Tiwari Savitri, Kumar Reetesh, Devi Sonia, Sharma Prakriti, Chaudhary Neil Roy, Negi Sushmita, Tandel Nikunj, Marepally Srujan, Pied Sylviane, Tyagi Rajeev K
School of Biological and Life Sciences, Galgotias University, Gautam Buddha Nagar, Greater Noida, 201310, India.
Faculty of Agricultural Sciences, Institute of Applied Sciences and Humanities, GLA University, Mathura, 281406, India.
Discov Nano. 2024 Aug 31;19(1):136. doi: 10.1186/s11671-024-04098-2.
The suboptimal efficacies of existing anti-malarial drugs attributed to the emergence of drug resistance dampen the clinical outcomes. Hence, there is a need for developing novel drug and drug targets. Recently silver nanoparticles (AgNPs) constructed with the leaf extracts of Euphorbia cotinifolia were shown to possess antimalarial activity. Therefore, the synthesized AgNPs from Euphorbia cotinifolia (EcAgNPs) were tested for their parasite clearance activity. We determined the antimalarial activity in the asexual blood stage infection of 3D7 (laboratory strain) P. falciparum. EcAgNPs demonstrated the significant inhibition of parasite growth (EC of 0.75 µg/ml) in the routine in vitro culture of P. falciparum. The synthesized silver nanoparticles were seen to induce apoptosis in P. falciparum through increased reactive oxygen species (ROS) ROS production and activated programmed cell death pathways characterized by the caspase-3 and calpain activity. Also, altered transcriptional regulation of Bax/Bcl-2 ratio indicated the enhanced apoptosis. Moreover, inhibited expression of PfLPL-1 by EcAgNPs is suggestive of the dysregulated host fatty acid flux via parasite lipid storage. Overall, our findings suggest that EcAgNPs are a non-toxic and targeted antimalarial treatment, and could be a promising therapeutic approach for clearing malaria infection.
现有抗疟药物因耐药性的出现而疗效欠佳,这降低了临床治疗效果。因此,有必要开发新型药物和药物靶点。最近,用紫锦木叶片提取物构建的银纳米颗粒(AgNPs)显示出抗疟活性。因此,对从紫锦木中合成的银纳米颗粒(EcAgNPs)的寄生虫清除活性进行了测试。我们测定了其对恶性疟原虫3D7(实验室菌株)无性血液期感染的抗疟活性。在恶性疟原虫的常规体外培养中,EcAgNPs对寄生虫生长表现出显著抑制作用(半数有效浓度为0.75µg/ml)。合成的银纳米颗粒通过增加活性氧(ROS)的产生诱导恶性疟原虫细胞凋亡,并激活以半胱天冬酶-3和钙蛋白酶活性为特征的程序性细胞死亡途径。此外,Bax/Bcl-2比值转录调控的改变表明细胞凋亡增强。此外,EcAgNPs对PfLPL-1表达的抑制表明寄生虫脂质储存导致宿主脂肪酸通量失调。总体而言,我们的研究结果表明,EcAgNPs是一种无毒且有针对性的抗疟治疗方法,可能是清除疟疾感染的一种有前景的治疗途径。