Pre-clinical efficacy assessment of Malva sylvestris on chronic skin inflammation Arthur S. Prudente, Graziela Sponchiado, Daniel A.G.B. Mendes, Bruna S. Soley, Daniela A. Cabrini, Michel F. Otuki* Department of Pharmacology, Universidade Federal does Paraná, Centro Politécnico, 81531-900, Curitiba, PR, Brazil A R T I C L E I N F O Article history: Received 3 March 2017 Received in revised form 1 June 2017 Accepted 20 June 2017 Keywords: Skin Malva sylvestris Keratinocyte hyperproliferation Inflammation Psoriasis A B S T R A C T In the search for improved quality of life, the treatment of skin diseases like psoriasis (hyperproliferative disease) is valid, since it causes huge social discomfort to the patient. In this context, earlier studies showed that Malva sylvestris L. has anti-inflammatory activity demonstrated by acute animal models of skin inflammation, becoming a promising target for further studies. The present investigation aimed to verify the effect of hydroalcoholic extract of M. sylvestris (HEMS) on the chronic inflammatory and hyperproliferative response caused by multiple applications of 12-O-tetradecanoylphorbol-13-acetate (TPA) on mouse ears. Topical application of HEMS reduced oedema, leukocyte migration (mono- and polymorphonuclear cells) and keratinocyte hyperproliferation, confirmed by histology and proliferating cell nuclear antigen (PCNA) immunostaining. It was found that the anti-inflammatory effects of the extract did not involve the glucocorticoid system, and its incubation with HaCaT keratinocytes caused low toxicity and reduced cell proliferation by apoptosis. Thus, HEMS proved to be effective as an anti- psoriatic therapy, with the ability to prevent keratinocyte hyperproliferation and with low toxicity by topical application. © 2017 Elsevier Masson SAS. All rights reserved. 1. Introduction Several plant-derived compounds are established in dermato- logic therapy, such as dithranol, an anthracene derivative isolated from Andira araroba, which shows great efficacy when employed as an anti-psoriatic therapy [1]. Some medicinal plants, such as Aloe vera (Aloe barbadensis) and the Chinese herb Indigo naturalis (Baphicacanthus cusia), have been employed in clinical trials and have demonstrated efficacy comparable to the drugs currently used in the treatment of psoriasis [2–4]. Psoriasis is a chronic relapsing and remitting inflammatory skin and joint disease that has an overall prevalence of 2%–3% of the world population [5–7]. In mild cases, the treatment of choice is the topical application of corticosteroids with or without associa- tion, but their prolonged use can cause adverse effects such as skin atrophy, appearance of stretch marks and telangiectasia [8,9]. Recently, we have demonstrated that Malva sylvestris leaves have topical anti-inflammatory activity in acute models of skin inflammation, and that the compound malvidin 3-glucoside seems to be responsible for this effect, with the participation of other anti-inflammatory compounds in the extract [10,11]. Gasparetto et al. [12] have highlighted the importance of M. sylvestris as a medicinal herb and functional food, and many studies have proven its potential for treating inflammation, gastric ulcers and skin problems. Consequently, interest in this plant has increased worldwide and, in recent years, the number of patents has increased considerably. On the other hand, only a few studies involving clinical and toxicological research have been performed, making necessary further studies to elucidate the relationships between phytochemicals and mechanisms of disease treatment [12,13]. Considering the evidence of M. sylvestris as a topical anti- inflammatory agent, the aim of this study was to evaluate its actions on an established skin inflammatory process similar to psoriasis. * Corresponding author at: Universidade Federal do Paraná, Setor de Ciências Biológicas, Departamento de Farmacologia, Av. Francisco Hoffman dos Santos, s/n, CEP: 81.530-900, PO Box 19031, Curitiba, Paraná, Brazil. E-mail address: michelotuki@yahoo.com.br (M.F. Otuki). http://dx.doi.org/10.1016/j.biopha.2017.06.083 0753-3322/© 2017 Elsevier Masson SAS. All rights reserved. Biomedicine & Pharmacotherapy 93 (2017) 852–860 Available online at ScienceDirect www.sciencedirect.com