N-acetyl-L-hydroxyproline – A potent skin anti-ageing active preventing advanced glycation end-product formation in vitro and ex vivo

IF 2.7 4区医学 Q2 DERMATOLOGY

International Journal of Cosmetic Science Pub Date : 2023-11-27 DOI:10.1111/ics.12930

Chiara Knoblich, Katja Dunckelmann, Andrea Krüger, Thomas Küper, Thomas Blatt, Julia M. Weise

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引用次数: 0

Abstract

Objective

Advanced glycation end-products (AGEs) represent a large group of compounds generated by a non-enzymatic reaction between reducing sugars and amino groups. The formation and accumulation of AGEs in the skin lead to protein crosslinking, dermal stiffening and yellowing, which ultimately contribute to cutaneous ageing. Amino acids have been described to exhibit anti-glycation effects. The objective of this study was to understand the inhibitory role of the amino acid derivative N-acetyl-L-hydroxyproline (NAHP) as an anti-glycation active for human skin.

Methods

A cell-free assay investigating the inhibition of glycation of serum albumin by NAHP was used to determine the capability of NAHP to decrease AGE formation. Also, by assessing the amount of the AGE N-(carboxymethyl)lysine (CML) the anti-glycation abilities of NAHP were investigated utilizing dot blot analysis. The improvement of cell–matrix interaction by NAHP was determined in vitro using a glycated fibroblast-populated collagen lattice (FPCL) dermis model. In skin biopsies, AGE autofluorescence was determined after treatment with NAHP and/or glucose ex vivo.

Results

NAHP significantly and dose-dependently inhibited levels of AGEs, which were induced by the glycation of a protein solution. This decrease could be visualized by showing that the brownish appearance as well as the AGE-specific fluorescence of glucose-treated samples were reduced after the application of increasing amounts of NAHP. Also, CML formation was dose-dependently inhibited by NAHP. In FPCLs, the contractile capacity of fibroblasts was significantly disturbed after glycation. This could be prevented by the addition of NAHP. Compared to glyoxal-treated samples, the co-application of NAHP significantly decreased the diameter as well as the weight of glycated FPCLs. Ex vivo application of glucose to skin explants showed a higher AGE fluorescence signal compared to control explants. Co-treatment with NAHP and glucose decreased the level of AGE fluorescence in comparison to glucose-treated explants.

Conclusion

These data provide clear evidence that under glycation stress conditions treatment with NAHP inhibited AGE formation in vitro and ex vivo and prevented the loss of cellular contractile forces in a glycated dermis model. Thus, NAHP obviously provides a beneficial treatment option to counteract AGE-related changes in human skin such as dermal stiffening and yellowish skin appearance.

Abstract Image

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n -乙酰- l-羟基脯氨酸-一种有效的皮肤抗衰老活性物质，可在体外和体外预防晚期糖基化终产物的形成。

目的:晚期糖基化终产物(AGEs)是由还原糖和氨基之间的非酶反应产生的一大类化合物。AGEs在皮肤中的形成和积累导致蛋白质交联，真皮硬化和变黄，最终导致皮肤老化。氨基酸已被描述为具有抗糖化作用。本研究的目的是了解氨基酸衍生物n -乙酰- l-羟基脯氨酸(NAHP)作为抗糖基化活性对人体皮肤的抑制作用。方法:采用无细胞法研究NAHP对血清白蛋白糖基化的抑制作用，以确定NAHP降低AGE形成的能力。同时，通过测定AGE N-(羧甲基)赖氨酸(CML)的量，采用点印迹法研究NAHP的抗糖基化能力。采用糖基化成纤维细胞填充的胶原晶格(FPCL)真皮模型，体外观察NAHP对细胞-基质相互作用的改善作用。在皮肤活检中，在体外用NAHP和/或葡萄糖治疗后测定AGE自身荧光。结果:NAHP显著且剂量依赖地抑制蛋白糖基化诱导的AGEs水平。这种减少可以通过显示增加NAHP用量后葡萄糖处理样品的褐色外观和age特异性荧光减少来可视化。此外，NAHP还能剂量依赖性地抑制CML的形成。在FPCLs中，糖基化后成纤维细胞的收缩能力明显受到干扰。这可以通过添加NAHP来防止。与乙二醛处理的样品相比，NAHP的共同应用显著降低了糖基化fpcl的直径和重量。与对照外植体相比，葡萄糖体外应用于皮肤外植体显示出更高的AGE荧光信号。与葡萄糖处理的外植体相比，NAHP和葡萄糖共同处理降低了AGE荧光水平。结论:这些数据提供了明确的证据，在糖基化应激条件下，NAHP治疗可抑制体外和离体糖基化真皮模型中AGE的形成，并防止细胞收缩力的丧失。因此，NAHP显然提供了一种有益的治疗选择，以抵消与年龄相关的人类皮肤变化，如真皮硬化和皮肤变黄。

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来源期刊

International Journal of Cosmetic Science DERMATOLOGY-

CiteScore

4.60

自引率

4.30%

发文量

期刊介绍： The Journal publishes original refereed papers, review papers and correspondence in the fields of cosmetic research. It is read by practising cosmetic scientists and dermatologists, as well as specialists in more diverse disciplines that are developing new products which contact the skin, hair, nails or mucous membranes. The aim of the Journal is to present current scientific research, both pure and applied, in: cosmetics, toiletries, perfumery and allied fields. Areas that are of particular interest include: studies in skin physiology and interactions with cosmetic ingredients, innovation in claim substantiation methods (in silico, in vitro, ex vivo, in vivo), human and in vitro safety testing of cosmetic ingredients and products, physical chemistry and technology of emulsion and dispersed systems, theory and application of surfactants, new developments in olfactive research, aerosol technology and selected aspects of analytical chemistry.