A Metabolism-Based Synergy for Total Coumarin Extract of Radix and Ligustrazine on Migraine Treatment in Rats

doi:10.3390/molecules23051004

	A Metabolism-Based Synergy for Total Coumarin Extract of Radix and Ligustrazine on Migraine Treatment in Rats
	Feng, Shan 2; He, Xin 1; Zhong, Peiru 1; Zhao, Jinyi 1; Huang, Cong 1; Hu, Zhuohan 3
刊名	Molecules (Basel, Switzerland)
	2018-04-25
卷号	23 期号:5
ISSN号	1420-3049
DOI	10.3390/molecules23051004
文献子类	Article
英文摘要	Radix , containing coumarins, which might affect cytochrome P450 enzyme (CYP450) activity, has been co-administered with ligustrazine, a substrate of CYP450s, for the clinical treatment of migraine. However, whether a pharmacokinetic-based synergy exists between Radix and ligustrazine is still unknown. In this study, the total coumarin extract (TCE) of Radix (50 mg/kg, orally) reinforced the anti-migraine activity of ligustrazine by declining head scratching, plasma calcitonin gene-related peptide, and serum nitric oxide, as well as increasing plasma endothelin levels in rats ( < 0.05). Moreover, the pharmacokinetic study reflected that TCE potentiated the area under the concentration⁻time curve of ligustrazine and prolonged its mean retention time in rats ( < 0.05). Besides, the IC for TCE, imperatorin and isoimperatorin inhibiting ligustrazine metabolism were 5.0 ± 1.02, 1.35 ± 0.46, 4.81 ± 1.14 µg/mL in human liver microsomes, and 13.69 ± 1.11, 1.19 ± 1.09, 1.69 ± 1.17 µg/mL in rat liver microsomes, respectively. Moreover, imperatorin and isoimperatorin were CYP450s inhibitors with IC < 10 µM for CYP1A2, 2C9, 2D6, and 3A4. Therefore, this study concluded that Radix could increase ligustrazine plasma concentration and then reinforce its pharmacological effect by inhibiting its metabolism through interference with CYP450s. This could be one mechanism for the synergy between Radix and ligustrazine on migraine treatment.
语种	英语
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/266756]
专题	中国科学院上海药物研究所
通讯作者	Feng, Shan; He, Xin; Zhong, Peiru; Zhao, Jinyi; Huang, Cong; Hu, Zhuohan
作者单位	1.School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, 312# Anshanxi Road, Nankai District, Tianjin 300193, China; 2.College of Pharmaceutical Sciences and Chinese Medicine, Southwest University, 2# Tiansheng Road, Beibei District, Chongqing 400715, China; 3.Research Institute for Liver Diseases (Shanghai) Co. Ltd., 200# Niudun Road, Shanghai 201203, China
推荐引用方式 GB/T 7714	Feng, Shan,He, Xin,Zhong, Peiru,et al. A Metabolism-Based Synergy for Total Coumarin Extract of Radix and Ligustrazine on Migraine Treatment in Rats[J]. Molecules (Basel, Switzerland),2018,23(5).
APA	Feng, Shan,He, Xin,Zhong, Peiru,Zhao, Jinyi,Huang, Cong,&Hu, Zhuohan.(2018).A Metabolism-Based Synergy for Total Coumarin Extract of Radix and Ligustrazine on Migraine Treatment in Rats.Molecules (Basel, Switzerland),23(5).
MLA	Feng, Shan,et al."A Metabolism-Based Synergy for Total Coumarin Extract of Radix and Ligustrazine on Migraine Treatment in Rats".Molecules (Basel, Switzerland) 23.5(2018).