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一种从核桃楸果实提取物中提取的化学化合物,通过 p-ERK 相关的 MITF 降解抑制黑色素生成。

A chemical compound from fruit extract of Juglans mandshurica inhibits melanogenesis through p-ERK-associated MITF degradation.

机构信息

Department of Dermatology and Cutaneous Biology Research Institute, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.

College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon 21983, Republic of Korea.

出版信息

Phytomedicine. 2019 Apr;57:57-64. doi: 10.1016/j.phymed.2018.12.007. Epub 2018 Dec 10.

DOI:10.1016/j.phymed.2018.12.007
PMID:30668323
Abstract

BACKGROUND

Trials for regulation of abnormal hyperpigmentation from the use of natural products have been going on for years. Leaf and root extracts from Juglans mandshurica are reported to function as antioxidants and to suppress allergic dermatitis. However, studies evaluating its fruit extract and the chemical compounds from the fruit extract are lacking in dermatology fields, including melanogenesis.

PURPOSE

The aim of this study is to understand the effect of the fruit extract from J. mandshurica on pigmentation and to search for specific chemical compounds that affect melanogenesis.

METHODS

After screening out any anti-melanotic effects of the fruit extract from J. mandshurica in B16F10 melanoma cells, three major phenolic compounds isolated from the fruit extract were tested by western blot analysis for expression of microphthalmia-associated transcription factor (MITF) and tyrosinase. Their effect on B16F10 melanoma cells with regard to melanogenesis was also confirmed in primary human epidermal melanocytes (PHEMs). PD98059 was tested to observe the compounds' signaling role in the extracellular signal-regulated protein kinase (ERK)-pathway.

RESULTS

Fruit extract from J. mandshurica showed anti-melanotic effects in B16F10 melanoma cells. After chemical compounds were isolated from the fruit extracts, three phenolic compounds were evaluated for anti-melanotic effects. 2-[4-(3-hydroxypropyl)-2-methoxyphenoxy]-1,3-propanediol (compound 1) showed the highest suppression effect among the three compounds. In B16F10 melanoma cells and PHEMs, reduced melanin contents were observed after treatment with the compound (1). Experiments using a blocker of ERK showed that the inhibitory effect of the compound (1) on melanogenesis was dependent on ERK-associated MITF degradation.

CONCLUSION

A chemical constituent of Juglans mandshurica Maxim. induces an inhibitory mechanism to melanogenesis. It has the potential to become a whitening agent in the medical field, though this requires further clinical investigation.

摘要

背景

针对天然产物调节异常色素沉着的试验已经进行了多年。据报道,胡桃楸的叶和根提取物具有抗氧化作用,并能抑制过敏性皮炎。然而,在皮肤科领域,包括黑色素生成,缺乏对其果实提取物及其果实提取物中化学化合物的研究。

目的

本研究旨在了解胡桃楸果实提取物对色素沉着的影响,并寻找影响黑色素生成的特定化学化合物。

方法

在筛选出胡桃楸果实提取物对 B16F10 黑色素瘤细胞无抗黑色素作用后,通过 Western blot 分析检测从果实提取物中分离出的三种主要酚类化合物对小眼畸形相关转录因子(MITF)和酪氨酸酶的表达。还在原代人表皮黑素细胞(PHEMs)中证实了它们对 B16F10 黑色素瘤细胞黑色素生成的影响。用 PD98059 检测化合物在细胞外信号调节蛋白激酶(ERK)通路中的信号作用。

结果

胡桃楸果实提取物对 B16F10 黑色素瘤细胞表现出抗黑色素作用。从果实提取物中分离出化学化合物后,评估了三种酚类化合物的抗黑色素作用。2-[4-(3-羟丙基)-2-甲氧基苯氧基]-1,3-丙二醇(化合物 1)在三种化合物中显示出最高的抑制作用。在 B16F10 黑色素瘤细胞和 PHEMs 中,用该化合物处理后观察到黑色素含量降低。使用 ERK 阻断剂的实验表明,该化合物(1)对黑色素生成的抑制作用依赖于 ERK 相关的 MITF 降解。

结论

胡桃楸的一种化学成分诱导了一种抑制黑色素生成的机制。它有可能成为医学领域的美白剂,尽管这需要进一步的临床研究。

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