Pharmacokinetic Effects of Cinnamic Acid, Amygdalin, Glycyrrhizic Acid and Liquiritin on Ephedra Alkaloids in Rats
Pharmacokinetic Effects of Cinnamic Acid, Amygdalin, Glycyrrhizic Acid and Liquiritin on Ephedra Alkaloids in Rats
复制标题
肉桂酸、苦杏仁苷、甘草酸和甘草苷对大鼠麻黄生物碱的药代动力学影响
DOI：
10.1007/s13318-016-0368-8
复制
发表时间：
2017-06
影响因子：
1.9
通讯作者：
Yu He
中科院分区：
文献类型：
--
作者：
Yinghong Tang;Mengkai Zheng;Yu-LinChen;Jianzhen Chen;Yu He
背景与目的麻黄生物碱（Ephedra alkaloids，Ephedra alkaloids）包括麻黄碱（ephedrine，EP）、伪麻黄碱（pseudoephedrine，PEP）和甲基麻黄碱（methylephedrine，MEP），是已知毒性较强的拟交感神经活性化合物。为探讨麻黄生物碱解毒的可能机制，研究了麻黄汤中4种代表性化合物（肉桂酸、苦杏仁苷、甘草酸和甘草苷）对麻黄生物碱在SD大鼠体内的药代动力学影响。大鼠经口给予EP-PEP-MEP（20 mg/kg EP + 20 mg/kg PEP + 20 mg/kg MEP）和肉桂酸的不同组合（3.03 mg/kg），苦杏仁苷（56.97 mg/kg），甘草酸（12.42 mg/kg），甘草苷（3.79 mg/kg）与EP-PEP-MEP，20 mg/kg EP + 20 mg/kg PEP + 20 mg/kg MEP + 3.03 mg/kg肉桂酸+ 56.97 mg/kg苦杏仁苷+ 12.42 mg/kg甘草酸+3.79 mg/kg甘草苷。在单次给药后5、10、20、30、45、60、90、120、180、240、300和360 min（每组每个时间点6只大鼠），从眶窦静脉丛采集血样（0.5 mL），置于肝素化试管中。结果EP、PEP和MEP的0 ~ 360 min药时曲线下面积（AUC 0-t）分别为666.99、650.76和632.37 μg·min/mL; EP、PEP和MEP的最大血药浓度（Cmax）分别为4.15、4.08和3.59 μg/mL。EP、PEP和MEP的平均滞留时间（MRT）分别为197.00、173.97和183.87 min。肉桂酸增加EP的AUC 0-t，降低EP的Cmax，苦杏仁苷和甘草酸增加EP和PEP的Cmax和AUC 0-t，甘草苷降低EP和PEP的AUC 0-t。4个代表性化合物降低EP、PEP和MEP的MRT，4个化合物降低MEP的AUC 0-tof。EP-PEP-MEP +肉桂酸+苦杏仁苷+甘草酸+甘草苷组增加EP的AUC 0-tofEP，降低EP的MRT，增加PEP的MRT，降低PEP的AUC 0-tofPEP。EP-PEP-MEP +肉桂酸+苦杏仁苷+甘草酸+甘草苷组能降低MEP的MRT、AUC 0-t和Cmax。本研究结果可为麻黄生物碱的临床应用提供参考。
Background and ObjectivesEphedra alkaloids, including ephedrine (EP), pseudoephedrine (PEP) and methylephedrine (MEP), are sympathomimetic compounds with known toxicities but many Ephedra (Ephedrae herba) preparations, such as Ephedra decoction, have been clinically applied for centuries. In order to explore the possible detoxification mechanism of Ephedra alkaloids, four representative compounds in Ephedra decoction (cinnamic acid, amygdalin, glycyrrhizic acid and liquiritin) were studied for their pharmacokinetic effects on Ephedra alkaloids in Sprague–Dawley rats.MethodsAnimals were randomly divided into six groups, with six rats in each. Rats were treated orally with EP–PEP–MEP (20 mg/kg EP + 20 mg/kg PEP + 20 mg/kg MEP) and different combinations of cinnamic acid (3.03 mg/kg), amygdalin (56.97 mg/kg), glycyrrhizic acid (12.42 mg/kg), liquiritin (3.79 mg/kg) with EP–PEP–MEP, and 20 mg/kg EP + 20 mg/kg PEP + 20 mg/kg MEP + 3.03 mg/kg cinnamic acid + 56.97 mg/kg amygdalin + 12.42 mg/kg glycyrrhizic acid + 3.79 mg/kg liquiritin. Blood samples (0.5 mL) were taken from the orbital sinus venous plexus into heparinized tubes at 5, 10, 20, 30, 45, 60, 90, 120, 180, 240, 300 and 360 min (6 rats per time point in each group) following single administration. The concentrations of Ephedra alkaloids in rat plasma were determined using a validated high performance liquid chromatography method.ResultsArea under the concentration-time curve from 0 to 360 min (AUC0–t) of EP, PEP and MEP were 666.99, 650.76 and 632.37 µg·min/mL, respectively. Maximum plasma concentration (Cmax) of EP, PEP and MEP were 4.15, 4.08 and 3.59 μg/mL, respectively. Mean residence time (MRT) of EP, PEP and MEP were 197.00, 173.97 and 183.87 min, respectively, when the rats were treated with EP–PEP–MEP. Cinnamic acid increased the AUC0–tof EP while decreasedCmaxof EP, amygdalin and glycyrrhizic acid increasedCmaxand AUC0–tof EP and PEP, while liquiritin decreased AUC0–tof EP and PEP. The four representative compounds reduced MRT of EP, PEP and MEP, four compounds decreased AUC0–tof MEP. The EP–PEP–MEP + cinnamic acid + amygdalin + glycyrrhizic acid + liquiritin group increased AUC0–tof EP while decreased MRT of EP, increased MRT of PEP while decreased AUC0–tof PEP. The EP–PEP–MEP + cinnamic acid + amygdalin + glycyrrhizic acid + liquiritin group decreased MRT, AUC0–tandCmaxof MEP.ConclusionsSignificant changes in pharmacokinetic parameters of EP, PEP and MEP were observed after oral administration with different combinations. The pharmacokinetic results reported here might provide reference for clinical usage of Ephedra alkaloids.
登录
查看更多内容
影响因子：
3.2
作者：
Hansen, Deborah K.;George, Nysia I.;Fabricant, Daniel
通讯作者：
Fabricant, Daniel
影响因子：
1.1
作者：
Macaulay Onuigbo;Mahmood Alikhan
通讯作者：
Macaulay Onuigbo;Mahmood Alikhan
影响因子：
--
作者：
Luo Jia-bo
通讯作者：
Luo Jia-bo
影响因子：
3.3
作者：
S. Kapoor
通讯作者：
S. Kapoor
DOI：
--
发表时间：
2005
期刊：
Traditional Chinese Drug Research and Clinical Pharmacology
影响因子：
--
作者：
Luo Jia-bo
通讯作者：
Luo Jia-bo