Effect of embelin on inhibition of cell growth and induction of apoptosis in Acanthamoeba castellanii

Acanthamoeba castellanii is the causative agent of fatal encephalitis and blinding keratitis. Current therapies remain a challenge, hence there is a need to search for new therapeutics. Here, we tested embelin (EMB) and silver nanoparticles doped with embelin (EMB–AgNPs) against A. castellanii . Usi...

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Bibliographic Details
Published in:Archives of microbiology 2023-11, Vol.205 (12), p.360-360, Article 360
Main Authors: Ahmed, Usman, Ong, Seng-Kai, Khan, Khalid Mohammed, Siddiqui, Ruqaiyyah, Khan, Naveed Ahmed, Shaikh, Mohd Farooq, Alawfi, Bader Saleem, Anwar, Ayaz
Format: Article
Language:English
Subjects:
Acanthamoeba castellanii
Apoptosis
Biochemistry
Biomedical and Life Sciences
Biotechnology
Cell Biology
Cytochrome P450
Cytochromes P450
Cytotoxicity
Ecology
Encephalitis
Genes
Keratitis
Life Sciences
Microbial Ecology
Microbiology
Microorganisms
Mode of action
Nanoparticles
Original Paper
Oxidative stress
Oxytocin
Pharmacology
Rap1 protein
Signal transduction
Silver
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Summary:Acanthamoeba castellanii is the causative agent of fatal encephalitis and blinding keratitis. Current therapies remain a challenge, hence there is a need to search for new therapeutics. Here, we tested embelin (EMB) and silver nanoparticles doped with embelin (EMB–AgNPs) against A. castellanii . Using amoebicidal assays, the results revealed that both compounds inhibited the viability of Acanthamoeba , having an IC 50 of 27.16 ± 0.63 and 13.63 ± 1.08 μM, respectively, while causing minimal cytotoxicity against HaCaT cells in vitro. The findings suggest that both samples induced apoptosis through the mitochondria-mediated pathway. Differentially expressed genes analysis showed that 652 genes were uniquely expressed in treated versus untreated cells, out of which 191 were significantly regulated in the negative control vs. conjugate. Combining the analysis, seven genes ( ARIH1 , RAP1 , H3 , SDR16C5 , GST , SRX1, and PFN ) were highlighted as the most significant (Log2 (FC) value ± 4) for the molecular mode of action in vitro. The KEGG analysis linked most of the genes to apoptosis, the oxidative stress signaling pathway, cytochrome P450, Rap1, and the oxytocin signaling pathways. In summary, this study provides a thorough framework for developing therapeutic agents against microbial infections using EMB and EMB–AgNPs. Graphical abstract
ISSN:0302-8933
1432-072X
DOI:10.1007/s00203-023-03698-3