Lin Longfei, Li Hui, Lin Hongmei, Zhang Miao, Qu Changhai, Yan Lei, Yin Xingbin, Ni Jian
Institute Chinese materia medica china academy of Chinese medical sciences, Beijing, China.
School of Chinese material medica, Beijing University of Chinese Medicine, Beijing, China.
Cell Physiol Biochem. 2017;43(5):2102-2116. doi: 10.1159/000484229. Epub 2017 Oct 24.
BACKGROUND/AIMS: Clinical reports on adverse reactions that result from Polygonum multiflorum (PM) and its preparations, especially regarding liver injury, have recently received widespread attention. This study aimed to investigate the mechanism of hepatotoxicity induced by different PM extracts through iTRAQ quantitative proteomics.
The different PM extracts were orally administrated for 90 days to rats, and the hepatotoxicity effect was evaluated through measurement of biochemical indexes, oxidative damage indexes and hematoxylin-eosin (HE) staining. Then, the hepatotoxicity mechanism was investigated by iTRAQ quantitative proteomics.
The results of biochemical and histopathological analyses showed that liver injury occurred in all groups of rats given by various PM extracts, which proved all of the PM extracts could induce hepatotoxicity. The hepatotoxicity mechanism may differ between the total extract group and the other groups through the results of biochemical indicators. The iTRAQ proteomics study showed that hepatotoxicity resulting from PM was mainly related to the abnormal activity of mitochondrion function-related oxidative phosphorylation pathways.
This iTRAQ proteomics study revealed that the hepatotoxicity induced by PM is primarily related to the oxidative phosphorylation pathways. NADH dehydrogenase family proteins and Slc16a2 could be potential biomarkers of hepatotoxicity resulting from PM.
背景/目的：何首乌（PM）及其制剂引起不良反应的临床报道，尤其是关于肝损伤的报道，近来受到广泛关注。本研究旨在通过iTRAQ定量蛋白质组学研究不同PM提取物诱导肝毒性的机制。
将不同的PM提取物经口给予大鼠90天，通过检测生化指标、氧化损伤指标及苏木精-伊红（HE）染色评估肝毒性作用。然后，通过iTRAQ定量蛋白质组学研究肝毒性机制。
生化和组织病理学分析结果显示，给予各种PM提取物的所有大鼠组均发生肝损伤，这证明所有PM提取物均可诱导肝毒性。通过生化指标结果表明，总提取物组与其他组之间的肝毒性机制可能不同。iTRAQ蛋白质组学研究表明，PM引起的肝毒性主要与线粒体功能相关的氧化磷酸化途径的异常活性有关。
本iTRAQ蛋白质组学研究表明，PM诱导的肝毒性主要与氧化磷酸化途径有关。NADH脱氢酶家族蛋白和Slc16a2可能是PM所致肝毒性的潜在生物标志物。
