title: Topical application of Acheflan on rat skin injury accelerates wound healing: a histopathological, immunohistochemical and biochemical study.
abstract: BACKGROUND
  Dermal wound healing involves a cascade of complex events including angiogenesis and extracellular matrix remodeling. Several groups have focused in the study of the skin wound healing activity of natural products. The phytomedicine Acheflan®, and its main active constituent is the oil from Cordia verbenacea which has known anti-inflammatory, analgesic and antimicrobial activities. To our knowledge, no investigation has evaluated the effect of Acheflan® in an experimental model of skin wound healing. The present study has explored the wound healing property of Acheflan® and has compared it with topical effectiveness of collagenase and fibrinolysin by using Wistar rat cutaneous excision wound model.
  
  
  METHODS
  Animals were divided into four groups: untreated animals are negative control (NC), wounds were treated topically every day with Collagenase ointment (TC), with Fibrinolysin ointment (TF) and with cream Acheflan (TAc). Skin samples were collected on zero, 8th and 15th days after wounding. The healing was assessed by hematoxylin-eosin (HE), picrosirius red, hydoxyproline content and immunohistochemical analysis of the vascular endothelial growth factor (VEGF) and matrix metalloprotease-9 (MMP-9). Statistical analysis was done by ANOVA and Student t-test (p < 0.05).
  
  
  RESULTS
  The histological analysis HE of wound in the TAc group was more efficient because it was possible to observe the complete remodeling of the epidermis indicating the regression of lesions compared with the NC. The evaluation of picrosirius staining has demonstrated a significant increase of collagen distribution in the TC and TAc treatments compared with NC and TF groups. These results are corroborated with hydroxyproline content. Skin TC and TAc treated rats have showed an increase of VEGF and MMP-9 compared with NC and TF groups. All parameters were significant (P < 0.05).
  
  
  CONCLUSIONS
  The phytomedicine Acheflan® (oil of Cordia verbenacea) and TC possess higher therapeutic properties for wound healing compared with TF. These ointments seem to accelerate wound healing, probably due to their involvement with the increase of angiogenesis and dermal remodeling.
authors.affiliation: Laboratório de Pesquisa de Ciências Farmacêuticas, Unidade de Farmácia, Centro Universitário Estadual da Zona Oeste, Av. Manoel Caldeira de Alvarenga, 1203, Campo Grande, 23070-200, Rio de Janeiro, RJ, Brazil. jamilaperini@uezo.rj.gov.br.|Programa de Pós-Graduação em Saúde Pública e Meio Ambiente, Escola Nacional de Saúde Pública, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil. jamilaperini@uezo.rj.gov.br.
authors.forename: Jamila Alessandra
authors.initials: JA
authors.lastname: Perini
authors.affiliation: Laboratório de Pesquisa de Ciências Farmacêuticas, Unidade de Farmácia, Centro Universitário Estadual da Zona Oeste, Av. Manoel Caldeira de Alvarenga, 1203, Campo Grande, 23070-200, Rio de Janeiro, RJ, Brazil. thaysangeli@yahoo.com.br.
authors.forename: Thais
authors.initials: T
authors.lastname: Angeli-Gamba
authors.affiliation: Laboratório de Pesquisa de Ciências Farmacêuticas, Unidade de Farmácia, Centro Universitário Estadual da Zona Oeste, Av. Manoel Caldeira de Alvarenga, 1203, Campo Grande, 23070-200, Rio de Janeiro, RJ, Brazil. jessicaperini@yahoo.com.br.|Programa de Pós-Graduação em Saúde Pública e Meio Ambiente, Escola Nacional de Saúde Pública, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil. jessicaperini@yahoo.com.br.
authors.forename: Jessica
authors.initials: J
authors.lastname: Alessandra-Perini
authors.affiliation: Programa de Pós-Graduação em Saúde Pública e Meio Ambiente, Escola Nacional de Saúde Pública, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil. luiz.ferreira@ini.fiocruz.br.
authors.forename: Luiz Claudio
authors.initials: LC
authors.lastname: Ferreira
authors.affiliation: Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil. luiz.nasciutti@histo.ufrj.br.
authors.forename: Luiz Eurico
authors.initials: LE
authors.lastname: Nasciutti
authors.affiliation: Laboratório de Pesquisa de Ciências Farmacêuticas, Unidade de Farmácia, Centro Universitário Estadual da Zona Oeste, Av. Manoel Caldeira de Alvarenga, 1203, Campo Grande, 23070-200, Rio de Janeiro, RJ, Brazil. danielescorsim@yahoo.com.br.|Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil. danielescorsim@yahoo.com.br.
authors.forename: Daniel Escorsim
authors.initials: DE
authors.lastname: Machado
mesh_terms: D000818:Animals; D007150:Immunohistochemistry; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000187:drug effects / Q000293:injuries; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D010936:Plant Extracts