title: Harpagophytum Procumbens Ethyl Acetate Fraction Reduces Fluphenazine-Induced Vacuous Chewing Movements and Oxidative Stress in Rat Brain.
abstract: Long-term treatment with fluphenazine is associated with manifestation of extrapyramidal side effects, such as tardive dyskinesia. The molecular mechanisms related to the pathophysiology of TD remain unclear, and several hypotheses, including a role for oxidative stress, have been proposed. Harpagophytum procumbens is an herbal medicine used mainly due to anti-inflammatory effects, but it also exhibits antioxidant effects. We investigated the effect of ethyl acetate fraction of H. procumbens (EAF HP) in fluphenazine-induced orofacial dyskinesia by evaluating behavioral parameters at different times (vacuous chewing movements (VCM's) and locomotor and exploratory activity), biochemical serological analyses, and biochemical markers of oxidative stress of the liver, kidney, cortex, and striatum. Chronic administration of fluphenazine (25 mg/kg, intramuscular (i.m) significantly increased the VCMs at all analyzed times (2, 7, 14, and 21 days), and this was inhibited by EAF HP (especially at a dose of 30 mg/kg). Fluphenazine decreased locomotion and exploratory activity, and EAF HP did not improve this decrease. Fluphenazine induced oxidative damage, as identified by changes in catalase activity and ROS levels in the cortex and striatum, which was reduced by EAF HP, especially in the striatum. In the cortex, EAF HP was protective against fluphenazine-induced changes in catalase activity but not against the increase in ROS level. Furthermore, EAF HP was shown to be safe, since affected serum biochemical parameters or parameters of oxidative stress in the liver and kidney. These findings suggest that the H. procumbens is a promising therapeutic agent for the treatment of involuntary oral movements.
authors.affiliation: Programa de Pós-Graduação em Farmacologia, Universidade Federal de Santa Maria, Santa Maria, RS, 97105-900, Brazil.
authors.forename: Larissa Finger
authors.initials: LF
authors.lastname: Schaffer
authors.affiliation: Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica, Universidade Federal de Santa Maria, Santa Maria, RS, 97105-900, Brazil.
authors.forename: Catiuscia Molz
authors.initials: CM
authors.lastname: de Freitas
authors.affiliation: Programa de Pós-Graduação em Farmacologia, Universidade Federal de Santa Maria, Santa Maria, RS, 97105-900, Brazil.
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Chiapinotto Ceretta
authors.affiliation: Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica, Universidade Federal de Santa Maria, Santa Maria, RS, 97105-900, Brazil.
authors.forename: Luis Ricardo
authors.initials: LR
authors.lastname: Peroza
authors.affiliation: Programa de Pós-Graduação em Farmacologia, Universidade Federal de Santa Maria, Santa Maria, RS, 97105-900, Brazil.
authors.forename: Elizete
authors.initials: E
authors.lastname: de Moraes Reis
authors.affiliation: Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica, Universidade Federal de Santa Maria, Santa Maria, RS, 97105-900, Brazil.
authors.forename: Bárbara Nunes
authors.initials: BN
authors.lastname: Krum
authors.affiliation: Programa de Pós-Graduação em Farmacologia, Universidade Federal de Santa Maria, Santa Maria, RS, 97105-900, Brazil.
authors.forename: Alcindo
authors.initials: A
authors.lastname: Busanello
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal de Santa Maria, Santa Maria, RS, 97105-900, Brazil.
authors.forename: Aline Augusti
authors.initials: AA
authors.lastname: Boligon
authors.affiliation: Universidade Federal do Pampa, Dom Pedrito, RS, 9645-000, Brazil.
authors.forename: Jéssie Haigert
authors.initials: JH
authors.lastname: Sudati
authors.affiliation: Programa de Pós-Graduação em Farmacologia, Universidade Federal de Santa Maria, Santa Maria, RS, 97105-900, Brazil.|Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica, Universidade Federal de Santa Maria, Santa Maria, RS, 97105-900, Brazil.
authors.forename: Roselei
authors.initials: R
authors.lastname: Fachinetto
authors.affiliation: Programa de Pós-Graduação em Farmacologia, Universidade Federal de Santa Maria, Santa Maria, RS, 97105-900, Brazil. carolinewagner@unipampa.edu.br.|Universidade Federal do Pampa, Campus Caçapava do Sul, Caçapava do Sul, RS, 96570-000, Brazil. carolinewagner@unipampa.edu.br.
authors.forename: Caroline
authors.initials: C
authors.lastname: Wagner
mesh_terms: D000085:Acetates / Q000737:chemistry*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000633:toxicity*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D005106:Exploratory Behavior / Q000187:drug effects; D005476:Fluphenazine / Q000633:toxicity*; D016166:Free Radical Scavengers / Q000494:pharmacology / Q000627:therapeutic use; D031684:Harpagophytum / Q000737:chemistry*; D008297:Male; D008409:Mastication / Q000187:drug effects*; D009043:Motor Activity / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D017208:Rats, Wistar; D012997:Solvents; D000071057:Tardive Dyskinesia / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology
chemical_list: D000085:Acetates; D000975:Antioxidants; D014150:Antipsychotic Agents; D016166:Free Radical Scavengers; D010936:Plant Extracts; D012997:Solvents; C007650:ethyl acetate; D005476:Fluphenazine
keywords: Antioxidant; Antipsychotic; Devil’s claw; Harpagoside; Tardive dyskinesia