title: Interaction between different extracts of Hypericum perforatum L. from Serbia and pentobarbital, diazepam and paracetamol.
abstract: Herb-drug interactions are an important safety concern and this study was conducted regarding the interaction between the natural top-selling antidepressant remedy Hypericum perforatum (Hypericaceae) and conventional drugs. This study examined the influence of acute pretreatment with different extracts of Hypericum perforatum from Serbia on pentobarbital-induced sleeping time, impairment of motor coordination caused by diazepam and paracetamol pharmacokinetics in mice. Ethanolic extract, aqueous extract, infusion, tablet and capsule of Hypericum perforatum were used in this experiment. The profile of Hypericum perforatum extracts as well as paracetamol plasma concentration was determined using RP-HPLC analysis. By quantitative HPLC analysis of active principles, it has been proven that Hypericum perforatum ethanolic extract has the largest content of naphtodianthrones: hypericin (57.77 µg/mL) and pseudohypericin (155.38 µg/mL). Pretreatment with ethanolic extract of Hypericum perforatum potentiated the hypnotic effect of pentobarbital and impairment of motor coordination caused by diazepam to the greatest extent and also increased paracetamol plasma concentration in comparison to the control group. These results were in correlation with naphtodianthrone concentrations. The obtained results have shown a considerable influence of Hypericum perforatum on pentobarbital and diazepam pharmacodynamics and paracetamol pharmacokinetics.
authors.affiliation: Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, Hajduk Veljkova 3, Novi Sad 21000, Serbia. araskovic@hotmail.com.
authors.forename: Aleksandar
authors.initials: A
authors.lastname: Rašković
authors.affiliation: Laboratory for Pharmaceutical and Natural Products Analysis, Department of Pharmacy, Faculty of Medicine, University of Novi Sad, Hajduk Veljkova 3, Novi Sad 21000, Serbia. cvejich@hotmail.com.
authors.forename: Jelena
authors.initials: J
authors.lastname: Cvejić
authors.affiliation: Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, Hajduk Veljkova 3, Novi Sad 21000, Serbia. nebojsa.stilinovic@gmail.com.
authors.forename: Nebojša
authors.initials: N
authors.lastname: Stilinović
authors.affiliation: Laboratory for Pharmaceutical and Natural Products Analysis, Department of Pharmacy, Faculty of Medicine, University of Novi Sad, Hajduk Veljkova 3, Novi Sad 21000, Serbia. magistrakon@orcon.net.nz.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Goločorbin-Kon
authors.affiliation: Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, Hajduk Veljkova 3, Novi Sad 21000, Serbia. sasavukmirovic99@gmail.com.
authors.forename: Saša
authors.initials: S
authors.lastname: Vukmirović
authors.affiliation: Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences, University of Novi Sad, Trg Dositeja Obradovića 3, Novi Sad 21000, Serbia. neda.mimica-dukic@dh.uns.ac.rs.
authors.forename: Neda
authors.initials: N
authors.lastname: Mimica-Dukić
authors.affiliation: Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, Hajduk Veljkova 3, Novi Sad 21000, Serbia. momir.mikov@otago.ac.nz.
authors.forename: Momir
authors.initials: M
authors.lastname: Mikov
mesh_terms: D000082:Acetaminophen / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D018712:Analgesics, Non-Narcotic / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D000873:Anthracenes; D014151:Anti-Anxiety Agents / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D002214:Capsules; D003975:Diazepam / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D005260:Female; D041743:Herb-Drug Interactions; D020902:Hypericum / Q000737:chemistry*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010424:Pentobarbital / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D010569:Perylene / Q000031:analogs & derivatives / Q000032:analysis; D010936:Plant Extracts / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D010946:Plants, Medicinal; D055771:Serbia; D012997:Solvents; D013607:Tablets
chemical_list: D018712:Analgesics, Non-Narcotic; D000873:Anthracenes; D014151:Anti-Anxiety Agents; D002214:Capsules; D010936:Plant Extracts; D012997:Solvents; D013607:Tablets; D000082:Acetaminophen; D010569:Perylene; C004965:hypericin; D010424:Pentobarbital; C056602:pseudohypericin; D003975:Diazepam