Pharmacokinetic Comparison of Scutellarin and Paeoniflorin in Sham-Operated and Middle Cerebral Artery Occlusion Ischemia and Reperfusion Injury Rats after Intravenous Administration of Xin-Shao Formula.
Xin-Shao formula is a folk remedy widely used in China to prevent and cure stroke. Cerebral ischemic reperfusion (I/R) injury often takes place during the treatment of stroke. Information about the pharmacokinetic behavior of the remedy under cerebral I/R injury conditions is lacking. The present study aimed to compare the pharmacokinetic properties of scutellarin and paeoniflorin, two major bioactive components of Xin-Shao formula, under physiological state in cerebral I/R injury rats. Neurobehavioral dysfunction was evaluated and cerebral infarcted volume was measured in middle cerebral artery occlusion I/R injury (MCAO) rats. Plasma samples were collected at various time points after a single dose (intravenous, i.v.) of Xin-Shao formula. The levels of plasma scutellarin and paeoniflorin at the designed time points were determined by a UPLC-MS/MS method, and drug concentration versus time plots were constructed to estimate pharmacokinetic parameters. Increase in terminal elimination half-life (t1/2z) and mean residence time (MRT(0-t)) of scutellarin as well as elevation in area under the plasma drug concentration-time curve from 0 h to the terminal time point (AUC(0-t)) and maximum plasma drug concentration (Cmax) of paeoniflorin, along with decreased clearance of paeoniflorin and scutellarin as well as reduced apparent volume of distribution (Vz) of paeoniflorin, were observed in MCAO rats, compared with those in sham-operated animals. The elimination of scutellarin and paeoniflorin were reduced in cerebral I/R injury reduced rats.
Key Laboratory of Pharmaceutics of Guizhou Province, Guizhou Medical University, No.9, Beijing Road, Yunyan District, Guiyang 550004, China. nhwslyt@163.com.|National Engineering Research Center of Miao's Medicines, Guiyang 550004, China. nhwslyt@163.com.
Yueting
Y
Li
Key Laboratory of Pharmaceutics of Guizhou Province, Guizhou Medical University, No.9, Beijing Road, Yunyan District, Guiyang 550004, China. 18798090340@163.com.
Yuan
Y
Lu
Key Laboratory of Pharmaceutics of Guizhou Province, Guizhou Medical University, No.9, Beijing Road, Yunyan District, Guiyang 550004, China. jianchun89@163.com.|School of Pharmacy, Guizhou Medical University, No. 9, Beijing Road, Yunyan District, Guiyang 550004, China. jianchun89@163.com.
Jianchun
J
Hu
Key Laboratory of Pharmaceutics of Guizhou Province, Guizhou Medical University, No.9, Beijing Road, Yunyan District, Guiyang 550004, China. gzp4012607@126.com.
Zipeng
Z
Gong
Key Laboratory of Pharmaceutics of Guizhou Province, Guizhou Medical University, No.9, Beijing Road, Yunyan District, Guiyang 550004, China. 18798090340@163.com.|School of Pharmacy, Guizhou Medical University, No. 9, Beijing Road, Yunyan District, Guiyang 550004, China. 18798090340@163.com.
Wu
W
Yang
Engineering Research Center for the Development and Applications of Ethnic Medicines and Traditional Chinese Medicine (TCM), Ministry of Education, Guizhou Medical University, No. 9, Beijing Road, Yunyan District, Guiyang 550004, China. gywam100@163.com.
Aimin
A
Wang
Key Laboratory of Pharmaceutics of Guizhou Province, Guizhou Medical University, No.9, Beijing Road, Yunyan District, Guiyang 550004, China. zhengneu@yahoo.com.
Jiang
J
Zheng
Key Laboratory of Pharmaceutics of Guizhou Province, Guizhou Medical University, No.9, Beijing Road, Yunyan District, Guiyang 550004, China. t-liu@163.com.
Ting
T
Liu
Key Laboratory of Pharmaceutics of Guizhou Province, Guizhou Medical University, No.9, Beijing Road, Yunyan District, Guiyang 550004, China. 18798846132@163.com.|School of Pharmacy, Guizhou Medical University, No. 9, Beijing Road, Yunyan District, Guiyang 550004, China. 18798846132@163.com.
Tingting
T
Chen
Key Laboratory of Pharmaceutics of Guizhou Province, Guizhou Medical University, No.9, Beijing Road, Yunyan District, Guiyang 550004, China. hujie51619@sina.cn.|School of Pharmacy, Guizhou Medical University, No. 9, Beijing Road, Yunyan District, Guiyang 550004, China. hujie51619@sina.cn.
Jie
J
Hu
Key Laboratory of Pharmaceutics of Guizhou Province, Guizhou Medical University, No.9, Beijing Road, Yunyan District, Guiyang 550004, China. 18798860432@163.com.|School of Pharmacy, Guizhou Medical University, No. 9, Beijing Road, Yunyan District, Guiyang 550004, China. 18798860432@163.com.
Ling
L
Mi
Engineering Research Center for the Development and Applications of Ethnic Medicines and Traditional Chinese Medicine (TCM), Ministry of Education, Guizhou Medical University, No. 9, Beijing Road, Yunyan District, Guiyang 550004, China. liyongjun026@126.com.
Yongjun
Y
Li
Engineering Research Center for the Development and Applications of Ethnic Medicines and Traditional Chinese Medicine (TCM), Ministry of Education, Guizhou Medical University, No. 9, Beijing Road, Yunyan District, Guiyang 550004, China. yanyu626@126.com.
Yanyu
Y
Lan
Key Laboratory of Pharmaceutics of Guizhou Province, Guizhou Medical University, No.9, Beijing Road, Yunyan District, Guiyang 550004, China. ylwang_gmc@163.com.
Yonglin
Y
Wang
D000818:Animals; D047310:Apigenin / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D004195:Disease Models, Animal; D005960:Glucosides / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D005965:Glucuronates / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008516:Medicine, Chinese Traditional; D039821:Monoterpenes / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D010936:Plant Extracts / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D020521:Stroke / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D006027:Glycosides
D047310:Apigenin; D005960:Glucosides; D005965:Glucuronates; D039821:Monoterpenes; D010936:Plant Extracts; C484876:scutellarin; C015423:peoniflorin; D006027:Glycosides
MCAO; UPLC-MS/MS; Xin-Shao formula; paeoniflorin; pharmacokinetics; scutellarin