhibitory effect that was 220 and 22 times more powerful than kojic acid in the presence of l-tyrosine and l-dopa, respectively. A kinetic study utilizing mushroom tyrosinase showed that analogs 1 and 3 competitively inhibited tyrosinase, whereas analogs 2 and 5 inhibited tyrosinase in a mixed manner. A docking simulation study indicated that analogs 2 and 5 could bind to both the tyrosinase active and allosteric sites with high binding affinities. In cell-based experiments using B16F10 cells, analogs 1, 3, and 5 effectively inhibited melanin production; their anti-melanogenic effects were attributed to their ability to inhibit intracellular tyrosinase activity. Moreover, analogs 1, 3, and 5 inhibited in situ B16F10 cellular tyrosinase activity. In three antioxidant experiments, analogs 2 and 3 exhibited strong antioxidant efficacy, similar to that of the positive controls. These results suggest that the BMTTZD analogs are promising tyrosinase inhibitors for the treatment of hyperpigmentation-related disorders.

We present a case involving a patient whose clinical phenotype aligns with oculocutaneous albinism (OCA), yet exhibits a complex genotype primarily characterized by variants of unknown significance (VUS). An 11-year-old boy manifested iris hypopigmentation and translucency, pronounced photophobia, diminished visual acuity and stereopsis, nystagmus, reduced pigmentation of the retina, and foveal hypoplasia. Genetic testing was performed. A heterozygous missense VUS CAPN5 c.230A>G, p.(Gln77Arg), a heterozygous missense VUS TYR c.1307G>C, p.(Gly436Ala), and a heterozygous missense variant TYR c.1205G>A, p.(Arg402Gln) which was classified as a risk factor, were identified. We hypothesized that the TYR c.1307G>C, p.(Gly436Ala) variant is in genetic disequilibrium with the TYR c.1205G>A, p.(Arg402Gln) variant leading to deficient expression of melanogenic enzymes in retinal cells, resulting in the manifestation of mild OCA. Additionally, this study represents the case where we did not detect chiasmal misrouting in visual evoked potentials, nor did we observe a shift in the distribution of ganglion cell thickness from a temporal to a central position. Moreover, our patient\'s case supports the probable benign nature of the CAPN5 c.230A>G, p.(Gln77Arg) variant.

Metabolites exploration of the ethyl acetate extract of Fusarium solani culture broth that was isolated from Euphorbia tirucalli root afforded five compounds; 4-hydroxybenzaldehyde (1), 4-hydroxybenzoic acid (2), tyrosol (3), azelaic acid (4), malic acid (5), and fusaric acid (6). Fungal extract as well as its metabolites were evaluated for their anti-inflammatory and anti-hyperpigmentation potential via in vitro cyclooxygenases and tyrosinase inhibition assays, respectively. Azelaic acid (4) exhibited powerful and selective COX-2 inhibition followed by fusaric acid (6) with IC50 values (2.21 ± 0.06 and 4.81 ± 0.14 μM, respectively). As well, azelaic acid (4) had the most impressive tyrosinase inhibitory effect with IC50 value of 8.75 ± 0.18 μM compared to kojic acid (IC50 = 9.27 ± 0.19 μM). Exclusive computational studies of azelaic acid and fusaric acid with COX-2 were in good accord with the in vitro results. Interestingly, this is the first time to investigate and report the potential of compounds 3-6 to inhibit cyclooxygenase enzymes. One of the most invasive forms of skin cancer is melanoma, a molecular docking study using a set of enzymes related to melanoma suggested pirin to be therapeutic target for azelaic acid and fusaric acid as a plausible mechanism for their anti-melanoma activity.

Lichens are symbiotic associations of algae and fungi. They are edible as food and have been used in traditional medicine for years. It is aimed to screen Peltigera praetextata (Flörke ex Sommerf.) Zopfand and Peltigera elisabethae Gyeln. phytochemically by LC/QTOF/MS and according to the constituents to evaluate the antioxidant, tyrosinase inhibitory, and antibacterial activities. In total 54 of metabolites detected by LC/QTOF/MS were common in both species. According to LC/QTOF/MS scanning results, alkaloids, iridoid glycosides, phenolics, cyanogenetic glycosides, and terpenic structures were detected. DPPH, ABTS, superoxide radical scavenging activities, and metal chelating capacity IC50 values were 84.55, 9.349; 51.27, 9.127; 95.01, 58.65 and 20.57, 70.08 µg/mL., respectively. The CUPRAC reducing power was determined as 4.69 and 9.57 TEACCUPRAC, respectively. Tyrosinase inhibitor activity were found to be 86.95 and 196.7 µg/mL. Both lichens did not show antimicrobial effects. As a result of the antioxidant and tyrosinase inhibitor activities it was seen that their activities were significant and further in vivo studies could be carried out on this lichens.

This study aimed to isolate and purify resveratrol and oxyresveratrol from the heartwoods of Maclura cochinchinensis, and to evaluate their inhibitory effects on melanogenesis in B16F10 murine melanoma cells. A methanol maceration process yielded a crude extract comprising 24.86% of the initial mass, which was subsequently analyzed through HPTLC, HPLC, and LC-MS/MS. These analyses revealed the presence of resveratrol and oxyresveratrol at concentrations of 4.32 mg/g and 33.6 mg/g in the extract, respectively. Initial purification employing food-grade silica gel column chromatography separated the extract into two fractions: FA, exhibiting potent inhibition of both tyrosinase activity and melanogenesis, and FM, showing no such inhibitory activity. Further purification processes led to the isolation of fractions Y11 and Gn12 with enhanced concentrations of resveratrol (94.9 and 110.21 mg/g, respectively) and fractions Gn15 and Gn16 with elevated levels of oxyresveratrol (321.93 and 274.59 mg/g, respectively), all of which significantly reduced melanin synthesis. These outcomes affirm the substantial presence of resveratrol and oxyresveratrol in the heartwood of M. cochinchinensis, indicating their promising role as natural agents for skin lightening.

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.

Cadmium (Cd) is a hazardous element that may jeopardize environmental safety and human health through biotransfer and trophic accumulation. Here, we tested Cd toxicity on cotton plants, cotton bollworms, and their responses. Results demonstrated that Cd accumulated in plant roots, aerial parts, insect larvae, pupae, and frass in a dose-dependent pattern. The ∼9.35 mg kg-1 of Cd in plant aerial parts, ∼3.68 in larvae, ∼6.43 in pupae, and high transfer coefficient (∼5.59) indicate significant mobility. The ∼19.61 mg kg-1 of Cd in larvae frass suggests an effective detoxification strategy, while BAFcotton (∼1.14) and BAFworm (∼0.54) indicated low bioaccumulation. Cadmium exposure resulted in compromised plant growth and yield as well as alterations in photosynthetic pigment contents, antioxidant enzyme activities, and certain life history traits of cotton bollworms. Furthermore, carboxylesterase activity and encapsulation rates of insect larvae decreased with increasing Cd concentrations, whereas acetylcholinesterase, phenol oxidase, glutathione S-transferase, and multifunctional oxidase exhibited hormesis responses.

The efficacy of nanoencapsulation as a technology for enhancing the solubility of active substances has been demonstrated. In this particular investigation, Ganoderic acid DM (GA-DM) was encapsulated within sodium alginate nanoparticles (NPs) using the ionic crosslinking method. The confirmation of the successful loading of GA-DM was ascertained through the analysis of Fourier transform infrared spectrum (FTIR). Empirical evidence derived from the examination of scanning electron microscope (SEM) images, transmission electron microscope (TEM) images, atomic force microscope (AFM) images, and dynamic light scattering (DLS) demonstrated a regular distribution and spherical morphology, with an average particle size of approximately 133 nm. The investigation yielded an encapsulation efficiency of 95.27 ± 0.11 % and a drug loading efficiency of 21.17 ± 0.02 % for the prepared sample. The release kinetics of SGPN was fitted with the Korsmeyer-Peppas kinetic model corresponding to diffusion-controlled release. The incorporation of GA-DM into sodium alginate nanocarriers exhibited a mitigating effect on the cytotoxicity of HaCat and B16, while also demonstrating inhibitory properties against tyrosinase activity and melanin formation.

The skin microbiome maintains healthy human skin, and disruption of the microbiome balance leads to inflammatory skin diseases such as folliculitis and atopic dermatitis. Staphylococcus aureus and Cutibacterium acnes are pathogenic bacteria that simultaneously inhabit the skin and cause inflammatory diseases of the skin through the activation of innate immune responses. Silkworms are useful invertebrate animal models for evaluating innate immune responses. In silkworms, phenoloxidase generates melanin as an indicator of innate immune activation upon the recognition of bacterial or fungal components. We hypothesized that S. aureus and C. acnes interact to increase the innate immunity-activating properties of S. aureus. In the present study, we showed that acidification is involved in the activation of silkworm hemolymph melanization by S. aureus. Autoclaved-killed S. aureus (S. aureus [AC]) alone does not greatly activate silkworm hemolymph melanization. On the other hand, applying S. aureus [AC] treated with C. acnes culture supernatant increased the silkworm hemolymph melanization. Adding C. acnes culture supernatant to the medium decreased the pH. S. aureus [AC] treated with propionic acid, acetic acid, or lactic acid induced higher silkworm hemolymph melanization activity than untreated S. aureus [AC]. S. aureus [AC] treated with hydrochloric acid also induced silkworm hemolymph melanization. The silkworm hemolymph melanization activity of S. aureus [AC] treated with hydrochloric acid was inhibited by protease treatment of S. aureus [AC]. These results suggest that acid treatment of S. aureus induces innate immune activation in silkworms and that S. aureus proteins are involved in the induction of innate immunity in silkworms.