Objective: The characteristics of excretion kinetics of euphorbia factor L1, L2 and L3 in rat urine and feces were studied after intragastric administration of crude and frost extracts of Euphorbiae Semen based on UPLC-MS/MS technology. Methods: The SD rats were respectively gavaged with crude and frost extracts of Euphorbiae Semen, then urine and feces of the rats were collected before and after administration. The concentrations of three diterpene esters of Euphorbiae Semen before and after frosting were determined by the established UPLC-MS/MS method. The urinary excretion kinetic parameters were calculated by DAS 2.0 software, the cumulative excretion rate and excretion rate curves were drawn, and the differences of excretion kinetics before and after frosting were compared. Results: After 96 hours of oral administration of Euphorbiae Semen extract, the cumulative excretion rates of euphorbia factor L1, L2 and L3 in urine were 0.009%, 0.008% and 0.009%, respectively, and the cumulative excretion rates in feces were 16.05%, 51.57% and 36.33%, respectively. After 96 hours of oral administration of Euphorbiae Semen pulveratum extract, the cumulative excretion rates of euphorbia factor L1, L2 and L3 in urine were 0.014%, 0.01% and 0.011%, respectively, and the cumulative excretion rates in feces were 27.32%, 59.03% and 35.97%, respectively. Conclusion: The three diterpenoid alcohol esters of Euphorbiae Semen were mainly excreted through feces. After frosting, the t1/2 of euphorbia factor L1, L2 and L3 decreased, while the ke increased. The decrease of toxicity Euphorbiae Semen after frosting may be related to the increase of drug excretion from the body and the decrease of drug accumulation in vivo.
WANG Pei-hua, WANG Ying-zi, WANG Hui-nan, YANG Zi-ye, ZHANG Gui-mei, CHEN Meng-yu, JIANG Ming-rui, YUE Zhu-zhu, WANG Zhi-cheng, ZHANG Jing-qiu
. Study on excretion kinetics of three main diterpene esters in rats of Euphorbiae Semen before and after frosting based on UPLC-MS/MS technique*[J]. Chinese Journal of Pharmaceutical Analysis, 2021
, 41(11)
: 1904
-1913
.
DOI: 10.16155/j.0254-1793.2021.11.07
[1] 中国科学院中国植物志编辑委员会.中国植物志[M]. 北京: 科学出版社, 1997
Editorial Committee of Chinese Flora. Chinese Academy of Sciences,Flora Republicae Popularis Sinicae[M]. Beijing: Science Press, 1997
[2] 中华人民共和国药典2020年版.一部[S]. 2020: 36
ChP 2020.Vol Ⅰ [S]. 2020:36
[3] 宋卫国, 孙付军, 张敏, 等. 千金子和千金子霜及其主要成分泻下作用研究[J].中药药理与临床, 2010, 26(4):40
SONG WG, SUN FJ, ZHANG M, et al. Study on the purging effect of Euphorbiae Semen and Euphorbiae Semen pulveratum and its main components[J].Pharmacol Clin Chin Mater Med, 2010, 26(4):40
[4] 赵俊峰, 李豪, 肖耀军, 等. 千金子对肾癌Renca细胞周期及侵袭能力的影响[J].中国老年学杂志, 2019, 39(22):5599
ZHAO JF, LI H, XIAO YJ, et al. Effect of Euphorbiae Semen on cell cycle and invasive ability of Renca renal cell[J].Chin J Gerontol, 2019, 39(22):5599
[5] ZHANG JY, LIN MT, YI T, et al. Apoptosis sensitization by Euphorbia factor L1 in ABCB1-mediated multidrug resistant K562/ADR cells[J].Molecules, 2013, 18(10):12793
[6] 余霞, 张卫明, 孙力军. 千金子不同极性部位对酪氨酸酶活性的影响[J].中国野生植物资源, 2011, 30(2):51
YU X, ZHANG WM, SUN LJ. The effect of different polarity fractions of extract from Semen Euphorbiae Lathyridis on the activity of tyrosinase[J].Chin Wild Plant Res, 2011, 30(2):51
[7] 孟夏, 侯朋艺, 陈晓辉. 千金子毒性作用的研究进展[J].中国药房, 2013, 24(7):657
MENG X, HOU PY, CHEN XH. Research progress on toxicity of Euphorbiae Semen[J].J China Pharm, 2013, 24(7):657
[8] 冯堃, 杜正浩, 李成文. 峻下逐水药千金子药用价值商榷[J].中医药学报, 2008, 36(3):77
FENG K, DU ZH, LI CW. Discussion on the medicinal value of Euphorbiae Semen, a drastichydrogogues[J].Acta Chin Med Pharm, 2008, 36(3):77
[9] 朱娟娟, 辛义周, 马传江. 千金子炮制减毒机理的研究进展[J].药学研究, 2020, 39(3):153
ZHU JJ, XIN YZ, MA CJ. Study on attenuation mechanism of processing of Semen Euphorbiae[J].J Pharm Res, 2020, 39(3):153
[10] 张晓菲. 基于药代动力学研究诃子对草乌“解毒存效”的机理[D]. 呼和浩特:内蒙古医科大学, 2019
ZHANG XF. The Mechanism of Detoxification and Retention Effect of Terminalia Chebula on Radix Aconiti Kusnezoffii based on Pharmacokinetics[D]. Hohhot: Inner Mongolia Medical University, 2019
[11] 王莉. 丹参、人参标准提取物复方配伍在大鼠体内的药动学研究[D]. 沈阳:沈阳药科大学, 2010
WANG L. Studies on Pharmacokinetics of Extract of Radix et Rhizoma Salviae miltiorrhiza and Extract of Radix et ginseng in Rat[D]. Shenyang: Shenyang Pharmaceutical University, 2010
[12] 闫海霞. 鼠尾草酸在大鼠体内的药物动力学及代谢研究[D]. 沈阳:沈阳药科大学, 2008
YAN HX. Studies on the Pharmacokinetics and Metabolism of Carnosic Acid in Rats[D]. Shenyang: Shenyang Pharmaceutical University, 2008
[13] 张超, 朱娟娟, 王英姿, 等. HPLC法测定千金子不同极性部位中二萜酯类化合物含量[J].山东中医药大学学报, 2014, 38(5):485
ZHANG C, ZHU JJ, WANG YZ, et al. Comparison of content of diterpene esters from different polar fractions in Euphorbiae Semen by HPLC method[J].J Shandong Univ Tradit Chin Med, 2014, 38(5):485
[14] 朱娟娟, 张超, 王英姿, 等. 千金子石油醚部位化学成分的研究[J].山东中医药大学学报, 2014, 38(4):381
ZHU JJ, ZHANG C, WANG YZ, et al. Study on chemical constituents of petroleum ether extractant of semen euphorbiae[J].J Shandong Univ Tradit Chin Med, 2014, 38(4):381
[15] 李志华, 颜苗, 张毕奎, 等. 基于药动学的甘草配伍减毒机制研究进展[J].中草药, 2015, 46(23):3611
LI ZH, YAN M, ZHANG BK, et al. Advances in study on compatibility of licorice and its mechanism of detoxification based on pharmacokinetics[J].Chin Tradit Herbal Drugs, 2015, 46(23): 3611
