Octyl Gallate Exhibits Trypanocidal Activity Through Trypanothione Reductase Inhibition and Immunomodulation In Vitro

Area of Science:

• Parasitology
• Pharmacology
• Immunology

Background:

• Chagas disease, caused by Trypanosoma cruzi, poses a significant public health concern due to limitations in current treatment options.
• Octyl gallate (OG), a gallic acid derivative, exhibits potential antiparasitic properties.

Purpose of the Study:

• To evaluate the in vitro trypanocidal activity and immunomodulatory effects of Octyl gallate (OG) against Trypanosoma cruzi.
• To investigate the mechanism of action of OG, including its impact on parasite redox metabolism and host immune responses.

Main Methods:

• In vitro viability assays (MTT) to determine OG's efficacy against different T. cruzi forms.
• Flow cytometry for cell death pathway analysis and assessment of cytokine production (TNF-α, IL-12, IL-10, IL-6).
• Molecular docking and biochemical assays to elucidate the inhibition of trypanothione reductase (TR); ultrastructural analysis for morphological changes.

Main Results:

• OG demonstrated significant trypanocidal activity across epimastigote, trypomastigote, and intracellular amastigote forms of T. cruzi, with favorable selectivity indices.
• OG modulated host immune responses by increasing TNF-α and IL-12 while decreasing IL-10 and IL-6, alongside stimulating ROS and NO production.
• Mechanism studies indicated OG inhibits trypanothione reductase (TR) and induces apoptosis-like cell death in T. cruzi, evidenced by morphological damage.

Conclusions:

• Octyl gallate exhibits potent and selective trypanocidal activity against Trypanosoma cruzi.
• OG's efficacy is linked to immunomodulatory effects, induction of parasite cell death, and disruption of redox metabolism via TR inhibition.
• These findings support OG's potential as a candidate for further preclinical development against Chagas disease.