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.

Antiedematogenic activity of Petiveria alliacea L. in bothropic poisoning

“…Other studies also report biological activities for compounds obtained from chemical extraction in medicinal plants, which have anti-inflammatory, anticoagulant and antioxidant activities associated with the presence of phenolic compounds, flavonoids, alkaloids, coumarins and saponins (Dailey and Vuong, 2015;Guillamón Enrique, 2018). These compounds, obtained from medicinal plants, can interact in metabolism and biochemical pathways involved in inflammatory processes, highlighting the possibility of being inhibitors of phospholipase, cyclooxygenases, lipoxygenases, and of prostaglandins and leukotrienes and cytosines, interleukins (Adrião et al, 2022).…”

Building an explanatory model for snakebite envenoming care in the Brazilian Amazon from the indigenous caregivers’ perspective

“…Although the symbolic properties are of greater interest to indigenous people, these plants commonly produce tannins as secondary metabolites, whose astringent and healing properties could have an effect on the injury caused by snake venom. Moreover, the efficacy of the SBE treatment due to an inhibitory activity on snake toxins cannot be completely ruled out, since many plant-derived molecules have had this ability demonstrated in vitro [ 36 ]. However, according to our findings, explaining the efficacy of the SBE treatment prescribed by caregivers in the study area in terms of the particular chemical composition of the plants used as vehicles for incantation does not do justice to the indigenous conception of therapeutic efficacy.…”

Revolutionizing snakebite care with novel antivenoms: Breakthroughs and barriers

“…Venomous snakes have specialized venom glands that produce a combination of toxins, which they utilize for defensive or survival functions. Using their fangs, these toxins are delivered by the snakes into other animals to incapacitate and aid in the digestion process [ 4 , 5 ]. Snake venom toxins can be classified into 63 distinct families, and among these, four families are identified as significant in clinical contexts.…”

“…Currently, despite significant progress in technology and science, immunotherapy remains the primary treatment for snakebite envenoming. While existing antivenoms are playing a crucial role in saving lives, their limitations have spurred researchers to seek alternative neutralizing agents that can enhance or complement traditional antivenom treatment [ 4 ]. The development of next-generation antivenoms is actively underway, employing various approaches including phage display technology, humanized antibody technology, DNA immunization methods, small molecular therapeutics, and single-domain antibodies (nanobodies).…”