Screening and identification of hepatotoxic component in Evodia rutaecarpa based on spectrum-effect relationship and UPLC-Q-TOFMS
Screening and identification of hepatotoxic component in Evodia rutaecarpa based on spectrum-effect relationship and UPLC-Q-TOFMS
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DOI：
10.1002/bmc.3774
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发表时间：
2016-12-01
影响因子：
1.8
通讯作者：
Ji, Yubin
中科院分区：
文献类型：
--
作者：
Li, Wenlan;Sun, Xiangming;Ji, Yubin
吴茱萸(Evodia Rutaecarpa)在中医中被用来治疗疼痛、呕吐和痢疾。然而，作为一种毒性较小的草本植物，其毒性成分尚未阐明。对吴茱萸的肝毒性成分进行了研究。用19种不同来源的吴茱萸50%乙醇提取物建立超微结构指纹图谱，给小鼠灌胃35g/kg(生药量/小鼠体重)，每日1次，连续14d。以血清丙氨酸氨基转移酶、天冬氨酸氨基转移酶和肝系数作为肝损伤指标。此外，还鉴定了19个指纹图谱的特征峰。采用双变量相关分析(BCA)分析指纹图谱与肝毒性指标之间的光谱效应关系。建立了超高效液相色谱指纹图谱，共鉴定出28种主要化合物。由于化学成分的内在差异，来自19个产地的吴茱萸样品的肝脏损伤程度不同。生物化学分析结果表明，初步确定化合物二氢乌甲卡品、6-乙酰氧基-5-表皮藤素、钩藤酰胺I、1-甲基-2-[(Z)-5-十一烯基]-4(1H)-喹诺酮、1-methyl-2-[(4Z，7Z)-4，7-tridecadienyl]-4(1H)-quinolone，吴茱萸碱和1-methyl-2-[(6Z，9Z)-6，9-pentadecadienyl]-4(1H)-quinolone为主要的肝毒性成分。本研究为利用指纹图谱和肝毒性指数相结合的方法发现肝毒性成分提供了一种有价值的方法。
Evodia rutaecarpa (E. rutaecarpa) has been used to treat aches, vomiting and dysentery in traditional Chinese medicine. However, as a mildly toxic herb its toxic components have not been elucidated. An attempt was made to illuminate the hepatotoxic constituents of E. rutaecarpa. The 50% ethanol extracts of E. rutaecarpa from 19 different sources were used to establish UPLC fingerprints and administered to mice at a dose of 35g/kg (crude medicine weight/mouse weight) once daily for 14days. Serum levels of alanine transaminase, aspartate aminotransferase and liver coefficient were used as indices of liver injury. Additionally, the characteristic peaks of 19 fingerprints were identified. Spectrum-effect relationships between fingerprints and hepatotoxic indicators were analyzed using bivariate correlation analysis (BCA). The UPLC fingerprints were established and a total of 28 main compounds were identified. Because of the inherent variations in chemical compositions, the liver injury levels were different among the E. rutaecarpa samples from 19 sites of production. BCA results indicated that compounds dihydrorutaecarpine, 6-acetoxy-5-epilimonin, goshuyuamide I, 1-methyl-2-[(Z)-5-undecenyl]-4(1H)-quinolone, 1-methyl-2-[(4Z,7Z)-4,7-tridecadienyl]-4(1H)-quinolone, evocarpine and 1-methyl-2-[(6Z,9Z)-6,9-pentadecadienyl]-4(1H)-quinolone were tentatively determined as the primary hepatotoxic components. The present study provides a valuable method for the discovery of hepatotoxic constituents by combination of fingerprints and hepatotoxicity index.