南方医科大学学报

南方医科大学学报 ›› 2023, Vol. 43 ›› Issue (5): 825-831.doi: 10.12122/j.issn.1673-4254.2023.05.19

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决明子总蒽醌提取物抗氟尿嘧啶致小鼠肝损伤的谱效关系

王 恒，李梦奇，李燊星，史精干，黄 莉，程索婷，邹纯才，鄢海燕   

  1. 皖南医学院药学院，安徽 芜湖 241002
  • 出版日期:2023-05-20 发布日期:2023-06-12

Spectrum-effect relationship of total anthraquinone extract of Cassia seeds against fluorouracil-induced liver injury in mice

WANG Heng, LI Mengqi, LI Shenxing, SHI Jinggan, HUANG Li, CHENG Suoting, ZOU Chuncai, YAN Haiyan   

  1. School of Pharmacy, Wannan Medical College, Wuhu 241002, China
  • Online:2023-05-20 Published:2023-06-12

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摘要： 目的 研究决明子总蒽醌提取物抗氟尿嘧啶（5-Fu）致小鼠肝损伤的谱效关系，明确其药效成分群。方法 通过腹腔注射5-Fu建立小鼠肝损伤模型，以联苯双酯为阳性对照，检测各组小鼠血清丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）以及肝组织中髓过氧化物酶（MPO）、超氧化物歧化酶（SOD）、总抗氧化能力（T-AOC）的活性，考察决明子总蒽醌提取物（0.4、0.8和1.6 g/kg）抗5-Fu致小鼠肝损伤的作用。建立10批决明子总蒽醌提取物HPLC指纹图谱。基于灰色关联度法研究决明子总蒽醌提取物抗5-Fu致小鼠肝损伤的谱效关系并筛选其药效成分群。结果 与正常组比较，模型组各项指标差异均有统计学意义（P<0.05），提示造模成功。与模型组比较，决明子总蒽醌提取物各剂量组小鼠血清中ALT、AST活性显著降低（P<0.05）；SOD、T-AOC活性显著升高（P<0.05）；MPO水平显著降低（P<0.05）。决明子总蒽醌提取物HPLC指纹图谱中31个成分与抗5-Fu致小鼠肝损伤的药效指标具有较好的关联性，但关联度不同。位于关联度前15位且已知的成分分别为橙黄决明素（第6号峰）、大黄酸（第11号峰）、大黄素（第22号峰）、大黄酚（第29号峰）及大黄素甲醚（第30号峰）。结论 决明子总蒽醌提取物各成分相互协调发挥抗5-Fu致小鼠肝损伤的保护作用，其中橙黄决明素、大黄酸、大黄素、大黄酚及大黄素甲醚是决明子总蒽醌提取物抗5-Fu致小鼠肝损伤的药效成分群。

关键词: 决明子总蒽醌提取物；氟尿嘧啶；肝损伤；谱效关系；药效成分群

Abstract: Objective To investigate the spectrum-effect relationship between the total anthraquinone extract of Cassia seeds and fluorouracil (5-Fu)-induced liver injury in mice and identify the effective components in the extract. Methods A mouse model of liver injury was established by intraperitoneal injection of 5-Fu, with bifendate as the positive control. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and myeloperoxidase (MPO), superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) in the liver tissue were detected to investigate the effect of the total anthraquinone extract of Cassia seeds (0.4, 0.8 and 1.6 g/kg) on liver injury induced by 5-Fu. HPLC fingerprints of 10 batches of the total anthraquinone extracts were established to analyze the spectrum- effectiveness of the extract against 5- Fu-induced liver injury in mice and screen the effective components using the grey correlation method. Results The 5- Fu- treated mice showed significant differences in liver function parameters from the normal control mice (P<0.05), suggesting successful modelling. Compared with those in the model group, serum ALT and AST activities were decreased, SOD and T-AOC activities significantly increased, and MPO level was significantly lowered in the mice treated with the total anthraquinone extract (all P<0.05). HPLC fingerprints of the 31 components in the total anthraquinone extract of Cassia seeds showed good correlations with the potency index of 5-Fu-induced liver injury but with varying correlation strengths. The top 15 components with known correlations included aurantio-obtusina (peak 6), rhein (peak 11), emodin (peak 22), chrysophanol (peak 29) and physcion (peak 30). Conclusion The effective components in the total anthraquinone extract of Cassia seeds, including aurantio-obtusina, rhein, emodin, chrysophanol, and physcion, are coordinated to produce protective effects against 5-Fu-induced liver injury in mice.

Key words: total anthraquinone extract from Cassia seeds; fluorouracil; liver injury; spectral effect relationships; effective components