Centre de Recherche en Organogénèse Expérimentale de l'Université Laval/LOEX, Axe Médecine Régénératrice, Centre de Recherche du CHU de Québec-Université Laval, 1401 18e Rue, Quebec City, QC G1J 2Z4, Canada.
Faculté de Pharmacie, Université Laval, 1050 avenue de la Médecine, Quebec City, QC G1V 0A6, Canada.
Int J Mol Sci. 2024 May 22;25(11):5639. doi: 10.3390/ijms25115639.
Plaque psoriasis is a chronic inflammatory skin disease causing red inflamed lesions covered by scales. Leukocytes, including dendritic cells and T cells, participate in the inflammation of the skin by producing multiple cytokines, thus contributing to the hyperproliferation of keratinocytes. Lack of effectiveness and toxic side effects are the main concerns with conventional treatments, and research involving new antipsoriatic molecules is essential. In this study, the anti-inflammatory and antiproliferative effects of two natural polyphenols, phloretin and balsacone C, were investigated using the coculture of T cells and psoriatic keratinocytes. Phloretin exerted antiproliferative activity by regulating the expression of antigen Ki67 and proliferating cell nuclear antigen (PCNA). These effects were comparable to those of methotrexate, a reference treatment for moderate to severe psoriasis. With balsacone C, the expression of Ki67 was also reduced. Additionally, phloretin decreased the levels of multiple pro-inflammatory cytokines: monocyte chemoattractant protein-1 (MCP-1/CCL2), macrophage inflammatory protein-1α (MIP-1α), granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-1 alpha (IL-1α), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), interleukin-17A (IL-17A), and tumor necrosis factor alpha (TNF-α). The increased interleukin-2 (IL-2) levels with phloretin and methotrexate also represented anti-inflammatory activity. Balsacone C and methotrexate decreased the levels of IL-1α and IL-1β, but methotrexate exerted a higher reduction. In summary, the anti-inflammatory effects of phloretin were more pronounced than those of methotrexate and balsacone C. In addition, the expression of lymphocyte common antigen (CD45) was more similar to that of the healthy condition after using phloretin or methotrexate. Finally, phloretin stood out from the other compounds and appears promising for psoriasis treatment.
斑块型银屑病是一种慢性炎症性皮肤病，导致红色炎症性病变，覆盖着鳞屑。白细胞，包括树突状细胞和 T 细胞，通过产生多种细胞因子参与皮肤炎症，从而导致角质形成细胞的过度增殖。传统治疗方法的主要问题是疗效不佳和毒副作用，因此研究新的抗银屑病分子至关重要。在这项研究中，使用 T 细胞和银屑病角质形成细胞的共培养物，研究了两种天然多酚，根皮素和巴尔萨酮 C 的抗炎和抗增殖作用。根皮素通过调节抗原 Ki67 和增殖细胞核抗原 (PCNA) 的表达发挥抗增殖作用。这些作用与甲氨蝶呤相当，甲氨蝶呤是治疗中重度银屑病的参考治疗方法。用巴尔萨酮 C，Ki67 的表达也减少了。此外，根皮素还降低了多种促炎细胞因子的水平：单核细胞趋化蛋白-1 (MCP-1/CCL2)、巨噬细胞炎性蛋白-1α (MIP-1α)、粒细胞集落刺激因子 (G-CSF)、粒细胞-巨噬细胞集落刺激因子 (GM-CSF)、白细胞介素-1α (IL-1α)、白细胞介素-1β (IL-1β)、白细胞介素-6 (IL-6)、白细胞介素-17A (IL-17A)和肿瘤坏死因子-α (TNF-α)。根皮素和甲氨蝶呤增加的白细胞介素-2 (IL-2) 水平也代表了抗炎活性。巴尔萨酮 C 和甲氨蝶呤降低了 IL-1α 和 IL-1β 的水平，但甲氨蝶呤的降低幅度更大。总之，根皮素的抗炎作用比甲氨蝶呤和巴尔萨酮 C 更为明显。此外，使用根皮素或甲氨蝶呤后，淋巴细胞共同抗原 (CD45) 的表达更接近健康状态。最后，根皮素与其他化合物相比脱颖而出，有望用于治疗银屑病。
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