Compounds with sulfhydryl substituents and azole compounds exhibit potent anti-tyrosinase potency. 2-Thiobenzothiazole (2-TBT), a hybrid structure of sulfhydryl and azole, exists in two tautomeric forms, with the thione form being predominant according to several studies. 2-TBT derivatives were synthesized as potential tyrosinase inhibitors as the thione tautomeric form has the same N-CS moiety as phenylthiourea (PTU), which is suitable for chelation with the copper ions present in the tyrosinase active site. Eight of the ten 2-TBT derivatives inhibited the monophenolase and diphenolase activities of mushroom tyrosinase, with IC50 values of 0.02-0.83 μM. Kinetic studies and molecular dynamics simulations were performed to determine their mode of action and confirm that the 2-TBT derivatives bind to the tyrosinase active site with high stability. Derivatives 3, 4, 8, and 10 strongly inhibited melanogenesis in B16F10 cells in a pattern similar to the results of cellular tyrosinase inhibition, thereby suggesting that their ability to inhibit melanogenesis was due to their tyrosinase inhibitory activity. In a depigmentation experiment using zebrafish embryos, all 2-TBT derivatives showed better potency than kojic acid, even at 400 to 2000 times lower concentration, and 1 and 10 reduced zebrafish larva pigmentation more strongly than PTU even at 20 times lower concentration. Experiments investigating the changes in tyrosinase inhibitory activity of 2-TBT derivatives in the presence and absence of CuSO4 and their copper chelating ability supported that these derivatives exert their anti-melanogenic effect by chelating the copper ions of tyrosinase. These results suggest that 2-TBT derivatives are promising candidates for the treatment of hyperpigmentation-related disorders.

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.

Appropriate biodegradability to meet the demands of wound repair is critical for superficial wound repair membrane applications. Tyrosinase-catalyzed crosslinking SF (c-SF) membranes were constructed and regulated the degradation behavior in this study. The crosslinking degree of the c-SF membranes could be adjusted by reaction ratios of tyrosinase against SF (TYR/SF). Upon reaching a TYR/SF ratio of 20/6000, the degree of crosslinking increased to 88.17 ± 0.20%, without obvious changes in the crystal structure. The degradation behavior was regulated by the TYR/SF ratio and the degradation environment. All c-SF membranes remained stable after immersion without collagenase but showed an adjustable degradation behavior in the presence of collagenase. As the TYR/SF ratio increased, the residual weights increased from 23.31 ± 1.35% to 60.12 ± 0.82% after 7 days of degradation, occurring with low increased amounts of β-sheet structure and free amino acids. This work provides a new c-SF membrane with controllable rapid degradability and favorable cytocompatibility, which can help to meet requirements for biodegradable superficial wound repair membranes.

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 excessive production of melanin can cause skin diseases and hyperpigmentation. In this study, resveratrol contained in Dongjin rice seed (DJ526) was increased through callus induction. The antioxidant capacity of resveratrol-enriched rice callus was evaluated using the ABTS radical scavenging method and was equivalent to that of vitamin C. DJ526 rice callus extract significantly increased antioxidant activities in a concentration-dependent manner. The anti-melanogenesis effects of DJ526 rice callus extract were also evaluated in melan-a cells. Resveratrol-enriched rice callus extract significantly (i) decreased the size and number of melanin-containing cells, (ii) suppressed the activity of cellular tyrosinase and melanin content, (iii) downregulated the expression of microphthalmia-associated transcription factor, tyrosinase, tyrosinase-related protein-1, and tyrosinase-related protein-2, (iv) increased the expression of phosphorylated extracellular signal-regulated kinase 1/2 and protein kinase B, and (v) inhibited the activation of phosphorylated p38 in melan-a cells. From the above observations, DJ526 rice callus extract showed strong antioxidant and anti-melanogenesis activity at the concentration test. These findings indicate the potential of resveratrol-enriched rice callus as a novel agent for controlling hyperpigmentation.

Hydroalcoholic extracts from Malbec and Torrontés wine pomaces (Vitis vinifera L.) originating from the high-altitude vineyards of Argentina\'s Calchaquí Valleys were characterized. Total phenolics, hydroxycinnamic acids, orthodiphenols, anthocyanins, non-flavonoid phenolics, total flavonoids, flavones/flavonols, flavanones/dihydroflavonols, and tannins were quantified through spectrophotometric methods, with the Malbec extract exhibiting higher concentrations in most of phytochemical groups when compared to Torrontés. HPLC-DAD identified more than 30 phenolic compounds in both extracts. Malbec displayed superior antiradical activity (ABTS cation, nitric oxide, and superoxide anion radicals), reduction power (iron, copper, and phosphomolybdenum), hypochlorite scavenging, and iron chelating ability compared to Torrontés. The cytotoxicity assessments revealed that Torrontés affected the viability of HT29-MTX and Caco-2 colon cancer cells by 70% and 50%, respectively, at the highest tested concentration (1 mg/mL). At the same time, both extracts did not demonstrate acute toxicity in Artemia salina or in red blood cell assays at 500 µg/mL. Both extracts inhibited the lipoxygenase enzyme (IC50: 154.7 and 784.7 µg/mL for Malbec and Torrontés), with Malbec also reducing the tyrosinase activity (IC50: 89.9 µg/mL), and neither inhibited the xanthine oxidase. The substantial phenolic content and diverse biological activities in the Calchaquí Valleys\' pomaces underline their potentialities to be valorized for pharmaceutical, cosmetic, and food industries.

OBJECTIVE: Methylsulfonylmethane (MSM), which contains organic sulphur, has been used for a long time as a medicinal ingredient because of its benefits to human health. MSM is reported to be protective against certain skin disorders, but it is unknown whether it affects melanin synthesis. Therefore, in our current research, we examined the possibility of MSM controlling the production of melanin in Mel-Ab melanocytes.
METHODS: In Mel-Ab cells, melanin contents and tyrosinase activities were assessed and quantified. The expression of microphthalmia-associated transcription factor (MITF) and tyrosinase was evaluated using western blot analysis, while MSM-induced signalling pathways were investigated.
RESULTS: The MSM treatment significantly resulted in a dose-dependent increase in melanin production. Furthermore, MSM elevated melanin-related proteins, including MITF and tyrosinase. However, the rate-limiting enzyme of melanin production, tyrosinase, was not directly influenced by it. Therefore, we investigated potential melanogenesis-related signalling pathways that may have been triggered by MSM. Our findings showed that MSM did not influence the signalling pathways associated with glycogen synthase kinase 3β, cAMP response-element binding protein, extracellular signal-regulated kinase, or p38 mitogen-activated protein kinase. However, MSM phosphorylated c-Jun N-terminal kinases/stress-activated protein kinase (JNK/SAPK), which is known to induce melanogenesis. SP600125, a specific JNK inhibitor, inhibited MSM-induced melanogenesis.
CONCLUSIONS: Taken together, our study indicates that MSM induces melanin synthesis and may serve as a therapeutic option for hypopigmentary skin disorders such as vitiligo.
ZIEL: Methylsulfonylmethan (MSM), das organischen Schwefel enthält, wird aufgrund seiner Vorteile für die menschliche Gesundheit seit langem als medizinischer Inhaltsstoff verwendet. Es wird berichtet, dass MSM vor bestimmten Hauterkrankungen schützt, es ist jedoch nicht bekannt, ob es die Melaninsynthese beeinflusst. Daher haben wir in unserer aktuellen Forschung die Möglichkeit untersucht, dass MSM die Melaninproduktion in Mel‐Ab‐Melanozyten kontrolliert.
METHODS: In Mel‐Ab‐Zellen wurden der Melaningehalt und die Tyrosinase‐Aktivitäten bewertet und quantifiziert. Die Expression von Mikrophthalmie‐assoziiertem Transkriptionsfaktor (MITF) und Tyrosinase wurde mittels Western‐Blot‐Analyse bewertet, während MSM‐induzierte Signalwege untersucht wurden.
UNASSIGNED: Die MSM‐Behandlung führte signifikant zu einer dosisabhängigen Steigerung der Melaninproduktion. Darüber hinaus erhöhte MSM Melanin‐verwandte Proteine, einschließlich MITF und Tyrosinase. Das geschwindigkeitsbestimmende Enzym der Melaninproduktion, die Tyrosinase, wurde davon jedoch nicht direkt beeinflusst. Daher untersuchten wir mögliche Signalwege im Zusammenhang mit der Melanogenese, die möglicherweise durch MSM ausgelöst wurden. Unsere Ergebnisse zeigten, dass MSM keinen Einfluss auf die Signalwege hatte, die mit der Glykogensynthase‐Kinase 3β, dem cAMP‐Response‐Element‐Bindungsprotein, der extrazellulären signalregulierten Kinase oder der p38‐Mitogen‐aktivierten Proteinkinase verbunden sind. Allerdings phosphorylierte MSM c‐Jun N‐terminale Kinasen/stressaktivierte Proteinkinase (JNK/SAPK), von der bekannt ist, dass sie die Melanogenese induziert. SP600125, ein spezifischer JNK‐Inhibitor, hemmte die MSM‐induzierte Melanogenese.
UNASSIGNED: Zusammenfassend lässt unsere Studie darauf schließen, dass MSM die Melaninsynthese induziert und als Therapieoption für hypopigmentäre Hauterkrankungen wie Vitiligo dienen kann.
OBJECTIVE: le méthylsulfonylméthane (MSM), qui contient du soufre organique, est utilisé depuis longtemps comme ingrédient médicamenteux en raison de ses bénéfices pour la santé humaine. Le MSM aurait un effet protecteur contre certains troubles cutanés, mais on ignore s’il affecte la synthèse de la mélanine. Par conséquent, dans notre étude actuelle, nous avons examiné la possibilité que le MSM contrôle la production de mélanine dans les mélanocytes Mel‐Ab. MÉTHODES: dans les cellules Mel‐Ab, la teneur en mélanine et les activités de la tyrosinase ont été évaluées et quantifiées. L’expression du facteur de transcription associé à la microphtalmie (microphthalmia‐associated transcription factor, MITF) et de la tyrosinase a été évaluée à l’aide d’une analyse Western blot, tandis que les voies de signalisation induites par le MSM ont été étudiées. RÉSULTATS: le traitement par MSM a entraîné de manière significative une augmentation dose‐dépendante de la production de mélanine. En outre, le MSM a élevé les taux de protéines liées à la mélanine, notamment le MITF et la tyrosinase. Cependant, l’enzyme limitant la vitesse de production de la mélanine, la tyrosinase, n’a pas été directement influencée par celui‐ci. Par conséquent, nous avons étudié les voies de signalisation potentielles liées à la mélanogenèse qui pourraient avoir été déclenchées par le MSM. Nos résultats ont montré que le MSM n’influe pas sur les voies de signalisation associées à la protéine glycogène synthase kinase 3β, à la protéine de liaison à l’élément de réponse AMPc, à la kinase régulée par signal extracellulaire ou à la protéine kinase activée par mitogène p38. Cependant, le MSM a phosphorylé les kinases N‐terminales c‐Jun/la protéine kinase activée par le stress (c‐Jun N‐terminal kinases/stress‐activated protein kinase, JNK/SAPK), réaction connue pour induire une mélanogenèse. Le SP600125, un inhibiteur spécifique de la JNK, a inhibé la mélanogenèse induite par le MSM.
CONCLUSIONS: dans l’ensemble, notre étude indique que le MSM induit la synthèse de la mélanine et peut servir d’option thérapeutique pour les troubles cutanés hypopigmentaires tels que le vitiligo.

Tyrosinase is one important rate limiting enzyme in melanin synthesis, directly affecting the melanin synthesis. Quercetagetin is one active ingredient from marigold. Thence, the inhibition effects of quercetagetin against tyrosinase were investigated. The results showed quercetagetin could inhibit tyrosinase activity with IC50 value of 0.19 ± 0.01 mM and the inhibition type was a reversible mixed-type. Results of fluorescence quenching showed quercetagetin could quench tyrosinase fluorescence in static process. CD and 3D fluorescence results showed the interaction of quercetagetin to tyrosinase could change tyrosinase conformation to inhibit activity. Moreover, docking revealed details of quercetagetin\'s interactions with tyrosinase.

The skin-brain axis has been suggested to play a role in several pathophysiological conditions, including opioid addiction, Parkinson\'s disease and many others. Recent evidence suggests that pathways regulating skin pigmentation may directly and indirectly regulate behaviour. Conversely, CNS-driven neural and hormonal responses have been demonstrated to regulate pigmentation, e.g., under stress. Additionally, due to the shared neuroectodermal origins of the melanocytes and neurons in the CNS, certain CNS diseases may be linked to pigmentation-related changes due to common regulators, e.g., MC1R variations. Furthermore, the HPA analogue of the skin connects skin pigmentation to the endocrine system, thereby allowing the skin to index possible hormonal abnormalities visibly. In this review, insight is provided into skin pigment production and neuromelanin synthesis in the brain and recent findings are summarised on how signalling pathways in the skin, with a particular focus on pigmentation, are interconnected with the central nervous system. Thus, this review may supply a better understanding of the mechanism of several skin-brain associations in health and disease.

The health of calves has a significant impact on the production of cows and livestock. Some desert plants have pharmacological importance, as they can be used to reduce antibiotic resistance. Our hypothesis is designed to detect Virulent- Multidrug-Resistant and Extended- spectrum Beta- lactamase Enterobacteriaceae (Virulent-MDR-ESBL Enterobacteriaceae and to determine whether Moringa oleifera has antibacterial activity against the detected isolates. A total of 39 Enterobacteriaceae isolates from 28 diarrheic samples were collected from calves aged between 20 days and 20 months from 3 different flocks in North Sinai, Sahl-Eltina region, Egypt. E.coli 46% (18/39), O157 13% (5/39), Klebsiella pneumoniae 41% (16/39). MDR members accounted for 87%, while ESBL isolates accounted for 43%. The antibacterial activity is represented by microdilution. Minimum inhibition concentration (MIC) for the methanol extract of Moringa oleifera ranged from 2.5,5,10, and 25mg/ ml among E.coli isolates, and O157 was susceptible to (2.5mg/ ml), Klebsiella pneumoniae isolates were susceptible to (5-50mg/ ml). Analysis of the methanol extract revealed that ferulic acid was the dominant phenolic compound with a concentration of 29,832 parts per million (ppm). In silico docking study expected the active site of ferulic acid to act on the tyrosine bacterial enzyme through Pi-alkyl, Pi-anion, Carbon hydrogen bonds, and extra ionic attractive interactions with copper ions which can stabilize ferulic acid inside the targeted pocket Diverse virulent gene profiles were observed in E. coli. The Shiga toxin-producing Escherichia coli (STEC) was reported in 83% of the isolated E. coli, while the DNA gyrase (gyrA) was harbored in 100% of Klebsiella pneumoniae isolates. Various profiles of antibiotic resistance genes for both E. coli and Klebsiella pneumoniae isolates were distinguished. blaTEM genes were detected in 99% of E. coli and 100% of Klebsiella pneumoniae. Sequence analysis for E. coli strain DRC-North Sinai-Eg was placed in accession numbers (OP955786) for the Shiga toxin 2 gene (Stx2A), (OP997748) and (OP997749) for the Adhesion to host cell gene (Eae). For the hemolysine gene (hylA), the accession number was (OP946183). Klebsiella pneumoniae strain DRC-North Sinai-Eg was placed in (OP946180) for (gyrA). This study has proven the broad range of Moringa oliefera\'s antibacterial effects in vitro against the virulent-MDR- ESBL E. coli and Klebsiella pneumoniae isolated from North Sinai calves diarrhea. These are congruent with the disability effect on bacterial tyrosinase enzyme through docking study therefore, we recommend the usage of this desert plant as a prospective feed additive, we endorse this as an antibacterial new insight natural source and for the medication of considered pathogens with zoonotic impacts.