目的 辨识菊花水提物中具有平肝降压作用的质量标志物（Q-Marker），建立其含量测定方法，为菊花及其相关产品的质量评价与质量标准完善提供科学依据。方法 采用超高效液相色谱（UPLC）技术构建10批不同产地菊花水提物的指纹图谱；建立肝旺痰阻型高血压大鼠模型，检测大鼠收缩压（SBP）、舒张压（DBP），采用试剂盒法测定血清总胆固醇（TC）、三酰甘油（TG）、天冬氨酸氨基转移酶（AST）、丙氨酸氨基转移酶（ALT）、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）水平；通过肝脏苏木精-伊红（HE）染色观察肝组织病理损伤情况，胸主动脉Masson染色观察胶原纤维增生及血管壁增厚程度；结合层次分析法（AHP）与灰色关联度法（GRA）进行谱效关联分析，筛选潜在Q-Marker并建立其UPLC含量测定方法。结果 10批菊花水提物样品指纹图谱相似度为0.740～0.989，共标定21个共有峰，成功指认15个化学成分；各批次样品均能显著降低模型大鼠SBP（P＜0.001）和DBP，有效调节血清TC、TG、AST、ALT、LDL-C、HDLC水平紊乱； HE染色结果显示，各批次样品可明显改善模型大鼠肝组织脂肪变性、水样变性，使肝索排列趋于规整； Masson染色结果表明，样品可减少胸主动脉胶原纤维增生，缓解血管壁增厚；经AHP-GRA筛选，确定绿原酸、木犀草苷、3,4-O-二咖啡酰奎宁酸、1,5-O-二咖啡酰奎宁酸、3,5-O-二咖啡酰奎宁酸、芹菜素-7-O-β-D-葡萄糖苷、4,5-O-二咖啡酰奎宁酸、香叶木素-7-O-β-D-葡萄糖苷8个成分为潜在Q-Marker。含量测定显示，8种成分的质量分数分别为3.59～11.50、1.88～20.22、4.84～19.49、2.47～8.18、3.33～9.05、0.87～16.63、6.27～18.62、0～5.37 mg·g^-1。结论 基于8个平肝降压Q-Marker建立的UPLC多指标定量方法准确、稳定、可靠，可用于菊花水提物的质量控制，为完善菊花质量标准、保障其临床功效稳定性提供实验支撑。

Objective To identify the quality markers (Q-Markers) with liver-calming and blood pressure-lowering effects in the aqueous extract of Chrysanthemum morifolium, establish a method for their content determination, and provide a scientific basis for the quality evaluation and standard improvement of C. morifolium and its related products. Methods Ultra-performance liquid chromatography (UPLC) was used to construct the fingerprint chromatograms of 10 batches of aqueous extracts of C. morifolium from different origins. A rat model of liver hyperactivity and phlegm obstruction type hypertension was established. The systolic blood pressure (SBP) and diastolic blood pressure (DBP) of the rats were measured. The levels of total cholesterol (TC), triglyceride (TG), aspartate aminotransferase (AST), alanine aminotransferase (ALT), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) in the serum were determined by kit methods. The pathological damage of liver tissue was observed by hematoxylin-eosin (HE) staining, and the degree of collagen fiber hyperplasia and vascular wall thickening in the thoracic aorta was observed by Masson staining. The spectral-effect correlation analysis was conducted by combining the analytic hierarchy process (AHP) and the grey relational analysis (GRA) to screen potential Q-Markers and establish their UPLC content determination methods. Results The similarity of the fingerprint chromatograms of the 10 batches of C. morifolium aqueous extracts was 0.740—0.989, and 21 common peaks were identified, with 15 chemical components successfully recognized. All batches of samples could significantly reduce the SBP (P<0.001) and DBP of the model rats, effectively regulate the disorder of serum TC, TG, AST, ALT, LDL-C, and HDL-C levels. The HE staining results showed that all batches of samples could significantly improve the fatty degeneration and hydropic degeneration of liver tissue in the model rats, and make the arrangement of hepatic cords more regular. The Masson staining results indicated that the samples could reduce the hyperplasia of collagen fibers in the thoracic aorta and alleviate the thickening of the vascular wall. Through AHP-GRA screening, eight components, namely chlorogenic acid, cynaroside, 3, 4-O-dicaffeoylquinic acid, 1, 5-O-dicaffeoylquinic acid, 3, 5-O-dicaffeoylquinic acid, apigenin-7-O-β-D-glucoside, 4, 5-O-dicaffeoylquinic acid, and diosmetin-7-O-β-D-glucoside, were identified as potential Q-Markers. The content determination showed that the mass fractions of the eight components were 3.59—11.50, 1.88—20.22, 4.84—19.49, 2.47—8.18, 3.33—9.05, 0.87—16.63, 6.27—18.62, and 0—5.37 mg·g^-1, respectively. Conclusion The UPLC multi-index quantitative method based on the eight Q-Markers for liver-calming and blood pressure-lowering effects is accurate, stable, and reliable, and can be used for the quality control of C. morifolium aqueous extracts, providing experimental support for improving the quality standards of C. morifolium and ensuring the stability of its clinical efficacy.

R284.1

湖北省自然科学基金资助项目（2025AFB681，2020CFA024）；国家留学基金委项目（201708420116）