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Malaria remains a major health issue worldwide that affects many people, particularly in developing nations. Since, the malarial parasite has developed resistance against nearly every antimalarial drug now in use, it is imperative to search for novel antimalarial medications. Toxins produced by skin glands of toads have been shown to possess antiparasitic properties against a variety of protozoan parasites because of the bufadienolides they contain. Even though several studies have been conducted to show that toad skin secretions have antimalarial properties, very little information is known about the precise mechanism by which they work against Plasmodium infection. Thus, the goal of this study was to evaluate the antiplasmodial activity of crude skin extracts from Common Asian Toads, Duttaphrynus melanostictus , of different sizes and illustrate how they work against Plasmodium falciparum 3D7 cells. The findings demonstrated a negative correlation between the toad size and percent yield of the extracts. HPTLC and UPLC-MS/MS analysis of the extracts exhibited varied composition of bufadienolides depending on the size of the animal. The extract obtained from small toads containing resibufagin and marinobufagin lactate demonstrated highest antiplasmodial activity and showed lowest cytotoxicity on peripheral blood mononuclear cells. It was discovered that the extract was effective against the trophozoite stage of the parasite. The extract was reported to inhibit Na + /H + ATPase of Plasmodium by binding to sodium-enzyme complex at ATP binding site. The study offers baseline data that can be used to assess the antimalarial potential of individual components in the skin extract derived from small toads., Supplementary Information: The online version contains supplementary material available at 10.1007/s12639-024-01716-9., Competing Interests: Conflict of interestThe authors have no conflict of interest to declare., (© Indian Society for Parasitology 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: Skin secretions of toads are widely used in medicine all over the world for their antiviral, anti-infective, and cardiotonic properties. Because these secretions are mostly employed to combat blood parasite infection, it is important to understand their potential toxic effects on human erythrocytes. Therefore, the objective of the current investigation was to elucidate the effects of Duttaphrynus melanostictus (Schneider) skin extracts on the physiology of human erythrocytes., Methods: Toads captured from their natural habitat were separated into three groups according to their body size. Hydroalcoholic extracts of toad skin were prepared by reflux heating. These extracts were then evaluated for their hemolytic and hemoglobin denaturation potential. The effects of the extracts on cytosolic and membrane-bound enzymes of human erythrocytes were assessed., Results: The hemolysis and hemoglobin denaturation caused by these extracts correlated positively with the respective toad sizes. Extracts from medium and large toads led to increased osmotic fragility even at near iso-osmotic concentrations. Biochemical analysis of hemolysate showed that the treatment induced a shift of metabolic flux toward the glutathione pathway. Analysis of membrane-bound enzymes revealed a significant decrease in the activity of Na+/K+ ATPase and acetylcholinesterase. SDS-PAGE analysis of the erythrocyte membrane did not show the band of tropomodulin for the cells treated with 1000 𝜇g/ml extract from large toads., Conclusions: In conclusion, the present study demonstrates that the toxicity of toad skin secretions aggravates with the size of the animal and interferes with the physiology of human erythrocytes, leading to their membrane disruption and rapid lysis., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)