Topical continuous use of Lippia sidoides Cham. essential oil induces cutaneous inflammatory response, but does not delay wound healing process Maria Liduína Maia de Oliveira a , Belise Maria Oliveira Bezerra a , Luana Oliveira Leite a , Virgínia Cláudia Carneiro Girão b , Diana Célia Sousa Nunes-Pinheiro a,n a Programa de Pós-Graduação em Ciências Veterinárias, Faculdade de Veterinária, Universidade Estadual do Ceará, Campus do Itaperi, CEP 60740-903 Fortaleza, Ceará, Brazil b Departamento de Morfologia, Faculdade de Medicina, Universidade Federal do Ceará, Campus do Porangabuçu, CEP 60430-170 Fortaleza, Ceará, Brazil article info Article history: Received 14 October 2013 Received in revised form 5 February 2014 Accepted 15 February 2014 Available online 25 February 2014 Keywords: Lippia sidoides Verbenaceae Essential oil Inflammation Wound healing Skin abstract Ethnopharmacological relevance: The essential oil of Lippia sidoides (EOLS) has been used in Brazilian folk medicine as a topical antiseptic agent in skin for treatment of wounds and superficial infections of the body. The aim of this study was to investigate the effects of EOLS on intact and damaged skin, including its action on expression of mediators, COX-2 and VEGF, involved in healing full-thickness cutaneous lesions in vivo. Material and methods: EOLS was analyzed chemically and used at different concentrations to dose- response experiments in skin mice. Skin irritation tests by one-dosage and multiple-dosages and irritation to damaged skin were assessed by macroscopy, morphometry and histological and immuno- histochemical analyses. To evaluate the effects of EOLS on wound healing, excision wounds were surgically created on the dorsum of rats, and the ointments at 6% and 12% were applied daily to the wound area. Cutaneous lesions were assessed by planimetric (wound contraction) and macroscopic parameters. Results: Skin irritation tests showed that topical application of EOLS promoted cutaneous inflammation in varying degrees, which was demonstrated by increase of skin thickness and formation of cutaneous edema and erythema. Topical administration of EOLS in high concentrations presented an irritant response to skin, but this irritation is lighter when low concentrations this oil were used. Histological evaluation supported the outcome of these models, which revealed accentuated presence of inflamma- tory cells infiltration. In wound healing process, the lesions treated with EOLS showed intense edema and exsudation up to day 5, but there were not significant differences in the wound contraction on days 14 and 21. No immunohistochemical staining was verified to COX-2 and VEGF mediators in skin treated with EOLS 12%. Conclusion: The continuous application of EOLS in adequate concentrations on cutaneous wounds increases inflammatory response without delay the lesions closure. The association of these results with antimicrobial action previously related to EOLS allows its indication as an alternative therapeutic modality for topical treatment of infected cutaneous wound. Nevertheless, further studies need to be performed to determine the mechanism of action and support its application in clinical practice. & 2014 Elsevier Ireland Ltd. All rights reserved. 1. Introduction As the primary interface between the body and the environ- ment, the skin provides a first line of defense against infection, trauma, or injury. Upon skin injury, a series of events take place aiming at the reconstruction of the wounded and cutaneous homeostasis maintenance (Bangert et al., 2011). Wound repair is a natural process of regenerating tissue with multiple pathways, which are immediately activated after an injurious stimulus and can be divided into three overlapping phases: inflammation, proliferation or granulation tissue formation, and tissue remodel- ing (Velnar et al., 2009). During the inflammatory phase, leukocyte cells play a key role in protecting the tissue against infections through phagocytosis, the antibacterial effects of oxygen radicals, and the activation of complement (Rock et al., 2010). This response is executed and regulated by an equally complex signaling network Contents lists available at ScienceDirect journal homepage: www.elsevier.com/locate/jep Journal of Ethnopharmacology http://dx.doi.org/10.1016/j.jep.2014.02.030 0378-8741 & 2014 Elsevier Ireland Ltd. All rights reserved. n Corresponding author. Tel.: þ55 85 32270804; fax: þ55 85 31019840. E-mail address: diana.pinheiro@uece.br (D.C.S. Nunes-Pinheiro). Journal of Ethnopharmacology 153 (2014) 283–289