Topical Application of Cinnamaldehyde Promotes Faster Healing of Skin Wounds Infected with Pseudomonas aeruginosa

• Type of Material: Article
• Authors: Thiago A.F. Ferro, Universidade Ceuma; Eliene B. Souza, Universidade Ceuma; Mariela A.M. Suarez, Universidade Ceuma; Joao F.S. Rodrigues, Universidade Ceuma; Domingos M.S. Pereira, Universidade Ceuma; Saulo J.F. Mendes, Universidade Ceuma; Laoane F. Gonzaga, Universidade Ceuma; Marcia C.A.M. Machado, Universidade Ceuma; Maria R.Q. Bomfim, Universidade Ceuma; Joao B. Calixto, Centro de Inovação e Ensaios Pré-Clínicos-CIEnP; Jack Arbiser, Emory University; Valerio Monteiro-Neto, Universidade Ceuma; Eunice Andre, Universidade Federal do Paraná; Elizabeth S. Fernandes, Universidade Ceuma
• Language: English
• Date: 2019-04-02
• Publisher: MDPI
• Publication Version: Final Published Version
• Copyright Statement: © 2019 by the authors.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3390/molecules24081627
• Title of Journal or Parent Work: Molecules
• ISSN: 1420-3049
• Volume: 24
• Issue: 8
• Start Page: 1627
• Grant/Funding Information: L.F.G. is an undergraduate student receiving a grant from CNPq.; J.F.S.R. is a PhD student receiving a grant from FAPEMA.; This work was supported by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES; grant number 3325/2015; finance code 001), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq; grant numbers 309046/2016-5 to E.S.F. and 305058/2018-5 to E.A.), Fundação de Amparo à Pesquisa e ao Desenvolvimento Científico e Tecnológico do Maranhão (FAPEMA; grant number 00740/13) and Programa INCT-INOVAMED.; E.B.S. and M.A.M.S. are MSc students receiving grants from FAPEMA.; D.M.S.P. and S.J.F.M. are PhD students receiving grants from CAPES.
• Keywords: cinnamaldehyde; Chemistry; skin wound; Life Sciences & Biomedicine; EXPRESSION; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Pseudomonas aeruginosa; BIOFILMS; ACTIVATION; wound healing; Physical Sciences; TRPA1; GROWTH-FACTOR; IMPAIRMENT; Science & Technology
• Research Categories: Chemistry, Biochemistry; Chemistry, Pharmaceutical

Abstract

Wound healing can be delayed following colonization and infection with the common bacterium Pseudomonas aeruginosa. While multiple therapies are used for their treatment, these are ineffective, expensive, and labour-intensive. Thus, there is an enormous unmet need for the treatment of infected wounds. Cinnamaldehyde, the major component of cinnamon oil, is well known for its antimicrobial properties. Herein, we investigated the effects of sub-inhibitory concentrations of cinnamaldehyde in the virulence of P. aeruginosa. We also assessed its healing potential in P. aeruginosa-infected mouse skin wounds and the mechanisms involved in this response. Sub-inhibitory concentrations of cinnamaldehyde reduced P. aeruginosa metabolic rate and its ability to form biofilm and to cause haemolysis. Daily topical application of cinnamaldehyde on P. aeruginosa-infected skin wounds reduced tissue bacterial load and promoted faster healing. Lower interleukin-17 (IL-17), vascular endothelial growth factor (VEGF) and nitric oxide levels were detected in cinnamaldehyde-treated wound samples. Blockage of transient receptor potential ankyrin 1, the pharmacological target of cinnamaldehyde, abrogated its healing activity and partially reversed the inhibitory actions of this compound on VEGF and IL-17 generation. We suggest that topical application of sub-inhibitory concentrations of cinnamaldehyde may represent an interesting approach to improve the healing of P. aeruginosa-infected skin wounds.