Department of Biological Sciences, School of Medical and Life Sciences, Sunway University, 47500, Subang Jaya, Selangor, Malaysia.
H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan.
Int Microbiol. 2024 Aug;27(4):1063-1081. doi: 10.1007/s10123-023-00450-1. Epub 2023 Nov 28.
Acanthamoeba are free living amoebae that are the causative agent of keratitis and granulomatous amoebic encephalitis. Alpha-Mangostin (AMS) is a significant xanthone; that demonstrates a wide range of biological activities. Here, the anti-amoebic activity of α-Mangostin and its silver nano conjugates (AMS-AgNPs) were evaluated against pathogenic A. castellanii trophozoites and cysts in vitro. Amoebicidal assays showed that both AMS and AMS-AgNPs inhibited the viability of A. castellanii dose-dependently, with an IC of 88.5 ± 2.04 and 20.2 ± 2.17 μM, respectively. Both formulations inhibited A. castellanii-mediated human keratinocyte cell cytopathogenicity. Functional assays showed that both samples caused apoptosis through the mitochondrial pathway and reduced mitochondrial membrane potential and ATP production, while increasing reactive oxygen species (ROS) and nicotinamide adenine dinucleotide phosphate (NADPH) cytochrome-c reductase in the cytosol. Whole transcriptome sequencing of A. castellanii showed the expression of 826 genes, with 447 genes being up-regulated and 379 genes being down-regulated post treatment. The Kyoto Encyclopedia of Genes and Genomes analysis showed that the majority of genes were linked to apoptosis, autophagy, RAP1, AGE-RAGE and oxytocin signalling pathways. Seven genes (PTEN, H3, ARIH1, SDR16C5, PFN, glnA GLUL, and SRX1) were identified as the most significant (Log2 (FC) value 4) for molecular mode of action in vitro. Future in vivo studies with AMS and nanoconjugates are needed to realize the clinical potential of this work.
棘阿米巴是自由生活的阿米巴原虫，是角膜炎和肉芽肿性阿米巴脑炎的病原体。α-倒捻子素（AMS）是一种重要的黄烷酮，具有广泛的生物活性。在这里，评估了 α-倒捻子素及其银纳米缀合物（AMS-AgNPs）对致病性棘阿米巴滋养体和包囊的体外抗阿米巴活性。杀阿米巴试验表明，AMS 和 AMS-AgNPs 均以剂量依赖性方式抑制棘阿米巴的活力，IC 分别为 88.5±2.04 和 20.2±2.17μM。两种制剂均抑制棘阿米巴介导的人角质形成细胞细胞病变作用。功能试验表明，两种样品均通过线粒体途径诱导细胞凋亡，并降低线粒体膜电位和 ATP 产生，同时增加细胞浆中的活性氧（ROS）和烟酰胺腺嘌呤二核苷酸磷酸（NADPH）细胞色素-c 还原酶。棘阿米巴的全转录组测序显示，826 个基因表达，其中 447 个基因上调，379 个基因下调。京都基因与基因组百科全书分析表明，大多数基因与细胞凋亡、自噬、RAP1、AGE-RAGE 和催产素信号通路有关。7 个基因（PTEN、H3、ARIH1、SDR16C5、PFN、glnA GLUL 和 SRX1）被确定为体外分子作用模式的最显著基因（Log2（FC）值为 4）。需要进行 AMS 和纳米缀合物的未来体内研究，以实现这项工作的临床潜力。
