title: In vitro Cytotoxicity and Anti-herpes Simplex Virus Type 1 Activity of Hydroethanolic Extract, Fractions, and Isolated Compounds from Stem Bark of Schinus terebinthifolius Raddi.
abstract: BACKGROUND
  Herpes simplex virus type 1 (HSV-1) is associated with orofacial infections and is transmitted by direct contact with infected secretions. Several efforts have been expended in the search for drugs to the treatment for herpes. Schinus terebinthifolius is used in several illnesses and among them, for the topical treatment of skin wounds, especially wounds of mucous membranes, whether infected or not.
  
  
  OBJECTIVE
  To evaluate the cytotoxicity and anti-HSV-1 activity of the crude hydroethanolic extract (CHE) from the stem bark of S. terebinthifolius, as well as its fractions and isolated compounds.
  
  
  METHODS
  The CHE was subjected to bioguided fractionation. The anti-HSV-1 activity and the cytotoxicity of the CHE, its fractions, and isolated compounds were evaluated in vitro by SRB method. A preliminar investigation of the action of CHE in the virus-host interaction was conducted by the same assay.
  
  
  RESULTS
  CHE presented flavan-3-ols and showed anti-HSV-1 activity, better than its fractions and isolated compounds. The class of substances found in CHE can bind to proteins to form unstable complexes and enveloped viruses, as HSV-1 may be vulnerable to this action. Our results suggest that the CHE interfered with virion envelope structures, masking viral receptors that are necessary for adsorption or entry into host cells.
  
  
  CONCLUSIONS
  The plant investigated exhibited potential for future development treatment against HSV-1, but further tests are necessary, especially to elucidate the mechanism of action of CHE, as well as preclinical and clinical studies to confirm its safety and efficacy.
  
  
  CONCLUSIONS
  Crude hydroethanolic extract (CHE) presents promising activity against herpes simplex virus type 1 (HSV 1), with selectivity index (SI) = 22.50CHE has flavan-3-ols in its composition, such as catechin and gallocatechinThe fractions and isolated compounds obtained from CHE by bioguided fractionation are less active than the CHE against HSV-1CHE interferes with viral entry process in the host cell and acts directly on the viral particle. Abbreviations used: HSV: Herpes simplex virus, CHE: Crude hydroethanolic extract, WF: Water fraction, AF: Ethyl-acetate fraction, MPLC: Medium-performance liquid chromatography, TLC: Thin-layer chromatography, NMR: Nuclear magnetic resonance, ESI-MS: Electrospray ionization mass spectrometry, SRB: Sulforhodamine B, CPE: Cytopathic effect, CC50: 50% cytotoxic concentration, EC50: 50% effective concentration, PBS: Phosphate-buffered saline.
authors.affiliation: Post-Graduate Program in Pharmaceutical Sciences, State University of Maringá, Maringá, Paraná, Brazil.
authors.forename: Samara Requena
authors.initials: SR
authors.lastname: Nocchi
authors.affiliation: Post-Graduate Program in Pharmaceutical Sciences, State University of Maringá, Maringá, Paraná, Brazil.
authors.forename: Gislaine Franco
authors.initials: GF
authors.lastname: de Moura-Costa
authors.affiliation: Coordination of Chemical Engineering, Federal Technical University of Paraná, Francisco Beltrão Campus, Santa Barbara Line s/n, BR-85601-970, Francisco Beltrão, Paraná, Brazil.
authors.forename: Claudio Roberto
authors.initials: CR
authors.lastname: Novello
authors.affiliation: Post-Graduate Program in Pharmaceutical Sciences, State University of Maringá, Maringá, Paraná, Brazil.
authors.forename: Juliana
authors.initials: J
authors.lastname: Rodrigues
authors.affiliation: Department of Pharmacy, State University of Maringá, Av. Colombo 5790, BR-87020-900, Maringá, Paraná, Brazil.
authors.forename: Renata
authors.initials: R
authors.lastname: Longhini
authors.affiliation: Post-Graduate Program in Pharmaceutical Sciences, State University of Maringá, Maringá, Paraná, Brazil; Department of Pharmacy, State University of Maringá, Av. Colombo 5790, BR-87020-900, Maringá, Paraná, Brazil.
authors.forename: João Carlos Palazzo
authors.initials: JC
authors.lastname: de Mello
authors.affiliation: Post-Graduate Program in Pharmaceutical Sciences, State University of Maringá, Maringá, Paraná, Brazil; Department of Health Basic Sciences, State University of Maringá, Av. Colombo 5790, BR-87020-900, Maringá, Paraná, Brazil.
authors.forename: Benedito Prado Dias
authors.initials: BP
authors.lastname: Filho
authors.affiliation: Post-Graduate Program in Pharmaceutical Sciences, State University of Maringá, Maringá, Paraná, Brazil; Department of Health Basic Sciences, State University of Maringá, Av. Colombo 5790, BR-87020-900, Maringá, Paraná, Brazil.
authors.forename: Celso Vataru
authors.initials: CV
authors.lastname: Nakamura
authors.affiliation: Post-Graduate Program in Pharmaceutical Sciences, State University of Maringá, Maringá, Paraná, Brazil; Department of Health Basic Sciences, State University of Maringá, Av. Colombo 5790, BR-87020-900, Maringá, Paraná, Brazil.
authors.forename: Tânia
authors.initials: T
authors.lastname: Ueda-Nakamura
keywords: Antiviral activity; Aroeira; Schinus terebinthifolius Raddi; cytotoxicity; herpes simplex virus; herpes simplex virus type 1