Investigation into Propolis Components Responsible for Inducing Skin Allergy: Air Oxidation of Caffeic Acid and Its Esters Contribute to Hapten Formation.
Investigation into Propolis Components Responsible for Inducing Skin Allergy: Air Oxidation of Caffeic Acid and Its Esters Contribute to Hapten Formation.
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DOI：
10.1021/acs.chemrestox.2c00386
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发表时间：
2023-06-19
影响因子：
4.1
通讯作者：
Hagvall, Lina
中科院分区：
文献类型：
--
作者：
Ndreu, Lorena;Hurben, Alexander K.;Nyman, Gunnar S. A.;Tretyakova, Natalia Y.;Karlsson, Isabella;Hagvall, Lina
蜂胶是蜜蜂从杨树芽和针叶树芽中采集的一种类似树脂的物质，用于蜂巢的建造。尽管蜂胶是一种众所周知的接触性过敏诱因，但它仍是各类生物化妆品和健康相关产品中常见的添加剂。咖啡酸及其酯类一直被认为是蜂胶引发接触性过敏致敏能力背后的主要嫌疑物质。然而，在皮肤致敏过程中，这些半抗原与皮肤蛋白质之间形成的蛋白质加合物的化学结构仍不明确。在本研究中，对蜂胶中发现的三种主要接触性过敏原，即咖啡酸（CA）、咖啡酸1,1 - 二甲基烯丙酯（CAAE）和咖啡酸苯乙酯（CAPE）的反应活性进行了研究。这些化合物最初通过动力学直接肽反应测定法，对CA、CAAE和CAPE的致敏能力进行分类，但所获得的数据被认为可靠性太低，仅基于此测定法无法确切地对它们的皮肤致敏潜力进行分类。为了进一步研究可能引发皮肤过敏的蛋白质加合物生成过程中涉及的化学反应，进行了CA、CAAE和CAPE与模型肽的反应，并通过液相色谱 - 高分辨率质谱法进行分析。在封闭和开放体系中，在特定时间点监测CA、CAAE和CAPE与含半胱氨酸的肽在有氧条件下的反应。这些研究揭示了两种不同加合物的形成，一种是巯基加成到咖啡酸结构的α,β - 不饱和羰基区域，另一种是在空气氧化为邻醌后，巯基加成到儿茶酚上。对这些肽加合物的观察将这些化合物归类为前半抗原。有趣的是，当在无氧条件下进行相同反应时，未观察到加合物的形成，这突出了空气氧化过程在CA、CAAE和CAPE加合物形成中的重要性。此外，通过核磁共振分析，我们发现巯基加成发生在CA衍生物芳环的C - 2位置。我们的研究结果强调了空气氧化在蜂胶致敏能力中的重要性，并阐明了可能在体内引发过敏反应的半抗原的化学结构。
Propolis is a resin-like material produced by bees from the buds of poplar and cone-bearing trees and is used in beehive construction. Propolis is a common additive in various biocosmetics and health-related products, despite the fact that it is a well-known cause of contact allergy. Caffeic acid and its esters have been the primary suspects behind the sensitization potency of propolis-induced contact allergy. However, the chemical structures of the protein adducts formed between these haptens and skin proteins during the process of skin sensitization remain unknown. In this study, the reactivity of three main contact allergens found in propolis, namely, caffeic acid (CA), caffeic acid 1,1-dimethylallyl ester (CAAE), and caffeic acid phenethyl ester (CAPE), was investigated. These compounds were initially subjected to the kinetic direct peptide reactivity assay to categorize the sensitization potency of CA, CAAE, and CAPE, but the data obtained was deemed too unreliable to confidently classify their skin sensitization potential based on this assay alone. To further investigate the chemistry involved in generating possible skin allergy-inducing protein adducts, model peptide reactions with CA, CAAE, and CAPE were conducted and analyzed via liquid chromatography–high-resolution mass spectrometry. Reactions between CA, CAAE, and CAPE and a cysteine-containing peptide in the presence of oxygen, both in closed and open systems, were monitored at specific time points. These studies revealed the formation of two different adducts, one corresponding to thiol addition to the α,β-unsaturated carbonyl region of the caffeic structure and the second corresponding to thiol addition to the catechol, after air oxidation to o-quinone. Observation of these peptide adducts classifies these compounds as prehaptens. Interestingly, no adduct formation was observed when the same reactions were performed under oxygen-free conditions, highlighting the importance of air oxidation processes in CA, CAAE, and CAPE adduct formation. Additionally, through NMR analysis, we found that thiol addition occurs at the C-2 position in the aromatic ring of the CA derivatives. Our results emphasize the importance of air oxidation in the sensitization potency of propolis and shed light on the chemical structures of the resultant haptens which could trigger allergic reactions in vivo.
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影响因子：
4
作者：
Hurben, Alexander K.;Erber, Luke N.;Tretyakova, Natalia Y.;Doran, Todd M.
通讯作者：
Doran, Todd M.
DOI：
10.1002/chem.201703919
发表时间：
2018-04-03
期刊：
Chemistry (Weinheim an der Bergstrasse, Germany)
影响因子：
--
作者：
Bruins JJ;Albada B;van Delft F
通讯作者：
van Delft F
影响因子：
--
作者：
Posner, T
通讯作者：
Posner, T
影响因子：
5.5
作者：
HAUSEN, BM;WOLLENWEBER, E;POST, B
通讯作者：
POST, B
影响因子：
4.1
作者：
Johansson, Staffan;Redeby, Theres;Borje, Anna
通讯作者：
Borje, Anna