Quercetin induces keratinocytes apoptosis via triple inhibition of Notch, PI3K/AKT signaling and Glut1 in the treatment of psoriasis

IF 4.2 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Molecular basis of disease Pub Date : 2025-04-30 DOI:10.1016/j.bbadis.2025.167879

Bai-lin Chen , Wei-ming Zhang , Xiao-wan Dong , Jia-yi Liu , Yan-ping Bai

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引用次数: 0

Abstract

Background

Psoriasis is an immune-mediated inflammatory skin disorder marked by excessive keratinocyte proliferation and inflammatory cell infiltration. Quercetin has shown a range of biological activities, highlighting its potential as a therapeutic agent for psoriasis.

Purpose

This study aims to explore the mechanisms by which quercetin treats psoriasis.

Methods

An Imiquimod-induced psoriasis mouse model and a TNF-α-induced keratinocyte proliferation model were utilized, supplemented with quercetin and DAPT. The expression of K10, K14, Notch1, NICD, AKT and Glut1 in psoriatic lesions and normal skin was assessed. Techniques employed included hematoxylin-eosin staining, immunohistochemical staining, western blotting, quantitative polymerase chain reaction, cell counting kit-8 assay, flow cytometry, and enzyme-linked immunosorbent assay.

Results

Notch1, AKT, and Glut1 were highly expressed in psoriasis. Quercetin induced keratinocyte apoptosis and inhibited the Notch signaling pathway, as well as the expression of AKT and Glut1. Inhibition of Notch signaling led to keratinocyte apoptosis and downregulation of the AKT and Glut1 expression. The results of network pharmacology and molecular docking are consistent with this.

Conclusion

This study provides the first evidence that quercetin induces keratinocyte apoptosis and promotes keratinocyte differentiation to treat psoriasis through the triple inhibition of the Notch and PI3K/AKT signaling pathways, as well as Glut1. The downregulation of the PI3K/AKT pathway and Glut1 is achieved partially via Notch inhibition. These findings suggest that quercetin could be a novel agent for improving psoriasis treatment, especially in patients exhibiting high expression of Notch1, AKT, and Glut1 in their skin lesions.

Abstract Image

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槲皮素通过三重抑制Notch、PI3K/AKT信号通路和Glut1诱导角化细胞凋亡治疗银屑病

背景银屑病是一种免疫介导的炎症性皮肤疾病，其特征是角质细胞过度增殖和炎症细胞浸润。槲皮素已显示出一系列的生物活性，突出了其作为银屑病治疗剂的潜力。目的探讨槲皮素治疗银屑病的作用机制。方法采用吡喹莫德诱导的银屑病小鼠模型和TNF-α-诱导的角质细胞增殖模型，并辅以槲皮素和DAPT。比较K10、K14、Notch1、NICD、AKT、Glut1在银屑病皮损和正常皮肤中的表达情况。采用的技术包括苏木精-伊红染色、免疫组织化学染色、免疫印迹、定量聚合酶链反应、细胞计数试剂盒-8测定、流式细胞术和酶联免疫吸附测定。结果notch1、AKT、Glut1在银屑病中高表达。槲皮素诱导角质细胞凋亡，抑制Notch信号通路，抑制AKT和Glut1的表达。Notch信号的抑制导致角化细胞凋亡，AKT和Glut1表达下调。网络药理学和分子对接的结果与此一致。结论槲皮素通过对Notch、PI3K/AKT信号通路及Glut1的三重抑制，诱导角质细胞凋亡，促进角质细胞分化，治疗银屑病。PI3K/AKT通路和Glut1的下调部分是通过Notch抑制实现的。这些发现表明槲皮素可能是一种改善牛皮癣治疗的新药物，特别是在皮肤病变中Notch1、AKT和Glut1高表达的患者中。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biochimica et biophysica acta. Molecular basis of disease 生物-生化与分子生物学

CiteScore

12.30

自引率

0.00%

发文量

218

审稿时长

32 days

期刊介绍： BBA Molecular Basis of Disease addresses the biochemistry and molecular genetics of disease processes and models of human disease. This journal covers aspects of aging, cancer, metabolic-, neurological-, and immunological-based disease. Manuscripts focused on using animal models to elucidate biochemical and mechanistic insight in each of these conditions, are particularly encouraged. Manuscripts should emphasize the underlying mechanisms of disease pathways and provide novel contributions to the understanding and/or treatment of these disorders. Highly descriptive and method development submissions may be declined without full review. The submission of uninvited reviews to BBA - Molecular Basis of Disease is strongly discouraged, and any such uninvited review should be accompanied by a coverletter outlining the compelling reasons why the review should be considered.