Chen Bai-Lin, Zhang Wei-Ming, Dong Xiao-Wan, Liu Jia-Yi, Bai Yan-Ping
Institute of Dermatology and Venereology, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu 610072, China; Beijing University of Chinese Medicine, Beijing 100029, China.
Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China.
Biochim Biophys Acta Mol Basis Dis. 2025 Aug;1871(6):167879. doi: 10.1016/j.bbadis.2025.167879. Epub 2025 Apr 30.
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.
This study aims to explore the mechanisms by which quercetin treats psoriasis.
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.
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.
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.
银屑病是一种免疫介导的炎症性皮肤病，其特征为角质形成细胞过度增殖和炎症细胞浸润。槲皮素已显示出一系列生物学活性，凸显了其作为银屑病治疗药物的潜力。
本研究旨在探讨槲皮素治疗银屑病的机制。
利用咪喹莫特诱导的银屑病小鼠模型和肿瘤坏死因子-α诱导的角质形成细胞增殖模型，并给予槲皮素和DAPT。评估银屑病皮损和正常皮肤中K10、K14、Notch1、NICD、AKT和Glut1的表达。所采用的技术包括苏木精-伊红染色、免疫组织化学染色、蛋白质免疫印迹法、定量聚合酶链反应、细胞计数试剂盒-8检测、流式细胞术和酶联免疫吸附测定。
Notch1、AKT和Glut1在银屑病中高表达。槲皮素诱导角质形成细胞凋亡并抑制Notch信号通路以及AKT和Glut1的表达。抑制Notch信号通路导致角质形成细胞凋亡以及AKT和Glut1表达下调。网络药理学和分子对接的结果与此一致。
本研究首次提供证据表明，槲皮素通过对Notch和PI3K/AKT信号通路以及Glut1的三重抑制诱导角质形成细胞凋亡并促进角质形成细胞分化以治疗银屑病。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银屑病治疗的新型药物，尤其是对于皮损中Notch1、AKT和Glut1高表达的患者。
