Melanin Inhibition Research Articles

K-Nearest Neighbor and Random Forest-Based Prediction of Putative Tyrosinase Inhibitory Peptides of Abalone Haliotis diversicolor.

Skin pigment disorders are common cosmetic and medical problems. Many known compounds inhibit the key melanin-producing enzyme, tyrosinase, but their use is limited due to side effects. Natural-derived peptides also display tyrosinase inhibition. Abalone is a good source of peptides, and the abalone proteins have been used widely in pharmaceutical and cosmetic products, but not for melanin inhibition. This study aimed to predict putative tyrosinase inhibitory peptides (TIPs) from abalone, Haliotis diversicolor, using k-nearest neighbor (kNN) and random forest (RF) algorithms. The kNN and RF predictors were trained and tested against 133 peptides with known anti-tyrosinase properties with 97% and 99% accuracy. The kNN predictor suggested 1075 putative TIPs and six TIPs from the RF predictor. Two helical peptides were predicted by both methods and showed possible interaction with the predicted structure of mushroom tyrosinase, similar to those of the known TIPs. These two peptides had arginine and aromatic amino acids, which were common to the known TIPs, suggesting non-competitive inhibition on the tyrosinase. Therefore, the first version of the TIP predictors could suggest a reasonable number of the TIP candidates for further experiments. More experimental data will be important for improving the performance of these predictors, and they can be extended to discover more TIPs from other organisms. The confirmation of TIPs in abalone will be a new commercial opportunity for abalone farmers and industry.

Glyphosate inhibits melanization and increases susceptibility to infection in insects.

Melanin, a black-brown pigment found throughout all kingdoms of life, has diverse biological functions including UV protection, thermoregulation, oxidant scavenging, arthropod immunity, and microbial virulence. Given melanin's broad roles in the biosphere, particularly in insect immune defenses, it is important to understand how exposure to ubiquitous environmental contaminants affects melanization. Glyphosate-the most widely used herbicide globally-inhibits melanin production, which could have wide-ranging implications in the health of many organisms, including insects. Here, we demonstrate that glyphosate has deleterious effects on insect health in 2 evolutionary distant species, Galleria mellonella (Lepidoptera: Pyralidae) and Anopheles gambiae (Diptera: Culicidae), suggesting a broad effect in insects. Glyphosate reduced survival of G. mellonella caterpillars following infection with the fungus Cryptococcus neoformans and decreased the size of melanized nodules formed in hemolymph, which normally help eliminate infection. Glyphosate also increased the burden of the malaria-causing parasite Plasmodium falciparum in A. gambiae mosquitoes, altered uninfected mosquito survival, and perturbed the microbial composition of adult mosquito midguts. Our results show that glyphosate's mechanism of melanin inhibition involves antioxidant synergy and disruption of the reaction oxidation-reduction balance. Overall, these findings suggest that glyphosate's environmental accumulation could render insects more susceptible to microbial pathogens due to melanin inhibition, immune impairment, and perturbations in microbiota composition, potentially contributing to declines in insect populations.

Isolation of leaf and root extracts from Allium sativum and Mentha piperita plants; evaluation of their antioxidant and anti-tyrosinase activities in-vitro

Abstract-Tyrosinase is a key enzyme of melanogenesis which determines the mammalian skin, hair and eye colour. Hyper-pigmentation leads to various skin disorders like melasma, sunspots, age spots and freckles. Moreover, abnormal skin pigmentation is a serious aesthetic concern which leads to psychosocial problems. Thus to achieve melanin inhibition, inhibition of tyrosinase might be an effective approach. To this end we prepared methanolic (MeOH) extracts from leaves and roots of Allium sativum (AS) and Mentha piperita (MP), which were further processed for 1:1 fractional distillation to prepare methanolic n-hexane (MeOH_n-Hx), methanolic ethyl acetate (MeOH_EA) and methanolic chloroform (MeOH_CHCl3) extracts, aiming to evaluate tyrosinase and anti-oxidant activities in-vitro. Our results confirmed that all MeOH-crude AS and MP extracts showed significant anti-oxidant activity with IC50 values ranging from 0.05 ± 0.2 mg/ml to 4.3 ± 2.3mg/ml. Moreover, AS and MP all 16 extracts have significant anti-tyrosinase activity with IC50 range from 0.014 ± 0mg/ml to 1.205 ± 0.07mg/ml. Interestingly, AS leaf MetOH_EA, AS leaf MetOH_CHCl3, AS root MetOH_EA and MP leaf MetOH_CHCl3 showed significant anti-tyrosinase activity even higher than positive control kojic acid. AS leaf MetOH_CHCl3 extract being the most potent among all tested extracts is proposed as potential candidate to treat tyrosinase rooted hyper-pigmentation in future.

Glabridin Liposome Ameliorating UVB-Induced Erythema and Lethery Skin by Suppressing Inflammatory Cytokine Production.

Glabridin, a compound of the flavonoid, has shown outstanding skin-whitening and anti-aging properties, but its water insolubility limits its wide application. Therefore, glabridin liposome (GL) has been developed to improve its poor bioavailability, while there are few studies to evaluate its amelioration of UVB- induced photoaging. This study is performed to investigate the amelioration of GL against UVB- induced cutaneous photoaging. The prepared GL has a spheroidal morphology with an average diameter of 200 nm. The GL shows lower cytotoxicity than glabridin, but it has a more effective role in inhibition of melanin. Moreover, the application of GL can effectively relieve UV radiation induced erythema and leathery skin, associated with the down-regulated expression of inflammatory cytokines (TNF-α, IL-6 and IL-10). Taken together, these results demonstrate that GL has potentials as topical therapeutic agents against UVB radiation induced skin damage through inhibiting inflammation.

Melanin production in coelomycetous agents of black grain eumycetoma.

BackgroundEumycetoma is a fungal infection characterised by the formation of black grains by causative agents. The melanin biosynthetic pathways used by the most common causative agents of black-grain mycetoma are unknown and unravelling them could identify potential new therapeutic targets.MethodMelanin biosynthetic pathways in the causative fungi were identified by the use of specific melanin inhibitors.ResultsIn Trematosphaeria grisea and Falciformispora tompkinsii, 1,8-dihydroxynaphthalene (DHN)-melanin synthesis was inhibited, while DHN-, 3,4-dihydroxyphenylalanine (DOPA)- and pyo-melanin were inhibited in Medicopsis romeroi and Falciformispora senegalensis.ConclusionOur data suggest that Me. romeroi and F. senegalensis synthesise DHN-, DOPA- and pyo-melanin, while T. grisea and F. tompkinsii only synthesise DHN-melanin.

Melanin synthesis and regulation in vivo and commonly used melanin inhibitors from natural products and traditional Chinese medicine

Melanin is an important factor affecting human skin color. This study defines its synthetic pathways and regulatory pathways have the practical significance for the treatment of diseases caused by pigmentation problems, such as chloasma. Besides, it also provides a theoretical basis for screening out melanin inhibitors and developing whitening and freckle products. At present, the melanin inhibitors used in whitening and freckle products mainly come from natural products and traditional Chinese medicine. This article first introduces the melanin biosynthesis pathway with tyrosinase as the core, defines the synthesis, transport and catalytic activity of tyrosinase as the three key factors affecting melanin synthesis, and then reviews two common types of melanin inhibitors, namely tyrosinase synthesis inhibitors and tyrosinase inhibitors derived from natural products and traditional Chinese medicine. This article provides guidance for the development of new melanin inhibitors, and puts forward the idea for combining and synergizing inhibitors according to different mechanisms, in order to develop new whitening formulas.

The effect of isolates from Cassipourea flanaganii (Schinz) alston, a plant used as a skin lightning agent, on melanin production and tyrosinase inhibition

Ethnopharmacological relevanceThe Zulu and Xhosa people of South Africa use the stem bark of Cassipourea flanaganii as a skin-lightning cosmetic. Aim of the studyTo isolate and identify compounds responsible for the skin lightning properties from the stem bark of Cassipourea flanaganii and to evaluate their cytotoxicity towards skin cells. Materials and methodsExtracts from the stem bark of Cassipourea flanaganii were isolated using chromatographic methods and structures were determined using NMR, IR and MS analysis. The tyrosinase inhibitory activity and the ability to inhibit the production of melanin were determined using human primary epidermal melanocyte cells. Cytoxicity was established using the same melanocytes and a neutral red assay. ResultsOne previously undescribed compound, ent-atis-16-en-19-al (1) along with the known ent-atis-16-en-19-oic acid (2), ent-atis-16-en-19-ol (3), ent-kaur-16-en-19-oic acid (4), ent-kaur-16-en-19-al (5), ent-manoyl oxide (6), guinesine A (7), guinesine B (8), guinesine C (9), lichenxanthone (10), 2,4-dihydroxy-3,6-dimethyl benzoic acid methyl ester (11), lynoside (12), lupeol (13), β-amyrin (14), docosyl ferulate (15), stigmasterol, sitosterol and sitosterol-O-glucoside were isolated in this investigation. An impure fraction containing compound 3 was acetylated to obtain 19-acetoxy-ent-atis-16-ene (3a). Compounds 10 and 11 are usually isolated from lichen, hence they are possible contaminants of lichen harvested with the bark. Compounds 1, 3a, 5–14 were not significantly cytotoxic to the primary epidermal melanocyte cells (P > 0.05) when compared to the negative and positive controls (DMSO, 0.1% and hydrogen peroxide, 30 wt% in water). Inhibition of tyrosinase was significantly greater with respect to the negative control (P < 0.001) for compounds 3a, 5–8 and 9–10 at 10 μM and for compounds 5–8 and 9–10 at 100 μM. Compared to hydroquinone (the positive control) at 10 μM, the level of inhibition was comparable or to that of compounds 3a, 5, 6, and 8–10 at 10 μM, with 9 and 10 showing a greater level of inhibition. Inhibition of melanin was both concentration and time dependent for all compounds tested with higher melanin content at 24 h compared to 48 h s and at 10 mM compared to100 mM at both time points; melanin content was significantly lower for hydroquinone at both time points and concentrations. ConclusionsCompounds 1, 5–14, isolated from Cassipourea flanaganii and the derivative 3a showed low cytotoxicity. All compounds had a clear time and concentration dependent effect on melanin content which did not appear to be dependent on their inhibition of tyrosinase.

Inhibitory Effects of the Bioactive Thermorubin Isolated from the Fungus Thermoactinomyces Antibioticus on Melanogenesis

Skin hyperpigmentation disorders arise due to aberrant regulation of melanin synthesis and export. Current treatments include natural compounds like kojic acid and hydroquinone, which suffer from limitations due to adverse reactions. Thermorubin (TR) is a secondary metabolite derived from the fungus Thermoactinomyces antibioticus and has previously demonstrated to possess anti-inflammatory properties by inhibition of matrix metalloproteinases (MMPs), as well as antimicrobial activity. In the current study, we explored whether TR might be a used as a candidate for the treatment of skin hyperpigmentation disorders by studying its effects on melanin synthesis and melanin export in B16F10 mouse melanoma cells and primary human melanocytes derived from darkly-pigmented (DP) skin. Non-toxic doses of TR were first identified in B16F10 mouse melanoma cells. These doses were subsequently tested for their effects on both extracellular and intracellular melanin levels under conditions of basal and hormone-stimulated melanogenesis. Our results demonstrated that TR at 25 µM inhibited total melanin levels with selective inhibition of extracellular melanin in B16F10 cells under both basal and hormone-stimulated conditions. The mechanisms of inhibition did not include tyrosinase inhibition, either in cellular lysates or cell-free system. However, TR potently inhibited activity of α-glucosidase enzyme in vitro and exhibited antioxidant activity. Furthermore, our results with primary human melanocytes from DP skin showed that TR at 10 µM significantly suppressed dendricity along with an increase in accumulation of intracellular melanin. These findings point to a mechanism of action of TR as an exclusive inhibitor of melanosome export. Taken together, our preliminary results demonstrate that TR might offer a novel ingredient as a skin depigmenting agent for inclusion in cosmetic formulations. Further studies delineating molecular mechanisms of hypopigmentation of TR and testing in human skin tissue-equivalents are warranted.

Selective inhibition of Rhizopus eumelanin biosynthesis by novel natural product scaffold-based designs caused significant inhibition of fungal pathogenesis.

Melanin is a dark color pigment biosynthesized naturally in most living organisms. Fungal melanin is a major putative virulence factor of Mucorales fungi that allows intracellular persistence by inducing phagosome maturation arrest. Recently, it has been shown that the black pigments of Rhizopus delemar is of eumelanin type, that requires the involvement of tyrosinase (a copper-dependent enzyme) in its biosynthesis. Herein, we have developed a series of compounds (UOSC-1-14) to selectively target Rhizopus melanin and explored this mechanism therapeutically. The compounds were designed based on the scaffold of the natural product, cuminaldehyde, identified from plant sources and has been shown to develop non-selective inhibition of melanin production. While all synthesized compounds showed significant inhibition of Rhizopus melanin production and limited toxicity to mammalian cells, only four compounds (UOSC-1, 2, 13, and 14) were selected as promising candidates based on their selective inhibition to fungal melanin. The activity of compound UOSC-2 was comparable to the positive control kojic acid. The selected candidates showed significant inhibition of Rhizopus melanin but not human melanin by targeting the fungal tyrosinase, and with an IC50 that are 9 times lower than the reference standard, kojic acid. Furthermore, the produced white spores were phagocytized easily and cleared faster from the lungs of infected immunocompetent mice and from the human macrophages when compared with wild-type spores. Collectively, the results suggested that the newly designed derivatives, particularly UOSC-2 can serve as promising candidate to overcome persistence mechanisms of fungal melanin production and hence make them accessible to host defenses.

The pigmentation interference of bisphenol F and bisphenol A

Bisphenol A (BPA) and bisphenol F (BPF) are widely distributed in the environment and daily consumptions, leading to exposure toward human and environmental animals. The potential risk of bisphenol analogs on pigment and skin health is not well documented. In this study, we found that 0.05 mg/L BPF (tolerated daily intake (TDI) value of BPA) affected the particle size and color density of zebrafish melanin. While BPA caused less depigmentation effect toward zebrafish with effective concentration of 5.0 mg/L. The downregulation of melanin synthases induced by BPF is associated with the reduction in melanin. Molecular dynamics indicated that both BPF and BPA could act as ligands of zebrafish and human Tyr family proteins; however, these compounds have completely different energetics and spatial steric effects, potentially explaining their varying depigmentation effects. Additionally, an in vitro assay using A375 melanoma cells demonstrated that the inhibitory effect of BPF on human melanin production was primarily attributed to Tyr inhibition. These findings provide an important basis for understanding the molecular mechanisms of BPF and BPA in melanin inhibition, and the results reflect the skin pigmentation interference risk of these compounds, which are ubiquitous in everyday personal products.

Exploration of Mechanistic Insights of Acemetacin in Melanogenesis Through Zebrafish Model, Enzyme Kinetics, Molecular Docking and Simulation Approaches

The present study describes the anti- melanogenesis effect of Acemetacin (ACE). Essential protein (melanin) that is vital for the skin for defense from UV rays. In the present research, emerging drug ACE was examined for its melanin inhibition using three different (in vitro, in vivo and computational) methods. ACE showed remarkable potency (IC50 = 0.353 ± 0.003 μM) against tyrosinase in the comparison of standard, kojic acid (IC50 = 16.841 ± 1.161 μM) and ACE exhibited competitive inhibition. In the in vivo study zebrafish embryos were exposed with 5, 10, 15 and 20 μM of ACE and same doses for positive control (Kojic Acid). At 72 h treatment, ACE expressively (P<0.001) reduced the level of pigmentation (62.89%) at a concentration of 20 μM, relative to that of kojic acid (39.64%). The binding profile of ACE was confirmed by molecular docking and the stability of the docked complexes was justified by MD simulation. Based on our results, it was concluded

Synthesis and Biological Evaluation of the Anti-Melanogenesis Effect of Coumaric and Caffeic Acid-Conjugated Peptides in Human Melanocytes.

Excessive pigmentation and reduced elasticity are the major skin problems that dermatologists and cosmetologists address. Compounds that inhibit melanin production might contribute to improving skin problems. In this study, we investigated whether coumaric acid- and caffeic acid-conjugated peptides might affect alpha-melanocyte stimulating hormone-induced melanin production, tyrosinase activity, and melanin synthesis-related gene expression in SK-MEL-2 human melanoma cells. Coumaric acid and caffeic acid showed no significant cytotoxicity, and they inhibited melanin production. In addition, coumaric acid- and caffeic acid-conjugated peptides suppressed tyrosinase activity more than arbutin, a known tyrosinase inhibitor. Quantitative real-time PCR (qRT-PCR) results also showed that both peptides inhibited the expression of melanin synthesis-related genes, TYR, TYRP1, TYRP2, and MITF. In particular, among the nine conjugated peptides tested, caffeic acid linked to a Gly-Gly-Gly linker and conjugated to the tripeptide, ARP, showed the greatest inhibition of gene expression in the qRT-PCR analysis. These results suggested that the inhibition of melanin exerted by coumaric acid- and caffeic acid-conjugated peptides might provide important information for the development of pigmentation-related skin diseases and cosmetic products.

Unravelling the Role of Melanin in Cd and Zn Tolerance and Accumulation of Three Dark Septate Endophytic Species.

Dark septate endophytes (DSEs) are often trace element (TE)-tolerant fungi and are abundant in TE-polluted environments. The production of melanin, a black polymer found in cell walls, was hypothesized by several authors to play a role in the TE tolerance of DSEs. To test this hypothesis, we established a series of experiments using albino strains and melanin inhibitors and examined the responses to Cd and Zn. Six DSEs belonging to genera Cadophora sp., Leptodontidium sp. and Phialophora mustea, were evaluated. The strains mainly produced 1,8-dihydroxynaphthalene (DHN) melanin whereas 3,4-dihydroxyphenylalanin melanin was also synthetized. Cd and Zn decreased melanin synthesis in most of the strains. A reduction in melanin concentration in hyphae through the use of tricyclazole, an inhibitor of DHN-melanin synthesis, did not reduce the tolerance of the strains to Cd and Zn. Similarly, albino mutants of Leptodontidium sp. were not more sensitive to Cd and Zn than the WT strain. Moreover, tricyclazole-treated colonies accumulated less Cd but more Zn compared to untreated colonies. The Cd and Zn contents of Leptodontidium albino strains were variable and similar to that of the WT. The results suggest that melanin production is not an important functional trait that contributes to Cd and Zn tolerance, but might contribute to Cd accumulation.

Padina boryana, a brown alga from the Maldives: inhibition of \u03b1-MSH-stimulated melanogenesis via the activation of ERK in B16F10 cells

BackgroundThe present study investigates the potent skin whitening ability of ethanol extract from the brown alga, Padina boryana (PBE) which was collected in the shores of Fulhadhoo Island, the Maldives, and its specific pathways of action. The effect of PBE which contains a rich amount of polyphenols was evaluated using B16F10 murine melanoma cells and provides insight to the underlying mechanisms with reference to the inhibition of melanin formation.MethodsMelanin synthesis and cellular tyrosinase inhibition were assessed in the α-MSH-stimulated melanocytes. Melanogenic pathway-related protein expressions were investigated via Western blotting. ERK 42/44 was particularly examined considering its involvement in the melanogenic pathway. Further, RT-qPCR techniques were involved in gene expression analysis.ResultsPBE dose-dependently inhibited the cellular melanin synthesis and tyrosinase levels. Western blotting revealed the potential of PBE to downregulate microphthalmia-associated transcription factor (MITF), tyrosinase, and tyrosinase-related protein-1 and protein-2 (TRP-1 and TRP-2). Moreover, results explained the phosphorylation of ERK was sustained via PBE and hence declined the ultimate melanin synthesis. Gene expression analysis reinforced the results obtained.ConclusionsThe study provides substantial evidence to express the potential of PBE to inhibit B16F10 melanoma cell melanin synthesis. Concisely, results suggest the ability of PBE to be involved in medicinal and cosmeceutical applications.

Germinated Riceberry Rice Enhanced Protocatechuic Acid and Vanillic Acid to Suppress Melanogenesis through Cellular Oxidant-Related Tyrosinase Activity in B16 Cells.

The anti-melanogenic bioactivities of phytophenolic compounds have been well recognized. Riceberry rice contains a rich source of phenolic compounds that act as melanin inhibitors through their antioxidant and anti-tyrosinase properties. Germination has been shown to be an effective process to improve targeted phenolic compounds. In this study, germinated riceberry rice extract was tested for antioxidant activity. Total phenolic content was determined while the tyrosinase inhibitory effect was screened by the in vitro mushroom tyrosinase assay. Cytotoxicity of germinated riceberry rice extract was investigated in B16 cells before evaluating its activities on cellular tyrosinase, melanogenesis, melanin excretion, morphological appearance, and cellular oxidants. Germinated riceberry rice extract showed increased potency of antioxidants and was also twice as effective for mushroom tyrosinase inhibition when compared with ungerminated riceberry rice extract. In B16 cells, the extract inhibited cellular tyrosinase, melanogenesis, and cellular oxidants in a dose-dependent manner when compared with untreated cells. Germinated riceberry rice extract also displayed an effect on B16 cells morphology by reducing the number of melanin- containing cells and their dendriticity. Additionally, the germination of riceberry rice dominantly enhanced two phenolic acids, protocatechuic acid and vanillic acid, which have the potential for antioxidant-associated hyperpigmentation control. Thus, the restricted germination of riceberry rice tended to promote protocatechuic acid and vanillic acid, which dominantly displayed antioxidants and tyrosinase-related melanogenic inhibition.

Prenylated Flavonoids as Antioxidant and Melanin Inhibitors From Stingless Bee (Wallacetrigona incisa) Propolis

Propolis from 4 stingless bees ( Homotrigona apicalis, Wallacetrigona incisa, Tetragonula fuscobalteata, and Tetragonula fuscibasis) was investigated in the search for medicinal and cosmetic materials from tropical rainforest resources. Methanol extracts of the propolis were screened using antioxidant and antimelanogenesis assays (tyrosinase enzyme activity and melanin inhibitor in B16 melanoma). The extract of H. apicalis showed the strongest antioxidant activity, both in the 2,2-diphenyl-1-picrylhydrazyl and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) assays, with half-maximal inhibitory concentration values of 0.72 ± 0.01 (mg/mL) and 0.26 ± 0.00 (mg/mL), respectively. The H. apicalis extract also displayed the strongest inhibition of tyrosinase (53% at 100 µg/mL). In the B16 melanoma cell assay, the W. incisa extract showed the strongest inhibition of melanin (21%) and was less cytotoxic. The W. incisa extract was fractioned to isolate the compounds with biological activities. Two prenylated flavonoids were obtained, named broussoflavonol F and glyasperin A. Both showed potent antioxidant activities, as well as inhibiting melanin in B16 melanoma, but not tyrosinase activity. These results indicated the potential of methanol extract of W. incisa to be developed for cosmetic material, but further experiments are needed to verify the function.

Inhibitory Effect of Sesamolin on Melanogenesis in B16F10 Cells Determined by In Vitro and Molecular Docking Analyses.

Melanin protects the skin against the harmful effects of ultraviolet irradiation. However, melanin overproduction can result in several aesthetic problems, including melasma, freckles, age spots and chloasma. Therefore, development of anti-melanogenic agents is important for the prevention of serious hyperpigmentation diseases. Sesamolin is a lignan compound isolated from sesame seeds with several beneficial properties, including potential for melanin inhibition. The aim of this study was to evaluate the anti-melanogenic effect of sesamolin in cell culture in vitro and the underlying mechanism of inhibition using molecular docking simulation. Melanogenesis was induced by 3-isobutyl-1-methylxanthine in B16F10 melanoma cells, and the inhibitory effects of sesamolin were evaluated using zymography, a tyrosinase inhibitory activity assay, western blotting, and real-time reverse transcription-polymerase chain reaction analysis. Docking simulations between sesamolin and tyrosinase were performed using Autodock vina. Sesamolin significantly inhibited the expression of melanogenesis-related factors tyrosinase, and tyrosinase-related proteins 1 and 2 at the mRNA and protein levels. Treatment of melanoma cells with 50 µM sesamolin demonstrated the strongest inhibition against intercellular tyrosinase and melanin synthesis without exerting cytotoxic effects. Sesamolin significantly reduced mushroom tyrosinase activity in a dose-dependent manner via a competitive inhibition mechanism. Tyrosinase docking simulations supported that sesamolin (-6.5 kcal/mol) bound to the active site of tyrosinase more strongly than the positive control (arbutin, -5.7 kcal/mol). Sesamolin could be developed as a melanogenesis inhibiting agent owing to its dual function in blocking the generation of melanogenesis-related enzymes and inhibiting the enzymatic response of tyrosinase.

Melanin has a Small Inhibitory Effect on Cutaneous Vitamin D Synthesis: A Comparison of Extreme Phenotypes

Epidemiology suggests that melanin inhibits cutaneous vitamin D3 synthesis by UVR. Laboratory investigations assessing the impact of melanin on vitamin D production have produced contradictory results. We determined the effect of melanin on vitamin D3 photosynthesis in healthy young volunteers (n= 102) of Fitzpatrick skin types II-VI (white to black). Participants, irrespective of skin type, were exposed to the same suberythemal UVR dose, to 85% body surface area, using solar simulated UVR or narrowband UVB (311 nm). This was repeated five times with intervals of 3-4 days between UVR exposures. Blood was taken before, during, and after the irradiation and assessed for serum 25-hydroxyvitamin D3 (25[OH]D3) as a marker of vitamin D3 status. Linear UVR dose-dependent increases in 25(OH)D3 were highly significant (P ≤ 7.7 x 10-11). The ratios of regression slopes of the different skin type groups were compared, and only skin type II was significantly steeper than the other groups. Comparisons between extreme skin types II and VI showed melanin inhibition factors of approximately 1.3-1.4, depending on the UVR source. We conclude that the inhibitory effect of melanin on vitamin D3 synthesis is small, compared with erythema, but that this difference may be sufficient to explain the epidemiological data.

The role of carbon sources in relation to pathogenicity of Sclerotinia sclerotiorum on Valencia peanut

Sclerotinia sclerotiorum is a necrotrophic fungal pathogen with a very wide host range. Isolates of this pathogen are normally described as having fluffy and white mycelium; however, isolates of S. sclerotiorum with darkly-pigmented mycelium on potato dextrose agar medium have been identified in eastern New Mexico and western Texas from Valencia peanut fields. Mutant non-pigmented S. sclerotiorum isolates (SW) were created in an earlier study from wild-type pigmented isolates (SD) using melanin inhibitors. The SD isolates were pathogenic on Valencia peanut, whereas the SW isolates were not. The current study was conducted to further characterize the differences between SD and SW isolates in regards to metabolite production and utilization, including the effects of carbon sources and oxalic acid precursors on oxalic acid production and pathogenicity on Valencia peanut. Gas chromatography–mass spectrometry (GC/MS) metabolomics analysis revealed a down-regulation of several sugars and compounds within the citric acid cycle as well as oxalic acid for SW isolates of S. sclerotiorum. The addition of glucose to potato dextrose agar medium allowed for the production of oxalic acid and restored pathogenicity in SW isolates that were previously non-pathogenic on Valencia peanut. This study indicates that glucose alone plays a major role in oxalic acid production and pathogenicity of S. sclerotiorum.

Synthesis, molecular docking, dynamic simulations, kinetic mechanism, cytotoxicity evaluation of N-(substituted-phenyl)-4-{(4-[(E)-3-phenyl-2-propenyl]-1-piperazinyl} butanamides as tyrosinase and melanin inhibitors: In vitro, in vivo and in silico approaches.

In the current research work, different N-(substituted-phenyl)-4-{(4-[(E)-3-phenyl-2-propenyl]-1-piperazinyl}butanamides have been synthesized according to the protocol described in scheme 1. The synthesis was initiated by reacting various substituted anilines (1a-e) with 4-chlorobutanoyl chloride (2) in aqueous basic medium to give various electrophiles, 4-chloro-N-(substituted-phenyl)butanamides (3a-e). These electrophiles were then coupled with 1-[(E)-3-phenyl-2-propenyl]piperazine (4) in polar aprotic medium to attain the targeted N-(substituted-phenyl)-4-{(4-[(E)-3-phenyl-2-propenyl]-1-piperazinyl}butanamides (5a-e). The structures of all derivatives were identified and characterized by proton-nuclear magnetic resonance (1H NMR), carbon-nuclear magnetic resonance (13C NMR) and Infra-Red (IR) spectral data along with CHN analysis. The in vitro inhibitory potential of these butanamides was evaluated against Mushroom tyrosinase, whereby all compounds were found to be biologically active. Among them, 5b exhibited highest inhibitory potential with IC50 value of 0.013±0.001µM. The same compound 5b was also assayed through in vivo approach, and it was explored that it significantly reduced the pigments in zebrafish. The in silico studies were also in agreement with aforesaid results. Moreover, these molecules were profiled for their cytotoxicity through hemolytic activity, and it was found that except 5e, all other compounds showed minimal toxicity. The compound 5a also exhibited comparable results. Hence, some of these compounds might be worthy candidates for the formulation and development of depigmentation drugs with minimum side effects.