Antiophidic potential of chlorogenic acid and rosmarinic acid against Bothrops leucurus snake venom.

Autor: Silva DPD; Laboratory of Technology and Pharmaceutical Biotechnology (Tecbiofar), College of Pharmacy, Federal University of Rio Grande do Norte, Avenue General Gustavo Cordeiro de Farias, S/N, Petrópolis, Natal 59012-570, Brazil. Electronic address: diana.pontes.016@ufrn.edu.br., Ferreira SS; Laboratory of Technology and Pharmaceutical Biotechnology (Tecbiofar), College of Pharmacy, Federal University of Rio Grande do Norte, Avenue General Gustavo Cordeiro de Farias, S/N, Petrópolis, Natal 59012-570, Brazil. Electronic address: sarah.ferreira.041@ufrn.edu.br., Torres-Rêgo M; Laboratory of Technology and Pharmaceutical Biotechnology (Tecbiofar), College of Pharmacy, Federal University of Rio Grande do Norte, Avenue General Gustavo Cordeiro de Farias, S/N, Petrópolis, Natal 59012-570, Brazil; Chemistry Institute, Federal University of Rio Grande do Norte, Avenue Senador Salgado Filho, 3000, Lagoa Nova, Natal 59072-970, Brazil. Electronic address: manoelatorres@ufrn.edu.br., Furtado AA; Laboratory of Technology and Pharmaceutical Biotechnology (Tecbiofar), College of Pharmacy, Federal University of Rio Grande do Norte, Avenue General Gustavo Cordeiro de Farias, S/N, Petrópolis, Natal 59012-570, Brazil. Electronic address: allannyfurtado@ufrn.edu.br., Yamashita FO; Laboratory of Technology and Pharmaceutical Biotechnology (Tecbiofar), College of Pharmacy, Federal University of Rio Grande do Norte, Avenue General Gustavo Cordeiro de Farias, S/N, Petrópolis, Natal 59012-570, Brazil. Electronic address: fabianayamashita@hotmail.com., Diniz EADS; Chemistry Institute, Federal University of Rio Grande do Norte, Avenue Senador Salgado Filho, 3000, Lagoa Nova, Natal 59072-970, Brazil. Electronic address: eduardo.diniz.012@ufrn.edu.br., Vieira DS; Chemistry Institute, Federal University of Rio Grande do Norte, Avenue Senador Salgado Filho, 3000, Lagoa Nova, Natal 59072-970, Brazil. Electronic address: davisv07@gmail.com., Ururahy MAG; Biochemistry Laboratory, Department of Clinical Analysis and Toxicological, College of Pharmacy, Federal University of Rio Grande do Norte, Rua General Gustavo Cordeiro de Farias, S/N, Petrópolis, Natal 59012-570, Brazil. Electronic address: marcelaururahy@yahoo.com.br., Silva-Júnior AAD; Laboratory of Technology and Pharmaceutical Biotechnology (Tecbiofar), College of Pharmacy, Federal University of Rio Grande do Norte, Avenue General Gustavo Cordeiro de Farias, S/N, Petrópolis, Natal 59012-570, Brazil. Electronic address: arnobiosilva@ufrnet.br., Luna KPO; Center of Biological and Health Sciences, State University of Paraíba, Avenue Baraúnas, S/N, Bodocongó, Campina Grande 58429-500, Brazil. Electronic address: karlaceatox@yahoo.com.br., Fernandes-Pedrosa MF; Laboratory of Technology and Pharmaceutical Biotechnology (Tecbiofar), College of Pharmacy, Federal University of Rio Grande do Norte, Avenue General Gustavo Cordeiro de Farias, S/N, Petrópolis, Natal 59012-570, Brazil. Electronic address: matheus.pedrosa@ufrn.br.
Jazyk: angličtina
Zdroj: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2022 Apr; Vol. 148, pp. 112766. Date of Electronic Publication: 2022 Mar 02.
DOI: 10.1016/j.biopha.2022.112766
Abstrakt: Bothrops leucurus is responsible for most cases of snakebite in Northeast Brazil; however, this species is not included in the pool of venoms used in antivenom production in Brazil. The serotherapy has logistical and effectiveness limitations, which stimulates the search for therapeutic alternatives. Chlorogenic acid and rosmarinic acid present several biological activities, but their antiophidic potential has been poorly explored. Thus, the aim of this approach was to evaluate the potential inhibitory effects of these compounds on B. leucurus venom. Initially, the enzymatic inhibition of toxins was evaluated in vitro. Then, anti-hemorrhagic, anti-myotoxic, and anti-edematogenic assays were performed in vivo, as well analysis of several biochemical markers and hemostatic parameters. In addition, the interaction of inhibitors with SVMP and PLA 2 was investigated by docking analysis. Results revealed that compounds inhibited in vitro the enzymatic activities and venom-induced edema, with a decrease in both myeloperoxidase and interleukin quantification. The inhibitors also attenuated the hemorrhagic and myotoxic actions and mitigated changes in serum biochemical and hemostatic markers, as well as decreased lipid peroxidation in liver and kidney tissues. Docking analysis revealed attractive interactions of both inhibitors with the zinc-binding site of SVMP and, in the case of PLA 2 , chlorogenic acid showed a similar inhibition mechanism to that described for rosmarinic acid. The results evidenced the antiophidic potential of both compounds, which showed higher efficiency than antivenom serum. Thus, both inhibitors are promising candidates for future adjuvants to be used to complement antivenom serotherapy.
(Copyright © 2022. Published by Elsevier Masson SAS.)
Databáze: MEDLINE