The effects of Glycyrrhizae uralenis and its major bioactive components on pharmacokinetics of daphnetin in Cortex daphnes in rats.
BACKGROUND
Glycyrrhizae uralenis (GU) is often prescribed together with Cortex daphnes (CD) in traditional Chinese medicinal practice to increase the efficacy of CD on the treatment of rheumatoid arthritis (RA), but the reasons were still unknown. In order to clarify the rationality of herbaceous compatibility between CD and GU, the comparative evaluations on pharmacokinetic behaviors of daphnetin (a predominantly active ingredient in CD) after intragastric administration of CD and CD-GU (combination of CD and GU) extract were studied. In addition, the effects of glycyrrhizin and liquiritin, active ingredients of Glycyrrhiza triterpenes and Glycyrrhiza flavones respectively, on the pharmacokinetics of daphnetin were also investigated.


METHODS
Five groups of rats were orally administered with CD extract, CD-GU extract, pure daphnetin, co-administration of daphnetin and glycyrrhizin as well as co-administration of daphnetin and liquiritin at the same single dose of daphnetin (20 mg/kg). The rat plasma concentrations of daphnetin were determined by our developed UPLC-MS/MS method. The pharmacokinetics of daphnetin in above groups were investigated and compared.


RESULTS
Comparing with oral administration of CD extract, AUC and Tmax of daphnetin significantly increased after giving CD-GU (p<0.05). In addition, in comparison to daphnetin alone, co-administration of daphnetin with liquiritin significantly increased the AUC and Cmax of daphnetin for ~1.5-fold, while co-administered with glycyrrhizin showed limited impact on the pharmacokinetics of daphnetin.


CONCLUSIONS
In this study, it was found that liquiritin, one of the major components of GU, significantly enhanced the bioavailability of the main component daphnetin in CD. In addition, the bioavailability of daphnetin in the CD-GU prescription was also significantly higher than that in CD alone, which could be due to liquiritin. Such results explained the mechanism of the increased efficacy in treating RA with the combined use of CD and GU.
School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, PR China; Jiangsu Engineering Research Center for Efficient Delivery System of TCM, PR China; Nanjing Engineering Research Center for Industrialization of Chinese Medicine Pellets, PR China.
Wen
W
Zhang
School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, PR China; Jiangsu Engineering Research Center for Efficient Delivery System of TCM, PR China; Nanjing Engineering Research Center for Industrialization of Chinese Medicine Pellets, PR China. Electronic address: diliuqing928@163.com.
Liu-qing
LQ
Di
School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, PR China; Jiangsu Engineering Research Center for Efficient Delivery System of TCM, PR China; Nanjing Engineering Research Center for Industrialization of Chinese Medicine Pellets, PR China.
Jun-Song
JS
Li
First Medicine School, Nanjing University of Chinese Medicine, Nanjing 210046, PR China.
Jin-jun
JJ
Shan
School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, PR China.
An
A
Kang
School of Pharmacy, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, PR China.
Shuai
S
Qian
School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, PR China.
Le-tian
LT
Chen
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D032364:Daphne / Q000737:chemistry*; D044950:Flavanones / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D005960:Glucosides / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D029882:Glycyrrhiza uralensis / Q000737:chemistry*; D008297:Male; D010936:Plant Extracts / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014468:Umbelliferones / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
D044950:Flavanones; D005960:Glucosides; D010936:Plant Extracts; D014468:Umbelliferones; C512196:liquiritin; C039952:daphnetin
Comparative pharmacokinetics; Daphnetin; Daphnetin (Pubchem CID: 5280569); Daphnin (Pubchem CID: 439499); Glycyrrhizin; Glycyrrhizin (Pubchem CID: 14982); Liquiritigenin (Pubchem CID: 114829); Liquiritin; Liquiritin (Pubchem CID: 503737); Osthole (Pubchem CID: 10228); Rheumatoid arthritis; UPLC–MS/MS