Analgesic activity and mechanism of action of a Beta vulgaris dye enriched in betalains in inflammatory models in mice
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Inflammopharmacology
ORIGINAL ARTICLE
Analgesic activity and mechanism of action of a Beta vulgaris dye enriched in betalains in inflammatory models in mice Renata M. Martinez1 · Miriam S. Hohmann2 · Daniela T. Longhi‑Balbinot2 · Ana C. Zarpelon2 · Marcela M. Baracat1 · Sandra R. Georgetti1 · Fabiana T. M. C. Vicentini3 · Rogério Côrte Sassonia4 · Waldiceu A. Verri Jr.2 · Rubia Casagrande1 Received: 26 October 2019 / Accepted: 4 February 2020 © Springer Nature Switzerland AG 2020
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 PBQinduced 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 carrageenininduced 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 irondependent 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. Keywords Beta vulgaris · Betalains · Overt pain-like behaviour · Hyperalgesia · Cytokines · Scavenging free radicals, antioxidant activity Renata M. Martinez, Miriam S. Hohmann, Daniela T. LonghiBalbinot, and Ana C. Zarpelon have contributed equally to this work. * Waldiceu A. Verri Jr. [email protected]; [email protected] * Rubia Casagrande [email protected]; [email protected] 1
Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Estadual de Londrina, Londrina, Paraná, Brazil
2
Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Londrina, Paraná, Brazil
3
Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, Ribeirã
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