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

Comp Biochem Physiol C Toxicol Pharmacol. 2021 Jul:245:109028. doi: 10.1016/j.cbpc.2021.109028. Epub 2021 Mar 3.

Abstract

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.

Keywords: Antiophidic; Bothrops pauloensis; Naphthoquinone; Pachira aquatica Aubl; Snake venom.

MeSH terms

  • Animals
  • Bombacaceae / chemistry*
  • Crotalid Venoms / antagonists & inhibitors*
  • Male
  • Metalloproteases / metabolism
  • Mice
  • Naphthoquinones* / chemistry
  • Naphthoquinones* / pharmacology
  • Phospholipases A2 / metabolism
  • Plant Bark / chemistry
  • Plant Extracts* / pharmacology
  • Snake Bites / drug therapy*

Substances

  • Crotalid Venoms
  • Naphthoquinones
  • Plant Extracts
  • Phospholipases A2
  • Metalloproteases