Glabridin is the main ingredient of hydrophobic fraction in licorice extract and has been shown to have anti-melanogenesis activity in skins.However,the underlying mechanism(s)remain not completely understood.The aim ...Glabridin is the main ingredient of hydrophobic fraction in licorice extract and has been shown to have anti-melanogenesis activity in skins.However,the underlying mechanism(s)remain not completely understood.The aim of this study is thus to elucidate the possible mechanisms related to the melanogenesis suppression by glabridin in cultured B16 murine melanoma cells and in UVA radiation induced hyperpigmentation model of BALB/c mice as well.Molecular docking simulations revealed that between catalytic core residues and the compound.The treatment by glabridin significantly downregulated both transcriptional and/or protein expression of melanogenesis-related factors including melanocyte stimulating hormone receptor(MC1R),microphthalmia-associated transcription factor(MITF),tyrosinase(TYR),TYR-related protein-1(TRP-1)and TRP-2 in B16 cells.Both PKA/MITF and MAPK/MITF signaling pathways were found to be involved in the suppression of melanogenesis by glabridin in B16 cells.Also in vivo glabridin therapy significantly reduced hyperpigmentation,epidermal thickening,roughness and inflammation induced by frequent UVA exposure in mice skins,thus beneficial for skin healthcare.These data further look insights into the molecular mechanisms of melanogenesis suppression by glabridin,rationalizing the application of the natural compound for skin healthcare.展开更多
Perilla frutescens seed (PFS) oil is reported to inhibit skin photoaging;however, its effect on melanogenesis has not yet been investigated. Herein, we tested the anti-melanogenesis activity of an oil-based extract fr...Perilla frutescens seed (PFS) oil is reported to inhibit skin photoaging;however, its effect on melanogenesis has not yet been investigated. Herein, we tested the anti-melanogenesis activity of an oil-based extract from PFS with supercritical carbon dioxide (scCO<sub>2</sub>). In a cell culture system, B16 mouse melanoma cells were treated with the PFS scCO<sub>2</sub> extract and other samples. The PFS scCO<sub>2</sub> extract decreased melanin production by approximately 90% in B16 mouse melanoma cells without cytotoxicity at 100 μg/mL. This effect was greater than that of the well-known melanogenesis inhibitor, kojic acid. Although a hexane-extracted PFS oil and a squeezed PFS oil also decreased melanin production in the B16 cells, the inhibitory effect of the PFS scCO<sub>2</sub> extract was higher than both of these. Chemical analysis of the PFS scCO<sub>2</sub> extract and squeezed PFS oil showed that almost 90% of the components of both oils were α-linolenic acid, linoleic acid, and oleic acid. Furthermore, the ratio of those three fatty acids across both samples was almost the same. When the three fatty acids were mixed in the same ratio as in the PFS scCO<sub>2</sub> extract, the IC<sub>50</sub> of the mixture for melanin production in B16 melanoma cells was identical to that of the PFS scCO<sub>2</sub> extract. However, the IC<sub>50</sub> of the squeezed PFS oil was approximately 6.6 times higher than that of the mixture. Although those fatty acids are the main inhibitory ingredients against melanin production in all of the extracts, some factor(s) in the squeezed PFS reduce their affinity with the cells. These results indicated that the PFS scCO<sub>2</sub> extract could be a superior melanogenesis inhibitor. Although its main ingredients are probably the same as those of the squeezed PFS oil, it is necessary to extract with scCO<sub>2</sub> for stronger anti-melanogenesis activity.展开更多
Objective:To explore the anti-melanogenic potential of Cyrtomium falcatum.Methods:The effects of Cyrtomium falcatum crude extract and its solvent fractions on tyrosinase activity,melanin content,and the expressions of...Objective:To explore the anti-melanogenic potential of Cyrtomium falcatum.Methods:The effects of Cyrtomium falcatum crude extract and its solvent fractions on tyrosinase activity,melanin content,and the expressions of melanogenesis-related genes and proteins were analyzed inα-melanocyte-stimulating hormone(α-MSH)-stimulated B16F10 cells.Results:α-MSH treatment significantly increased tyrosinase activity,and extracellular and intracellular melanin content,as well as the expression levels of tyrosinase,microphthalmia-associated transcription factor(MITF),tyrosinase-related protein(TRP)-1,and TRP-2 in B16F10 cells.Treatment with Cyrtomium falcatum crude extract and its solvent fractions reduced tyrosinase activity and extracellular and intracellular melanin content and downregulated the expression levels of tyrosinase,MITF,TRP-1,and TRP-2 in a dose-dependent manner.Conclusions:Cyrtomium falcatum has potential anti-melanogenesis effects and can be used as a potential source material in cosmeceutical industry for the research and development of novel lead molecules with whitening properties.展开更多
旨在筛选对黑色素生成起调节作用的小RNA,并探究其对山羊肤色及毛色的调控机制。本研究采集了健康酉州乌羊(Youzhou dark goat, YZDG)、川东白山羊(Chuandong white goat, CDWG)100日龄胎羊皮肤样本(n=3),和健康2~3周岁大足黑山羊(Dazu ...旨在筛选对黑色素生成起调节作用的小RNA,并探究其对山羊肤色及毛色的调控机制。本研究采集了健康酉州乌羊(Youzhou dark goat, YZDG)、川东白山羊(Chuandong white goat, CDWG)100日龄胎羊皮肤样本(n=3),和健康2~3周岁大足黑山羊(Dazu black goat, DBG)、内蒙古绒山羊(Inner Mongolia cashmere goat, IMCG)个体皮肤样本(n=3),利用组织切片染色技术观察皮肤中黑色素沉积情况;通过小RNA测序技术筛选差异miRNAs;培养B16-F10皮肤黑色素瘤细胞,利用细胞转染、qPCR、Western Blot、黑色素含量检测等技术验证miR-129-5p对黑色素生成的影响。结果显示,黑色素颗粒明显在YZDG胎羊皮肤和DBG毛囊的毛球、毛干、外根鞘等部位沉积,而在CDWG胎羊皮肤和IMCG表皮、毛囊中没有被观察到。经测序分析,在肤色差异的YZDG和CDWG中筛选到62个差异表达miRNAs,其中31个在乌皮山羊中上调,31个下调。在毛色差异的DBG和IMCG中,筛选到38个差异表达miRNAs,其中10个在黑色被毛山羊中表达上调,28个表达下调。两组测序结果均显示miR-129-5p在乌皮和黑色被毛山羊皮肤中高表达(P<0.05)。在细胞中过表达miR-129-5p后,相比于对照组,mimics组细胞黑色素沉积量提高了18.9%(P<0.05),TYR、TYRP1基因表达量分别上调57.3%和16.5%(P<0.05),蛋白表达量分别显著上调49.2%和40.2%(P<0.05);但MITF基因及其蛋白表达量无显著变化(P>0.05)。在抑制miR-129-5p后,inhibitor组TYR基因mRNA表达下调38.9%、蛋白表达水平下调21.1%(P<0.05);TYRP1、MITF蛋白表达水平分别下调25.3%及28.4%(P<0.05)。本研究发现,miR-129-5p在不同肤色及毛色的山羊皮肤中差异表达,且可通过调控TYR、TYRP1等关键基因的表达影响黑色素的生成,是山羊肤色和毛色形成过程的重要调节因子。展开更多
Epimedin B(EB)is one of the main flavonoid ingredients present in Epimedium brevicornum Maxim.,a traditional herb widely used in China.Our previous study showed that EB was a stronger inducer of melanogenesis and an a...Epimedin B(EB)is one of the main flavonoid ingredients present in Epimedium brevicornum Maxim.,a traditional herb widely used in China.Our previous study showed that EB was a stronger inducer of melanogenesis and an activator of tyrosinase(TYR).However,the role of EB in melanogenesis and the mechanism underlying the regulation remain unclear.Herein,as an extension to our previous investigation,we provide comprehensive evidence of EB-induced pigmentation in vivo and in vitro and elucidate the melanogenesis mechanism by assessing its effects on the TYR family of proteins(TYRs)in terms of expression,activity,and stability.The results showed that EB increased TYRs expression through microphthalmia-associated transcription factor-mediated p-Akt(referred to as protein kinase B(PKB))/glycogen synthase kinase 3β(GSK3β)/β-catenin,p-p70 S6 kinase cascades,and protein 38(p38)/mitogen-activated protein(MAP)kinase(MAPK)and extracellular regulated protein kinases(ERK)/MAPK pathways,after which EB increased the number of melanosomes and promoted their maturation for melanogenesis in melanoma cells and human primary melanocytes/skin tissues.Furthermore,EB exerted repigmentation by stimulating TYR activity in hydroquinone-and N-phenylthiourea-induced TYR inhibitive models,including melanoma cells,zebrafish,and mice.Finally,EB ameliorated monobenzone-induced depigmentation in vitro and in vivo through the enhancement of TYRs stability by inhibiting TYR misfolding,TYR-related protein 1 formation,and retention in the endoplasmic reticulum and then by downregulating the ubiquitination and proteolysis processes.These data conclude that EB can target TYRs and alter their expression,activity,and stability,thus stimulating their pigmentation function,which might provide a novel rational strategy for hypopigmentation treatment in the pharmaceutical and cosmetic industries.展开更多
Vitiligo has a significant impact on a substantial number of individuals worldwide.Traditional Chinese medicine has a long history of serving as a therapeutic treatment for vitiligo.Nevertheless,given the increasing v...Vitiligo has a significant impact on a substantial number of individuals worldwide.Traditional Chinese medicine has a long history of serving as a therapeutic treatment for vitiligo.Nevertheless,given the increasing volume of research on the utilization of traditional Chinese medicine for vitiligo treatment,it is imperative to conduct a comprehensive review that elucidates the efficacy of Chinese traditional medicine and other active ingredients in the treatment of vitiligo.This paper presents a comprehensive overview of the clinical preparations used to treat vitiligo,while also highlighting the potential monomers and extracts derived from traditional Chinese medicine for vitiligo treatment.A thorough analysis of the pharmacological effects of traditional Chinese medicine on vitiligo treatment will provide valuable insights and reliable information for the development of new treatment strategies.展开更多
Background:Platycladus orientalis,which has been employed in traditional Chinese medicine for cool blood,antibacterial,promotion of hair growth and therapy of poliosis for centuries.However,there have been few reports...Background:Platycladus orientalis,which has been employed in traditional Chinese medicine for cool blood,antibacterial,promotion of hair growth and therapy of poliosis for centuries.However,there have been few reports focusing on Platycladus orientalis shells treating pigmentary disorders.Methods:In present study,gas chromatography–mass spectrometry was applied to analyzing the volatile composition of Platycladus orientalis shells and cellular metabolism.Experiments in vivo were carried out to evaluate the effect of Platycladus orientalis shells treating pigmentation disorders in C57BL/6J mice.Results:Our results indicated that cedrol occupied the largest percentage in Platycladus orientalis shells(17.1%).Meanwhile,Platycladus orientalis shells up-regulated the content of palmitic acid and increased melanin content and tyrosinase activity.Its mechanism possibly involved in the inhibiting phosphorylation of AKT and β-catenin,increasing phosphorylation of p38 to promote microphthalmia-associated transcription factor expression.The animal experiment also proved that Platycladus orientalis shells promoted melanogensis and hair blacken in C57BL/6J mice.Conclusion:All in all,Platycladus orientalis shells potentially promoted melanogenesis in vitro and in vivo.Cedrol was regarded as the main active substance in Platycladus orientalis shells.Therefore,it could be used for treatment of pigmentary disorders under safe concentration in the prospective application.展开更多
In this study, we explored the effects of unripe fruit extracts of Mangifera indica L. on the anti-aging activity in skin cells. Mangifera indica L. is a popular economical and medicinal plant with numerous health-ben...In this study, we explored the effects of unripe fruit extracts of Mangifera indica L. on the anti-aging activity in skin cells. Mangifera indica L. is a popular economical and medicinal plant with numerous health-beneficial properties. The aqueous extracts of unripe fruit of Mangifera indica L. were obtained and subjected to HPLC and NMR analyses for the identification of bioactive compounds. The anti-glycation effect of Mango unripe fruit extracts was monitored by in vitro model system of AGEs (Advanced glycation end products) formation. Mango unripe fruit extracts significantly inhibited the AGEs formation in a dose-dependent manner. Meanwhile, Mango unripe fruit extracts possessed a comparable efficiency to commercialized Kojic acids in the inhibition of melanogenesis in B16-F10 melanoma cells. The UVA-induced cell damages can be prevented and repaired by Mango unripe fruit extracts in skin fibroblast CCD-966SK. Compared to the untreated control, Mango unripe fruit extracts significantly increased the cell viability while being applied before (36%) or after (43%) UVA irradiation. These results verified the potential application of Mango unripe fruit extracts in the skin protection and recovery from UVA irradiation, as well as the suppression of AGEs formation and melanogenesis.展开更多
In order to develop melanoma-targeted in situ peptide vaccine immunotherapy, magnetite nanoparticles were conjugated with a melanogenesis substrate, N-propionyl cysteaminylphenol (NPrCAP). Magnetite nanoparticles intr...In order to develop melanoma-targeted in situ peptide vaccine immunotherapy, magnetite nanoparticles were conjugated with a melanogenesis substrate, N-propionyl cysteaminylphenol (NPrCAP). Magnetite nanoparticles introduced thermotherapy which caused non-apoptotic cell death and generation of heat shock protein (HSP) upon exposure to alternating magnetic field (AMF). NPrCAP was expected to develop a melanoma-targeted therapeutic drug because of its selective incorporation into melanoma cells and production of highly reactive free radicals, that result in not only oxidative stress but also apoptotic cell death by reacting with tyrosinase.展开更多
Over the past years, natural products have been used as useful candidates for prevention and treatment of skin disorders such as skin darkening. In this current research, <i><span style="font-family:Verd...Over the past years, natural products have been used as useful candidates for prevention and treatment of skin disorders such as skin darkening. In this current research, <i><span style="font-family:Verdana;">Daniellia oliveri</span></i><span style="font-family:Verdana;"> which was a potential source of cosmeceutical agent was selected to investigate its active components. Daniellic acid isolated from the oleoresin was characterized by using data from </span><sup><span style="font-family:Verdana;">1</span></sup><span style="font-family:Verdana;">H-NMR, </span><sup><span style="font-family:Verdana;">13</span></sup><span style="font-family:Verdana;">C-NMR, HSQC, IR, and online chemo-informatic analysis. The daniellic acid antioxidant, anti-proliferative, and tyrosinase inhibition capabilities were evaluated. This compound possessed an anti-DPPH and iron (III) reducing effect compared to quercetin. It was able to inhibit 9 tumor cells with IC</span><sub><span style="font-family:Verdana;">50</span></sub><span style="font-family:Verdana;"> going from 0.03 mM (U373) to 0.14 mM (Malme-3M). Interestingly daniellic acid inhibit</span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">s</span></span></span><span><span><span style="font-family:;" "=""><span style="font-family:Verdana;"> tyrosinase activity with 1.20 mM as IC</span><sub><span style="font-family:Verdana;">50</span></sub><span style="font-family:Verdana;">. The tyrosinase inhibition mechanism was noncompetitive mixed-type with un-significant effect on cell melanogenesis. Daniellic acids induced a half-reduction of melanin production in B16F10 cell in IBMX stimulation (p</span></span></span></span><span><span><span style="font-family:;" "=""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"><</span></span></span><span><span><span style="font-family:;" "=""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">0.05). The same observation was effective in Malme-3M melanin production with a significant daniellic acid action than kojic acid (p</span></span></span><span><span><span style="font-family:;" "=""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"><</span></span></span><span><span><span style="font-family:;" "=""> </span></span></span><span><span><span style="font-family:;" "=""><span style="font-family:Verdana;">0.05) without reducing cell viabilities. This bioactive daniellic acid could explain the traditional uses of oleoresins from </span><i><span style="font-family:Verdana;">Daniellia oliveri</span></i><span style="font-family:Verdana;"> for genitor-urinary tract diseases treatments, wound healing, and skin ailments in Burkina Faso.</span></span></span></span>展开更多
Forsythia fructus has been shown to have antioxidative, anti-inflammatory, antibacterial, anti-aging and whitening effects. Hoechunyangkyeok-san (Forsythia viridissima-prescription) is a traditional herbal medicine, w...Forsythia fructus has been shown to have antioxidative, anti-inflammatory, antibacterial, anti-aging and whitening effects. Hoechunyangkyeok-san (Forsythia viridissima-prescription) is a traditional herbal medicine, which has been clinically used for treating febrile and inflammatory disorders. This work was carried out to investigate the skin whitening effects of Forsythia viridissima-prescription extract (a hydrolyzed extract of Hoechunyangkyeok-san: SID White HYC) on skin. The effects of SID White HYC were assessed the melanin contents in B161 melanoma cells and the pigmented equivalent with HMB45 and Fontana Masson staining in 3D skin model. Then, we examined the expression of major pigment enzymes regulating melanin synthesis and melanosome transport related proteins in B16F1 cells. SID White HYC significantly inhibited the melanin synthesis (56.7% and 30.6% inhibition at 100 μg/mL, intracellular and secreted, respectively) in B16F1 cells and 3D skin model. In addition, western blotting analysis showed that SID White HYC reduced the expression of melanin synthesis and melanosome transport related proteins in B16F1 cells. In clinical trials, the cream containing 0.05% SID White HYC showed skin depigmentation effect without any irritation. These results suggest that SID White HYC may be useful inhibition of melanogenesis and melanosome transport. Therefore, SID White HYC may have potential as a skin-whitening ingredient in cosmetics.展开更多
In mammals,microRNAs(miRNAs)play key roles in multiple biological processes by regulating the expression of target genes.Studies have found that the levels of miR-370-5p expression differ significantly in the skins of...In mammals,microRNAs(miRNAs)play key roles in multiple biological processes by regulating the expression of target genes.Studies have found that the levels of miR-370-5p expression differ significantly in the skins of sheep with different hair colors;however,its function remains unclear.In this study,we investigated the roles of miR-370-5p in sheep melanocytes and found that the overexpression of miR-370-5p significantly inhibited cell proliferation(P<0.01),tyrosinase activity(P=0.001)and significantly reduced(P<0.001)melanin production.Functional prediction revealed that the 3′-untranslated region(UTR)of MAP3K8 has a putative miR-370-5p binding site,and the interaction between these two molecules was confirmed using luciferase reporter assays.In situ hybridization assays revealed that MAP3K8 is expressed in the cytoplasm of melanocytes.The results of quantitative RT-PCR and Western blotting analyses revealed that overexpression of miR-370-5p in melanocytes significantly inhibits(P<0.01)MAP3K8 expression via direct targeting of its 3′UTR.Inhibition of MAP3K8 expression by siRNA-MAP3K8 transfection induced a significant inhibition(P<0.01)of melanocyte proliferation and significant reduction(P<0.001)in melanin production,which is consistent with our observations for miR-370-5p.Target gene rescue experiments indicated that the expression of MAP3K8 in melanocytes co-transfected with miR-370-5p and MAP3K8-cDNA(containing sites for the targeted binding to miR-370-5p)was significantly rescued(P≤0.001),which subsequently promoted significant increases in cell proliferation(P<0.001)and melanin production(P<0.01).Collectively,these findings indicate that miR-370-5p plays a functional role in inhibiting sheep melanocyte proliferation and melanogenesis by downregulating the expression of MAP3K8.展开更多
基金supported by the Inner Mongolia Autonomous Region Science and Technology Revitalization Foundation (2021CG0029)the National Natural Science Foundation of China (22178070)
文摘Glabridin is the main ingredient of hydrophobic fraction in licorice extract and has been shown to have anti-melanogenesis activity in skins.However,the underlying mechanism(s)remain not completely understood.The aim of this study is thus to elucidate the possible mechanisms related to the melanogenesis suppression by glabridin in cultured B16 murine melanoma cells and in UVA radiation induced hyperpigmentation model of BALB/c mice as well.Molecular docking simulations revealed that between catalytic core residues and the compound.The treatment by glabridin significantly downregulated both transcriptional and/or protein expression of melanogenesis-related factors including melanocyte stimulating hormone receptor(MC1R),microphthalmia-associated transcription factor(MITF),tyrosinase(TYR),TYR-related protein-1(TRP-1)and TRP-2 in B16 cells.Both PKA/MITF and MAPK/MITF signaling pathways were found to be involved in the suppression of melanogenesis by glabridin in B16 cells.Also in vivo glabridin therapy significantly reduced hyperpigmentation,epidermal thickening,roughness and inflammation induced by frequent UVA exposure in mice skins,thus beneficial for skin healthcare.These data further look insights into the molecular mechanisms of melanogenesis suppression by glabridin,rationalizing the application of the natural compound for skin healthcare.
文摘Perilla frutescens seed (PFS) oil is reported to inhibit skin photoaging;however, its effect on melanogenesis has not yet been investigated. Herein, we tested the anti-melanogenesis activity of an oil-based extract from PFS with supercritical carbon dioxide (scCO<sub>2</sub>). In a cell culture system, B16 mouse melanoma cells were treated with the PFS scCO<sub>2</sub> extract and other samples. The PFS scCO<sub>2</sub> extract decreased melanin production by approximately 90% in B16 mouse melanoma cells without cytotoxicity at 100 μg/mL. This effect was greater than that of the well-known melanogenesis inhibitor, kojic acid. Although a hexane-extracted PFS oil and a squeezed PFS oil also decreased melanin production in the B16 cells, the inhibitory effect of the PFS scCO<sub>2</sub> extract was higher than both of these. Chemical analysis of the PFS scCO<sub>2</sub> extract and squeezed PFS oil showed that almost 90% of the components of both oils were α-linolenic acid, linoleic acid, and oleic acid. Furthermore, the ratio of those three fatty acids across both samples was almost the same. When the three fatty acids were mixed in the same ratio as in the PFS scCO<sub>2</sub> extract, the IC<sub>50</sub> of the mixture for melanin production in B16 melanoma cells was identical to that of the PFS scCO<sub>2</sub> extract. However, the IC<sub>50</sub> of the squeezed PFS oil was approximately 6.6 times higher than that of the mixture. Although those fatty acids are the main inhibitory ingredients against melanin production in all of the extracts, some factor(s) in the squeezed PFS reduce their affinity with the cells. These results indicated that the PFS scCO<sub>2</sub> extract could be a superior melanogenesis inhibitor. Although its main ingredients are probably the same as those of the squeezed PFS oil, it is necessary to extract with scCO<sub>2</sub> for stronger anti-melanogenesis activity.
基金This work was supported by the National Research Foundation of Korea(NRF)grant funded by the Korea government(MSIT)(No.2023R1A2C1006268 and RS-2023-00212560).
文摘Objective:To explore the anti-melanogenic potential of Cyrtomium falcatum.Methods:The effects of Cyrtomium falcatum crude extract and its solvent fractions on tyrosinase activity,melanin content,and the expressions of melanogenesis-related genes and proteins were analyzed inα-melanocyte-stimulating hormone(α-MSH)-stimulated B16F10 cells.Results:α-MSH treatment significantly increased tyrosinase activity,and extracellular and intracellular melanin content,as well as the expression levels of tyrosinase,microphthalmia-associated transcription factor(MITF),tyrosinase-related protein(TRP)-1,and TRP-2 in B16F10 cells.Treatment with Cyrtomium falcatum crude extract and its solvent fractions reduced tyrosinase activity and extracellular and intracellular melanin content and downregulated the expression levels of tyrosinase,MITF,TRP-1,and TRP-2 in a dose-dependent manner.Conclusions:Cyrtomium falcatum has potential anti-melanogenesis effects and can be used as a potential source material in cosmeceutical industry for the research and development of novel lead molecules with whitening properties.
文摘旨在筛选对黑色素生成起调节作用的小RNA,并探究其对山羊肤色及毛色的调控机制。本研究采集了健康酉州乌羊(Youzhou dark goat, YZDG)、川东白山羊(Chuandong white goat, CDWG)100日龄胎羊皮肤样本(n=3),和健康2~3周岁大足黑山羊(Dazu black goat, DBG)、内蒙古绒山羊(Inner Mongolia cashmere goat, IMCG)个体皮肤样本(n=3),利用组织切片染色技术观察皮肤中黑色素沉积情况;通过小RNA测序技术筛选差异miRNAs;培养B16-F10皮肤黑色素瘤细胞,利用细胞转染、qPCR、Western Blot、黑色素含量检测等技术验证miR-129-5p对黑色素生成的影响。结果显示,黑色素颗粒明显在YZDG胎羊皮肤和DBG毛囊的毛球、毛干、外根鞘等部位沉积,而在CDWG胎羊皮肤和IMCG表皮、毛囊中没有被观察到。经测序分析,在肤色差异的YZDG和CDWG中筛选到62个差异表达miRNAs,其中31个在乌皮山羊中上调,31个下调。在毛色差异的DBG和IMCG中,筛选到38个差异表达miRNAs,其中10个在黑色被毛山羊中表达上调,28个表达下调。两组测序结果均显示miR-129-5p在乌皮和黑色被毛山羊皮肤中高表达(P<0.05)。在细胞中过表达miR-129-5p后,相比于对照组,mimics组细胞黑色素沉积量提高了18.9%(P<0.05),TYR、TYRP1基因表达量分别上调57.3%和16.5%(P<0.05),蛋白表达量分别显著上调49.2%和40.2%(P<0.05);但MITF基因及其蛋白表达量无显著变化(P>0.05)。在抑制miR-129-5p后,inhibitor组TYR基因mRNA表达下调38.9%、蛋白表达水平下调21.1%(P<0.05);TYRP1、MITF蛋白表达水平分别下调25.3%及28.4%(P<0.05)。本研究发现,miR-129-5p在不同肤色及毛色的山羊皮肤中差异表达,且可通过调控TYR、TYRP1等关键基因的表达影响黑色素的生成,是山羊肤色和毛色形成过程的重要调节因子。
基金supported by the Open Project of National Major Science and Technology Infrastructure of Translational Medicine,China(Grant No.:TMSK-2021−404)the SIMM-SHUTCM Joint Innovation Research Program,China(2022)+1 种基金the Youth Innovation Research Foundation,China(Grant No.:A1-U21-205-01010109)the National Natural Science Foundation of China(Grant No.:81972932).
文摘Epimedin B(EB)is one of the main flavonoid ingredients present in Epimedium brevicornum Maxim.,a traditional herb widely used in China.Our previous study showed that EB was a stronger inducer of melanogenesis and an activator of tyrosinase(TYR).However,the role of EB in melanogenesis and the mechanism underlying the regulation remain unclear.Herein,as an extension to our previous investigation,we provide comprehensive evidence of EB-induced pigmentation in vivo and in vitro and elucidate the melanogenesis mechanism by assessing its effects on the TYR family of proteins(TYRs)in terms of expression,activity,and stability.The results showed that EB increased TYRs expression through microphthalmia-associated transcription factor-mediated p-Akt(referred to as protein kinase B(PKB))/glycogen synthase kinase 3β(GSK3β)/β-catenin,p-p70 S6 kinase cascades,and protein 38(p38)/mitogen-activated protein(MAP)kinase(MAPK)and extracellular regulated protein kinases(ERK)/MAPK pathways,after which EB increased the number of melanosomes and promoted their maturation for melanogenesis in melanoma cells and human primary melanocytes/skin tissues.Furthermore,EB exerted repigmentation by stimulating TYR activity in hydroquinone-and N-phenylthiourea-induced TYR inhibitive models,including melanoma cells,zebrafish,and mice.Finally,EB ameliorated monobenzone-induced depigmentation in vitro and in vivo through the enhancement of TYRs stability by inhibiting TYR misfolding,TYR-related protein 1 formation,and retention in the endoplasmic reticulum and then by downregulating the ubiquitination and proteolysis processes.These data conclude that EB can target TYRs and alter their expression,activity,and stability,thus stimulating their pigmentation function,which might provide a novel rational strategy for hypopigmentation treatment in the pharmaceutical and cosmetic industries.
基金supported by the National Natural Science Foundation of China(82003808)the Open Project of Jiangsu Provincial Science and Technology Resources(Clinical Resources)Coordination Service Platform(No.TC2022B015)the Shuangchuang Doctor Project of Jiangsu Province(No.JSSCBS20220147)。
文摘Vitiligo has a significant impact on a substantial number of individuals worldwide.Traditional Chinese medicine has a long history of serving as a therapeutic treatment for vitiligo.Nevertheless,given the increasing volume of research on the utilization of traditional Chinese medicine for vitiligo treatment,it is imperative to conduct a comprehensive review that elucidates the efficacy of Chinese traditional medicine and other active ingredients in the treatment of vitiligo.This paper presents a comprehensive overview of the clinical preparations used to treat vitiligo,while also highlighting the potential monomers and extracts derived from traditional Chinese medicine for vitiligo treatment.A thorough analysis of the pharmacological effects of traditional Chinese medicine on vitiligo treatment will provide valuable insights and reliable information for the development of new treatment strategies.
基金National Natural Science Foundation of China(No.82074069,No.32072309).
文摘Background:Platycladus orientalis,which has been employed in traditional Chinese medicine for cool blood,antibacterial,promotion of hair growth and therapy of poliosis for centuries.However,there have been few reports focusing on Platycladus orientalis shells treating pigmentary disorders.Methods:In present study,gas chromatography–mass spectrometry was applied to analyzing the volatile composition of Platycladus orientalis shells and cellular metabolism.Experiments in vivo were carried out to evaluate the effect of Platycladus orientalis shells treating pigmentation disorders in C57BL/6J mice.Results:Our results indicated that cedrol occupied the largest percentage in Platycladus orientalis shells(17.1%).Meanwhile,Platycladus orientalis shells up-regulated the content of palmitic acid and increased melanin content and tyrosinase activity.Its mechanism possibly involved in the inhibiting phosphorylation of AKT and β-catenin,increasing phosphorylation of p38 to promote microphthalmia-associated transcription factor expression.The animal experiment also proved that Platycladus orientalis shells promoted melanogensis and hair blacken in C57BL/6J mice.Conclusion:All in all,Platycladus orientalis shells potentially promoted melanogenesis in vitro and in vivo.Cedrol was regarded as the main active substance in Platycladus orientalis shells.Therefore,it could be used for treatment of pigmentary disorders under safe concentration in the prospective application.
文摘In this study, we explored the effects of unripe fruit extracts of Mangifera indica L. on the anti-aging activity in skin cells. Mangifera indica L. is a popular economical and medicinal plant with numerous health-beneficial properties. The aqueous extracts of unripe fruit of Mangifera indica L. were obtained and subjected to HPLC and NMR analyses for the identification of bioactive compounds. The anti-glycation effect of Mango unripe fruit extracts was monitored by in vitro model system of AGEs (Advanced glycation end products) formation. Mango unripe fruit extracts significantly inhibited the AGEs formation in a dose-dependent manner. Meanwhile, Mango unripe fruit extracts possessed a comparable efficiency to commercialized Kojic acids in the inhibition of melanogenesis in B16-F10 melanoma cells. The UVA-induced cell damages can be prevented and repaired by Mango unripe fruit extracts in skin fibroblast CCD-966SK. Compared to the untreated control, Mango unripe fruit extracts significantly increased the cell viability while being applied before (36%) or after (43%) UVA irradiation. These results verified the potential application of Mango unripe fruit extracts in the skin protection and recovery from UVA irradiation, as well as the suppression of AGEs formation and melanogenesis.
文摘In order to develop melanoma-targeted in situ peptide vaccine immunotherapy, magnetite nanoparticles were conjugated with a melanogenesis substrate, N-propionyl cysteaminylphenol (NPrCAP). Magnetite nanoparticles introduced thermotherapy which caused non-apoptotic cell death and generation of heat shock protein (HSP) upon exposure to alternating magnetic field (AMF). NPrCAP was expected to develop a melanoma-targeted therapeutic drug because of its selective incorporation into melanoma cells and production of highly reactive free radicals, that result in not only oxidative stress but also apoptotic cell death by reacting with tyrosinase.
文摘Over the past years, natural products have been used as useful candidates for prevention and treatment of skin disorders such as skin darkening. In this current research, <i><span style="font-family:Verdana;">Daniellia oliveri</span></i><span style="font-family:Verdana;"> which was a potential source of cosmeceutical agent was selected to investigate its active components. Daniellic acid isolated from the oleoresin was characterized by using data from </span><sup><span style="font-family:Verdana;">1</span></sup><span style="font-family:Verdana;">H-NMR, </span><sup><span style="font-family:Verdana;">13</span></sup><span style="font-family:Verdana;">C-NMR, HSQC, IR, and online chemo-informatic analysis. The daniellic acid antioxidant, anti-proliferative, and tyrosinase inhibition capabilities were evaluated. This compound possessed an anti-DPPH and iron (III) reducing effect compared to quercetin. It was able to inhibit 9 tumor cells with IC</span><sub><span style="font-family:Verdana;">50</span></sub><span style="font-family:Verdana;"> going from 0.03 mM (U373) to 0.14 mM (Malme-3M). Interestingly daniellic acid inhibit</span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">s</span></span></span><span><span><span style="font-family:;" "=""><span style="font-family:Verdana;"> tyrosinase activity with 1.20 mM as IC</span><sub><span style="font-family:Verdana;">50</span></sub><span style="font-family:Verdana;">. The tyrosinase inhibition mechanism was noncompetitive mixed-type with un-significant effect on cell melanogenesis. Daniellic acids induced a half-reduction of melanin production in B16F10 cell in IBMX stimulation (p</span></span></span></span><span><span><span style="font-family:;" "=""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"><</span></span></span><span><span><span style="font-family:;" "=""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">0.05). The same observation was effective in Malme-3M melanin production with a significant daniellic acid action than kojic acid (p</span></span></span><span><span><span style="font-family:;" "=""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"><</span></span></span><span><span><span style="font-family:;" "=""> </span></span></span><span><span><span style="font-family:;" "=""><span style="font-family:Verdana;">0.05) without reducing cell viabilities. This bioactive daniellic acid could explain the traditional uses of oleoresins from </span><i><span style="font-family:Verdana;">Daniellia oliveri</span></i><span style="font-family:Verdana;"> for genitor-urinary tract diseases treatments, wound healing, and skin ailments in Burkina Faso.</span></span></span></span>
文摘Forsythia fructus has been shown to have antioxidative, anti-inflammatory, antibacterial, anti-aging and whitening effects. Hoechunyangkyeok-san (Forsythia viridissima-prescription) is a traditional herbal medicine, which has been clinically used for treating febrile and inflammatory disorders. This work was carried out to investigate the skin whitening effects of Forsythia viridissima-prescription extract (a hydrolyzed extract of Hoechunyangkyeok-san: SID White HYC) on skin. The effects of SID White HYC were assessed the melanin contents in B161 melanoma cells and the pigmented equivalent with HMB45 and Fontana Masson staining in 3D skin model. Then, we examined the expression of major pigment enzymes regulating melanin synthesis and melanosome transport related proteins in B16F1 cells. SID White HYC significantly inhibited the melanin synthesis (56.7% and 30.6% inhibition at 100 μg/mL, intracellular and secreted, respectively) in B16F1 cells and 3D skin model. In addition, western blotting analysis showed that SID White HYC reduced the expression of melanin synthesis and melanosome transport related proteins in B16F1 cells. In clinical trials, the cream containing 0.05% SID White HYC showed skin depigmentation effect without any irritation. These results suggest that SID White HYC may be useful inhibition of melanogenesis and melanosome transport. Therefore, SID White HYC may have potential as a skin-whitening ingredient in cosmetics.
基金funded by the Natural Science Foundation of Anhui Province,China(2008085QC158)the University Natural Science Research Project of Anhui Province(KJ2019A0165)。
文摘In mammals,microRNAs(miRNAs)play key roles in multiple biological processes by regulating the expression of target genes.Studies have found that the levels of miR-370-5p expression differ significantly in the skins of sheep with different hair colors;however,its function remains unclear.In this study,we investigated the roles of miR-370-5p in sheep melanocytes and found that the overexpression of miR-370-5p significantly inhibited cell proliferation(P<0.01),tyrosinase activity(P=0.001)and significantly reduced(P<0.001)melanin production.Functional prediction revealed that the 3′-untranslated region(UTR)of MAP3K8 has a putative miR-370-5p binding site,and the interaction between these two molecules was confirmed using luciferase reporter assays.In situ hybridization assays revealed that MAP3K8 is expressed in the cytoplasm of melanocytes.The results of quantitative RT-PCR and Western blotting analyses revealed that overexpression of miR-370-5p in melanocytes significantly inhibits(P<0.01)MAP3K8 expression via direct targeting of its 3′UTR.Inhibition of MAP3K8 expression by siRNA-MAP3K8 transfection induced a significant inhibition(P<0.01)of melanocyte proliferation and significant reduction(P<0.001)in melanin production,which is consistent with our observations for miR-370-5p.Target gene rescue experiments indicated that the expression of MAP3K8 in melanocytes co-transfected with miR-370-5p and MAP3K8-cDNA(containing sites for the targeted binding to miR-370-5p)was significantly rescued(P≤0.001),which subsequently promoted significant increases in cell proliferation(P<0.001)and melanin production(P<0.01).Collectively,these findings indicate that miR-370-5p plays a functional role in inhibiting sheep melanocyte proliferation and melanogenesis by downregulating the expression of MAP3K8.