UPLC-Q-Exactive-MS analysis for hepatotoxicity components of Evodiae Fructus based on spectrum-toxicity relationship
UPLC-Q-Exactive-MS analysis for hepatotoxicity components of Evodiae Fructus based on spectrum-toxicity relationship
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基于谱毒关系的吴茱萸肝毒性成分UPLC-Q-Exactive-MS分析
DOI：
10.1016/j.jchromb.2021.122772
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发表时间：
2021
影响因子：
3
通讯作者：
Liu Xiaoqiu
中科院分区：
文献类型：
--
作者：
Zhang Wei;Ren Kun;Ren Shumeng;Lv Shuang;Pan Yingni;Wang Dongmei;Morikawa Toshio;Liu Xiaoqiu
在商品流通中，吴茱萸一般按果实大小分为小花吴茱萸、中花吴茱萸和大花吴茱萸三类。甘草是治疗胃肠功能紊乱引起的胃痛、头痛的常用中药，其肝毒性引起了广泛关注。然而，关于肝毒性的报道是有争议的，肝毒性成分是不确定的。本研究旨在解释EF肝毒性的争议，并根据谱毒关系筛选与EF肝毒性相关的成分。建立了39批不同产地羊栖菜的UPLC指纹图谱。结合L02细胞活力测定结果，采用正交偏最小二乘法（OPLS）对光谱-毒性关系进行了研究。结果表明，不同种类的EF毒性差异明显，其中SEF毒性较小，MEF（除掺伪品外）和BEF毒性较轻，MEF掺伪品（A-MEF）对L02细胞的损伤较大，EF肝毒性无区域特异性。其中，含量不符合《中国药典》要求的样品为掺假品。P11、P17、P20和P25与EF的肝毒性密切相关，分别鉴定为柠檬苦素（limonin，LIM）、吴茱萸碱（evodiamine，EVO）、1-甲基-2-壬基-4（1H）-喹诺酮（1-methyl-2-nonyl-4（1H）-quinolone，MNQ）、和1-甲基-2-十一烷基-4（1H）-喹诺酮（MUQ），通过UPLC-Q-Exactive-P11的肝保护作用和P17的肝毒性与谱毒关系的结果一致。总之，A-MEF的毒性高于其他类别，SEF的毒性低于其他类别。值得注意的是，EVO是EF的主要肝毒性成分，LIM是EF的主要肝保护成分。研究结果为更好地利用和开发EF提供了有价值的依据。
Evodiae Fructus (EF) is generally divided into three categories: small flower EF (SEF), medium flower EF (MEF) and big flower EF (BEF) in commodity circulation according to the size of the fruit. It is a well-known and frequently used herbal medicine for treating gastrointestinal disorder-related stomachache and headache, which has aroused wide attention for its hepatotoxicity. However, reports about hepatotoxicity is controversial and hepatotoxic components are inconclusive. The study aimed to explain the controversial hepatotoxicity of EF and screen the components associated with hepatotoxicity of EF based on the spectrum-toxicity relationship. UPLC fingerprints of 39 batches of EF collected from different regions were established. Combined with the results of L02 cell viability assays, the spectrum-toxicity relationship was investigated on the basic of orthogonal partial least squares (OPLS). The results of the research demonstrated that the toxicity of EF was obviously various among the different categories, in particularly, SEF was with less toxicity, MEF except for adulterants and BEF had mild toxicity and adulterants of MEF (A-MEF) produced more damage to L02 cell and no regions specificity in hepatotoxicity of EF. Thereinto, samples, the contents of which do not meet the requirements of Chinese Pharmacopoeia, were adulterants. It was worth noting that P11, P17, P20 and P25 were closely related to hepatotoxicity of EF and they were respectively identified as limonin (LIM), evodiamine (EVO), 1-methyl-2-.nonyl-4(1H)-quinolone (MNQ), and 1-methyl-2-undecyl-4(1H)-quinolone (MUQ) by UPLC-Q-Exactive-MS. The hepatoprotection of P11 and hepatotoxicity of P17 were consistent with the results of spectrum-toxicity relationship. In summary, A-MEF was more toxic than other categories and SEF was less toxic than the others. It was noteworthy that EVO was the main hepatotoxic component of EF and LIM was the main hepatoprotective component of EF. The results provided worthy evidence for better utilization and development of EF.