目的 采用谱效关联分析方法探索吴茱萸Euodia rutaecarpa抗炎活性的质量标志物（quality marker，Q-Marker），为其抗炎活性的质量控制提供依据。方法 采用超高效液相色谱（UPLC）对24批吴茱萸药材进行指纹图谱分析；以脂多糖诱导小鼠单核巨噬细胞RAW264.7建立体外炎症细胞模型，考察24批吴茱萸药材对细胞上清液中一氧化氮（nitric oxide，NO）以及细胞内诱导型一氧化氮合酶（inducible nitric oxide-synthase，iNOS）水平的影响；采用SPSS软件关联指纹图谱色谱峰峰面积与抗炎活性的关系，并采用UPLC-四级杆飞行时间质谱（QTOF-MS）对吴茱萸的抗炎活性成分进行指认。结果 24批吴茱萸药材对RAW264.7细胞上清液NO抑制率为12%～82%，谱效关联分析共筛选出14个吴茱萸潜在抗炎成分，分别为吴茱萸碱、吴茱萸次碱、去氢吴茱萸碱等吲哚喹唑啉类生物碱以及奎宁酸类成分、绿原酸类成分、喹诺酮类生物碱等。与模型组比较，柠檬苦素、吴茱萸碱、吴茱萸次碱、奎宁酸、去氢吴茱萸碱、二氢吴茱萸卡品碱、绿原酸、隐绿原酸可显著抑制RAW264.7细胞上清液中NO水平及细胞内iNOS水平（P<0.05、0.01）。结论 柠檬苦素、吴茱萸碱、吴茱萸次碱、奎宁酸、去氢吴茱萸碱、二氢吴茱萸卡品碱、绿原酸和隐绿原酸为吴茱萸抗炎活性的Q-Marker。

Objective To explore quality markers (Q-Marker) of anti-inflammatory activity of Wuzhuyu (Euodia rutaecarpa) by spectrum efficacy correlation analysis and provide basis for the quality control of anti-inflammatory effect of E. rutaecarpa. Methods Fingerprints of 24 batches of E. rutaecarpa were analyzed by ultra performance liquid chromatography (UPLC). LPS was used to induce RAW264.7 cells to establish an in vitro inflammatory cell model, the effect of 24 batches of E. rutaecarpa on nitric oxide (NO) levels in supernatant and intracellular inducible nitric oxide-synthase (iNOS) level were detected; SPSS software was used to correlate the relationship between fingerprint chromatographic peak area and anti-inflammatory drug efficacy. UPLC-quadrupole time-of-flight mass spectrometry (QTOF-MS) was used to identify anti-inflammatory active ingredients of E. rutaecarpa. Results NO inhibition rate of 24 batches of E. rutaecarpa extracts was 12% — 82%. A total of 14 potential anti-inflammatory components of E. rutaecarpa were screened out by spectrum-efficacy correlation, including indolequinazoline alkaloids such as evodiamine, rutaecarpine, dehydroaevodiamine, quinic acid, chlorogenic acid, and quinolone alkaloids. Compared with model group, limonin, evodiamine, rutaecarpine, quinic acid, dehydroaevodiamine, dihydroevodiacarpine, chlorogenic acid, and neochlorogenic acid significantly inhibited NO level in supernatant and iNOS level of RAW264.7 cells (P < 0.05, 0.01). Conclusion Limonin, evodiamine, rutaecarpine, quinic acid, dehydroaevodiamine, dihydroevodiacarpine, chlorogenic acid, and neochlorogenic acid may be anti-inflammatory Q-Marker of E. rutaecarpa.

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国家自然科学基金青年基金资助项目（81703707）；浙江省中医药科技计划项目（2019ZA038）；宁波市鄞州区农业与社会发展科技项目（20191YZQ010017）