In vitroand in silicostudies of the larvicidal and anticholinesterase activities of berberine and piperine alkaloids on Rhipicephalus microplus

Autor: da Silva, Gisele Dias, de Lima, Hélimar Gonçalves, de Freitas, Humberto Fonseca, da Rocha Pita, Samuel Silva, dos Santos Luz, Yann, de Figueiredo, Mauro Pereira, Uzêda, Rosângela Soares, Branco, Alexsandro, Costa, Silvia Lima, Batatinha, Maria José Moreira, Botura, Mariana Borges
Zdroj: Ticks and Tick-borne Diseases; March 2021, Vol. 12 Issue: 2
Abstrakt: Rhipicephalus microplusis responsible for high economic losses in livestock and its control has become difficult due to the establishment of tick populations resistant to commercial acaricides. This study aimed to evaluate the in vitrolarvicidal effect of the alkaloids berberine and piperine, and also to investigate their inhibitory mechanisms against the acetylcholinesterase enzyme. The effects of the alkaloids on larvae were observed through the immersion test at the following concentrations: 1.5; 3; 6; 12; 16 and 24 mM. Berberine and piperine presented larvicidal activity greater than 95 %, not differing from 100 % for the positive fipronil control (p > 0.05). Of the two alkaloids, piperine had a lower effective concentration (EC), with an EC50of 6.04 mM. The acetylcholinesterase enzyme used in the study was obtained from R. micropluslarvae (RmAChE) and the anticholinesterase activity was determined spectrophotometrically. The highest anticholinesterase activity, measured as inhibition concentration (IC), was observed for berberine (IC50 = 88.13 μM), while piperine showed lower activity (IC50 > 200 μM). Docking studies in RmAChE, followed by 10 ns molecular dynamics simulation, suggest that berberine stabilizes the RmAChE at lower Root-Mean-Square Deviation (RMSD) than Apoprotein. Few hydrogen-bond interactions between berberine and RmAChE residues were balanced by hydrophobic and π-type interactions. Berberine fills preferentially the peripheral anionic site (PAS), which correlates with its non-competitive mechanism. These results suggest that berberine and piperine alkaloids have an in vitroacaricidal action on R. micropluslarvae, and the likely mechanism of action of berberine is related to RmAChE inhibition when accessing the PAS residues. These findings could help the study of new natural products that could inhibit RmAChE and aid in the development of new acaricides.
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