Natural Terpenes Inhibit the Cytopathogenicity of <i>Naegleria fowleri</i> Causing Primary Amoebic Meningoencephalitis in the Human Cell Line Model

Rajendran, Kavitha; Ahmed, Usman; Meunier, Alexia Chloe; Shaikh, Mohd Farooq; Siddiqui, Ruqaiyyah; Anwar, Ayaz

doi:10.1021/acschemneuro.3c00258

Cited by 2 publications

(7 citation statements)

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“…In previous laboratory experiments, our research team conducted testing on FOR, AND, THY, and BOR within the context of a different pathogenic genus of free-living amoebae (FLA). The results of our investigations revealed that these compounds exhibited remarkable capability to effectively eradicate both life cycle stages of amoeba . These findings are significant not only in terms of advancing our understanding of the potential applications of FOR, AND, THY, and BOR in combating parasitic infections but also in highlighting the broad spectrum of activity these compounds may possess against various amoebic pathogens.…”

Section: Resultsmentioning

confidence: 59%

“…fowleri. These results showed that the antiamoebic potential of these nanoconjugates was higher than the previously calculated antiamoebic efficacy of compounds alone . Among the tested nanoconjugates, FOR-AgNPs showed the highest antiamoebic effects with an IC 50 of 26.35 μM.…”

Section: Resultsmentioning

confidence: 64%

“…The results of our investigations revealed that these compounds exhibited remarkable capability to effectively eradicate both life cycle stages of amoeba. 47 These findings are significant not only in terms of advancing our understanding of the potential applications of FOR, AND, THY, and BOR in combating parasitic infections but also in highlighting the broad spectrum of activity these compounds may possess against various amoebic pathogens. The former promising evidence 47 emphasizes the need for further research into the therapeutic potential of these compounds.…”

Section: Resultsmentioning

confidence: 99%

“…These findings are significant not only in terms of advancing our understanding of the potential applications of FOR, AND, THY, and BOR in combating parasitic infections but also in highlighting the broad spectrum of activity these compounds may possess against various amoebic pathogens. The former promising evidence emphasizes the need for further research into the therapeutic potential of these compounds. Therefore, FOR, AND, and BOR were successfully coated with AgNPs and tested for their ability to combat N.…”

Section: Resultsmentioning

confidence: 99%

“…As we know, N fowleri gains entry into the human body through the nasal mucosa, and the epithelial layer, primarily composed of keratinocytes, serves as the first line of defense against its invasion. Keratinocytes, which are key components of the epidermis, function as a vigorous barrier against external pathogens. , In the present study, we employed HaCaT cells, renowned for its extensive use in examining epidermal homeostasis. , The choice of HaCaT cells was driven by their facile replicability, maintaining an almost normal phenotype, serving as an effective keratinocyte model, and exhibiting characteristics conducive to the study of epidermal defense mechanisms. Additionally, their capacity to emulate barrier function against pathogens and drugs enhances their suitability for our research objectives.…”

Section: Resultsmentioning

confidence: 99%

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Nanoparticle-Terpene Fusion: A Game-Changer in Combating Primary Amoebic Meningoencephalitis Caused by Naegleria fowleri

Rajendran,

Ahmed,

Meunier

et al. 2024

ACS Omega

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Pathogenic Naegleria fowleri (N. fowleri) are opportunistic free-living amoebae and are the causative agents of a very rare but severe brain infection called primary amoebic meningoencephalitis (PAM). The fatality rate of PAM in reported cases is more than 95%. Most of the drugs used againstN. fowleri infections are repurposed drugs. Therefore, a large number of compounds have been tested againstN. fowleri in vitro, but most of the tested compounds showed high toxicity and an inability to cross the blood−brain barrier. Andrographolide, forskolin, and borneol are important natural compounds that have shown various valuable biological properties. In the present study, the nanoconjugates (AND-AgNPs, BOR-AgNPs, and FOR-AgNPs) of these compounds were synthesized and assessed against both stages (trophozoite and cyst) ofN. fowleri for their antiamoebic and cysticidal potential in vitro. In addition, cytotoxicity and host cell pathogenicity were also evaluated in vitro. FOR-AgNPs were the most potent nanoconjugate and showed potent antiamoebic activity againstN. fowleriwith an IC 50 of 26.35 μM. Nanoconjugates FOR-AgNPs, BOR-AgNPs, and AND-AgNPs also significantly inhibit the viability of N. fowleri cysts. Cytotoxicity assessment showed that these nanoconjugates caused minimum damage to human keratinocyte cells (HaCaT cells) at 100 μg/mL, while also effectively reducing the cytopathogenicity of N. fowleri trophozoites to the HaCaT cells. The outcomes of our experiments have unveiled substantial potential for AND-AgNPs, BOR-AgNPs, and FOR-AgNPs in the realm of developing innovative alternative therapeutic agents to combat infections caused by N. fowleri. This study represents a significant step forward in the pursuit of advanced strategies for managing such amoebic infections, laying the foundation for the development of novel and more effective therapeutic modalities in the fight against free-living amoebae.

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Section: Resultsmentioning

confidence: 59%

Section: Resultsmentioning

confidence: 64%