Synthesis and activity of the salicylic acid ester of bakuchiol in psoriasis-surrogate keratinocytes and skin substitutes.
Synthesis and activity of the salicylic acid ester of bakuchiol in psoriasis-surrogate keratinocytes and skin substitutes.
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补骨脂酚水杨酸酯在银屑病替代角质形成细胞和皮肤替代品中的合成和活性。
DOI：
10.1111/ced.13024
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发表时间：
2017
影响因子：
4.1
通讯作者：
Bojanowski,K
中科院分区：
文献类型：
--
作者：
Ma,S;Gobis,K;Swindell,WR;Chaudhuri,R;Bojanowski,R;Bojanowski,K
背景外用类维生素A可有效延缓皮肤老化，恢复银屑病等皮肤病的体内平衡。然而，它们的不良反应（AE），包括刺激（类维生素A皮炎）、光敏性和致畸性，限制了它们的使用和患者依从性。开发具有最小AE的维甲酸类似物将允许更广泛和更顺应性的使用。（bakusylan），具有与类维生素A类似的调节基因表达谱，使用三种处方类维生素A作为参照：维甲酸、他扎罗汀和阿达帕林。方法我们假设因为巴库留醇水杨酸酯具有与现有的类维生素A完全不同的结构，AE与该类维生素A的皮肤正常化活性至少部分脱钩。这一假设进行了测试，在银屑病细胞因子处理的角质形成细胞和器官型皮肤替代品的培养物中的转录水平，使用DNA微阵列和自定义PCR arrays.ResultsEvaluation的基因表达谱的bakuchiol水杨酸酯显示消除的几个组件的类维生素A样促炎反应和致畸签名，而没有大量的正常化潜力的损失。一个可能的作用机制，包括角质形成细胞脱敏银屑病细胞因子信号通过抑制信号转导和转录调节因子（STAT）1/3/干扰素炎症信号转导axis也identified.ConclusionBipartite材料获得合并两个皮肤活性实体与特定的，互补的生物活性，如巴古赤醇和水杨酸，可能会产生一类新的功能性维甲酸。
BackgroundTopical retinoids are effective in retarding skin ageing and restoring homeostasis in skin conditions such as psoriasis. However their adverse effects (AEs), which include irritation (retinoid dermatitis), photosensitivity and teratogenicity, limit their use and patient compliance. Development of retinoid analogues with minimal AEs would allow a broader and more compliant use.AimTo synthesise a novel molecule, bakuchiol salicylate (bakusylan), with a modulatory gene expression profile similar to retinoids, using as reference three prescription retinoids: tretinoin, tazarotene and adapalene.MethodsWe hypothesized that because bakuchiol salicylate has a structure entirely different from existing retinoids, there would be at least a partial uncoupling of AEs from the skin‐normalizing activity of this retinoid. This hypothesis was tested at the transcriptional level in psoriatic cytokine‐treated cultures of keratinocytes and organotypic skin substitutes, using DNA microarrays and custom PCR arrays.ResultsEvaluation of the gene expression profile of bakuchiol salicylate revealed elimination of several components of the retinoid‐like proinflammatory response and teratogenic signature, without a substantial loss of normalizing potential. A possible mechanism of action, consisting of keratinocyte desensitization to psoriatic cytokine signalling through inhibition of the signal transducer and regulator of transcription (STAT)1/3/interferon inflammatory signal transduction axis was also identified.ConclusionBipartite materials obtained by merging two skin‐active entities with specific, complementary bioactivities, such as bakuchiol and salicylic acid, may yield a new class of functional retinoids.