title: Investigations on the in vivo wound healing potential of Hypericum perforatum L.
abstract: BACKGROUND
  Olive oil extract of the flowering aerial parts of Hypericum perforatum L. (Hypericaceae) is a popular folk remedy for the treatment of wounds in Turkey.
  
  
  OBJECTIVE
  In order to prove the claimed utilization of the plant, the effects of the extracts and the fractions were investigated by using bioassay-guided procedures. For the wound healing activity assessment, in vivo excision and incision wound models were applied. For the anti-inflammatory activity, an in vivo model, based on the inhibition of acetic acid-induced increase in capillary permeability was used as well. Moreover, a parallel study was run on Hypericum scabrum L., which is a widespread species of the gender but not known as a folk remedy for wound healing, to provide a preliminary data to compare and emphasize the selection of correct plant species.
  
  
  RESULTS
  Initial investigations proved that the olive oil extract of Hypericum perforatum has a significant wound healing effect on excision (5.1-82.6% inhibition) and circular incision (20.2-100.0% inhibition) wound models. In order to determine the active wound healing ingredient(s), aerial parts of the plant was extracted with ethanol, noteworthy wound healing activity profile was observed with the wound models; between 18.3% and 95.6% in excision model and from 13.9% to 100.0% inhibitions in incision model were determined. The ethanolic extract was then submitted to successive solvent extractions with n-hexane, chloroform and ethyl acetate (EtOAc). Each solvent extract was also applied on the same wound models, consequently, EtOAc subextract was found to be the most active one by inhibiting wounds between 17.9% and 100.0% in excision model, subsequently between 9.4% and 100.0% in incision model. However, all subfractions obtained from the EtOAc subextract using Sephadex LH-20 column chromatography showed wound healing activity not more than the whole EtOAc subextract, which revealed that a possible synergistic activity that might be questioned. Among the active Sephadex fractions, Fr. A further yielded hyperoside, isoquercitrin, rutin and (-)-epicatechin and Fr. B yielded hypericin as the major components. Moreover, a dose-dependent anti-inflammatory activity was found for the ethanol extract, EtOAc subextract and Sephadex fractions of Hypericum perforatum. These results suggest that anti-inflammatory activity of the active fractions might have a contributory role in the wound healing effect of the plant.
  
  
  CONCLUSIONS
  Results of the present study have proved that aerial parts of Hypericum perforatum possess remarkable wound healing and anti-inflammatory activities supporting the folkloric assertion of the plant in Turkish folk medicine. Flavonoids [hyperoside, isoquercitrin, rutin and (-)-epicatechin] and naphthoquinones (hypericins) were found as the active components of Hypericum perforatum. On the other hand, ethanol extract of Hypericum scabrum showed neither remarkable wound healing nor anti-inflammatory activity demonstrating the importance of correct plant species selection in therapeutic applications.
authors.affiliation: Department of Pharmacognosy, Gazi University, Faculty of Pharmacy, Etiler 06330, Ankara, Turkey.
authors.forename: Ipek Peşin
authors.initials: IP
authors.lastname: Süntar
authors.forename: Esra Küpeli
authors.initials: EK
authors.lastname: Akkol
authors.forename: Demet
authors.initials: D
authors.lastname: Yilmazer
authors.forename: Turhan
authors.initials: T
authors.lastname: Baykal
authors.forename: Hasan
authors.initials: H
authors.lastname: Kirmizibekmez
authors.forename: Murat
authors.initials: M
authors.lastname: Alper
authors.forename: Erdem
authors.initials: E
authors.lastname: Yeşilada
mesh_terms: D000818:Animals; D020902:Hypericum; D008297:Male; D051379:Mice; D000069463:Olive Oil; D035261:Plant Components, Aerial; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D010938:Plant Oils / Q000302:isolation & purification / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology
chemical_list: D000069463:Olive Oil; D010936:Plant Extracts; D010938:Plant Oils