Plant-Derived Toxin Inhibitors as Potential Candidates to Complement Antivenom Treatment in Snakebite Envenomations

Abstract

Snakebite envenomations (SBEs) are a neglected medical condition of global importance that mainly affect the tropical and subtropical regions. Clinical manifestations include pain, edema, hemorrhage, tissue necrosis, and neurotoxic signs, and may evolve to functional loss of the affected limb, acute renal and/or respiratory failure, and even death. The standard treatment for snake envenomations is antivenom, which is produced from the hyperimmunization of animals with snake toxins. The inhibition of the effects of SBEs using natural or synthetic compounds has been suggested as a complementary treatment particularly before admission to hospital for antivenom treatment, since these alternative molecules are also able to inhibit toxins. Biodiversity-derived molecules, namely those extracted from medicinal plants, are promising sources of toxin inhibitors that can minimize the deleterious consequences of SBEs. In this review, we systematically synthesize the literature on plant metabolites that can be used as toxin-inhibiting agents, as well as present the potential mechanisms of action of molecules derived from natural sources. These findings aim to further our understanding of the potential of natural products and provide new lead compounds as auxiliary therapies for SBEs.

Keywords: bioactive compounds; envenomation; plants; snakebites; snakes.

Figure 1

Global distribution of snakebite cases. Adapted from J.M. Gutiérrez et al. (2017) Ref. (6) The final figure was prepared using canva.com.

Figure 2

Mind map of the topics covered in this review. Snake photo: Asenate A. X. Adrião. The final figure was prepared using canva.com.

Figure 3

Structures of representatives of the main toxin classes in snake venoms. Codes inside parentheses denote the PDB codes of the crustal strucutures of these proteins. The final figure was prepared using Pymol v. 1.6.

Figure 4

Chemical structures of snakebite treatment compounds 1-17.

Figure 5

Chemical structures of snakebite treatment compounds 18-33.

Figure 6

Chemical structures of snakebite treatment compounds 34-60.

Figure 7

Chemical structures of snakebite treatment compounds 61-72.

Figure 8

Chemical structures of snakebite treatment compounds 73-97.

Figure 9

Chemical structures of snakebite treatment compounds 98-114.