title: The protective effect of Hypericum connatum on stress-induced escape deficit in rat is related to its flavonoid content.
abstract: Context Hypericum perforatum L. (Hypericaceae), used in moderate depression treatment, is active in experimental tests for antidepressant activity. For H. connatum Lam., a South American species lacking hyperforin, antidepressant effects have not been demonstrated. Objective This study evaluates the antidepressant-like effect of H. connatum in rats and identifies the components involved in this activity. Materials and methods First, the effects of acute and 14-d oral administrations of an extract derived from H. connatum aerial parts were studied using the Escape Deficit (ED) test. Next, methanol-extracted flavonoid-enriched fractions B and C and fraction-purified flavonoids (quercetin, rutin and isoquercitrin) were evaluated in the ED test after acute administration. To rule out possible confounding effects of the flavonoids, we examined nociceptive threshold using the tail-flick test and anxious behaviour using the elevated plus maze (EPM) test. Results Hypericum connatum increased reactivity of unavoidable stress-exposed rats after acute (0.5 and 1 g/kg: ED = 18.6/30 and 19.8/30, respectively) and repeated administration (0.5 g/kg twice daily: ED = 17.8/30). Protective effects were observed for fractions B and C (250 mg/kg: ED = 18.1/30 and 18.8/30, respectively), quercetin (2.5, 5 and 10 mg/kg: ED = 15.3/30, 18.3/30 and 21.6/30, respectively), rutin (5 and 10 mg/kg: ED = 15.4/30 and 13.0/30, respectively) and isoquercitrin (2.5 mg/kg: ED = 19.2/30). The flavonoids did not modify nociceptive threshold or performance in the EPM test. Discussion and conclusion Hypericum connatum showed protective activity in the ED test, a correlate of potential antidepressant-like effects that appeared to be related to the flavonoid components of this species.
authors.affiliation: a Department of Molecular and Developmental Medicine , University of Siena , Siena , Italy ;
authors.forename: Simona
authors.initials: S
authors.lastname: Scheggi
authors.affiliation: b Department of Pharmacy , University of Salerno , Fisciano , Salerno , Italy ;
authors.forename: Aurelio
authors.initials: A
authors.lastname: Marandino
authors.affiliation: b Department of Pharmacy , University of Salerno , Fisciano , Salerno , Italy ;
authors.forename: Donato
authors.initials: D
authors.lastname: Del Monte
authors.affiliation: b Department of Pharmacy , University of Salerno , Fisciano , Salerno , Italy ;
authors.forename: Laura
authors.initials: L
authors.lastname: De Martino
authors.affiliation: a Department of Molecular and Developmental Medicine , University of Siena , Siena , Italy ;
authors.forename: Teresa
authors.initials: T
authors.lastname: Pelliccia
authors.affiliation: c School of Chemistry, Biochemistry, and Pharmacy , National University of San Luis , San Luis , Argentina.
authors.forename: Maria
authors.initials: M
authors.lastname: Del Rosario Fusco
authors.affiliation: c School of Chemistry, Biochemistry, and Pharmacy , National University of San Luis , San Luis , Argentina.
authors.forename: Elisa M
authors.initials: EM
authors.lastname: Petenatti
authors.affiliation: a Department of Molecular and Developmental Medicine , University of Siena , Siena , Italy ;
authors.forename: Carla
authors.initials: C
authors.lastname: Gambarana
authors.affiliation: b Department of Pharmacy , University of Salerno , Fisciano , Salerno , Italy ;
authors.forename: Vincenzo
authors.initials: V
authors.lastname: De Feo
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D003863:Depression / Q000188:drug therapy* / Q000523:psychology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004924:Escape Reaction / Q000187:drug effects*; D005419:Flavonoids / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D020902:Hypericum / Q000737:chemistry; D008124:Locomotion / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D059225:Nociception / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects; D008517:Phytotherapy; D035261:Plant Components, Aerial; D010936:Plant Extracts / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal; D011794:Quercetin / Q000031:analogs & derivatives / Q000302:isolation & purification / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D012431:Rutin / Q000302:isolation & purification / Q000494:pharmacology; D013315:Stress, Psychological / Q000188:drug therapy* / Q000523:psychology
chemical_list: D000928:Antidepressive Agents; D005419:Flavonoids; D010936:Plant Extracts; C016527:isoquercitrin; D012431:Rutin; D011794:Quercetin
keywords: Animal models; isoquercitrin; quercetin; rutin; unavoidable stress