基于谱⁃效关系的强力定眩片舒血管作用药效物质基础研究

Roles of pharmacodynamic substances of QiangliDingxuan tablets in vasodilation based on spectrum⁃effect relationships

目的研究强力定眩片高效液相(HPLC)指纹图谱与舒张血管作用药效之间的相关性,明确强力定眩片发挥舒张血管作用的潜在物质基础。方法采用离体肠系膜上动脉血管环舒张实验,以血管环舒张率为指标评价强力定眩片舒张血管作用,采用灰色关联度和偏最小二乘回归分析(PLSR)进行谱-效关联分析,快速筛选出其药效贡献较大成分。结果10批强力定眩片的HPLC指纹图谱共标定21个共有峰,相似度均在0.88以上,并指认了其中14个特征峰。离体血管环舒张实验表明,10批样品均有不同程度的舒张血管作用,21个共有色谱峰关联度均大于0.73,PLSR显示11种成分与强力定眩片的舒张血管作用成正相关,其中已知的6个化合物分别为巴利森苷A、巴利森苷C、5-羟甲基糠醛、木犀草素、蒙花苷和川芎嗪。结论强力定眩片的舒张血管是多种成分共同作用的结果。巴利森苷A、巴利森苷C、5-羟甲基糠醛、木犀草素、蒙花苷和川芎嗪与强力定眩片的舒张血管作用成正相关,可能是强力定眩片降压作用的主要药效物质基础。

Objective To establish the fingerprints of QiangliDingxuan tablets(QLDX),determine their pharmacodynamic indexes of vasodilation and study the spectrum-effect relationships between the chemical components of QLDX and the property of vasodilation.Methods The rate of vascular relaxation was used as an index to evaluate the extent to which QLDX relaxed isolated superior mesenteric artery ring.The Grey correlation degree and partial least square regression(PLSR)were used to analyze“spectrum-effect”correlations before components with greater contribution to drug efficacy were screened out.Results There were 21 common peaks in the HPLC fingerprint of QLDX,and the similarity exceeded 0.88.A comparison with the chromatogram of the reference substance revealed 14 characteristic peaks.Vasodilative experiments showed that all the 10 batches of samples had vasodilatory effects.The correlation between the 21 chromatographic peaks was greater than 0.73.PLSR showed that 11 components were positively correlated with the vasodilatory effect.Six known compounds included parishin A,parishin C,5-hydroxymethylfurfural,luteolin,Linarin and ligustrazine.Conclusion The vasodilatory effect of QLDX results from the combined action of multiple components.Parishin A,parishin C,5-hydroxymethylfurfural,luteolin,Linarin and ligustrazine are positively correlated with this effect,which may be the main pharmacodynamic substance basis of vascular relaxation.