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

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

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。

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 aurantioobtusina,rhein,emodin,chrysophanol,and physcion,are coordinated to produce protective effects against 5-Fu-induced liver injury in mice.