Effectiveness of phytoproducts against pathogenic free-living amoebae - A scoping and critical review paving the way toward plant-based pharmaceuticals

Abstract

Infections caused by free-living amoebae (FLA) have increased worldwide and are expected to worsen. The lack of drugs that are effective (especially against cysts), affordable, and safe to treat these infections exacerbates the concern. Plants present a promising source of bioactive compounds for developing effective drugs; however, the scientific literature on this topic has yet to be adequately synthesized. This work provides a critical scoping review summarizing the amoebicidal performance of plant-derived products and their potential for developing effective drugs to treat FLA infections. Out of 5889 articles retrieved from multiple databases, 119 articles were selected, from which data on 180 plant species belonging to 127 genera and 62 families were extracted. The extracts, essential oils, and compounds from these plants exhibited a diverse range of potency against cysts and trophozoites. Among the compounds studied, periglaucine A, kolavenic acid, and (+)-elatol are promising cysticidal drug candidates due to their high potency, as well as their known low toxicity to non-target cells. Tovophillin A, gartinin, 8-deoxygartinin, garcinone E, 9-hydroxycalabaxanthone, γ-mangostin, and borneol also exhibit high cysticidal potency, but their selectivity profile is unknown. Resveratrol, rosmarinic acid, β-amyrin, and vanillic acid stand out for their high potency against trophozoites and low toxicity to mammalian cells. Another group of compounds with similarly high trophocidal potency includes (−)-epicatechin, (−)-epigallocatechin, apigenin, costunolide, demethoxycurcumin, kaempferol, methyl-β-orcinolcarboxylate, sakuraetin, (+)-elatol, debromolaurinterol, luteolin, (−)-rogiolol, cystomexicone B, epigallocatechin gallate, quercetin, and α-bisabolol. These compounds are priority candidates for further studies on in vivo efficacy, safety, pharmacokinetics, and pharmacodynamics.