Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan.
Exp Parasitol. 2012 Dec;132(4):519-23. doi: 10.1016/j.exppara.2012.09.007. Epub 2012 Sep 23.
Acanthamoeba is an opportunist protist pathogen that is known to infect the cornea to produce eye keratitis and the central nervous system to produce fatal granulomatous encephalitis. Early diagnosis, followed by aggressive treatment using a combination of drugs is a prerequisite in successful treatment but even then, prognosis remains poor due to lack of effective drugs. The overall aim of the present study was to determine the anti-Acanthamoebic potential of natural compounds, resveratrol and curcuminoids. Adhesion and cytotoxicity assays were performed using primary human brain microvascular endothelial cells, which constitute the blood-brain barrier. Pre-exposure of organisms to 100 μg resveratrol and demethoxy curcumin prevented amoeba binding by 57% and 73%, respectively, while cytotoxicity of host cells was inhibited by 86%. In an assay for viability of amoebae in the absence of host cells, resveratrol and de-methoxy curcumin exhibited significant amoebicidal effects (23% and 25%, respectively) at 100 μg concentrations (P<0.01). Neither resveratrol nor demethoxycurcumin had any effect on the proteolytic activities of Acanthamoeba castellanii. Of both compounds, resveratrol is of most interest for further investigation, because of the selective toxicity of resveratrol on A. castellanii but not the human brain microvascular endothelial cells.
棘阿米巴是一种机会主义原生动物病原体，已知会感染角膜引起眼部角膜炎，并感染中枢神经系统引起致命的肉芽肿性脑炎。早期诊断，随后使用药物联合进行积极治疗是成功治疗的前提，但即使如此，由于缺乏有效药物，预后仍然不佳。本研究的总体目标是确定天然化合物白藜芦醇和姜黄素类化合物的抗棘阿米巴潜能。使用构成血脑屏障的原代人脑微血管内皮细胞进行粘附和细胞毒性测定。将生物体预先暴露于 100μg 白藜芦醇和脱甲氧基姜黄素可分别阻止 57%和 73%的阿米巴结合，而宿主细胞的细胞毒性则被抑制 86%。在没有宿主细胞的情况下测定阿米巴的生存能力的试验中，白藜芦醇和脱甲氧基姜黄素在 100μg 浓度下表现出显著的杀阿米巴作用（分别为 23%和 25%）（P<0.01）。白藜芦醇和脱甲氧基姜黄素均未对棘阿米巴 Castellani 的蛋白水解活性产生任何影响。在这两种化合物中，白藜芦醇最值得进一步研究，因为白藜芦醇对棘阿米巴 Castellani 的选择性毒性，而对人脑微血管内皮细胞没有毒性。
