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Ethyl Acetate Fraction of Harpagophytum procumbens Prevents Oxidative Stress In Vitro and Amphetamine-Induced Alterations in Mice Behavior

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Abstract

Microglial activation has been associated to the physiopathology of neurodegenerative diseases, such as schizophrenia, and can occur during inflammation and oxidative stress. Pharmacological treatment is associated with severe side effects, and studies for use of plant extracts may offer alternatives with lower toxicity. Harpagophytum procumbens (HP) is a plant known for its anti-inflammatory properties. In the present study, we characterized the ethyl acetate fraction of HP (EAF HP) by ESI-ToF-MS and investigated the effects EAF HP in a lipopolysaccharide (LPS) induced inflammation model on microglial cells (BV-2 lineage). MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), DCFH-DA (2′,7′-dichlorofluorescein diacetate) and cell cycle flow cytometer analysis were performed. In vivo was investigated the amphetamine-induced psychosis model through behavioral (locomotor and exploratory activities, stereotypies and working memory) and biochemical (DCFH-DA oxidation and protein thiols) parameters in cortex and striatum of mice. EAF HP reduced activation and proliferation of microglial cells in 48 h (300 µg/mL) and in 72 h after treatments (50–500 µg/mL). Reactive oxygen species levels were lower at the concentration of 100 µg/mL EAF HP. We detected a modulatory effect on the cell cycle, with reduction of cells in S and G2/M phases. In mice, the pre-treatment with EAF HP, for 7 days, protected against positive and cognitive symptoms, as well as stereotypies induced by amphetamine. No oxidative stress was observed in this amphetamine-induced model of psychosis. Such findings suggest that EAF HP can modulate the dopaminergic neurotransmission and be a promising adjuvant in the treatment of locomotor alterations, cognitive deficits, and neuropsychiatric disorders.

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Funding

Funding was provided by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Grant No. 001).

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Authors and Affiliations

  1. Mestrado em Ciências da Saúde e da Vida, Universidade Franciscana, Santa Maria, Rio Grande do Sul, Brazil

    Valtieri Bortoluzzi Lima, Narieli Felipetto, Natália Fernandes Mezzomo, Luis Ricardo Peroza & Larissa Finger Schaffer

  2. Programa de Pós-graduação em Nanociências, Universidade Franciscana, Santa Maria, Rio Grande do Sul, Brazil

    Altevir Rossato Viana & Alencar Kolinski Machado

  3. Departamento de Química, Universidade Franciscana, Santa Maria, Rio Grande do Sul, Brazil

    Daniel Santos & Erico Marlon Moraes Flores

  4. Curso de Farmácia, Universidade Franciscana, Santa Maria, Rio Grande do Sul, Brazil

    Adriana Maria Zago

  5. Programa de Pós-graduação em Medicina Veterinária, Universidade Federal de Santa Maria, Santa Maria, Rio Grande do Sul, Brazil

    Alexandre Krause

  6. Departamento de Morfologia, Universidade Federal de Santa Maria, Santa Maria, Rio Grande do Sul, Brazil

    Luciana Maria Fontanari Krause

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  1. Valtieri Bortoluzzi Lima
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Lima, V.B., Viana, A.R., Santos, D. et al. Ethyl Acetate Fraction of Harpagophytum procumbens Prevents Oxidative Stress In Vitro and Amphetamine-Induced Alterations in Mice Behavior. Neurochem Res 48, 1716–1727 (2023). https://doi.org/10.1007/s11064-022-03846-z

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