Abstract
Rosmarinic acid (RA) is a secondary metabolite present in several plant species that has already demonstrated antioxidant, antiallergic, anticancer, antimicrobial, neuroprotective, and hepatoprotective effects experimentally. Due to the promising pharmacological properties found previously, this study aimed to assess the oral acute toxicity and the gastroprotective effect of RA using animal models. Acute toxicity was assessed according to OECD guide 423. Ethanol, stress, NSAIDs, and pylorus ligature-induced gastric ulcer models were used to investigate antiulcer properties. The related mechanisms of action were also evaluated from ethanol-induced gastric lesions protocol. RA (300 and 2000 mg/kg) showed no changes in behavioral, water and food intake, body and organs weight parameters with LD50 set around 2500 mg/kg. RA presented gastroprotective activity in all assessed doses (25, 50, 100, and 200 mg/kg) using different animal models. Besides, it was observed that this effect is not related to the modulation of gastric juice parameters (pH, volume, and [H+]), the participation of nitric oxide, mucus, and prostaglandins. However, increased sulfhydryl groups, GSH and IL-10 levels as well as reduced of proinflammatory cytokine (TNF-α and IL-1β) levels were found for RA-treated groups. RA presents low acute toxicity and gastroprotective activity, preventing ulcer formation via cytoprotective, antioxidant, and anti-inflammatory mechanisms.
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We would like to thank the institutional support provided by the Universidade Federal da Paraíba (UFPB) and Programa de Pós-Graduação em Produtos Naturais e Sintéticos Bioativos (PPgPNSB) as well as the financial support provided by CAPES and CNPq.
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This research was partially funded by CNPq (CHAMADA UNIVERSAL– MCTI/CNPq N° 14/2014 Faixa B).
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Nascimento RF, Formiga RO, Machado FDF, Sales IRP, Lima GM, Alves Junior EB, and Batista LM contributed to the conception and design of the study, performed the in vivo experiments, coordinated the study, participated in writing the manuscript, and approved the final version of the article to be published. Barbosa-Filho JM provided rosmarinic acid for the present study. Araújo AA and Araújo Junior RF acted as contributors to the evaluation of immunomodulatory activity. Vieira GC, Pereira RF, and Alves Junior EB performed the histology essays.
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do Nascimento, R.F., de Oliveira Formiga, R., Machado, F.D.F. et al. Rosmarinic acid prevents gastric ulcers via sulfhydryl groups reinforcement, antioxidant and immunomodulatory effects. Naunyn-Schmiedeberg's Arch Pharmacol 393, 2265–2278 (2020). https://doi.org/10.1007/s00210-020-01894-2
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DOI: https://doi.org/10.1007/s00210-020-01894-2