Psychotria leiocarpa Extract and Vincosamide Reduce Chemically-Induced Inflammation in Mice and Inhibit the Acetylcholin

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ORIGINAL ARTICLE

Psychotria leiocarpa Extract and Vincosamide Reduce Chemically-Induced Inflammation in Mice and Inhibit the Acetylcholinesterase Activity Anelise Samara Nazari Formagio,1,2,6 Carla Roberta Ferreira Volobuff,2 Candida Aparecida Leite Kassuya,2 Claudia Andréa Lima Cardoso,3 Maria do Carmo Vieira,4 Zefa Valdevina Pereira,1 Mariane Cristovão Bagatin,5 and Gisele de Freitas Gauze5

Abstract— Species from Psychotria are used in folk medicine against inflammatory diseases,

respiratory disturbances, and anti-hallucinogenic. In the present study, the compound vincosamide (PL-1) was identified for the first time in methanolic extract of the Psychotria leiocarpa (ME-PL) leaves, as well as the anti-inflammatory and anticholinesteric effects in rodents and molecular docking simulations. The fractionation of the chloroform fraction (CFPL) through chromatographic methods afforded the known compound PL-1. The antiinflammatory activity of the ME-PL (30, 100, and 300 mg/kg) and PL-1 (3, 30, and 100 mg/kg) was analyzed using experimental models: paw edema, pleurisy, and mechanical and thermal hyperalgesia induced by carrageenan. The anticholinesterase activity of the MEPL (30 and 100 mg/kg) and PL-1 (30 mg/kg) was showed by acetylcholinesterase (AChE) inhibitory in brain structures. The molecular docking simulations were performed using Molegro Virtual Docker v6.0. Overall, the results indicated that ME-PL and PL-1 demonstrated an anti-edematogenic effect in Cg-induced paw edema, leukocyte migration in the pleurisy model, and significantly reduced mechanical hyperalgesia, cold response to acetone in mice. The samples exhibited maximal inhibition of enzyme acetylcholinesterase (AChE) in the frontal cortex. The molecular coupling of PL-1 with the AChE showed significant

1

Faculty of Biological and Environmental Sciences, Federal University of Grande Dourados UFGD, MS, Brazil, Dourados, Brazil 2 Faculty of Health Sciences, Federal University of Grande Dourados UFGD, do Sul State, Mato Grosso, Brazil 3 Course of Chemistry, University of Mato Grosso do Sul UEMS, do Sul State, Mato Grosso, Brazil 4 Faculty of Agricultural Science, Federal University of Grande Dourados UFGD, do Sul State, Mato Grosso, Brazil 5 Department of Chemistry, State University of Maringá UEM, Paraná, Brazil 6 To whom correspondence should be addressed at Faculty of Biological and Environmental Sciences, Federal University of Grande Dourados UFGD, MS, Brazil, Dourados, Brazil. E-mail: [email protected]; [email protected]

0360-3997/19/0000-0001/0 # 2019 Springer Science+Business Media, LLC, part of Springer Nature

Formagio, Volobuff, Kassuya, Cardoso, do Carmo Vieira, Pereira, Bagatin, and de Freitas Gauze interactions with the catalytic and peripheral site, corroborating the activity presented in the inhibition assay. The acute administration of ME-PL did not cause signs of toxicity in the treated animals. The results showed that P. leiocarpa inhibited AChE and anti-inflammatory activity, and alkaloid vincosamide could be res