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香附对川芎中阿魏酸在正常及偏头痛模型大鼠体内药代动力学的影响 |
张毅1,杨凌鉴1,王笑笑1,马晓毅1,于洁1,贾璞1,岳俏1,杨璞叶2,郑晓晖1,3* |
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(1. 西北大学生命科学学院中药学系, 西安 710069; 2. 北方医院感染科, 西安 710043; 3. 深圳创新中药及天然药物联合研究实验室, 深圳 518057*通信作者) |
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摘要: |
目的 研究香附对川芎中阿魏酸(ferulic acid,FA)在正常及偏头痛模型大鼠体内的药代动力学影响。方法 用硝酸甘油(10 mg/kg)制作偏头痛大鼠模型,SD大鼠分为正常川芎组、正常川芎-香附组、模型川芎组、模型川芎-香附组,灌胃给药,采用高效液相色谱法(HPLC)检测血药浓度,流动相为0.2%甲酸水(A)-甲醇(B),梯度洗脱,检测波长为322 nm,检测给药后0~8 h内大鼠血浆中FA的浓度,DAS 2.0软件计算药代动力学参数。结果 HPLC法的方法学考察均符合测定要求。正常组中川芎配伍香附后FA的吸收半衰期t1/2Ka缩短(P<0.05),达峰时间Tmax提前(P<0.05),但其他药代动力学参数与配伍前比较差异无统计学意义。模型组中川芎配伍香附后FA的达峰浓度Cmax、药时曲线下面积AUC(0-t)、分布半衰期t1/2α、表观分布容积增大(P<0.01或P<0.05),Tmax提前(P<0.05),清除率降低(P<0.01)。结论 在正常大鼠体内香附加快了FA的吸收,而在偏头痛模型大鼠体内香附减慢FA在体内的分布和代谢,延长药物在体内的作用时间,从而提高了FA的生物利用度。 |
关键词: 川芎 香附 阿魏酸 药代动力学 偏头痛 |
DOI:10.3724/SP.J.1008.2014.01024 |
投稿时间:2014-01-02修订日期:2014-05-13 |
基金项目:教育部长江学者和创新团队发展计划资助(IRT1174);陕西省重点科技创新团队计划(2013KCT-24);西北大学大学生创新基金(2012099). |
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Effect of rhizoma cyperi on pharmacokinetics of ferulic acid in ligusticum wallichii in normal and nitroglycerin-induced migraine rats |
ZHANG Yi1,YANG Ling-jian1,WANG Xiao-xiao1,MA Xiao-yi1,YU Jie1,JIA Pu1,YUE Qiao1,YANG Pu-ye2,ZHENG Xiao-hui1,3* |
(1. Department of Traditional Chinese Medicine, College of Life Science, Northwest University, Xi'an 710069, Shaanxi, China; 2. Department of Infectious Diseases, Northern Hospital, Xi'an 710043, Shaanxi, China; 3. Joint Lab for New Drug Research of TCM and Natural Medicine of Shenzhen, Shenzhen 518057, Guangdong, China * Corresponding author.) |
Abstract: |
Objective To investigate the effect of rhizoma cyperi on pharmacokinetics of ferulic acid in ligusticum wallichii in normal and nitroglycerin-induced migraine model rats. Methods The rat migraine model was created by nitroglycerin (10 mg/kg). SD rats were divided into normal rhizoma ligustici wallichii group, normal rhizoma ligustici wallichii and rhizoma cyperi group, model rhizoma ligustici wallichii group, and model rhizoma ligustici wallichii and rhizoma cyperi group. We used RP-HPLC (0.2% formic acid water [A]-methanol [B], gradient elution 322 nm) to detect the concentration of ferulic acid in rat plasma at 8 h after oral administration. DAS 2.0 software was used to calculate the pharmacokinetic parameters. Results Methodology inspection conformed that HPLC met the requirements for determination. Compared with normal rhizoma ligustici wallichii group, the absorption half time (t1/2Ka) of ferulic acid was significantly reduced in normal rhizoma ligustici wallichii and rhizoma cyperi group (P<0.05), and the peak time (Tmax) was significantly shortened (P<0.05), with no differences found for other parameters. Compared with model rhizoma ligustici wallichii group, model rhizoma ligustici wallichii and rhizoma cyperi group had significantly increased maximum plasma concentration (Cmax), area under curve (AUC), distribution half-life time (t1/2α), and apparent volume of distribution of ferulic acid (P<0.05 or P<0.01), significantly shortened Tmax (P<0.05), and significantly decreased the absorption rate and the clearance speed (P<0.01). Conclusion Rhizoma cyperi enhances the absorption of ferulic acid in normal rats, while in migraine model rats it reduces the distribution and metabolism of ferulic acid and prolongs functioning time, subsequently promoting the bioavailability of ferulic acid. |
Key words: Ligusticum wallichii Cyperus rotundus ferulic acid pharmacokinetics migraine disorders |