Citation: Bouchard, C.; Grenier, A.; Cardinal, S.; Bélanger, S.; Voyer, N.; Pouliot, R. Antipsoriatic Potential of Quebecol and Its Derivatives. Pharmaceutics 2022, 14, 1129. https://doi.org/10.3390/ pharmaceutics14061129 Academic Editor: Montse Mitjans Arnal Received: 12 April 2022 Accepted: 23 May 2022 Published: 26 May 2022 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). pharmaceutics Article Antipsoriatic Potential of Quebecol and Its Derivatives Corinne Bouchard 1,2,† , Alexe Grenier 1,2,† ,Sébastien Cardinal 3 , Sarah Bélanger 1,2 , Normand Voyer 4 and Roxane Pouliot 1,2, * 1 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; corinne.bouchard.2@ulaval.ca (C.B.); alexe.grenier.1@ulaval.ca (A.G.); sarah.belanger.5@ulaval.ca (S.B.) 2 Faculté de Pharmacie, Université Laval, Quebec, QC G1V 0A6, Canada 3 Département de Biologie, Chimie et Géographie, Université du Québec à Rimouski, Rimouski, QC G5L 3A1, Canada; sebastien_cardinal@uqar.ca 4 Département de Chimie and PROTEO, Faculté des Sciences et Génie, Université Laval, Quebec, QC G1V 0A6, Canada; normand.voyer@chm.ulaval.ca * Correspondence: roxane.pouliot@ulaval.pha.ca; Tel.: +1-418-525-4444-61706 † These authors contributed equally to this work. Abstract: Psoriasis is a chronic inflammatory skin disease mainly characterized by the hyperprolifera- tion and abnormal differentiation of the epidermal keratinocytes. An interesting phenolic compound, namely quebecol (2,3,3-tri-(3-methoxy-4-hydroxyphenyl)-1-propanol) (compound 1, 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 2, CPD2) and bis(4-hydroxy-3- methoxyphenyl)methane (compound 3, 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 pro- duced according to the self-assembly method. A sulforhodamine B (SRB) assay determining the concentration that inhibits 20% of cell growth (IC 20 ) was performed for CPD1, CPD2 and CPD3, and their IC 20 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 im- munofluorescence 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. Keywords: skin substitutes; in vitro culture; psoriasis; antipsoriatic treatment; quebecol; polyphenol; maple syrup 1. Introduction Psoriasis is an erythemato-squamous skin disease affecting about 2–3% of the world’s population [1]. This chronic inflammatory dermatosis is characterized by histopathological features including acanthosis, hyperkeratosis, parakeratosis, hypogranulosis or agranulosis, papillomatosis, the infiltration of immune cells and angiogenesis [2–4]. The etiology of psoriasis still remains unknown, which is why it can be difficult to find an appropriate treat- ment for patients. Moreover, for the exact same reason, there is still no curative treatment at the moment. Psoriasis is a multifactorial pathology that could benefit from new treatments to help patients control their symptoms without any drawbacks. A considerable portion of patients are not satisfied with their current treatment, mainly due to the undesirable side effects of treatments on the market or a lack of efficacy [5]. In a Scandinavian study, 30.5% of the patients were dissatisfied with systemic treatments, especially methotrexate, a Pharmaceutics 2022, 14, 1129. https://doi.org/10.3390/pharmaceutics14061129 https://www.mdpi.com/journal/pharmaceutics