Molecular Dermatology Laboratory, Department of Integrative Biotechnology, College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon City, 16419 Gyunggi Do, Republic of Korea.
Department of Bio and Chemical Engineering, Hongik University, 30016 Sejong City, Republic of Korea.
Phytomedicine. 2019 May;58:152877. doi: 10.1016/j.phymed.2019.152877. Epub 2019 Feb 26.
Melanin plays a crucial role in protecting human skin against exposure to ultraviolet (UV) radiation. However, its overproduction induces hyperpigmentation disorders of the skin.
To investigate effects of phenylethyl resorcinol as one resorcinol derivative on melanogenesis and its mechanisms using B16F10 mouse melanoma cells and human epidermal melanocytes.
Effects of phenylethyl resorcinol on melanogenesis and its mechanism of action were examined using several in vitro assays (i.e., cell survival, melanin content, cellular tyrosinase activity, real-time PCR analysis, luciferase-reporter assay, Western blot analysis, and ELISAs for cyclic AMP (cAMP), protein kinase A (PKA), cAMP response element binding (CREB) protein, and mitogen-activated protein kinases (MAPKs)).
Phenylethyl resorcinol reduced both melanin content and tyrosinase activity in these cells. Phenylethyl resorcinol also suppressed tyrosinase activity in cell-free tyrosinase enzyme assay. Although phenylethyl resorcinol decreased mRNA levels of tyrosinase and tyrosinase-related protein (TRP)-2, it did not affect mRNA levels of melanogenic gene microphthalmia-associated transcriptional factor (MITF) or TRP-1. Phenylethyl resorcinol had no effects on cAMP signaling or NF-κB signaling based on results of cyclic AMP response element (CRE)-luciferase reporter assay, cAMP production, protein kinase A (PKA) activity, Western blot assays for phosphorylated CRE-binding protein (CREB), NF-κB-luciferase reporter assay, and Western blot assays for phosphorylated NF-κB. However, phenylethyl resorcinol induced activation of activator protein-1 (AP-1) signaling. Specifically, phenylethyl resorcinol increased AP-1 reporter activity and increased phosphorylation of p44/42 MAPK, but not p38 MAPK or c-Jun N-terminal kinase (JNK). MEK1/2 and Src, upstream molecules of p44/42 MAPK were also phosphorylated by phenylethyl resorcinol. In addition, phenylethyl resorcinol-induced decreases in melanin content, tyrosinase activity, and MITF protein levels were attenuated by PD98059, a p44/42 MAPK inhibitor.
These data indicate that the anti-melanogenic activity of phenylethyl resorcinol is mediated by activation of p44/42 MAPK, indicating that phenylethyl resorcinol may be a potential therapeutic agent for treating hyperpigmentation skin disorders.
黑色素在保护人体皮肤免受紫外线（UV）辐射方面起着至关重要的作用。然而，其过度产生会导致皮肤出现色素沉着失调。
研究苯乙基间苯二酚作为间苯二酚衍生物之一对黑素生成的影响及其在 B16F10 小鼠黑素瘤细胞和人表皮黑素细胞中的作用机制。
通过几种体外实验（细胞存活、黑色素含量、细胞酪氨酸酶活性、实时 PCR 分析、荧光素酶报告基因分析、Western blot 分析和环磷酸腺苷（cAMP）、蛋白激酶 A（PKA）、cAMP 反应元件结合（CREB）蛋白和丝裂原激活蛋白激酶（MAPKs）的 ELISA）检测苯乙基间苯二酚对黑素生成的影响及其作用机制。
苯乙基间苯二酚降低了这些细胞中的黑色素含量和酪氨酸酶活性。苯乙基间苯二酚在无细胞酪氨酸酶酶促反应中也抑制了酪氨酸酶活性。尽管苯乙基间苯二酚降低了酪氨酸酶和酪氨酸酶相关蛋白（TRP）-2 的 mRNA 水平，但它不影响黑素生成基因小眼畸形相关转录因子（MITF）或 TRP-1 的 mRNA 水平。基于环磷酸腺苷反应元件（CRE）-荧光素酶报告基因检测、cAMP 产生、蛋白激酶 A（PKA）活性、磷酸化 CRE 结合蛋白（CREB）的 Western blot 分析、NF-κB 荧光素酶报告基因检测和磷酸化 NF-κB 的 Western blot 分析的结果，苯乙基间苯二酚对 cAMP 信号或 NF-κB 信号没有影响。然而，苯乙基间苯二酚诱导激活蛋白-1（AP-1）信号转导。具体而言，苯乙基间苯二酚增加了 AP-1 报告基因活性，并增加了 p44/42 MAPK 的磷酸化，但不增加 p38 MAPK 或 c-Jun N 端激酶（JNK）的磷酸化。苯乙基间苯二酚还磷酸化了 p44/42 MAPK 的上游分子 MEK1/2 和Src。此外，PD98059，一种 p44/42 MAPK 抑制剂，可减轻苯乙基间苯二酚诱导的黑色素含量、酪氨酸酶活性和 MITF 蛋白水平降低。
这些数据表明，苯乙基间苯二酚的抗黑素生成活性是通过激活 p44/42 MAPK 介导的，表明苯乙基间苯二酚可能是治疗色素沉着失调皮肤疾病的潜在治疗剂。
