药学学报, 2021, 56(7): 1804-1810
引用本文:
刘力榕, 贾志鑫, 闫晓宁, 朱美霞, 方聪, 冯梦晗, 黄蓓蓓, 刘洁, 李乾, 肖红斌. 川芎对白芷中4种香豆素类化合物吸收及清除的影响[J]. 药学学报, 2021, 56(7): 1804-1810.
LIU Li-rong, JIA Zhi-xin, YAN Xiao-ning, ZHU Mei-xia, FANG Cong, FENG Meng-han, HUANG Bei-bei, LIU Jie, LI Qian, XIAO Hong-bin. Effect of Chuanxiong Rhizoma on the absorption and clearance of four coumarins in Angelicae Dahuricae Radix[J]. Acta Pharmaceutica Sinica, 2021, 56(7): 1804-1810.

川芎对白芷中4种香豆素类化合物吸收及清除的影响
刘力榕1,2, 贾志鑫2,3*, 闫晓宁1,2, 朱美霞1,2, 方聪1,2, 冯梦晗1,2, 黄蓓蓓1,2, 刘洁2,3, 李乾1,2, 肖红斌1,2,3*
1. 北京中医药大学中药学院, 北京 100029;
2. 北京中医药大学, 中药分析与转化研究中心, 北京 100029;
3. 北京中医药大学, 北京中医药研究院, 北京 100029
摘要:
为研究白芷配伍川芎前后其中4种香豆素类化合物(佛手柑内酯、氧化前胡素、欧前胡素、异欧前胡素)在大鼠体内的药代动力学行为变化,建立超高效液相色谱-荧光检测法(UPLC-FLD法)并对大鼠单次给药后不同时间点血浆中的药物浓度进行测定,使用DAS 3.2.8求算药物的药代动力学参数,SPSS 20.0软件分析白芷配伍川芎前后主要药代动力学参数的变化。结果表明:配伍川芎后,佛手柑内酯、氧化前胡素及欧前胡素的药时曲线下面积(AUC0-24 h)分别增加177.2%、97.14%和54.43%,AUC0-分别增加282.3%、104.2%和75.40%,清除率(CLZ/F)分别降低68.26%、51.08%和43.98%;4种香豆素类化合物药峰浓度(Cmax)均显著升高;佛手柑内酯的表观分布容积(VZ/F)显著减小。该结果表明川芎可以促进白芷中香豆素类化合物的吸收,同时减缓其在体内的消除速率,提高其生物利用度。本研究中动物实验方案已获得北京中医药大学实验动物伦理委员会的批准(批准号:BUCM-4-2020083105-3072)。
关键词:    白芷      川芎      香豆素      药代动力学      UPLC-FLD     
Effect of Chuanxiong Rhizoma on the absorption and clearance of four coumarins in Angelicae Dahuricae Radix
LIU Li-rong1,2, JIA Zhi-xin2,3*, YAN Xiao-ning1,2, ZHU Mei-xia1,2, FANG Cong1,2, FENG Meng-han1,2, HUANG Bei-bei1,2, LIU Jie2,3, LI Qian1,2, XIAO Hong-bin1,2,3*
1. School of Chinese Materia Medical, Beijing University of Chinese Medicine, Beijing 100029, China;
2. Research Center for Chinese Medicine Analysis and Transformation, Beijing University of Chinese Medicine, Beijing 100029, China;
3. Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
Abstract:
To study the changes in the pharmacokinetic behavior of four coumarins (bergapten, oxypeucedanin, imperatorin and isoimperatorin) in rats before and after combinating Angelicae Dahuricae Radix with Chuanxiong Rhizoma. The plasma concentrations of the drugs were determined by ultra performance liquid chromatography-fluorescence detection (UPLC-FLD) for dose response and time dependent curves. The pharmacokinetic parameters were calculated by DAS 3.2.8, and SPSS 20.0 was used to analyze the differences of main pharmacokinetic parameters between the two groups. The result showed:comparing with Angelicae Dahuricae Radix group, the area under drug time curve (AUC0-24 h) of bergapten, oxypeucedanin and imperatorin increased by 177.2%, 97.14% and 54.43% respectively, AUC0-∞ increased by 282.3%, 104.2%, and 75.40% respectively, and clearance rate (CLZ/F) decreased by 68.26%, 51.08% and 43.98% respectively; the peak drug concentration (Cmax) of four coumarins was significantly increased; the distribution volume (VZ/F) of bergapten was significantly decreased. These data indicated that Chuanxiong Rhizoma can promote the absorption of coumarins in Angelicae Dahuricae Radix, slow down the elimination of coumarins, and increase their bioavailability in vivo. The animal experiment scheme in this study has been approved by the Experimental Animal Ethics Committee of Beijing University of Chinese Medicine (approval number:BUCM-4-2020083105-3072).
Key words:    Angelicae Dahuricae Radix    Chuanxiong Rhizoma    coumarin    pharmacokinetics    UPLC-FLD   
收稿日期: 2021-04-21
DOI: 10.16438/j.0513-4870.2021-0592
基金项目: 国家自然科学基金资助项目(81774155,81803703);北京市自然科学基金资助项目(7214284).
通讯作者: 贾志鑫,Tel:86-10-53911875,E-mail:jessiejzx@163.com;肖红斌,Tel:86-10-53911883,E-mail:hbxiao69@163.com
Email: jessiejzx@163.com;hbxiao69@163.com
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参考文献:
[1] Jin Y, Qu C, Tang YP, et al. Herb pairs containing Angelicae Sinensis Radix (Danggui):a review of bio-active constituents and compatibility effects[J]. J Ethnopharmacol, 2016, 181:158-171.
[2] Zhou MM, Hong YL, Lin X, et al. Recent pharmaceutical evidence on the compatibility rationality of traditional Chinese medicine[J]. J Ethnopharmacol, 2017, 206:363-375.
[3] Tang YP, Shang EX, Chen YY, et al. Modern research approaches and strategies for compatibility effects and efficacy components of herbal pairs[J]. Acta Pharm Sin (药学学报), 2019, 54:1564-1573.
[4] Chinese Pharmacopoeia Commission. Pharmacopoeia of the People's Republic of China (中华人民共和国药典一部)[S]. Part 1. Beijing:China Medical Science Press, 2020:1428.
[5] Wang R, Liu J, Yang DY, et al. Research progress in chemical constituents and pharmacological action of Angelica dahurica[J]. Inf Tradit Chin Med (中医药信息), 2020, 37:123-128.
[6] Wang MY, Jia MR, Ma YY, et al. Pharmacological effect of four linear furocoumarins in Radix Angelicae Dahuricae[J]. Nat Prod Res Dev (天然产物研究与开发), 2010, 22:485-489.
[7] Shi XY, Zhang FL, Liang S, et al. Study on pharmacokinetics of multi-component integration of total coumarin extracts from Angelica dahurica[C]//Proceedings of the Tenth National Conference on Drug and Chemical Foreign Body Metabolism and the Third International ISSX/CSSX Joint Conference (第十届全国药物和化学异物代谢学术会议暨第三届国际ISSX/CSSX联合学术会议论文集). Nanjing:Chinese Pharmacological Society, 2012:9.
[8] Zhang JP. Analysis and Pharmacokinetics of Coumarin Compounds in Radix Angelicae Dahuricae (白芷香豆素类成分含量测定及药代动力学研究)[D]. Suzhou:Soochow University, 2011.
[9] Huang YW, Chen XH, Huo YS, et al. Pharmacokinetic study of imperatorin in rat after oral administration of extractum Angelicae Dahuricae Siccum[J]. J Shenyang Pharm Univ (沈阳药科大学学报), 2008, 25:215-218.
[10] Xie Y. Study on Extraction, Preparation and Pharmacokinetic of Active Componentsfrom from Radix Angelicae Dahuricae (白芷活性成分的提取分离及其体内药代动力学研究)[D]. Shanghai:The Second Military Medical University, 2007.
[11] Deng JY. Study on the Method of Qulity Assessment of Radix Angelica Dahurica and the Pharmacokinetics of Imperatorin in Rats (白芷质量评价方法及欧前胡素在大鼠体内的药物动力学研究)[D]. Shenyang:Shenyang Pharmaceutical University, 2004.
[12] Chepyala D, Tsai IL, Sun HY, et al. Development and validation of a high-performance liquid chromatography-fluorescence detection method for the accurate quantification of colistin in human plasma[J]. J Chromatogr B Analyt Technol Biomed Life Sci, 2015, 980:48-54.
[13] Zhao AH, Zhang YB, Yang XW. Simultaneous determination and pharmacokinetics of sixteen Angelicae dahurica coumarins in vivo by LC-ESI-MS/MS following oral delivery in rats[J]. Phytomedicine, 2016, 23:1029-1036.
[14] Chen ZY, Zheng QS, Sun RY, et al. Functions of the DAS software for pharmacological calculation[J]. Chin J Clin Pharmacol Ther (中国临床药理学与治疗学), 2002, 7:562-564.
[15] Huang SK, Han KQ. Statistical approaches for assessment of bioequivalence[J]. Chin Pharm J (中国药学杂志), 1994, 29:312-314.
[16] Liu YT, Jiang QY, Huang GY, et al. Determining the effect of Huangqi on the pharmacokinetics of six different alkaloids from Fuzi in rats by LC-MS[J]. Acta Pharm Sin (药学学报), 2019, 54:2289-2295.
[17] Liang WQ, Li G, Liu JP. Biopharmaceutics and Pharmacokinetics (生物药剂学与药物动力学)[M]. 2nd Ed. Beijing:People's Medical Publishing House, 2007:176.
[18] Zhou Y, Wu XA, Deng Y. Effect of cooperation between transporters and metabolic enzymes on drug disposition by intestine and liver[J]. Acta Pharm Sin(药学学报), 2020, 55:1762-1767.
[19] Levêque D, Lemachatti J, Nivoix Y, et al. Mechanisms of pharmacokinetic drug-drug interactions[J]. Rev Med Interne, 2010, 31:170-179.
[20] Sparreboom A, Cox MC, Acharya MR, et al. Herbal remedies in the United States:potential adverse interactions with anticancer agents[J]. J Clin Oncol, 2004, 22:2489-2503.
[21] Qiu W, Liu CX, Ju Y, et al. Pharmacokinetic interaction of plant preparations with chemical drugs[J]. Chin J Nat Med (中国天然药物), 2010, 8:137-144.
[22] Dong W, Guan XJ, Liao ZG, et al. In vitro study on affinity of coumarins in Angelicae Dahuricae Radix and P-gp[J]. Chin Tradit Herb Drugs (中草药), 2016, 47:2893-2896.
[23] Song J, Tang J, He J, et al. Effects of tetramethylpyrazine on the function and expression of P-glycoprotein in Caco-2 cells[J]. Cent South Pharm (中南药学), 2007, 5:440-443.
[24] Liu XY, Lai Y. Preparation of drug-in adhesive patch of Angelica dahurica coumarins and study its in vitro permeability through excised anthony pig skin[J]. Chin J Mod Appl Pharm (中国现代应用药学), 2018, 35:330-334.
[25] Ni HX, Wang CM. Preventive effects of total coumarin and essential oil of Angelicae Dahuricae Radix on migraine rats and their mechanisms[J]. J Jilin Univ (Med Ed) (吉林大学学报医学版), 2018, 44:487-492.
[26] Su ZT, Xu JL, Liu Y, et al. The study on promotion of absorption and synergistic effect of Chuanxiong Rhizoma with helicid[J]. Chin J Exp Tradit Med Form (中国实验方剂学杂志), 2012, 18:176-178.
[27] Zhang FL, Huang YF, Yi J. Effects of Chuanxiong Rhizoma excract and different absorption enhancers on rat colonic absorption of Angelica Dahuricae Radix[J]. J Guangdong Pharm Univ (广东药学院学报), 2015, 31:300-304.
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