Inhibition of PI3K/AKT/GLUT1 Signaling Pathway by Quercetin in the Treatment of Psoriasis

Background: Psoriasis is an enduring inflammatory skin disorder defined by recurring attacks, distinguished primarily by red patches and scaly skin. Quercetin, a kind of natural flavonoid compound, is widely found in various vegetables, fruits, and Chinese herbs. Quercetin is a multifaceted compound with a wide range of potential health benefits. In addition to antioxidant, cardiovascular protection, and anti-tumor effects, quercetin has shown potential in regulating immune and inflammation effects. In the initial stages, in vivo studies have demonstrated that quercetin positively affects psoriasis and is connected with the phosphatidylinositol 3-kinase (PI3K)/Protein Kinase B (AKT)/glucose transporter 1 (GLUT1) signaling. Nevertheless, the precise mechanism by which quercetin influences the PI3K/AKT/GLUT1 signaling cascade in the context of psoriasis remains uncertain. Objective: The aim of this study was to investigate the potential therapeutic influence of quercetin on psoriasis and the relationship with the PI3K/AKT/GLUT1 signaling pathway. Methods: A mouse model for psoriasis induced by imiquimod was employed to assess alterations in the morphology of skin lesions and their histopathological characteristics. Cell Counting kit-8 (CCK-8) assay was used to assess the impact of proliferation of HaCaT human keratinocyte cells. HaCaT cells were examined using flow cytometry for the influence of quercetin on apoptosis. Additionally, Western blot analysis was used to evaluate the protein expression levels in the PI3K/AKT/GLUT1 signaling pathway. Results: concerning pathological alterations, the mice in the model group exhibited characteristic alterations associated with psoriasis. The extent of excessive keratinization in the epidermis and hypertrophy of the spinous layer observed in each quercetin dosage group was less pronounced compared to the model group. The CCK-8 assay laid out that quercetin can suppress the proliferation of HaCaT cells. Furthermore, it was found that quercetin facilitates the apoptosis of these cells. Analysis of immunoblotting demonstrated that the intervention of quercetin in HaCaT cells led to modifications in the proteins related to the PI3K/AKT/GLUT1 signaling pathway. Conclusion: Through in vivo and in vitro experiments, this study shows that quercetin may play a therapeutic role in psoriasis and inhibit the PI3K/AKT/GLUT1 signaling pathway.