Comparison of the Inhibitory Potential of Bavachalcone and Corylin against UDP-Glucuronosyltransferases.

Lina Shan,Yujun Feng,Gang Zhang,Hongxia Yuan,Zhenyu Qiu,Shuman Yang,Lei Tian,Dun Zhou,Xianbao Shi

doi:10.1155/2014/958937

Abstract

Bavachalcone and corylin are two major bioactive compounds isolated from Psoralea corylifolia L., which has been widely used as traditional Chinese medicine for many years. As two antibiotic or anticancer drugs, bavachalcone and corylin are used in combination with other drugs; thus it is necessary to evaluate potential pharmacokinetic herb-drug interactions (HDI) of the two bioactive compounds. The aim of the present study was to compare the effects of liver UDP-glucuronosyltransferase (UGT) 1A1, UGT1A3, UGT1A7, UGT1A8, UGT 1A10, and UGT2B4 inhibited by bavachalcone and corylin. 4-Methylumbelliferone (4-MU) was used as a nonspecific “probe” substrate. Bavachalcone had stronger inhibition on UGT1A1 and UGT1A7 than corylin which did not inhibit UGT1A1, UGT1A3, UGT1A7, UGT1A8, UGT1A10, and UGT2B4. Data fitting using Dixon and Lineweaver-Burk plots demonstrated the noncompetitive inhibition of bavachalcone against UGT1A1 and UGT1A7-mediated 4-MU glucuronidation reaction. The values of inhibition kinetic parameters (Ki) were 5.41 μM and 4.51 μM for UGT1A1 and UGT1A7, respectively. The results of present study suggested that there was a possibility of UGT1A1 and UGT1A7 inhibition-based herb-drug interaction associated with bavachalcone and provided the basis for further in vivo studies to investigate the HDI potential between bavachalcone and UGT substrates.

Highlights

Fructus Psoraleae, derived from dried ripe fruit of Psoralea corylifolia L., has been commonly used as a traditional Chinese medicine for warming kidney, activating yang, promoting inspiration, and checking diarrhea [1]
Modern pharmacological and clinical studies have shown that the extracts of Fructus Psoraleae possess different biological activities, such as antioxidative [3], antimicrobial [4], anti-inflammatory, and antitumor activities [5]
Fructus Psoraleae was effective in the treatment of lung carcinoma [8, 9]

Summary

Introduction

Fructus Psoraleae, derived from dried ripe fruit of Psoralea corylifolia L., has been commonly used as a traditional Chinese medicine for warming kidney, activating yang, promoting inspiration, and checking diarrhea [1]. It is listed in both the Chinese Pharmacopoeia and the “List of Herbal Materials that Can Be Used for Health Foods” under the Law on Food Hygiene by State Food and Drug Administration [2]. As two major compounds isolated from the seed of Fructus Psoraleae, bavachalcone and corylin (Figure 1) are extensively used in traditional medicine for the treatment of various diseases.

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Conclusion