盐肤木根中1个17-表-达玛烷型三萜rhuslactone的分离、含量测定及其预防斑马鱼冠心病及血栓活性研究  

Isolation and quantification of a 17-epi-dammarane triterpenoid rhuslactone from roots of Rhus chinensis and its preventive effects on coronary heart disease and thrombosis in zebrafish

作　　者：阮铃杰 黄丽娜 高鑫怡 赖长杰 张琳婧 吴渝凡 沙玫[1] 叶淼[1,2] RUAN Ling-jie;HUANG Li-na;GAO Xin-yi;LAI Chang-jie;ZHANG Lin-jing;WU Yu-fan;SHA Mei;YE Miao(College of Pharmacy,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China;Centre of Biomedical Research&Development,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China)

机构地区：[1]福建中医药大学药学院,福建福州350122 [2]福建中医药大学生物医药研发中心,福建福州350122

出　　处：《中国中药杂志》2023年第6期1558-1567,共10页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金项目(81803678);福建省自然科学基金项目(2020J01734)。

摘　　要：采用质谱引导分离技术,从盐肤木根中得到化合物1。其HR-ESI-MS、NMR数据及量子化学计算核磁共振参数(qcc-NMR)计算结果表明,化合物1(rhuslactone)为罕见的17-表-达玛烷型三萜,含17α侧链。建立HPLC-ELSD测定盐肤木根中rhuslactone含量,方法经验证后,应用于不同批次药材的含量测定。rhuslactone在0.0213~1.07μmol·mL^(-1)呈良好线性关系(r=0.9976),平均加样回收率为99.34%(RSD 2.9%)。预防斑马鱼冠心病及血栓活性评价实验表明,rhuslactone在0.11 nmol·mL^(-1)时显著减少冠心病斑马鱼的心脏扩大及静脉窦淤血面积,增加心输出量(CO)、血流速度(BFV)和心率,明显减少血栓形成。对CO和BFV的改善作用优于1.02 nmol·mL^(-1)的阳性药物地高辛,改善心率作用与地高辛相当。该研究为盐肤木根中rhuslactone的分离鉴定、质量控制及抗冠心病应用提供实验依据。值得一提的是,该研究指出现行版《中药化学》教材及部分科研论文在鉴定达玛烷型三萜C-17构型上存在的疏漏:未考虑化合物为17-表-达玛烷型三萜的可能性,作者还整理了确定C-17构型的步骤。Based on mass spectrometry(MS)-guided separation strategy,compound 1 was obtained from the roots of Rhus chinensis.By comprehensive analysis of high resolution-electrospray ionization-mass spectrometry(HR-ESI-MS),nuclear magnetic resonance(NMR)data,and quantum chemical calculation of NMR(qcc-NMR)parameters,compound 1 was elucidated as rhuslactone,a 17-epi-dammarane triterpenoid with a rare 17α-side chain.An HPLC-ELSD method for its quantification in R.chinensis was established and adopted for the quantification of rhuslactone in different batches of R.chinensis.Rhuslactone displayed a good linear relationship within the range of 0.0213-1.07μmol·mL^(-1)(r=0.9976),and the average recovery was 99.34%[relative standard deviation(RSD)2.9%).Moreover,the results of the evaluation test of the preventive effects of rhusalctone on coronary heart disease(CHD)and thrombosis showed that rhuslactone(0.11 nmol·mL^(-1))significantly alleviated heart enlargement and venous congestion and increased cardiac output(CO),blood flow velocity(BFV),and heart rate,thereby reducing thrombus formation in zebrafish with CHD.The effects of rhuslactone on CO and BFV were superior to that of digoxin(1.02 nmol·mL^(-1)),and its effect on improving heart rate was comparable to that of digoxin.This study provides experimental references for the isolation,identification,quality control,and application of rhuslactone from R.chinensis against CHD.It is worth mentioning that this study has discussed some omissions in the determination of the stereochemistry of C-17 in dammarane triterpenoids in the present coursebook Chemistry of Chinese Medicine and some research papers,that is,the compound may be 17-epi-dammarane triterpenoid.This paper has also proposed steps for the establishment of C-17 stereochemistry.

关 键 词：盐肤木 rhuslactone qcc-NMR 17-表-达玛烷型三萜 C-17立体构型 冠心病 血栓 

分 类 号：R284.1[医药卫生—中药学] R285[医药卫生—中医学]