Frontiers in Oncology
·
2025
·
IF 3.3
Qi Ouyang,Shengye Tian,Hengyu Zhou,Ying Mao,Xiang Li,Feng Yan,Ailong Liu,Xiang Hu,Changqiao You,Jun He
Background Melanomas are caused by the malignant transformation of melanocytes. Numerous studies have demonstrated that the tyrosol components of salidroside inhibit tyrosinase activity. The PI3K/Akt/mTOR signaling pathway plays a crucial role in biological pigment synthesis. However, how salidroside achieves its anti-melanoma effect in melanoma by regulating PI3K/Akt/mTOR remains poorly understood. This study aimed to explore the effect of salidroside on PI3K/Akt/mTOR in melanoma, which plays a role in regulating melanogenesis. Methods Network pharmacology was predicted that salidroside may exert an anti-melanoma effect through modulating melanin synthesis functions and signaling pathways. Zebrafish whole-embryo in situ hybridization, RT-qPCR, melanin synthesis and tumorigenesis assays, and were performed to investigate the therapeutic efficacy of salidroside in melanin synthesis. The mechanism of salidroside in anti-melanoma activity was examined by RT-qPCR, Western blot, immunofluorescence, in vivo imaging, immunohistochemistry. Results We confirmed salidroside may exert an anti-melanoma effect through modulating melanin synthesis-related gene expression and PI3K/Akt pathway by Network pharmacology. Furthermore, salidroside slowed melanin synthesis in zebrafish embryos and H 2 O 2 -induced B16F10 cells by inhibited oxidative stress. Moreover, we determined the effect of salidroside on anti-melanin synthesis via PI3K/Akt/mTOR pathway in vitro , and western blot results showed that salidroside increased the expression of Nrf2 in the nucleus, as well as inhibited the phosphorylation of mTOR and PI3K/Akt pathway. Finally, intratumoral administration showed salidroside suppressed melanoma growth. Conclusion Salidroside inhibits melanin synthesis and melanoma development most likely by its antioxidant properties and downregulating the PI3K/Akt/mTOR pathway. Our results may provide a novel therapeutic strategy for the treatment of melanoma.
研究领域:
肿瘤学
·
药理学
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生物化学
·
细胞生物学
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分子生物学
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皮肤病学
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生物医学研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanomaterials
·
2017
·Vol. 7
·期 3
·70
·
IF 3.553
Haixin Dong,Zhiming Liu,Huiqing Zhong,Hui Yang,Yan Zhou,Yuqing Hou,Jia Long,Jin Lin,Zhouyi Guo
Melanin plays an indispensable role in the human body. It serves as a biological reducer for the green synthesis of precious metal nanoparticles. Melanin–Ag nanocomposites were successfully produced which exhibited very strong surface-enhanced Raman scattering (SERS) effect because of the reducibility property of melanin. A melanin–Ag composite structure was synthesized in situ in melanin cells, and SERS technique was performed for the rapid imaging and quantitative assay of intracellular melanin. This imaging technique was also used to successfully trace the formation and secretion of intracellular melanin after stimulation with melanin-stimulating hormones. Based on the self-reducing property of melanin, the proposed SERS imaging method can provide potentially powerful analytical detection tools to study the biological functions of melanin and to prevent and cure melanin-related diseases.Keywords:surface-enhanced Raman scattering;melanin–Ag nanocomposites;bioimaging;melanogenesis
研究领域:
生物化学
·
纳米医学
·
分析化学
✓ 已验证
DOI
PubMed
高影响因子
BRAZILIAN ARCHIVES OF BIOLOGY AND TECHNOLOGY
·
2022
·
IF 1.18
Sun Tingwei,Guo Qingquan,Wu Shaojuan,Su Kui,Lun Jingwen,Zhang Yihan,Tan Wen,Zhao Haishan
HIGHLIGHTS It is the first time to compare mushroom tyrosinase model, B16 mouse melanoma cell model and zebrafish model. A high-throughput method for the quantification of melanin in zebrafish skin based on the Phyton for the first time.
研究领域:
药理学
·
细胞生物学
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动物学
·
化学生物学
✓ 已验证
产品关联
DOI
高影响因子
Toxins
·
2022
·Vol. 14
·期 7
·421
·
IF 5.075
Vivian Andoh,Liang Chen,Feifei Zhu,Qi Ge,Lin Ma,Qiang Wang,Keping Chen
Melanin has been reported to have potential applications in industries such as cosmetics and food due to its anti-UV and antioxidative qualities. However, the corresponding data on its safety evaluation or biological consequences are fairly limited; such data are critical given its widespread use. The effect of different concentrations (1, 2, 3, and 4%) of melanin on growth status (larvae length and weight, cocoon weight, and morphology), the microstructure of the various tissues (fat body, silk gland, and midgut), and silk properties was studied by using the silkworm (bombyx mori) as the model organism. The weight and length of silkworm larvae fed with melanin were lower than the control, indicating that melanin appears to have a negative effect on the growth status of silkworms; however, the histophysiology analysis indicates that the cell morphologies are not changed, the XRD and FTIR spectra indicate that the secondary and crystalline structures of silks are also well preserved, and the thermogravimetric analysis and tensile test indicate that the thermal stability and mechanical properties are well maintained and even improved to some extent. Generally, it indicates that melanin has a certain inhibitory effect on the growth of silkworm larva but causes no harm to the cell microstructures or silk properties; this demonstrates that the safety of melanin as a food addictive should be considered seriously. The increase of thermal stability and mechanical properties shows that melanin may be a good chemical modifier in textile industries.Keywords:melanin;biological effects;silkworm;silk propertiesKey Contribution:Melanin caused silkworms to lose weight. While silkworms provide an excellent platform for studying melanin toxicity, melanin substantially improved the mechanical characteristics of silkworm silk.
研究领域:
昆虫学
·
材料科学
✓ 已验证
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
·
分子生物学
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植物学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2021
·
IF 5.279
Haixia Xu,Xiaofeng Li,Xuan Xin,Lan Mo,Yucong Zou,Guanglei Zhao,Yigang Yu,Kebing Chen
Tyrosinase is a key enzyme responsible for enzymatic browning of fruits and vegetables and skin disorders due to overproduction of melanin. Arbutin is an inhibitor of tyrosinase; however, its high polarity and weak transdermal absorption capacity limit its applications. In this paper, a green solvent system was developed to successfully synthesize arbutin esters with improved liposolubilities (Clog P values = 0.27–5.03). Among the obtained esters, arbutin undecenoate (AU) showed the strongest tyrosinase-inhibiting activity (15.6%), which was 9.0 times higher than that of arbutin. An enzyme kinetics study indicated that AU was a competitive inhibitor with reversible inhibition. The esters inhibited tyrosinase by making the secondary structure of tyrosinase looser and less stable; moreover, the interactions between tyrosinase and AU driven by metal interactions and hydrogen bonds also offered a mechanism for inhibition of AU on tyrosinase. In addition, AU (100 μM) reduced the melanin content of B16 mouse melanoma cells to 61.3% of the control group.
研究领域:
生物化学
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药理学
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皮肤科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2021
·
IF 3.981
Zhuxian Wang,Yaqi Xue,Quanfu Zeng,Zhaoming Zhu,Yuan Wang,Yufan Wu,Chunyan Shen,Hongxia Zhu,Cuiping Jiang,Li Liu,Qiang Liu
Licochalcone A (LicA) is a natural chalcones , well-known for its anti-melanogenic activity, however, its poor solubility leads to a limited topical bioavailability and clinical outcomes. Therefore, LicA-encapsulated glycyrrhiza acid (GA) (GA-LicA) micelles were formulated for higher cellular uptake and improved cutaneous applications. The physicochemical properties (morphology, size and charge), topical penetration, endocytic pathways, cellular uptake amount (CUA) and intracellular distribution of the GA-LicA micelles were studied. Moreover, the anti-melanogenic mechanisms including antioxidant properties, melanogenesis-mediated enzymes and melanin generation as well as cell apoptosis in A375 cells were demonstrated. We found that significant increase amount of LicA was obtained into the epidermis after encapsulated in GA micelles, and the hair follicles were the preferential route for LicA permeation. Moreover, HaCaT and melanocytes possessed a significantly higher effective uptake and CUA for GA-LicA micelles than that of the crude LicA. Caveolae-mediated and actin filaments-mediated endocytosis, caveolae-mediated endocytosis were respectively involved in cellular uptake of GA-LicA micelles for HaCaT cells and melanocytes. Furthermore, GA-LicA micelles possessed a synergistic anti-melanogenic effect by scavenging the free radicals, reducing the activity of α-glucosidase and tyrosinase , and inducing the cell apoptosis. Taken together, GA micelles can enhance the bioavailability and anti-melanogenic effect of LicA, and the article provided principles for rational design of formulations in whitening cosmetics.
研究领域:
药学
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化妆品科学
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药理学
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细胞生物学
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皮肤科
✓ 已验证
产品关联
DOI
高影响因子
GENE
·
2015
·
IF 2.138
Ping Chen,Jiying Wang,Haiyin Li,Yan Li,Peng Chen,Tian Li,Xi Chen,Junjie Xiao,Liang Zhang
In insects, pigment patterns are formed by melanin, ommochromes, and pteridines. Here, the effects of pteridine synthesis on melanin formation were studied using 4th instar larvae of a wild-type silkworm strain, dazao ( Bombyx mori ), with normal color and markings. Results from injected larvae and in vitro integument culture indicated that decreased activity of guanosine triphosphate cyclohydrolase I (GTP-CH I, a rate-limiting enzyme for pteridine synthesis), lowers BH4 (6R- l -erythro-5,6,7,8-tetrahydrobiopterin, a production correlated with GTP-CH I activity) levels and eliminates markings and coloration. The conversion of phenylalanine and tyrosine to melanin was prevented when GTP-CH I was inhibited. When BH4 was added, phenylalanine was converted to tyrosine , and the tyrosine concentration increased. Tyrosine was then converted to melanin to create normal markings and coloration. Decreasing GTP-CH I activity did not affect L-DOPA (3,4- l -dihydroxyphenylalanine). GTP-CH I affected melanin synthesis by generating the BH4 used in two key reaction steps: (1) conversion of phenylalanine to tyrosine by PAH (phenylalanine hydroxylase) and (2) conversion of tyrosine to L-DOPA by TH (tyrosine hydroxylase). Expression profiles of BmGTPCH Ia , BmGTPCH Ib , BmTH , and BmPAH in the integument were consistent with the current findings.
研究领域:
昆虫学
·
生物化学
✓ 已验证
DOI
高影响因子
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY
·
2025
·
IF 4.3
Chanlin Fang,Shanshan Di,Yuekai Zhang,Xinquan Wang,Yuanxiang Jin
N-(1,3-Dimethylbutyl)- N ′-phenyl- p -phenylenediamine (6PPD), a critical antioxidant in rubber manufacturing, has raised global concerns due to its environmental persistence and toxic transformation products. While its developmental toxicity is increasingly recognized, the mechanisms underlying melanogenesis disruption in fish remain poorly understood. In this study, we systematically investigated 6PPD's effects on melanin synthesis in zebrafish embryos and murine melanoma cells (B16F10). Larval zebrafish were exposed to 10 and 100 μg/L 6PPD exhibited dose-dependent reductions in melanin deposition, suppressed tyrosinase activity and downregulation of melanogenesis-related genes ( tyr , mitfa , trp1 , trp2 , and dct ). Notably, the inhibition of tyrosinase activity was closely linked to behavioral impairments, as larvae exposed to 100 μg/L 6PPD showed significantly decreased swimming distance and velocity under light-dark cycles. Molecular docking revealed strong binding affinities between 6PPD and the key melanogenic proteins (Dct, Tyr, Tyrp1a, and Tyrp1b), suggesting direct interference with enzymatic function. Parallel experiments in B16F10 cells confirmed cross-species melanin suppression, with reduced gene expression and melanin synthesis-related protein (Mitfa and Tyr) at subtoxic concentrations (0.5 and 2.5 mg/L), which was also verified by Masson-Fontana staining. These findings demonstrated that 6PPD disrupted conserved melanogenic pathways by targeting enzymatic activity, posing ecological risks to aquatic and terrestrial organisms.
研究领域:
毒理学
·
发育生物学
·
环境科学
·
生物化学
·
药理学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
ACS Applied Bio Materials
·
2019
·
IF 0
Yu Li,Jianrong Wu,Gareth R. Williams,Shiwei Niu,Jianfeng Zhou,Yanbo Yang,Xuejing Zhang,Zi Fu,Dejian Li,Li-Min Zhu
Two-dimensional (2D) nanomaterials able to effectively absorb near-infrared (NIR) radiation have shown considerable potential as multifunctional platforms in the treatment of cancer. Here, we report a molybdenum dioxide (MoOx)-based system for synergistic chemo- and photothermal therapy of cancer. MoOx nanosheets were generated via a one-step hydrothermal route, grafted with poly(ethylene glycol) (PEG), and decorated with melanin (Mel), with successful functionalization confirmed by IR spectroscopy. The mean diameter and thickness of the MoOx particles were found to be 302 ± 34 nm and 19 ± 2 nm using atomic force microscopy. The hydrodynamic size of the MoOx nanosheets was 105 ± 17 nm, and the resulting final MoOx-PEG-Mel-DOX nanocomposite formulation had a uniform diameter of 161 ± 26 nm. The MoOx-PEG-Mel nanosheets efficiently convert NIR light to heat, possessing a photothermal conversion efficiency of 61.7%. They can also be loaded with doxorubicin hydrochloride (DOX), giving a high drug loading (325.6 mg DOX/g MoOx-PEG-Mel). DOX release from the formulation is influenced by both pH and NIR irradiation. Systematic in vitro and in vivo evaluations reveal that synergistic chemo- and photothermal therapy using MoOx-PEG-Mel-DOX can completely eradicate a tumor with no observable off-target cytotoxicity. This is the first report of the fabrication of enhanced photothermal agents by combining MoOx nanosheets and a natural product. This work proffers a strategy for efficiently treating cancer as well as potentially extending the photothermal applications of 2D nanomaterials by surface melanin functionalization.
研究领域:
生物医学工程
·
纳米医学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
Frontiers in Pharmacology
·
2023
·
IF 5.6
Gao Rongyin,Zhang Ximei,Zou Kun,Meng Duo,Lv Jinpeng
Cutaneous pigmentation was recently shown to be an event regulated by clock proteins. Cryptochrome (CRY) is a key protein composing the feedback loop of circadian clock, however, the function of CRY in melanocytes remains unclear. Here, we found that KL001, a synthetic small molecule modulator of CRY1, inhibited melanin synthesis, as well as reduced melanocyte dendrite elongation and melanosome transport. In addition, the dominant role of CRY1 in KL001-induced anti-melanogenesis was revealed by small interfering RNA transfection. Cellular tyrosinase activity and expression level of melanogenic proteins, including tyrosinase, TRP-1, TRP-2, and transport proteins like Rab27a, Cdc42 and Myosin Va induced by α-MSH were remarkably reversed after KL001 treatment. Mechanistically, CRY1 activation inhibited melanogenesis through CREB-dependent downregulation of MITF and CREB phosphorylation was mediated by classical cAMP/PKA pathway. In addition, the other CRY1 activator, KL044 also suppressed cAMP/PKA/CREB pathway and inhibited melanogenesis. Finally, anti-melanogenic efficacy of KL001 was confirmed by determination of melanin contents in UVB-tanning model of brown guinea pigs, which indicated that targeting CRY1 activity, via topical application of small molecule activator, can be utilized therapeutically to manage human pigmentary disorders.
研究领域:
细胞生物学
·
分子生物学
·
药理学
·
皮肤科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
·
2023
·Vol. 52
·期 6
·1-11
·
IF 5.4
Su-Ji Jeon,Eun-Young Choi,Eun-Ji Han,Sang-Woo Lee,Jun-Mo Moon,Soo-Hyun Jung,Ji-Youn Jung
Piperlongumine (PL) is an amide alkaloid with diverse pharmacological effects against cancer, bronchitis and asthma; however, research on its efficacy against melanoma is lacking. The present study investigated the anticancer effects of PL on A375SM and A375P human melanoma cells. PL decreased the survival rate of A375SM and A375P cells, as shown by MTT assay, increase of apoptotic cells by DAPI staining. And PL induced apoptosis by decreasing the expression of the anti‑apoptotic protein Bcl‑2 and increasing that of the pro‑apoptotic proteins cleaved‑PARP and Bax. PL also induced apoptosis in A375SM and A375P cells via the MAPK pathway, increasing expression of the MAPK pathway proteins, phosphorylated‑(p‑ERK), p‑JNK p‑p38. These proteins were confirmed by western blot. In addition, A375SM and A375P cells treated with PL showed an increased number of acidic vesicular organelles by acridine orange staining. Also, autophagy induced by the expression of 1A/1B‑light chain 3, Beclin 1and mTOR was investigated through western blot. When PL was applied following treatment with autophagy inhibitors 3‑methyladenine and hydroxychloroquine, autophagy exhibited a cytoprotective effect against apoptosis in MTT assay. Pretreatment of A375P cells with the ERK inhibitor PD98059 and the JNK inhibitor SP600125 followed by treatment with PL confirmed that apoptosis and autophagy were mediated via the MAPK/ERK pathway by western blot. In summary, the present study provided empirical evidence supporting the anticancer effects of PL on human melanoma cells and indicated the potential of PL as a treatment for melanoma.
研究领域:
肿瘤学
·
细胞生物学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）