EXPERIMENTAL CELL RESEARCH
·
2023
·
IF 3.7
Jinpeng Lv,Ximei Zhang,Xiaohong An,Yan Cao,Duo Meng,Kun Zou,Rongyin Gao,Ruzhi Zhang
The voltage-dependent anion channel 1 (VDAC1) forms an oligomeric structure on the mitochondrial outer membrane , which plays critical roles in many physiological processes . Research studies have demonstrated that the knockout of VDAC1 increases pigment content and up-regulates the expression of melanogenic genes. Due to its involvement in various physiological processes, the depletion of VDAC1 has significant detrimental effects on cellular functions and the inhibition of VDAC1 oligomerization has recently emerged as a promising strategy for the treatment of several diseases. In this study, we found that VDAC1 oligomerization inhibitors, VBIT-12 and NSC-15364, promote melanogenesis , dendrite formation and melanosome transport in human epidermal melanocytes (HEMCs). Mechanistically, treatment of HEMCs with an oligomerization inhibitor increased the level of cytoplasmic calcium ions , which activated calcium-calmodulin dependent protein kinase (CaMK) and led to the phosphorylation of CREB and the nuclear translocation of CREB-regulated transcription coactivators (CRTCs). Subsequently, CRTCs, p-CREB and CREB-binding protein (CBP) in the nucleus cooperatively recruit the transcription machinery to initiate the transcription of MITF thus promoting pigmentation . Importantly, our study also demonstrates that VDAC1 oligomerization inhibitors increase pigmentation in zebrafish and in human skin explants , highlighting their potential as a therapeutic strategy for skin pigmentation disorders.
研究领域:
细胞生物学
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分子生物学
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皮肤生理学
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药理学
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产品关联
DOI
PubMed
高影响因子
EXPERIMENTAL AND MOLECULAR PATHOLOGY
·
2025
·
IF 3.7
Jinpeng Lv,Kun Zou,Chuanwei Yin,Wenhui Xu,Duo Meng,Huansha Zhang,Wenhao Yu,Peiwen Jiang,Changjun Yun,Hui Xue,Nan Hu,Rongyin Gao
Daidzin, a prominent isoflavone found in soybeans, Pueraria lobata , and various legumes, has been extensively investigated for its diverse pharmacological activities, which include anticancer, antioxidant, anti-inflammatory, antiepileptic, and alcohol detoxification properties. Previous studies have shown that the dichloromethane fraction of Pueraria lobata stem (DCM-PLS) exhibits significant anti-melanogenic activity, with daidzin identified as the principal active compound. However, the precise role of daidzin in pigmentation remains incompletely understood. This study aimed to investigate the effects of daidzin on pigmentation and to elucidate the underlying mechanisms. Our findings revealed that daidzin not only inhibited basal melanin production but also reduced melanin synthesis induced by α-MSH, ACTH, and UV exposure. The effects of daidzin were primarily mediated through the activation of the extracellular signal-regulated protein kinase (ERK) and protein kinase B (AKT) pathways. Upon activation, these pathways facilitated the ubiquitination and degradation of Melanocytes Inducing Transcription Factor (MITF), resulting in decreased expression of tyrosinase, TRP-1, and TRP-2, ultimately inhibiting melanogenesis. Importantly, our research further demonstrated that daidzin reduced pigmentation in both zebrafish and human skin explants, highlighting its potential application as a therapeutic approach for disorders related to skin pigmentation.
研究领域:
药理学
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皮肤科学
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生物化学
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分子生物学
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植物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2021
·
IF 5.811
Lv Jinpeng,Yang Ying,Jia Bingyi,Li Siqi,Zhang Ximei,Gao Rongyin
The therapeutic use of curcumin and chemically modified curcumin (CMC) for suppressing melanogenesis and tyrosinase activity have been recognized. J147 is a modified version of curcumin with superior bioavailability and stability. However, there is no report about the effects of J147 on pigmentation in vitro and in vivo. In our studies, we investigated the hypopigmentary effects of J147 treatment on melanocytes and explored the underlying mechanism. The present studies suggested that J147 suppressed both basal and α-MSH-induced melanogenesis, as well as decreased melanocyte dendricity extension and melanosome transport. J147 played these roles mainly by activating the extracellular signal-regulated protein kinase (ERK) pathway. Once activated, it resulted in MITF degradation and further down-regulated the expression of tyrosinase, TRP-1, TRP-2, Myosin Va, Rab27a and Cdc42, ultimately inhibited melanin synthesis and melanosome transport. Furthermore, the hypopigmentary effects of J147 were demonstrated in vivo in a zebrafish model and UVB-induced hyperpigmentation model in brown guinea pigs. Our findings also suggested that J147 exhibited no cytotoxicity in vitro and in vivo. Taken together, these data confirmed that J147 may prove quite useful as a safer natural skin-whitening agent.
研究领域:
药理学
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皮肤病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2024
·Vol. 25
·期 11
·5939
·
IF 4.9
Jian Ouyang,Na Hu,Honglun Wang
Petanin, an acylated anthocyanin from the Solanaceae family, shows potential in tyrosinase inhibitory activity and anti-melanogenic effects; however, its mechanism remains unclear. Therefore, to investigate the underlying mechanism of petanin’s anti-melanogenic effects, the enzyme activity, protein expression and mRNA transcription of melanogenic and related signaling pathways in zebrafish using network pharmacology, molecular docking and molecular dynamics simulation were combined for analysis. The results showed that petanin could inhibit tyrosinase activity and melanogenesis, change the distribution and arrangement of melanocytes and the structure of melanosomes, reduce the activities of catalase (CAT) and peroxidase (POD) and enhance the activity of glutathione reductase (GR). It also up-regulated JNK phosphorylation, inhibited ERK/RSK phosphorylation and down-regulated CREB/MITF-related protein expression and mRNA transcription. These results were consistent with the predictions provided through network pharmacology and molecular docking. Thus, petanin could inhibit the activity of tyrosinase and the expression of tyrosinase by inhibiting and negatively regulating the tyrosinase-related signaling pathway ERK/CREB/MITF through p-JNK. In conclusion, petanin is a good tyrosinase inhibitor and anti-melanin natural compound with significant market prospects in melanogenesis-related diseases and skin whitening cosmetics.
研究领域:
药理学
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生物化学
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分子生物学
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斑马鱼研究
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化妆品科学
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产品关联
DOI
PubMed
高影响因子
Food Science and Human Wellness
·
2022
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IF 8.022
Chunxing Pan,Xiaoying Liu,Yating Zheng,Zejun Zhang,Yongliang Li,Biao Che,Guangrong Liu,Lanyue Zhang,Changzhi Dong,Haji Akber Aisa,Zhiyun Du,Zhengqiang Yuan
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.
研究领域:
药理学
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分子生物学
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皮肤科
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细胞生物学
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产品关联
DOI
高影响因子
EXPERIMENTAL DERMATOLOGY
·
2019
·Vol. 29
·期 2
·149-157
·
IF 2.868
Jinpeng Lv,Ying Fu,Yan Cao,Songzhou Jiang,Ying Yang,Guoqiang Song,Changjun Yun,Rongyin Gao
Isoliquiritigenin (ISL), a flavonoid component from the hydrolysis products of licorice root. It has been reported that ISL inhibited melanogenesis by suppressing the tyrosinase activity in human melanocytes. Recently, ISL was found to induce melanin degradation in human epidermal keratinocytes. However, the role of ISL in pigmentation is not fully understood. In the current study, we aimed to investigate the effects of ISL on pigmentation, and further explored the underlying mechanism. Our results suggested that ISL suppressed basal and α-MSH-, ACTH- and UV-induced melanin synthesis, in addition to inhibiting melanocyte dendricity and melanosome transport. ISL played these roles mainly by activating the extracellular signal-regulated protein kinase pathway. Once activated, it induced microphthalmia-associated transcription factor degradation and decreased the expression of tyrosinase, TRP-1, DCT, Rab27a and Cdc42, finally inhibited melanogenesis, melanocyte dendricity and melanosome transport. Our findings suggested that ISL exhibited no cytotoxicity in our research, it may prove quite useful as a safer natural skin-whitening agent.
研究领域:
药理学
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细胞生物学
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皮肤病学
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DOI
PubMed
高影响因子
CHEMISTRY & BIODIVERSITY
·
2026
·Vol. 23
·期 2
·e01698
·
IF 2.9
Zhongyi Chen,Fengkun Xiao,Chunhao Yang,Zhaoxiang Yang,Liping Qu,Feifei Wang
The cosmetic application of arbutin (AR) has recently been challenged due to concerns regarding the skin toxicity associated with its metabolite, hydroquinone (HQ). While the derivatization of AR provides a strategy to promote stability, the multistep and complicated chemical synthesis restricts its industrial production. The present study reported a naturally derived AR derivative, 6′-O-caffeoylarbutin (CA), which is hypothesized to resist hydrolysis to HQ owing to the conjugation effect and steric hindrance, resulting in better stability. To verify this hypothesis, the degradation of CA and AR was investigated using high-performance liquid chromatography with diode-array detection. The skin-lightening substances, AR and caffeic acid, were found in the degradation products of CA under acidic conditions, which also contained lower quantities of HQ compared to that generated by AR. However, CA was not degraded under enzymatic conditions, exhibiting better stability, which might contribute to its prolonged efficacy and reduced toxicity. The long-lasting skin-lightening efficacy of CA was further verified in a zebrafish drug-withdrawal model. Notably, Mechanistic investigations revealed that CA disrupts melanosome maturation and trafficking by modulating the melanocyte-inducing transcription factor-regulated pathway, providing molecular insights into its skin-lightening efficacy. Graphical This study investigates 6′-O-caffeoylarbutin (CA), a natural arbutin (AR) derivative, demonstrating greater stability than AR by resisting hydrolysis into hydroquinone under acidic and enzymatic conditions. In the zebrafish drug-withdrawal model, CA exhibits prolonged skin-lightening efficacy compared to AR. Mechanistic investigations in vitro further reveal that CA's skin-lightening efficacy is achieved by disrupting melanosome maturation via the MITF-regulated pathway.
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产品关联
DOI
PubMed
高影响因子
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
·
2025
·
IF 3
Jianbin Xiong,Jian Song,Xing Jiang,Zhuanzhuan Huang,Yijie Zhang
Chronic pancreatitis (CP) is a progressive inflammatory disorder with no effective treatment, which underscores the urgent need for novel therapeutic strategies. In this study, single-cell sequencing data retrieved from the Gene Expression Omnibus (GEO) database revealed that Prkcq and IL-4 were highly induced in group 2 innate lymphoid cells (ILC2s), while Mitf and Tgm2 were highly expressed in tissue-resident macrophages (TRMs). A mouse model of CP was established using dibutyltin dichloride (DBTC), and pathological evaluations via H&E, Masson, and Sirius Red staining confirmed typical features of CP, including acinar atrophy, inflammatory cell infiltration, and increased fibrosis. Notably, the numbers of ILC2s and TRMs in pancreatic tissues were significantly elevated in DBTC-treated mice. Functional experiments showed that the Prkcq knockdown in ILC2s suppressed the expression of IL-4, IL-5 and IL-13, while in TRMs, the transcription factor Mitf upregulated Tgm2 expression. In CP mice, Prkcq knockdown reduced TRM abundance, ultimately alleviating pancreatic fibrosis. Collectively, this study identifies Prkcq as a key regulator of CP by modulating TRM populations.
研究领域:
免疫学
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细胞生物学
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分子生物学
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病理学
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胃肠病学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Nutrition
·
2022
·
IF 6.59
Hui Jiang,Fei Wu,Xi Jiang,Yun-Feng Pu,Li-Rong Shen,Cui-Yun Wu,Hong-Jin Bai
Pear is one of the most popular fruits in the world. With the fruit ripening, a series of physiological changes have taken place in fragrant pear, but up to now, the research on the metabolism and biological activity of phenolic compounds in different growth stages of fragrant pear is still lacking. In this study, four kinds of Xinjiang pears were selected as research objects, and the changes of phenolic content, antioxidant capacity, cell protection and whitening activity during fruit development were analyzed. The results showed that the phenolic content and antioxidant capacity of four pear varieties presented a decreasing trend throughout the developmental stages. The phenolic content and antioxidant activity of the four pears in the young fruit stage were the highest, and the active ingredients of the Nanguo pear were higher than the other three pear fruits. Pear extract could protect cells by eliminating excessive ROS in cells, especially in young fruit stage. The western blot results showed that the extract of fragrant pear in the young fruit stage could inhibit the expression of TYR, TYR1 and MITF in B16 cells, and it was speculated that the extract of fragrant pear in the young fruit stage might have good whitening activity. Therefore, the findings suggest that young pear display a good antioxidant potential and could have a good application prospect in food preservation and health product industry.
研究领域:
食品科学
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药理学
·
植物生理学
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生物化学
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产品关联
DOI
PubMed
高影响因子
PROCESS BIOCHEMISTRY
·
2021
·
IF 3.757
Yonghua Hu,Yuan Zhou,Xiaohua Hu,Qiaoling Chen,Yan Shi,Jiangxing Zhuang,Qin Wang
Cefotaxime sodium (CTX) was found to inhibit the activity of mushroom tyrosinase. The present study was conducted to investigate its inhibition of melanogenesis in B16F10 cells. CTX was found to inhibit melanin synthesis in B16F10 cells at a concentrations less than 200 μmol/L with no cytotoxicity. CTX reduced tyrosinase activity in a dose-dependent manner. CTX inhibited melanin formation from the results of the Masson-Fontana melanin staining and transmission electron microscope CTX influenced melanin production by influencing the expression of the proteins MITF, TRP-1, TRP-2 and TYR. Furthermore, CTX could down-regulate the intracellular cAMP/PKA/CREB contents, affecting the expression of MITF, and further down-regulate the expression of TRP-1, TRP-2 and TYR to inhibit melanin. Furthermore, CTX has been shown to inhibit body pigmentation in zebrafish. These results may provide a theoretical foundation for the new application of CTX in the field of medicine.
研究领域:
药理学
·
细胞生物学
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分子生物学
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DOI
高影响因子
PROTEIN JOURNAL
·
2021
·Vol. 40
·期 5
·709-720
·
IF 2.371
Jiang Xuan,Zhang Xin,Fu Chao,Zhao Ruili,Jin Tianming,Liu Mengyue,Pan Chenhao,Li Liu An,Ma Jifei,Yu Enyuan,YU Xiaoxue,Hu Ye
Malignant melanoma, an increasingly common form of skin cancer, poses a significant threat to public health, especially when the disease progresses past skin lesions to the stage of advanced metastasis. In this work, a new anti-tumor peptide, temporin La (T-La), was selected from a cDNA library generated from bullfrog skin. Two new derivative antitumor peptides, T-La (S) and T-La (FS), were designed by bioinformatics analysis and coupled with the RGD small molecule peptide to create chimeric RGD peptides, (RGD-T-La [S] and RGD-T-La [FS]). Preliminary experiments showed that the new antitumor peptides had significant antitumor effects. After coupling to the chimeric RGD peptide, the targeted treatment of mouse melanoma was significantly improved. Our data demonstrate that the 4 peptides tested herein significantly inhibited the proliferation, migration, and invasion of B16F10 cells; with an increase in polypeptide concentration, the proportion of melanoma cells in the G0/G1 phase decreased or increased significantly, respectively, the reactive oxygen species (ROS) content increased significantly, the mitochondrial membrane potential decreased significantly, and the expression of pro-apoptotic Bax, Caspase-3, and Caspase-9 increased, and anti-apoptotic Bcl-2 decreased significantly. Tyr and MITF genes were significantly downregulated. In conclusion, the use of these new anti-tumor peptides, when combined with a chimeric RGD peptide, may increase ROS levels and decrease mitochondrial membrane potential by inhibiting the activity of mitochondria, thus releasing apoptosis-promoting factors in B16F10 cells. The present study describes a new potential strategy for the application of promising peptides in the treatment of various cancers.
研究领域:
肿瘤学
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药理学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
LWT-FOOD SCIENCE AND TECHNOLOGY
·
2022
·
IF 6.056
Zi-Yi Yu,Ke Xu,Xuan Wang,Yi-Ting Wen,Lin-Jun Wang,De-Qiang Huang,Xiao-Xin Chen,Wei-Ming Chai
The inhibition of punicalagin on tyrosinase and melanogenesis was investigated through multiple spectroscopic approaches, molecular docking, molecular dynamic simulation, cell assay, and preservation assays. The results confirmed that punicalagin significantly inhibited tyrosinase activity in vitro (IC 50 = 0.64 ± 0.05 mM) and B16F10 cells (IC 50 = 16 ± 0.7 μM). The binding of punicalagin to tyrosinase changed the conformation of the enzyme by influencing the hydrophobicity and polar environment of the binding site. The results of molecular docking and thermodynamic analysis showed that hydrophobic interaction and hydrogen bond were major driving forces in stabilizing the punicalagin-tyrosinase complex, influencing substrate-binding affinity to tyrosinase and resulting in tyrosinase activity reduction. Molecular dynamic analysis indicated that punicalagin stretched the basic framework structure of tyrosinase and lowered the surface hydrophobicity of the enzyme. Cell analyses further demonstrated that punicalagin inhibited melanogenesis by down-regulating the expressions of MITF and tyrosinase. What's more, preservation assays showed that punicalagin could reducing the oxidation of phenols to melanin by inhibiting the polyphenol oxidase, thereby preventing the browning of fresh-cut apples. These findings provided new perspectives on the inhibition mechanism of punicalagin on tyrosinase/melanogenesis and a theoretical support for its feasible application in the food and medicine industry.
研究领域:
生物化学
·
药理学
·
细胞生物学
·
食品科学
·
医学
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产品关联
DOI
高影响因子
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