Unilever R&D Shanghai, Shanghai, China.
Unilever R&D Trumbull, Trumbull, Connecticut, USA.
J Eur Acad Dermatol Venereol. 2024 Jan;38 Suppl 3:12-20. doi: 10.1111/jdv.19718.
UV radiation exposure causes skin irritation, erythema, darkening and barrier disruption by inducing oxidative stress and inflammation. Glutathione, a master antioxidant, plays an important role in the antioxidant defence network of the skin.
This study aimed to assess the in vitro protective effects of the glutathione amino acid precursors blend (GAP) on transcriptomic and phenotypic endpoints against UVB-induced challenges.
Normal human epidermal melanocytes (NHEMs) were exposed to GAP, ascorbic acid (AA) and its derivatives. Viability was assessed using the CCK8 method. Melakutis®, a pigmented living skin equivalent (pLSE) model, underwent repeated 50 mJ/cm UVB irradiation with or without GAP treatment. Images of the model were captured with consistent camera parameters, and the model's light intensity was measured using a spectrophotometer. Melanin content was determined by measuring absorbance at 405 nm. Confirmation of melanin deposition and distribution was achieved through Fontana-Masson staining. Transcriptomic analysis was conducted using RNA sequencing (RNA-Seq), and a machine learning approach was employed for transcriptomic aging clock analysis.
In NHEMs, all tested compounds exhibited over 85% viability compared to the vehicle control, indicating no heightened risk of cytotoxicity. Notably, GAP demonstrated greater efficacy in inhibiting melanin production than AA derivatives at equivalent concentrations. In pLSE models, GAP notably enhanced model lightness, and reduced melanin content and deposition following the UVB challenge, whereas AA showed minimal impact. GAP effectively counteracted UVB-induced alterations in gene expression linked to pigmentation, inflammation and aging. Moreover, recurrent UVB exposure substantially elevated the biological age of pLSE models, a phenomenon mitigated by GAP treatment.
In NHEMs, GAP exhibited enhanced effectiveness in inhibiting melanin production at identical tested doses in comparison to AA derivatives. Noteworthy protective effects of GAP against UVB irradiation were observed in the pLSE models, as evidenced by skin pigmentation measurements and transcriptomic changes.
紫外线辐射通过诱导氧化应激和炎症，导致皮肤刺激、红斑、变暗和屏障破坏。谷胱甘肽作为一种主要的抗氧化剂，在皮肤的抗氧化防御网络中发挥着重要作用。
本研究旨在评估谷胱甘肽氨基酸前体混合物（GAP）对转录组和表型终点的体外保护作用，以抵抗 UVB 诱导的挑战。
将正常人类表皮黑素细胞（NHEMs）暴露于 GAP、抗坏血酸（AA）及其衍生物中。使用 CCK8 法评估细胞活力。对色素沉着的活体皮肤等效物（pLSE）模型进行重复 50mJ/cm2 的 UVB 照射，并在照射前后给予 GAP 处理。使用一致的相机参数拍摄模型图像，并使用分光光度计测量模型的光强度。通过测量 405nm 处的吸光度来确定黑色素含量。通过 Fontana-Masson 染色确认黑色素的沉积和分布。使用 RNA 测序（RNA-Seq）进行转录组分析，并采用机器学习方法进行转录组衰老时钟分析。
在 NHEMs 中，与载体对照相比，所有测试化合物的细胞活力均超过 85%，表明没有更高的细胞毒性风险。值得注意的是，在等效浓度下，GAP 抑制黑色素生成的效果优于 AA 衍生物。在 pLSE 模型中，GAP 显著增强了模型的亮度，并减少了 UVB 挑战后的黑色素含量和沉积，而 AA 的影响则较小。GAP 有效地对抗了与色素沉着、炎症和衰老相关的 UVB 诱导的基因表达改变。此外，反复的 UVB 暴露会显著增加 pLSE 模型的生物年龄，而 GAP 处理可减轻这种现象。
在 NHEMs 中，与 AA 衍生物相比，GAP 在相同测试剂量下抑制黑色素生成的效果更为显著。在 pLSE 模型中观察到 GAP 对 UVB 照射的显著保护作用，这可通过皮肤色素沉着测量和转录组变化来证明。
