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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2024 · IF 7.7

Mitochondria−endoplasmic reticulum crosstalk in apoptosis: The interactions of cytochrome c with monooxygenase and its reductase

Han Xie,Jinping Tang,Li Song,Guangyang Xu,Wei Li,Jinyu Zhu,Yawen Liu,Hao Ma,Linjun Cai,Xiao Xia Han

The crosstalk between endoplasmic reticulum and mitochondria is of significance in apoptosis, in which cytochrome b 5 (Cyt b 5 ) is thought to be a major target for cytochrome c (Cyt c ) upon its release from the mitochondria. In the absence of Cyt b 5 , the role of interactions of Cyt c with CYP-dependent monooxygenase system in apoptotic regulation was explored in this study. NADPH-dependent and Cyt c -induced formation of reactive oxygen species (ROS) and NADPH-independent Cyt c unfolding were revealed. With the aid of a CPR inhibitor and CYP antibodies, the interactions among Cyt c , cytochrome P450 reductase (CPR) and cytochrome P450 (CYP) are evidenced, which are found crucial for monooxygenase-derived ROS formation. The underlying structural basis of Cyt c −CYP complex was unveiled by molecular dynamics simulations. This study provides novel insights into how Cyt c regulates ROS formation through the interactions with CPR and CYP, and is implicated for a deeper understanding of the regulation mechanism in the mitochondria–endoplasmic reticulum apoptotic pathway.

研究领域: 生物化学 · 细胞生物学 · 医学
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Frontiers in Pharmacology · 2023 · IF 5.6

Cryptochrome 1 activation inhibits melanogenesis and melanosome transport through negative regulation of cAMP/PKA/CREB signaling pathway

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
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MOLECULAR ECOLOGY · 2024 · IF 4.5

Expression patterns of melanin-related genes are linked to crypsis and conspicuousness in a pumpkin toadlet

Juliane P. C. Monteiro,Heike Pröhl,Mariana L. Lyra,Andrés E. Brunetti,Eli C. de Nardin,Thais H. Condez,Célio F. B. Haddad,Ariel Rodríguez

Colour signals play pivotal roles in different communication systems, and the evolution of these characters has been associated with behavioural ecology, integumentary production processes and perceptual mechanisms of the species involved. Here, we present the first insight into the molecular and histological basis of skin colour polymorphism within a miniaturized species of pumpkin toadlet, potentially representing the lowest size threshold for colour polytypism in tetrapods. Brachycephalus actaeus exhibits a coloration ranging from cryptic green to conspicuous orange skin, and our findings suggest that colour morphs differ in their capability to be detected by potential predators. We also found that the distribution and abundance of chromatophores are variable in the different colour morphs. The expression pattern of coloration related genes was predominantly associated with melanin synthesis (including dct , edn1 , mlana , oca2 , pmel , slc24a5 , tyrp1 and wnt9a ). Up-regulation of melanin genes in grey, green and brown skin was associated with higher melanophore abundance than in orange skin, where xanthophores predominate. Our findings provide a significant foundation for comparing and understanding the diverse pathways that contribute to the evolution of pigment production in the skin of amphibians.

研究领域: 进化生物学 · 分子生物学 · 动物行为学 · 两栖动物学
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FOOD CHEMISTRY · 2018 · IF 4.946

Effect of ultrasound on the production of xanthylium cation pigments in a model wine

Xi-Zhe Fu,Qing-An Zhang,Bao-Shan Zhang,Pei Liu

As a potential novel technique in the wine-making industry, ultrasound has received considerable attention. In this paper, a model wine system was constructed to investigate the effect of ultrasonic irradiation on the formation of xanthylium cation pigment derived from the (+)-catechin and the glyoxylic acid, an oxidation product of tartaric acid, so as to explore the changing mechanism of the wine color mediated by ultrasound. The results indicate that the long-term ultrasonic treatment can enhance the formation of the xanthylium cation pigment in the model wine, which is attributed to free radicals triggered by ultrasound, meanwhile, iron ions and oxygen can influence the ultrasonic effect. All these results suggest that ultrasound is promising to be employed in regulating the formation of the yellow pigment during wine aging thus modifying the wine organoleptic characteristic.

CAS / MDL: 69-65-8 7778-80-5
研究领域: 食品科学 · 生物化学
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY · 2023 · IF 6.1

Antimelanogenic Effect of Isoquinoline Alkaloids from Plumula Nelumbinis

Yi-Chi Chen,Yang-Yang Liu,Liqiang Chen,Dong-Mei Tang,YunLi Zhao,Xiao-Dong Luo

Plumula Nelumbinis, the green embryo of a lotus seed, is widely consumed in China as a well-known food with medicinal effects. In this study, 14 alkaloids, including 4 new and 10 known alkaloids, were isolated from it, which were elucidated by comprehensive spectroscopic analysis, and were investigated for their antimelanogenic effects in vitro and in vivo. As a result, melanogenesis in α-MSH-stimulated B16F10 cells was reduced significantly by a new compound 4 and known compound 12 at a concentration of 0.5 μg/mL, and the tyrosinase (TYR) activities were inhibited by 78.7 and 82.0% at 4 μg/mL, prior to α-arbutin (41.3%). Additionally, compounds 4 and 12 also exhibited superior antimelanogenic effects compared to α-arbutin on a zebrafish assay model at equivalent concentrations. Mechanistically, our preliminary findings suggested that compounds 4 and 12 exerted antimelanogenesis effect probably by inhibiting key proteins involved in melanin production such as microphthalmia-associated transcription factor, TYR, TRP-1, and TRP-2. The findings highlight the potential use of Plumula Nelumbinis containing compounds 4 and 12 as functional foods for treating hyperpigmentation.

CAS / MDL: 84380-01-8 298-93-1
研究领域: 药理学 · 生物化学 · 药物化学
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Frontiers in Oncology · 2025 · IF 3.3

Salidroside inhibits melanin synthesis and melanoma growth via mTOR and PI3K/Akt pathways

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.

CAS / MDL: 10338-51-9
研究领域: 肿瘤学 · 药理学 · 生物化学 · 细胞生物学 · 分子生物学 · 皮肤病学 · 生物医学研究
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ACS Omega · 2025 · IF 4.3

4-Hydroxyacetophenone is an Antipigmentation Reagent via Inhibiting Tryrosinase Activity

Qingquan Guo,Yudong Zhang,Chuanjin Tang,Qiuru Li,Fei Liu,Zhenming He,Chenyang Jiang,Jun Xu,Haishan Zhao

This study investigates the skin-whitening potential of 4-Hydroxyacetophenone (4-HAP), a compound commonly used as a preservative in cosmetics. Despite its widespread use, its whitening activity has not been extensively reported. Our preliminary research identified several commercial cosmetic formulations exhibiting whitening effects without known whitening agents. We hypothesized that 4-HAP might be a key ingredient. To test this, we employed a mushroom tyrosinase model, B16 mouse melanoma cells, and zebrafish to systematically evaluate the whitening activity of 4-HAP. Our findings demonstrate that 4-HAP is a potent tyrosinase inhibitor, significantly reducing melanin content in vitro and in vivo. Additionally, molecular docking and dynamics analyses revealed that the stable binding of 4-HAP to tyrosinase is crucial for its whitening effect. In formulations containing 2% 4-HAP, human skin models showed nearly complete recovery from UV-induced pigmentation after 4 weeks, while control groups exhibited persistent UV marks. These results confirm the efficacy of 4-HAP as a stable whitening agent in cosmetic formulations, highlighting its potential for further development in skin lightening products. This study has confirmed that 4-HAP holding the potential to become an effective whitening ingredient in the cosmetics field.

CAS / MDL: 59-92-7 97-59-6
研究领域: 化妆品科学 · 生物化学 · 药理学 · 分子生物学 · 皮肤科学
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AQUATIC TOXICOLOGY · 2020 · IF 4.346

Evaluation of hypopigmentation in embryonic zebrafish induced by emerging disinfection byproduct, 3, 5-di-I-tyrosylalanine

Lei Peng,Chang Wang,Pingdeng Li,Bo Cheng,Yeli Hu,Yang Cheng,Qi Zheng

Halogenated dipeptides, 3, 5-di-I-tyrosylalanine (DIYA), have been identified as novel disinfection byproducts (DBPs), following chloramination of authentic water. However, little is known about their toxicity. Zebrafish embryos were used to assess the toxicity of novel iodinated DBPs (I-DBPs). Although DIYA did not exhibit high acute toxicity to embryonic zebrafish (LC 50 > 2 mM), it significantly inhibited pigmentation of melanophores and xanthophores on head, trunk and tail at 500 μM as determined by photographic analysis. Whereas N-phenylthiourea (PTU) as a pigment inhibitor did not inhibit development of yellow pigments. Colorimetric detection of melanin further confirmed these results. Quantitative real time polymerase chain reaction (qRT-PCR) measurements indicated that genes ( dct , slc24a5 , tyr , tyrp1a , tyrp1b , silva ) associated with the melanogenesis pathway were dramatically down-regulated following exposure to 500 μM DIYA. In addition, enzymatic activity of tyrosinase (TYR) decreased, also demonstrating that the underlying mechanism of hypopigmentation was attributed to the disruption of melanogenesis pathway. Transcription levels of xanthophore genes ( gch2 , bnc2 , csf1a , csf1b , pax7a and pax7b ) were also monitored by qRT-PCR assay. DIYA exposure up-regulated expression of gch2 and bnc2 , but not csf1 and pax7 . Tested DIYA analogues, brominated tyrosine was unlikely to inhibit pigmentation, indicating that the iodine substitution and dipeptides structure are of important structural feature for the inhibition of pigmentation. In this study, we observed that DIYA inhibited melanogenesis related genes, which might contribute to pigmentation defects. Moreover, as an emerging I-DBPs, the developmental toxicity of aromatic dipeptides should be further studied.

CAS / MDL: 59-92-7
研究领域: 环境毒理学 · 发育生物学 · 水生毒理学
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES · 2023 ·Vol. 24 ·期 16 ·12810 · IF 5.6

Anti-Melanogenic and Antioxidant Activity of Bifidobacterium longum Strain ZJ1 Extracts, Isolated from a Chinese Centenarian

Jing Wu,Funa Zhang,Haixia Yu,Shimei Qi,Yu Wu,Weihua Xiao

Melanin produced by melanocytes protects our skin against ultraviolet (UV) radiation-induced cell damage and oxidative stress. Melanin overproduction by hyperactivated melanocytes is the direct cause of skin hyperpigmentary disorders, such as freckles and melasma. Exploring natural whitening agents without the concern of toxicity has been highly desired. In this study, we focused on aBifidobacterium longumstrain, ZJ1, isolated from a Chinese centenarian, and we evaluated the anti-melanogenic activity of the distinctive extracts of ZJ1. Our results demonstrated that whole lysate (WL) and bacterial lysate (BL) of ZJ1 ferments efficiently reduce α-melanocyte-stimulating hormone (α-MSH)-induced melanin production in B16-F10 cells as well as the melanin content in zebrafish embryos. BL and WL downregulate melanogenesis-related gene expression and indirectly inhibit intracellular tyrosinase activity. Furthermore, they both showed antioxidant activity in a menadione-induced zebrafish embryo model. Our results suggest that ZJ1 fermentation lysates have application potential as therapeutic reagents for hyperpigmentary disorders and whitening agents for cosmetics.Keywords:pigmentation;Bifidobacterium longum;anti-melanogenic;tyrosinase;zebrafish;antioxidant

研究领域: 药理学 · 皮肤科 · 微生物学
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Nanomaterials · 2017 ·Vol. 7 ·期 3 ·70 · IF 3.553

Melanin-Associated Synthesis of SERS-Active Nanostructures and the Application for Monitoring of Intracellular Melanogenesis

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
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BRAZILIAN ARCHIVES OF BIOLOGY AND TECHNOLOGY · 2022 · IF 1.18

Comparative Study of High-throughput Screening Models for Anti-hyperpigmentation Compounds

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 · 动物学 · 化学生物学
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BIOMEDICINE & PHARMACOTHERAPY · 2024 · IF 6.9

Carnosic acid ameliorates postinflammatory hyperpigmentation by inhibiting inflammatory reaction and melanin deposition

Heyi Su,Fan Yang,Keyi Lu,Jiaxian Ma,Guangming Huo,Shengjie Li,Jianmei Li

The potential therapeutic effects of carnosic acid (CA) on postinflammatory hyperpigmentation (PIH) were evaluated, including its effects on melanin deposition in zebrafish, melanogenesis and melanosome transfer in skin cells and skin wound healing in mice. Our results demonstrated that CA dose-dependently decreased melanin deposition in the skin of juvenile zebrafishes. It also inhibited melanogenesis in melanoma cells and melanosome transfer to keratinocytes. Next, CA was loaded in a liposome-hydrogel system (LP-GEL) to treat skin wounds in mice. The results showed that CA-LP-GEL, as well as LP-GEL, could accelerate skin wound healing and repair the structure of healing skins in mice. Comparatively, the levels of inflammatory factors (IL-1β and TNF-a) in healing skins were significantly increased by LP-GEL, but reduced by CA-LP-GEL. In addition, Fontana-Masson staining analysis of healing skin showed that the melanoma cells were restored by the treatment of LP-GEL and CA-LP-GEL, while the melanin content was significantly increased only by LP-GEL. Real-time PCR data showed that CA decreased the gene expression related with melanogenesis (MITF, TYR and TRP-1), melanosome transfer (MLPH, Myova and Rab27a) and inflammatory cytokines (IL-1β and TNF-α) in vitro and in vivo . In conclusion, CA could reduce melanin deposition in the skin by inhibiting melanogenesis and melanosome transfer. CA-LP-GEL was found to accelerate skin wound healing and suppress inflammation and hyperpigmentation in mice. These results suggest that CA has a big developing potentiality for PIH treatment.

研究领域: 药理学 · 皮肤科 · 炎症 · 伤口愈合 · 化妆品
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