Metabolic profiles of corydaline in rats by ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry

1. Corydaline, an isoquinoline alkaloid obtained from the rhizomes of Corydalis yanhusuo, exhibits anti-acetylcholinesterase, anti-angiogenic, anti-allergic and gastric-emptying activities. In this study, a rapid and reliable ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS) method was developed and employed for the comprehensive study of the metabolites of corydaline in rats.

2. Altogether, 43 metabolites were identified in the plasma (11), bile (9), urine (34) and feces (21) of rats after oral administration of corydaline at a dose of 4.5mg/kg.

3. It was demonstrated that demethylation, hydroxylation, sulfation and glucuronidation were the major metabolic transformation pathways. Among these, two metabolites were identified as tetrahydropalmatine and isocorybulbine, and 33 phase I and phase II products were inferred to be new metabolites arising from the in vivo metabolism of corydaline.

4. Importantly, this research provides scientific and reliable support for full understanding of the metabolic profiles of corydaline and the results could help to elucidate its safety and efficacy.     

延胡索提取物在大鼠肠外翻实验中的吸收研究

目的:利用肠外翻模型研究延胡索提取物不同剂量在大鼠不同肠段的吸收特征。方法:采用大鼠肠外翻模型,HPLC检测延胡索提取物中的延胡索甲素(CDL)和延胡索乙素(THP),计算各成分的吸收参数,分析它们在肠道不同部位的吸收特征。结果:不同浓度延胡索提取物中CDL和THP在各肠段均为线性吸收,R2均大于0.95,符合零级吸收;CDL和THP的吸收速率常数(Ka)均随延胡索提取物给药剂量的增加而增加(P<0.05),表明其为被动吸收。肠道不同部位的吸收实验表明,十二指肠,空肠,回肠对其均有较好的吸收,结肠吸收较差;且肠道对THP的吸收好于对CDL的吸收。结论:不同浓度延胡索提取物CDL和THP在肠道不同部位吸收均符合零级吸收速率,其吸收形式可能为被动吸收。     

Corydaline inhibits enterovirus 71 replication by regulating COX-2 expression

Enterovirus 71 (EV71) is a huge threat to the worldwide public health and there is no approved antiviral drug for EV71-induced disease therapy. Corydaline exists antiallergic and antinociceptive activities, but the anti-EV71 activity of corydaline is still not reported. In this study, corydaline could suppress the expression of viral structural and non-structural proteins. Furthermore, corydaline inhibits EV71 replication by suppressing the COX-2 expression and the phosphorylation of JNK MAPK and P38 MAPK but not ERK MAPK in vitro. Based on these findings, corydaline could be a potential lead or supplement for the development of new anti-EV71 agents in the future.     

高效液相色谱波长切换法联合梯度洗脱法同时测定理气散结颗粒中6种成分的研究

目的 探讨高效液相色谱(HPLC)波长切换联合梯度洗脱法同时测定理气散结颗粒中芍药苷、柴胡皂苷a、柴胡皂苷d、延胡索乙素、去氢紫堇碱和紫堇碱6种成分的含量可行性.方法 采用Agilent TC-C18色谱柱;以乙腈(A)-0.1%冰醋酸溶液(B)为流动相,梯度洗脱;检测波长分别为230 nm(芍药苷)、210 nm(柴胡皂苷a和柴胡皂苷d)、280 nm(延胡索乙素、去氢紫堇碱和紫堇碱);流速:1.0 mL·min-1;柱温:35℃.结果 芍药苷、柴胡皂苷a、柴胡皂苷d、延胡索乙素、去氢紫堇碱和紫堇碱分别在14.39~359.75 mg·L-1、1.96~49.00 mg·L-1、1.44~36.00 mg·L-1、1.36~34.00 mg·L-1、1.58~39.50 mg·L-1、2.12~53.00 mg·L-1范围内线性关系良好,r分别为0.9998、0.9995、0.9999、0.9994、0.9997、0.9999(n=6),其平均回收率分别为99.87%、97.75%、98.09%、97.46%、98.29%和96.97%,RSD分别为0.84%、1.74%、0.71%、1.39%、1.07%和1.11%.结论 该方法简便、准确、重复性好,可作为理气散结颗粒全面质量控制方法.     

Acetylcholinesterase and butyrylcholinesterase inhibitory compounds from Corydalis cava Schweigg. & Kort

In the course of screening plants used in Danish folk medicine as memory enhancers, a crude methanolic extract of tubers from Corydalis cava showed significant acetylcholinesterase inhibitory activity in a dose-dependent manner. Activity guided fractionation of the methanolic extract resulted in the isolation of three alkaloids, bulbocapnine (1), corydaline (2) and corydine (3) as active constituents. Bulbocapnine inhibited acetylcholinesterase as well as butyrylcholinesterase in a dose-dependent manner with IC(50) values of 40+/-2 microM and 83+/-3 microM, respectively. Corydaline inhibited acetylcholinesterase in a dose-dependent manner with an IC(50) value of 15+/-3 microM and corydine inhibited butyrylcholinesterase in a dose-dependent manner with an IC(50) value of 52+/-4 microM. Corydaline was considered inactive against butyrylcholinesterase and corydine against acetylcholinesterase, due to IC(50)>100 microM.     

白花土元胡药材中延胡索甲素和乙素的含量测定

目的 建立测定白花土元胡药材中延胡索甲素和乙素含量的方法.方法 采用RP-HPLC外标法,Symmetry C18色谱柱(150 mm×4.6 mm,5 μm);乙腈为流动相A,0.1%磷酸溶液(三乙胺调pH6)为流动相B,梯度洗脱;检测波长282 nm.结果 延胡索甲素在10.40～208.00 μg·ml-1范围内线性关系良好,平均回收率为98.5%,RSD=3.1%;延胡索乙素在10.10～505.00 μg·ml-1范围内线性关系良好,平均回收率为101.9%,RSD=2.3%.结论 所建方法结果准确可靠,适用于白花土元胡中延胡索甲素和乙素含量的同时测定.