Zhou Di, Chang Wenhui, Qi Jiaxin, Chen Gang, Li Ning
Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China.
Chin Herb Med. 2022 Nov 4;15(1):76-85. doi: 10.1016/j.chmed.2022.11.001. eCollection 2023 Jan.
To study the protective activities of the dietary malate esters derivatives of against SiO nanoparticles-induced A549 cell lines and its mechanism action.
The components were isolated and elucidated by spectroscopic methods such as 1D NMR and 2D NMR. And MTT assays was used to tested these components on the A549 cell survival rates and ROS or proteins levels were detected by Western blotting.
A new glucosyloxybenzyl 2-isobutylmalate (a malate ester derivative), along with 31 known compounds were isolated and identified from -BuOH extract of EtOH extract of . Among them, compounds , , , and possessed noteworthy proliferative effects for damaged cells, with ED of 14.0, 13.1, 3.7, 11.6 and 11.5 µmol/L, respectively, compared to positive control resveratrol (ED, 14.7 µmol/L). Militarine () prominently inhibited the intracellular ROS level, and increased the expression of Nrf2 and its downstream genes (- and -). Furthermore, Nrf2 activation mediates the interventional effects of compound against SiO nanoparticles (nm SiO)-induced lung injury. Moreover, treatment with compound significantly reduced lung inflammation and oxidative stress in nm SiO-instilled mice. Molecular docking experiment suggested that bound stably to the HO-1 protein by hydrogen bond interactions.
The dietary malate esters derivatives of could significantly increase the viability of nm SiO-induced A549 cells and decrease the finer particles-induced cell damages. Militarine is especially promising compound for chemoprevention of lung cancer induced by nm SiO through activation of Nrf2 pathway.
研究[具体物质]的膳食苹果酸酯衍生物对二氧化硅纳米颗粒诱导的A549细胞系的保护作用及其作用机制。
通过一维核磁共振（1D NMR）和二维核磁共振（2D NMR）等光谱方法对成分进行分离和鉴定。采用MTT法检测这些成分对A549细胞存活率的影响，并通过蛋白质免疫印迹法检测活性氧（ROS）或蛋白质水平。
从[具体物质]乙醇提取物的正丁醇提取物中分离并鉴定出一种新的葡萄糖氧基苄基2 - 异丁基苹果酸酯（一种苹果酸酯衍生物）以及31种已知化合物。其中，化合物[具体编号1]、[具体编号2]、[具体编号3]、[具体编号4]和[具体编号5]对受损细胞具有显著的增殖作用，其半数有效剂量（ED）分别为14.0、13.1、3.7、11.6和11.5 μmol/L，与阳性对照白藜芦醇（ED，14.7 μmol/L）相比。麦角硫因（[具体名称]）显著抑制细胞内ROS水平，并增加核因子E2相关因子2（Nrf2）及其下游基因（[具体基因1]和[具体基因2]）的表达。此外，Nrf2激活介导了化合物[具体编号]对二氧化硅纳米颗粒（nm SiO）诱导的肺损伤的干预作用。而且，用化合物[具体编号]处理可显著减轻nm SiO注入小鼠的肺部炎症和氧化应激。分子对接实验表明，[具体物质]通过氢键相互作用与血红素加氧酶-1（HO-1）蛋白稳定结合。
[具体物质]的膳食苹果酸酯衍生物可显著提高nm SiO诱导的A549细胞的活力，并减少细颗粒物诱导的细胞损伤。麦角硫因是一种特别有前景的化合物，可通过激活Nrf2途径对nm SiO诱导的肺癌进行化学预防。
