State Key Laboratory of Functions and Applications of Medicinal Plants, Key Laboratory of Pharmaceutics of Guizhou Province, Guizhou Medical University, Guiyang, Guizhou 550004, P. R. China.
Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China.
J Agric Food Chem. 2020 Dec 23;68(51):15134-15141. doi: 10.1021/acs.jafc.0c04880. Epub 2020 Dec 9.
Methyleugenol (ME) is a ubiquitous component in spices and other culinary herbal products. A prevailing theory in ME toxicity is its ability to be metabolically activated by P450 enzymes and sulfotransferases, which initiates sequential reactions of the resulting metabolites with functional biomolecules. The present study aimed at a potential interaction between the reactive metabolites of ME and RNA. Cultured mouse primary hepatocytes were incubated with ME followed by RNA extraction and NaOH and alkaline phosphatase-based RNA hydrolysis. Three adenosine adducts were detected in the hydrolytic mixture by LC-MS/MS. The same adenosine adducts were also detected in hepatic tissues harvested from ME-treated mice. These three adducts were chemically synthesized and structurally characterized by H NMR. Additionally, two guanosine adducts and one cytidine adduct were detected in the samples. These results provided solid evidence that the reactive metabolites of ME attacked RNA, resulting in RNA adduction.
甲氧基丁香酚（ME）是香料和其他烹饪草药产品中普遍存在的成分。ME 毒性的一个流行理论是它能够被 P450 酶和磺基转移酶代谢激活，这引发了代谢物与功能生物分子的连续反应。本研究旨在研究 ME 的反应性代谢物与 RNA 之间的潜在相互作用。用 ME 孵育培养的小鼠原代肝细胞，然后提取 RNA，并进行 NaOH 和碱性磷酸酶基础的 RNA 水解。通过 LC-MS/MS 在水解混合物中检测到三种腺苷加合物。在接受 ME 处理的小鼠的肝组织中也检测到相同的腺苷加合物。这三种加合物通过 1 H NMR 进行了化学合成和结构表征。此外，在样品中还检测到两种鸟苷加合物和一种胞嘧啶加合物。这些结果为 ME 的反应性代谢物攻击 RNA 导致 RNA 加合提供了确凿的证据。
