川芎对天麻中天麻素及其代谢产物体内药动学的影响  

Effects of Chuanxiong Rhizoma on the in vivo pharmacokinetics of gastrodin and its metabolites in Gastrodiae Rhizoma

作　　者：刘明妍 冯梦晗 刘洁[2,3] 刘力榕 闫晓宁 屈碧琼 潘绮雪 刘璐璐 贾志鑫 肖红斌 LIU Ming-yan;FENG Meng-han;LIU Jie;LIU Li-rong;YAN Xiao-ning;QU Bi-qiong;PAN Qi-xue;LIU Lu-lu;JIA Zhi-xin;XIAO Hong-bin(School of Chinese Medicine,Beijing University of Chinese Medicine,Beijing 102400,China;Research Center for Analysis and Transformation of Chinese Medicine,Beijing University of Chinese Medicine,Beijing 102400,China;Beijing Institute of Traditional Chinese Medicine,Beijing University of Chinese Medicine,Beijing 102400,China)

机构地区：[1]北京中医药大学中药学院,北京102400 [2]北京中医药大学中药分析与转化研究中心,北京102400 [3]北京中医药大学,北京中医药研究院,北京102400

出　　处：《中成药》2023年第11期3513-3519,共7页Chinese Traditional Patent Medicine

基　　金：国家自然科学基金资助项目(81774155,82173957)。

摘　　要：目的考察川芎对天麻中天麻素、对羟基苯甲醇、对羟基苯甲酸、对羟基苯甲醛-O-β-D-吡喃葡萄糖苷体内药动学的影响。方法12只大鼠随机分为2组,分别灌胃给予大川芎方(3.9 g/kg)、天麻(0.78 g/kg)溶液(10 mL/kg),于0、0.08、0.16、0.25、0.50、0.75、1、2、4、6、8、12、24 h采血;72只大鼠随机分为2组,分别灌胃给予大川芎方(7.8 g/kg)、天麻(1.56 g/kg)溶液(10 mL/kg),采集脑组织,HPLC-MS/MS法测定天麻素及其代谢产物血药浓度,计算主要药动学参数。结果与天麻组比较,大川芎方组大鼠血浆中对羟基苯甲醇、对羟基苯甲酸C_(max)升高(P<0.01),对羟基苯甲醛-O-β-D-吡喃葡萄糖C_(max)降低(P<0.01);天麻素T_(max)、MRT_(0~24)h延长(P<0.01);天麻素、对羟基苯甲醇、对羟基苯甲酸AUC_(0~24)h、AUC_(0~∞)升高(P<0.01),CL_(z/F)降低(P<0.01),对羟基苯甲醛-O-β-D-吡喃葡萄糖苷CL_(z/F)升高(P<0.05);对羟基苯甲醇V_(z/F)降低(P<0.01),而大川芎方组大鼠脑组织中C_(max)、AUC_(0~24)h、AUC_(0~∞)、V_(z/F)升高(P<0.05,P<0.01)。结论川芎配伍天麻后,可显著影响天麻素及其代谢产物在大鼠血浆、脑组织中的体内药动学。AIM To investigate the effects of Chuanxiong Rhizoma on in vivo pharmacokinetics of gastrodin,p-hydroxybenzyl alcohol,p-hydroxybenzoic acid and p-hydroxybenzaldehyde-O-β-D-glucopyranoside in Gastrodiae Rhizoma.METHODS Twelve rats were randomly assigned into two groups and given intragastric administration of Dachuanxiong Formula(3.9 g/kg)and gastrodin(0.78 g/kg)solutions(10 mL/kg),respectively,after which blood collection was made at 0,0.08,0.16,0.25,0.50,0.75,1,2,4,6,8,12,24 h;seventy-two rats were randomly assigned into two groups and given intragastric administration of Dachuanxiong Formula(7.8 g/kg)and gastrodin(1.56 g/kg)solutions(10 mL/kg),respectively,after which brain tissue collection was made.HPLC-MS/MS was adopted in the plasma concentration determination of gastrodin and its metabolites,and main pharmacokinetic parameters were calculated.RESULTS Compared with the Gastrodiae Rhizoma group,the Dachuanxiong Formula group demonstrated increased C_(max)of p-hydroxybenzyl alcohol,p-hydroxybenzoic acid(P<0.01),decreased C_(max)of p-hydroxybenzaldehyde-O-β-D-glucopyranoside(P<0.01)in rat plasma,along with prolonged T_(max),MRT_(0-24)h of gastrodin(P<0.01),increased AUC_(0-24)h,AUC_(0-∞)and decreased CL_(z/F)of gastrodin,p-hydroxybenzyl alcohol,p-hydroxybenzoic acid(P<0.01),increased CL_(z/F)of p-hydroxybenzaldehyde-O-β-D-glucopyranoside(P<0.05),decreased V_(z/F)of p-hydroxybenzyl alcohol(P<0.01),and also displayed increased C_(max),AUC_(0-24)h,AUC_(0-∞),V_(z/F)(P<0.05,P<0.01)in rat brain tissue.CONCLUSION After the compatibility of Chuanxiong Rhizoma and Gastrodiae Rhizoma,the in vivo pharmacokinetics of gastrodin and its metabolites in rat plasma and brain tissue can be significantly affected.

关 键 词：川芎 天麻 天麻素 对羟基苯甲醇 对羟基苯甲酸 对羟基苯甲醛-O-β-D-吡喃葡萄糖苷 体内药动学 HPLC-MS/MS 

分 类 号：R969[医药卫生—药理学]