Isohemigossypolone: Antiophidic properties of a naphthoquinone isolated from Pachira aquatica Aubl

• Published in: Comparative biochemistry and physiology. Toxicology & pharmacology Vol. 245; p. 109028
• Main Authors: Vieira, Sâmela Alves Pereira Batista, dos Santos, Benedito Matheus, Santos Júnior, Célio Dias, de Paula, Vanderlúcia Fonseca, Gomes, Mario Sergio Rocha, Ferreira, Glaucio Monteiro, Gonçalves, Ricardo Lemes, Hirata, Mario Hiroyuki, da Silva, Roosevelt Alves, Brandeburgo, Maria Inês Homsi, Mendes, Mirian Machado
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-07-2021
• Subjects: Antiophidic; Bothrops pauloensis; Naphthoquinone; Pachira aquatica Aubl; Snake venom; Antiophidic; BthMP; Snake venom; ISO; CK; MHD; PLA2; RMSD; Bothrops pauloensis; Pachira aquatica Aubl; BmooMPα-I; Pb; MD; EB; Naphthoquinone
• ISSN: 1532-0456; 1878-1659
• DOI: 10.1016/j.cbpc.2021.109028

We investigated the antiophidic properties of isohemigossypolone (ISO), a naphthoquinone isolated from the outer bark of the Pachira aquatic Aubl. The inhibition of phospholipase A2, coagulant, fibrinogenolytic, hemorrhagic and myotoxic activities induced by Bothrops pauloensis venom (Pb) was investigated. For this, we use samples resulting from the incubation of Pb with ISO in different concentrations (1:1, 1:5 and 1:10 w/w), we also evaluated the condition of treatment using ISO after 15 min of venom inoculation. The activities of phospholipase A2, coagulant, fibrinogenolytic, hemorrhagic and myotoxic induced by the B. pauloensis venom were significantly inhibited when the ISO was pre-incubated with the crude venom. For in vivo neutralization tests, the results were observed even when the ISO was applied after 15 min of inoculation of the venom or metalloprotease (BthMP). Also, to identify the inhibition mechanism, we performed in silico assays, across simulations of molecular coupling and molecular dynamics, it was possible to identify the modes of interaction between ISO and bothropic toxins BmooMPα-I, Jararacussin-I and BNSP-7. The present study shows that naphthoquinone isohemigossypolone isolated from the P. aquatica plant inhibited part of the local and systemic damage caused by venom proteins, demonstrating the pharmacological potential of this compound in neutralizing the harmful effects caused by snakebites.
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•Antiophidic serotherapy is ineffective in inhibiting local damage caused by bothropic envenomation.•Isohemigossypolone (ISO) showed promising antiophidic activities being able to reduce the damage caused by the venom.•The inhibitory effect promoted by ISO was observed even when administered after the inoculation of the venom.•ISO can interact with metalloproteases and thrombin-like toxins present in bothropic venom.