Bouchard Corinne, Grenier Alexe, Cardinal Sébastien, Bélanger Sarah, Voyer Normand, Pouliot Roxane
Centre de Recherche en Organogénèse Expérimentale de L'Université Laval/LOEX, Axe Médecine Régénératrice, Centre de Recherche du CHU de Québec-Université Laval, Quebec, QC GIJ 1Z4, Canada.
Faculté de Pharmacie, Université Laval, Quebec, QC G1V 0A6, Canada.
Pharmaceutics. 2022 May 26;14(6):1129. doi: 10.3390/pharmaceutics14061129.
Psoriasis is a chronic inflammatory skin disease mainly characterized by the hyperproliferation and abnormal differentiation of the epidermal keratinocytes. An interesting phenolic compound, namely quebecol (2,3,3-tri-(3-methoxy-4-hydroxyphenyl)-1-propanol) (compound , CPD1), was isolated from maple syrup in 2011 and was recently synthesized. Quebecol and its derivatives ethyl 2,3,3-tris(3-hydroxy-4-methoxyphenyl)propenoate (compound , CPD2) and bis(4-hydroxy-3-methoxyphenyl)methane (compound , CPD3) have shown antiproliferative and anti-inflammatory potential, making them promising candidates for the treatment of psoriasis. This study aimed to evaluate the antipsoriatic potential of quebecol and its derivatives on psoriatic skin substitutes produced according to the self-assembly method. A sulforhodamine B (SRB) assay determining the concentration that inhibits 20% of cell growth (IC) was performed for CPD1, CPD2 and CPD3, and their IC values were 400, 150 and 350 μM, respectively. At these concentrations, cell viability was 97%, 94% and 97%, respectively. The comparative control methotrexate (MTX) had a cell viability of 85% at a concentration of 734 μM. Histological analyses of psoriatic skin substitutes treated with CPD1, CPD2 and CPD3 exhibited significantly reduced epidermal thickness compared with untreated psoriatic substitutes, which agreed with a decrease in keratinocyte proliferation as shown by Ki67 immunofluorescence staining. The immunofluorescence staining of differentiation markers (keratin 14, involucrin and loricrin) showed improved epidermal differentiation. Taken together, these results highlight the promising potential of quebecol and its derivatives for the treatment of psoriasis.
银屑病是一种慢性炎症性皮肤病，主要特征为表皮角质形成细胞的过度增殖和异常分化。一种有趣的酚类化合物，即魁北克醇（2,3,3-三-（3-甲氧基-4-羟基苯基）-1-丙醇）（化合物 ，CPD1），于2011年从枫糖浆中分离出来，最近已被合成。魁北克醇及其衍生物2,3,3-三（3-羟基-4-甲氧基苯基）丙烯酸乙酯（化合物 ，CPD2）和双（4-羟基-3-甲氧基苯基）甲烷（化合物 ，CPD3）已显示出抗增殖和抗炎潜力，使其成为治疗银屑病的有希望的候选药物。本研究旨在评估魁北克醇及其衍生物对根据自组装方法制备的银屑病皮肤替代物的抗银屑病潜力。对CPD1、CPD2和CPD3进行了磺酰罗丹明B（SRB）测定，以确定抑制20%细胞生长的浓度（IC），其IC值分别为400、150和350 μM。在这些浓度下，细胞活力分别为97%、94%和97%。对比对照甲氨蝶呤（MTX）在浓度为734 μM时细胞活力为85%。与未处理的银屑病替代物相比，用CPD1、CPD2和CPD3处理的银屑病皮肤替代物的组织学分析显示表皮厚度显著降低，这与Ki67免疫荧光染色所示的角质形成细胞增殖减少一致。分化标志物（角蛋白14、内披蛋白和兜甲蛋白）的免疫荧光染色显示表皮分化得到改善。综上所述，这些结果突出了魁北克醇及其衍生物治疗银屑病的有希望的潜力。
