Annona muricata Polyphenols Induce Cytoskeletal Alterations and Predicted Aldose Reductase Binding in Giardia lamblia

Abstract

Giardiasis has been classified as a neglected disease by the World Health Organization since 2004. Despite ongoing efforts, challenges such as drug resistance and treatment failures continue to hinder effective management. In recent years, the exploration of plant‐derived compounds as antiparasitic agents has emerged as a promising strategy. This is supported by the discovery of plant‐derived compounds such as quinine and artemisinin in antiparasitic pharmacology. The identification of specific molecular targets in Giardia lamblia, a protozoan with unique cytoskeletal and metabolic features, has further advanced drug discovery efforts. In this study, we evaluated the in vitro and in silico effects of a polyphenol‐enriched extract from Annona muricata (soursop) leaves against G. lamblia trophozoites. The extract had a noticeable impact on parasite growth, cell adhesion, and morphology. Ultrastructural analyses revealed elongation, flagellar abnormalities, and damage to the ventral disk. Western blot and immunofluorescence assays demonstrated reduced α‐tubulin expression and altered localization, indicating cytoskeletal alterations in treated trophozoites. Molecular docking analyses predicted favorable interactions between soursop polyphenols and Giardia aldose reductase, particularly involving the catalytic residues Y40 and K71. Collectively, these findings suggest that A. muricata polyphenols exert antigiardial effects through multiple cellular alterations and support the hypothesis that metabolic and cytoskeletal processes may both contribute to the observed biological effects. Further studies are required to experimentally validate the role of aldose reductase and its relationship with cytoskeletal disruption.