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Analgesic activity and mechanism of action of a Beta vulgaris dye enriched in betalains in inflammatory models in mice

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Abstract

Evidence demonstrates the pronounced anti-inflammatory activity of a beetroot (Beta vulgaris) dye enriched in betalains obtained using precipitation with ethanol. Herein, we expand upon our previous observations and demonstrate the analgesic and antioxidant effect of betalains. Betalains [10–1000 mg/kg; intraperitoneal route (i.p.)] diminished acetic acid- and PBQ-induced abdominal contortions, and the overt pain-like behaviour induced by complete Freund`s adjuvant (CFA) and formalin (intraplantar; i.pl.) injection. Moreover, betalains (100 mg/kg) administered by various routes [i.p. or subcutaneous (s.c.)] or as a post-treatment reduced carrageenin- or CFA-induced hyperalgesia. Mechanistically, betalains mitigated carrageenin-induced tumour necrosis factor-alpha (TNF-α), interleukin (IL)-1β, superoxide anion levels, and lipid peroxidation. Betalains also stopped the depletion of reduced glutathione (GSH) levels and ferric reducing ability produced by carrageenin, as well as upregulated Nrf2 and Ho1 transcript expression in the plantar tissue of mice. Furthermore, betalains showed hydroxyl radical, 2,2′-azino-di-(3-ethylbenzthiazoline-6-sulphonic acid) radical (ABTS+), and 2,2-diphenyl-1-picryl-hydrazyl radical (DPPH•) scavenging ability and iron-chelating activity (bathophenantroline assay), and inhibited iron-independent and iron-dependent lipid peroxidation (LPO) in vitro. Finally, betalains-treated bone marrow-derived macrophages exhibited lower levels of cytokines (TNF-α and IL-1β), and superoxide anion levels and nuclear factor kappa B (NF-κB) activation following lipopolysaccharide (LPS) stimulation. Therefore, this betalain-rich dye extracted using a novel precipitation approach presents prominent analgesic effect in varied models of pain by mechanisms targeting cytokines and oxidative stress.

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Acknowledgements

This work was supported by Brazilian grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível superior (CAPES, finance code 001), PPSUS Grant (agreement 041/2017, protocol 48.095), Programa de Apoio a Grupos de Excelência (PRONEX) grant supported by SETI/Araucária Foundation and MCTI/CNPq; and Paraná State Government (agreement 014/2017, protocol 46.843). The authors have no conflict of interest to declare.

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  1. Renata M. Martinez, Miriam S. Hohmann, Daniela T. Longhi-Balbinot, and Ana C. Zarpelon have contributed equally to this work.

Authors and Affiliations

  1. Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Estadual de Londrina, Londrina, Paraná, Brazil

    Renata M. Martinez, Marcela M. Baracat, Sandra R. Georgetti & Rubia Casagrande

  2. Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Londrina, Paraná, Brazil

    Miriam S. Hohmann, Daniela T. Longhi-Balbinot, Ana C. Zarpelon & Waldiceu A. Verri Jr.

  3. Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil

    Fabiana T. M. C. Vicentini

  4. Centro de Ciências Integradas, Universidade Federal do Tocantins, Araguaína, Tocantins, Brazil

    Rogério Côrte Sassonia

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  1. Renata M. Martinez
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Martinez, R.M., Hohmann, M.S., Longhi-Balbinot, D.T. et al. Analgesic activity and mechanism of action of a Beta vulgaris dye enriched in betalains in inflammatory models in mice. Inflammopharmacol 28, 1663–1675 (2020). https://doi.org/10.1007/s10787-020-00689-4

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