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Harpagophytum Procumbens Ethyl Acetate Fraction Reduces Fluphenazine-Induced Vacuous Chewing Movements and Oxidative Stress in Rat Brain

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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.

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Acknowledgments

Coordination of Improvement of Higher Education Personnel (CAPES), National Council for Scientific and Technological Development (CNPq - Universal - 475210/2013-1), Foundation for Research of the State of Rio Grande do Sul (FAPERGS- PRONEM #11/2029-1 and PqG - 2080-2551/13-5), Department of Science and Technology (DECIT), and Secretariat of Science and Technology and Strategic Inputs. R.F. has received fellowship from CNPq. L.F.S.,C.M.F., A.P.C., L.R.P., E.M.R., B.N.K., and A.B. are recipient of fellowships from CAPES. Sincere posthumous thanks to our beloved professor in memorian Margareth Linde Athayde.

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  1. Programa de Pós-Graduação em Farmacologia, Universidade Federal de Santa Maria, Santa Maria, RS, 97105-900, Brazil

    Larissa Finger Schaffer, Ana Paula Chiapinotto Ceretta, Elizete de Moraes Reis, Alcindo Busanello, Roselei Fachinetto & Caroline Wagner

  2. Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica, Universidade Federal de Santa Maria, Santa Maria, RS, 97105-900, Brazil

    Catiuscia Molz de Freitas, Luis Ricardo Peroza, Bárbara Nunes Krum & Roselei Fachinetto

  3. Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal de Santa Maria, Santa Maria, RS, 97105-900, Brazil

    Aline Augusti Boligon

  4. Universidade Federal do Pampa, Dom Pedrito, RS, 9645-000, Brazil

    Jéssie Haigert Sudati

  5. Universidade Federal do Pampa, Campus Caçapava do Sul, Caçapava do Sul, RS, 96570-000, Brazil

    Caroline Wagner

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  1. Larissa Finger Schaffer
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Schaffer, L.F., de Freitas, C.M., Chiapinotto Ceretta, A.P. et al. Harpagophytum Procumbens Ethyl Acetate Fraction Reduces Fluphenazine-Induced Vacuous Chewing Movements and Oxidative Stress in Rat Brain. Neurochem Res 41, 1170–1184 (2016). https://doi.org/10.1007/s11064-015-1811-y

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