Kumar Jitendra, Mitra Murli Dhar, Hussain Ahmad, Kaul Gautam
Animal Biochemistry Division, ICAR-National Dairy Research Institute, Karnal, Haryana, 132001, India.
Department of Chemistry, Indian Institute of Technology (IIT), Banaras Hindu University (BHU), Varanasi, Uttar Pradesh, 221005, India.
Mol Biol Rep. 2019 Apr;46(2):2447-2459. doi: 10.1007/s11033-019-04705-x. Epub 2019 Mar 7.
The current study was undertaken to investigate the immunomodulatory and protective effects of Withania somnifera (WS) extract and Withaferin A (WA) supplementation on zinc oxide nanoparticles mediated toxicity in Balb/c mice. The animals were exposed to ZnO NPs along with WS and WA for 28 days and various parameters like body weight, organ coefficient, cytotoxicity, nitric oxide (NO), total serum protein, phagocytosis, and the gene expression levels of TLR6 and ARG genes were determined. In vivo study showed that, dose-dependent reduction in phagocytosis, an increase in the levels of NO production along with up-regulation of TLR6, arginase gene was significant (P < 0.05) when ZnO NPs were given. However toxicity of ZnO NP was reduced in presence of WS and WA with decreased TLR6 over expression and restoration of phagocytic activities. Our results provided a valuable insight into the underlying mechanism for the protective effects of WS. Mechanism of toxicity induced by Zinc oxide nanoparticles ZnO NPs and immunomodulatory protective effects of Withania somnifera extract (WS) and Withaferin A (WA), in Balb/c mice modal of peritoneal macrophages. Red arrows: effect of ZnO NPs independently leads to ROS production which attenuated the phagocytosis of yeast by macrophages through, up-regulation of TLR6 and down-regulation of arginase gene expression. Green arrows: co-treatment, Impact of Withania somnifera extract with zinc oxide nanoparticles (WS + ZnO NPs), Withaferin A along with zinc oxide nanoparticles (WA + ZnO NPs)-enhance phagocytic activity by counteracting mechanism of ZnO NPs toxicity. Black arrows: increasing or decreasing effects. Per oral (P.O).
本研究旨在探讨印度人参（WS）提取物和睡茄内酯A（WA）对氧化锌纳米颗粒介导的Balb/c小鼠毒性的免疫调节和保护作用。将动物暴露于氧化锌纳米颗粒以及WS和WA中28天，并测定体重、器官系数、细胞毒性、一氧化氮（NO）、总血清蛋白、吞噬作用以及TLR6和精氨酸酶基因的基因表达水平等各种参数。体内研究表明，给予氧化锌纳米颗粒时，吞噬作用呈剂量依赖性降低，NO产生水平增加，同时TLR6、精氨酸酶基因上调显著（P < 0.05）。然而，在WS和WA存在的情况下，氧化锌纳米颗粒的毒性降低，TLR6过表达减少，吞噬活性恢复。我们的结果为WS保护作用的潜在机制提供了有价值的见解。在Balb/c小鼠腹腔巨噬细胞模型中，氧化锌纳米颗粒（ZnO NPs）诱导的毒性机制以及印度人参提取物（WS）和睡茄内酯A（WA）的免疫调节保护作用。红色箭头：ZnO NPs的作用独立导致活性氧生成，通过上调TLR6和下调精氨酸酶基因表达减弱巨噬细胞对酵母的吞噬作用。绿色箭头：联合处理，印度人参提取物与氧化锌纳米颗粒（WS + ZnO NPs）、睡茄内酯A与氧化锌纳米颗粒（WA + ZnO NPs）的作用——通过抵消ZnO NPs毒性机制增强吞噬活性。黑色箭头：增加或减少作用。口服（P.O）。
