Transcriptome-based investigation of Zingiberaceous essential oils against Naegleria fowleri and Acanthamoeba castellanii - A comprehensive mechanistic approach.

Free-living amoebas, such as Naegleria fowleri and Acanthamoeba castellanii, pose significant health threats. causing conditions like Acanthamoeba keratitis, granulomatous amoebic encephalitis, and primary amoebic meningoencephalitis. Unfortunately, there is no single effective drug, resulting in a high fatality rate. Current drug treatments lack efficacy due to challenges like limited blood-brain barrier penetration, ineffectiveness against cyst stages, and infection recurrence. Essential Oils (EOs) from Zingiberaceae plants, known for their anti-parasitic antiprotozoal, and anticancer properties, emerge as a promising avenue for developing effective therapies against these formidable amoebic infections. EOs exhibit anti-inflammatory effects by modulating key markers in rats, potentially influenced by Acanthamoeba pathogenesis. Notably, the EOs demonstrate anti-tumor properties by binding with Caspase 3, suggesting a potential mode of action in cancer cells. Additionally, their antibacterial activity disrupts cell walls, making them promising for combating amoebic cysts and infections. With low cytotoxicity, these EOs hold promise as natural additives in health products and antiamoebic drugs. They reportedly penetrate the BBB, distinguishing them as promising candidates for GAE and PAM. Therefore, in
search for new therapeutics and understanding the mode of action of poorly understood organisms, we will test the potential of Zingiberaceae EO’s of common ginger and its two varieties, red ginger and Bentong ginger against N. fowleri and A. castellanii for the first time. The possible toxicity of tested Essential oil will be evaluated against HaCaT and SH-SY5Y cells. Next-gen sequencing will conduct a comprehensive transcriptomic analysis, unveiling differential gene expression in programmed cell death. This reveals molecular events, regulatory pathways, and potential therapeutic targets vital for advancing treatments in FLA diseases. To the best of our knowledge, this is the first study demonstrating PCD processes and transcriptome sequencing in amoebae, induced by the tested EOs. These findings suggest the potential of these EOs as innovative therapeutic agents against amoebic infections.