Piceatannol Induces Mitochondrial Dysfunction in Toxoplasma gondii

TL;DR

Piceatannol, a natural compound, shows promise against Toxoplasma gondii by damaging its mitochondria, reducing its energy and increasing harmful molecules.

Contribution

This study reveals that piceatannol induces mitochondrial dysfunction in Toxoplasma gondii, offering a novel anti-parasitic mechanism.

Findings

Piceatannol disrupts mitochondrial integrity in T. gondii, lowering membrane potential and ATP production.

The compound increases reactive oxygen species levels and suppresses oxidative phosphorylation-related genes.

Piceatannol inhibits T. gondii proliferation without host cell toxicity.

Abstract

Toxoplasma gondii, an obligate intracellular protozoan parasite infecting nucleated cells of warm-blooded vertebrates, causes severe complications in immunocompromised hosts. Current therapies remain limited by suboptimal efficacy and toxicity, necessitating novel anti-toxoplasmic agents. Piceatannol (PIC), a natural stilbenoid, demonstrates multifaceted bioactivity including antimicrobial and anti-parasitic effects, suggesting therapeutic potential against T. gondii. Our previous study revealed PIC’s potent anti-parasitic activity, selectively inhibiting T. gondii proliferation and altering parasite morphology without host cytotoxicity. In this study, mechanistic analyses indicated that PIC disrupts mitochondrial integrity in tachyzoites, reducing mitochondrial membrane potential and ATP production while elevating ROS levels. Transcriptomic profiling identified significant suppression of oxidative phosphorylation-related genes, consistent with mitochondrial dysfunction. These findings establish PIC as a promising candidate targeting T. gondii through the mechanism of mitochondrial impairment.

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