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白藜芦醇的代谢产物白皮杉醇通过作用于Janus激酶1减轻特应性皮炎。

Piceatannol, a metabolite of resveratrol, attenuates atopic dermatitis by targeting Janus kinase 1.

作者信息

Lee Chang Hyung, Yang Hee, Park Jung Han Yoon, Kim Jong-Eun, Lee Ki Won

机构信息

Biomodulation Major, Department of Agricultural Biotechnology, Seoul National University, Seoul 08826, Republic of Korea; Bio-MAX Institute, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea.

Bio-MAX Institute, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea.

出版信息

Phytomedicine. 2022 May;99:153981. doi: 10.1016/j.phymed.2022.153981. Epub 2022 Feb 12.

DOI:10.1016/j.phymed.2022.153981
PMID:35235887
Abstract

BACKGROUND

Piceatannol is a resveratrol metabolite commonly found in red wine, grapes. Several studies have investigated the immune-modulating effects of piceatannol on processes related to allergic reactions. However, the relationship between piceatannol and atopic dermatitis (AD) has not yet been reported. This study sought to investigate the effects of piceatannol in animal and cell line models.

METHODS

AD-like symptoms and skin lesions were triggered by repeated topical treatment of Dermatophagoides farinae extract (DFE) on the skin of NC/Nga mice. The molecular mechanism of piceatannol was studied in the TNFα/IFNγ-induced HaCaT cell line.

RESULTS

Piceatannol attenuated DFE-induced AD-like symptoms, as shown by skin thickness, dermatitis score, scratching time, and skin water loss. Histopathological analysis showed that piceatannol suppressed DFE-induced immune cell infiltration into the skin. These results occurred concomitantly with the downregulation of inflammatory markers, including serum and skin TARC and MDC. Piceatannol decreased phosphorylation of JAK-STAT protein in the TNFα/IFNγ-induced HaCaT cell line. A molecular docking study showed that piceatannol strongly interacts with JAK1, suggesting a possible mode of action.

CONCLUSION

The study results showed that piceatannol, a metabolite of resveratrol, attenuates atopic dermatitis and provide important implication of development of piceatannol as functional ingredients or therapeutic agents.

摘要

背景

白皮杉醇是一种常见于红酒和葡萄中的白藜芦醇代谢产物。多项研究调查了白皮杉醇对过敏反应相关过程的免疫调节作用。然而,白皮杉醇与特应性皮炎(AD)之间的关系尚未见报道。本研究旨在调查白皮杉醇在动物和细胞系模型中的作用。

方法

通过对NC/Nga小鼠皮肤反复局部涂抹粉尘螨提取物(DFE)引发类AD症状和皮肤损伤。在TNFα/IFNγ诱导的HaCaT细胞系中研究白皮杉醇的分子机制。

结果

白皮杉醇减轻了DFE诱导的类AD症状,表现为皮肤厚度、皮炎评分、搔抓时间和皮肤水分流失。组织病理学分析表明,白皮杉醇抑制了DFE诱导的免疫细胞浸润到皮肤中。这些结果与炎症标志物(包括血清和皮肤中的TARC和MDC)的下调同时出现。白皮杉醇降低了TNFα/IFNγ诱导的HaCaT细胞系中JAK-STAT蛋白的磷酸化。分子对接研究表明,白皮杉醇与JAK1强烈相互作用,提示了一种可能的作用模式。

结论

研究结果表明,白藜芦醇的代谢产物白皮杉醇可减轻特应性皮炎,并为将白皮杉醇开发为功能性成分或治疗药物提供了重要启示。

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