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

Cosmetics ◽  
2020 ◽  
Vol 7 (3) ◽  
pp. 61
Author(s):  
Shilpi Goenka ◽  
Sanford R. Simon
Keyword(s):  
Molecular Mechanisms ◽  
Selective Inhibition ◽  
Melanoma Cells ◽  
Melanin Synthesis ◽  
Free System ◽  
Mouse Melanoma ◽  
B16f10 Cells ◽  
Skin Hyperpigmentation ◽  
Human Melanocytes

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.

scholarly journals Molecular Mechanisms of Anti-Melanogenic Gedunin Derived from Neem Tree (Azadirachta indica) Using B16F10 Mouse Melanoma Cells and Early-Stage Zebrafish

Plants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 330
Author(s):  
Hwang-Ju Jeon ◽  
Kyeongnam Kim ◽  
Chaeeun Kim ◽  
Myoung-Jin Kim ◽  
Tae-Oh Kim ◽  
...  
Keyword(s):  
Skin Color ◽  
Molecular Mechanisms ◽  
Early Stage ◽  
Melanoma Cells ◽  
Ultraviolet Rays ◽  
Melanin Production ◽  
Zebrafish Model ◽  
Mouse Melanoma

Melanogenesis represents a series of processes that produce melanin, a protective skin pigment (against ultraviolet rays), and determines human skin color. Chemicals reducing melanin production have always been in demand in the cosmetic market because of skincare interests, such as whitening. The main mechanism for inhibiting melanin production is the inhibition of tyrosinase (TYR), a key enzyme for melanogenesis. Here, we evaluated gedunin (Ged), a representative limonoid, for its anti-melanogenesis action. Melanin production in vitro was stimulated by alpha-melanocyte stimulating hormone (α-MSH) in B16F10 mouse melanoma cells. Ged reduced α-MSH-stimulated melanin production, inhibiting TYR activity and protein amount. We confirmed this result in vivo in a zebrafish model for melanogenesis. There was no sign of toxicity and malformation of zebrafish embryos during development in all treated concentrations. Ged reduced the number of produced zebrafish embryo pigment dots and melanin contents of embryos. The highly active concentration of Ged (100 µM) was much lower than the positive control, kojic acid (8 mM). Hence, Ged could be a fascinating candidate for anti-melanogenesis reagents.

scholarly journals Inonotus obliquus Extract as An Inhibitor of α-MSH-Induced Melanogenesis in B16F10 Mouse Melanoma Cells

Cosmetics ◽  
2019 ◽  
Vol 6 (1) ◽  
pp. 9
Author(s):  
Eun Ji Lee ◽  
Hwa Jun Cha
Keyword(s):  
Melanoma Cells ◽  
Potential Candidate ◽  
Melanin Synthesis ◽  
Inonotus Obliquus ◽  
Mouse Melanoma ◽  
B16f10 Cells ◽  
Key Enzyme ◽  
Good Potential ◽  
Tyrosinase Enzyme ◽  
Melanin Contents

Melanogenesis is a biosynthetic pathway that produces the pigment melanin in human skin. The catalyzation of the key enzyme tyrosinase is the first step in melanogenesis, and the downregulation of tyrosinase enzyme activity is the most reported method for inhibiting melanogenesis. Hyperpigmentation is an important issue in the cosmetic industry, and there is great demand for melanogenesis inhibitors. In the present study, we demonstrated the anti-melanogenic effect of Inonotus obliquus in alpha-melanocyte-stimulating hormone (α-MSH)-induced B16F10 mouse melanoma cells and identified it as a new melanogenesis inhibitor. Comparing the B16F10 cells treated with the control and the Inonotus obliquus extract, we identified the melanin contents, mRNA and protein expression of tyrosinase, tyrosinase activity, and microphthalmia-associated transcription factor (Mitf) activity using a constructed plasmid. Through these experiments, we confirmed that Inonotus obliquus extract inhibits melanin synthesis by downregulating the activity and expression of tyrosinase. Furthermore, we revealed that tyrosinase expression is regulated by Inonotus obliquus extract via the repression of Mitf transcriptional activity. Thus, in this study, we found that Inonotus obliquus extract has anti-melanogenic effects via the suppression of melanin synthesis. Taken together, we demonstrated that Inonotus obliquus extract is a good potential candidate for use as a natural source for the therapeutic treatment of hyperpigmentation and for applications in whitening cosmetic products.

scholarly journals Human amniotic stem cells-derived exosmal miR-181a-5p and miR-199a inhibit melanogenesis and promote melanosome degradation in skin hyperpigmentation, respectively

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Xiao-Yu Wang ◽  
Xiao-Hui Guan ◽  
Zhen-Ping Yu ◽  
Jie Wu ◽  
Qi-Ming Huang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Western Blot ◽  
Melanin Synthesis ◽  
Skin Substitutes ◽  
Rt Pcr ◽  
B16f10 Cells ◽  
Skin Hyperpigmentation ◽  
Underlying Mechanisms

Abstract Background Hyperpigmentation of skin is caused by an imbalance between the melanosome/melanin synthesis in melanocytes and the melanosome/melanin degradation in keratinocytes. Although studies showed that stem cells play a role in hypopigmentation, the underlying mechanisms are far not elucidated. Human amniotic stem cells (hASCs) including human amniotic mesenchymal stem cells (hAMSCs) and human amniotic epithelial stem cells (hAESCs) were considered to be a promising cell source for stem cells-based therapy of many diseases clinically due to their pluripotent potential, no tumorigenesis and immunogenicity, no ethical issues, and potent paracrine effects. Here, we reported that both hASCs and their conditional medium (CM) had a potent anti-hyperpigmentation in skin in vivo and in vitro. Methods hAESCs and hAMSCs were identified by RT-PCR, flow cytometric analysis and immunofluorescence. Effects of hASCs and hASC-CM on pigmentation were evaluated in B16F10 cells stimulated with α-melanocyte-stimulating hormone (α-MSH), and mouse ears or human skin substitutes treated with ultraviolet radiation B (UVB). Expressions of the key proteins related with melanogenesis and autophagic flux were detected by western blot in B16F10 cells for further exploring the effects and the underlying mechanisms of hAESC-CM and hAMSC-CM on melanogenesis and melanosome degradation. The hAMSCs exosomes-derived miRNAs were determined by sequencing. RT-PCR, western blot, melanin content analysis and luciferase activity assay were used to determine the hypopigmentation of miR-181a-5p and miR-199a. Results In our study, we observed that both hASCs and their CM significantly alleviated the α-MSH in B16F10 cells or UVB-induced hyperpigmentation in mouse ears or human skin substitutes by suppressing melanin synthesis and promoting melanosome degradation in vivo and in vitro. Furthermore, we demonstrated that miR-181a-5p and miR-199a derived from hASCs exosomes remarkably inhibited melanogenesis by suppressing MITF (microphthalmia-associated transcription factor) which is a master regulator for governing melanogenesis and promoting melanosome degradation through activating autophagy, respectively. Conclusions Our studies provided strong evidence that the conditional medium and exosomes derived from hAMSCs inhibit skin hyperpigmentation by suppressing melanogenesis and promoting melanosome degradation, indicating that the hASCs exosomes or their released microRNAs might be as reagents for cell-free therapy in hyperpigmented disorders clinically.

scholarly journals Molecular and Biochemical Basis of Minocycline-Induced Hyperpigmentation—The Study on Normal Human Melanocytes Exposed to UVA and UVB Radiation

2021 ◽  
Vol 22 (7) ◽  
pp. 3755
Author(s):  
Jakub Rok ◽  
Zuzanna Rzepka ◽  
Justyna Kowalska ◽  
Klaudia Banach ◽  
Artur Beberok ◽  
...  
Keyword(s):  
Uv Radiation ◽  
Therapeutic Potential ◽  
Melanin Synthesis ◽  
Uvb Radiation ◽  
Biochemical Basis ◽  
Skin Hyperpigmentation ◽  
Human Melanocytes ◽  
Anti Cancer ◽  
Normal Human

Minocycline is a drug which induces skin hyperpigmentation. Its frequency reaches up to 50% of treated patients. The adverse effect diminishes the great therapeutic potential of minocycline, including antibacterial, neuroprotective, anti-inflammatory and anti-cancer actions. It is supposed that an elevated melanin level and drug accumulation in melanin-containing cells are related to skin hyperpigmentation. This study aimed to evaluate molecular and biochemical mechanism of minocycline-induced hyperpigmentation in human normal melanocytes, as well as the contribution of UV radiation to this side effect. The experiments involved the evaluation of cyto- and phototoxic potential of the drug using cell imaging with light and confocal microscopes as well as biochemical and molecular analysis of melanogenesis. We showed that minocycline induced melanin synthesis in epidermal melanocytes. The action was intensified by UV irradiation, especially with the UVB spectrum. Minocycline stimulated the expression of microphthalmia-associated transcription factor (MITF) and tyrosinase (TYR) gene. Higher levels of melanin and increased activity of tyrosinase were also observed in treated cells. Moreover, minocycline triggered the supranuclear accumulation of tyrosinase, similar to UV radiation. The decreased level of premelanosome protein PMEL17 observed in all minocycline-treated cultures suggests disorder of the formation, maturation or distribution of melanosomes. The study revealed that minocycline itself was able to enhance melanin synthesis. The action was intensified by irradiation, especially with the UVB spectrum. Demonstrated results confirmed the potential role of melanin and UV radiation minocycline-induced skin hyperpigmentation.

scholarly journals Treatment with Uncaria tomentosa Promotes Apoptosis in B16-BL6 Mouse Melanoma Cells and Inhibits the Growth of B16-BL6 Tumours

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 1066
Author(s):  
Ali Zari ◽  
Hajer Alfarteesh ◽  
Carly Buckner ◽  
Robert Lafrenie
Keyword(s):  
Tumour Size ◽  
Melanoma Cells ◽  
Tunel Staining ◽  
Aqueous Extracts ◽  
Ki 67 ◽  
Uncaria Tomentosa ◽  
Mouse Melanoma ◽  
Anti Cancer

Uncaria tomentosa is a medicinal plant native to Peru that has been traditionally used in the treatment of various inflammatory disorders. In this study, the effectiveness of U. tomentosa as an anti-cancer agent was assessed using the growth and survival of B16-BL6 mouse melanoma cells. B16-BL6 cell cultures treated with both ethanol and phosphate-buffered saline (PBS) extracts of U. tomentosa displayed up to 80% lower levels of growth and increased apoptosis compared to vehicle controls. Treatment with ethanolic extracts of Uncaria tomentosa were much more effective than treatment with aqueous extracts. U. tomentosa was also shown to inhibit B16-BL6 cell growth in C57/bl mice in vivo. Mice injected with both the ethanolic and aqueous extracts of U. tomentosa showed a 59 ± 13% decrease in B16-BL6 tumour weight and a 40 ± 9% decrease in tumour size. Histochemical analysis of the B16-BL6 tumours showed a strong reduction in the Ki-67 cell proliferation marker in U. tomentosa-treated mice and a small, but insignificant increase in terminal transferase dUTP nick labelling (TUNEL) staining. Furthermore, U. tomentosa extracts reduced angiogenic markers and reduced the infiltration of T cells into the tumours. Collectively, the results in this study concluded that U. tomentosa has potent anti-cancer activity that significantly inhibited cancer cells in vitro and in vivo.

Stimulation of melanin synthesis of B16-F10 mouse melanoma cells by bufalin

Life Sciences ◽  
1992 ◽  
Vol 51 (1) ◽  
pp. 17-24 ◽  
Author(s):  
Lisha Zhang ◽  
Takemi Yoshida ◽  
Yukio Kuroiwa
Keyword(s):  
Melanoma Cells ◽  
Melanin Synthesis ◽  
Mouse Melanoma ◽  
Stimulation Of

Role of the ligand in intracellular receptor function: receptor affinity determines activation in vitro of the latent dioxin receptor to a DNA-binding form

1991 ◽  
Vol 11 (1) ◽  
pp. 401-411
Author(s):  
S Cuthill ◽  
A Wilhelmsson ◽  
L Poellinger
Keyword(s):  
Dna Binding ◽  
Cellular Response ◽  
Molecular Mechanisms ◽  
Nuclear Translocation ◽  
Rank Order ◽  
Receptor Ligands ◽  
Free System ◽  
Dioxin Receptor

To reconstitute the molecular mechanisms underlying the cellular response to soluble receptor ligands, we have exploited a cell-free system that exhibits signal- (dioxin-)induced activation of the latent cytosolic dioxin receptor to an active DNA-binding species. The DNA-binding properties of the in vitro-activated form were qualitatively indistinguishable from those of in vivo-activated nuclear receptor extracted from dioxin-treated cells. In vitro activation of the receptor by dioxin was dose dependent and was mimicked by other dioxin receptor ligands in a manner that followed the rank order of their relative affinities for the receptor in vitro and their relative potencies to induce target gene transcription in vivo. Thus, in addition to triggering the initial release of inhibition of DNA binding and presumably allowing nuclear translocation, the ligand appears to play a crucial role in the direct control of the level of functional activity of a given ligand-receptor complex.

scholarly journals Docosahexaenoic acid inhibits melanin synthesis in murine melanoma cells in vitro through increasing tyrosinase degradation

2014 ◽  
Vol 35 (4) ◽  
pp. 489-495 ◽  
Author(s):  
Marie Carmel Balcos ◽  
Su Yeon Kim ◽  
Hyo-soon Jeong ◽  
Hye-young Yun ◽  
Kwang Jin Baek ◽  
...  
Keyword(s):  
Docosahexaenoic Acid ◽  
Melanoma Cells ◽  
Melanin Synthesis ◽  
Murine Melanoma ◽  
Murine Melanoma Cells

scholarly journals Inhibitory effects of Lang-du extract on the in vitro and in vivo growth of melanoma cells and its molecular mechanisms of action

2010 ◽  
Vol 62 (4) ◽  
pp. 357-366 ◽  
Author(s):  
Liping Wang ◽  
Huiying Duan ◽  
Yishan Wang ◽  
Kun Liu ◽  
Peng Jiang ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Melanoma Cells ◽  
Mechanisms Of Action ◽  
Inhibitory Effects ◽  
In Vivo Growth

scholarly journals CMT-308, a Nonantimicrobial Chemically-Modified Tetracycline, Exhibits Anti-Melanogenic Activity by Suppression of Melanosome Export

Biomedicines ◽  
2020 ◽  
Vol 8 (10) ◽  
pp. 411
Author(s):  
Shilpi Goenka ◽  
Sanford R. Simon
Keyword(s):  
Cell Cultures ◽  
Mammalian Cells ◽  
Selective Reduction ◽  
Mushroom Tyrosinase ◽  
Free System ◽  
Melanin Biosynthesis ◽  
Chemically Modified ◽  
B16f10 Cells ◽  
Chemically Modified Tetracycline

CMT-308 is a nonantimicrobial chemically-modified tetracycline (CMT), which we have previously shown exhibits antifungal activity and pleiotropic anti-inflammatory activities, including inhibition of the enzymatic activity of matrix metalloproteinases (MMPs). Based on its chemical structure, we hypothesized that CMT-308 could inhibit melanogenesis and might be a candidate for the treatment of skin hyperpigmentation disorders which occur due to unregulated melanin biosynthesis and/or transport. CMT-308 was first studied for any effects on activity of the enzyme tyrosinase in vitro using a purified preparation of mushroom tyrosinase; the mode of inhibition of the soluble fungal enzyme was evaluated by Lineweaver-Burk and Dixon plots as well as by non-linear least squares fitting. Next, the effects of CMT-308 were tested in mammalian cell cultures using B16F10 mouse melanoma cells and further validated in darkly-pigmented human melanocytes (HEMn-DP). Our results showed that micromolar concentrations of CMT-308 inhibited mushroom tyrosinase enzyme activity, using the first two substrates in the melanogenesis pathway (l-tyrosine and l-3,4-dihydroxyphenylalanine (l-DOPA)); CMT-308 inhibited mushroom tyrosinase primarily via a mixed mode of inhibition, with the major contribution from a competitive mode. In B16F10 cell cultures, CMT-308 (10 µM) significantly diminished total melanin levels with a selective reduction of extracellular melanin levels, under both basal and hormone-stimulated conditions without any cytotoxicity over a duration of 72 h. Studies of potential mechanisms of inhibition of melanogenesis in B16F10 cells showed that, in mammalian cells, CMT-308 did not inhibit intracellular tyrosinase activity or the activity of α-glucosidase, an enzyme that regulates maturation of tyrosinase. However, CMT-308 suppressed MITF protein expression in B16F10 cells and showed copper chelating activity and antioxidant activity in a cell-free system. The significantly lower extracellular melanin levels obtained at 10 µM indicate that CMT-308’s anti-melanogenic action may be attributed to a selective inhibition of melanosome export with the perinuclear aggregation of melanosomes, rather than a direct effect on the tyrosinase-catalyzed steps in melanin biosynthesis. These results were validated in HEMn-DP cells where CMT-308 suppressed dendricity in a fully reversible manner without affecting intracellular melanin synthesis. Furthermore, the capacity of CMT-308 to inhibit melanosome export was retained in cocultures of HEMn-DP and HaCaT. In summary, our results offer promise for therapeutic strategies to combat the effects of hyperpigmentation by use of CMT-308 at low micromolar concentrations.

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