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

• Published in: Biomedicine & pharmacotherapy 2022-04, Vol.148, p.112766, Article 112766
• Main Authors: Silva, Diana Pontes da, Ferreira, Sarah de Sousa, Torres-Rêgo, Manoela, Furtado, Allanny Alves, Yamashita, Fabiana de Oliveira, Diniz, Eduardo Augusto da Silva, Vieira, Davi Serradella, Ururahy, Marcela Abbott Galvão, Silva-Júnior, Arnóbio Antônio da, Luna, Karla Patrícia de Oliveira, Fernandes-Pedrosa, Matheus de Freitas
• Format: Article
• Language: English
• Subjects: Animals; Antiophidic activity; Biomarkers; Bothrops; Bothrops leucurus; Chlorogenic Acid - pharmacology; Cinnamates - pharmacology; Crotalid Venoms - toxicity; Depsides - pharmacology; Female; Hematologic Tests; Inhibition of toxins; Interleukins - metabolism; Lipid Peroxidation - drug effects; Male; Metalloproteases - drug effects; Mice; Peroxidase - drug effects; Phenolic compounds; Phospholipases A2 - drug effects; Rosmarinic Acid
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2022.112766

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 PLA2 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 PLA2, 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. [Display omitted] •Chlorogenic acid and rosmarinic acid mitigated the effects of B. leucurus venom.•Edema, myotoxicity, hemorrhage, and systemic changes in vivo were inhibited.•The enzymatic action in vitro of the venom was reduced by the compounds.•Both inhibitors show promise as therapeutic alternatives for snakebites.