Comparison of the Inhibitory Potential of Bavachalcone and Corylin against UDP‐Glucuronosyltransferases

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.

Bavachalcone-Induced Manganese Superoxide Dismutase Expression through the AMP-Activated Protein Kinase Pathway in Human Endothelial Cells

“…In osteoclasts, bavachalcone reduced the activation of MEK, ERK and Akt and suppressed osteoclast differentiation through NFATc1 [14]. In addition, a strong inhibitory effect of bavachalcone against two important isoforms of UDP-glucuronosyltransferases (UGT), UGT1A1 and UGT1A7, has been observed [15]. However, studies on the effect of bavachalcone on MnSOD remain very limited.…”

Identification of cytochrome P450 isoforms involved in the metabolism of artocarpin and assessment of its drug–drug interaction

“…CYP3A4 is the most abundant CYP isoform expressed in human liver and contributes to the metabolism of approximately half of the drugs in use today (Guengerich, ). UGT1A3 and UGT1A7 are phase II enzymes in the liver and extrahepatic tissues, respectively (Iwai et al, ; Shan et al, ). The kinetic parameters including IC 50 and K i for UGT1A3, UGT 1A7 and CYP3A4 were determined.…”

“…4‐MU, the nonspecific probe substrate for UGT isoforms, was used to assess the inhibition of artocarpin against UGT isoforms. Incubations with each UGT isoform have been reported previously (Shan et al, ). The reaction system (200 mL total volume) consisted of recombinant UGT isoforms, UDPGA (5 m m , 20 μL), MgCl 2 (5 m m 20 μL), Tris–HCl buffer (50 m m , pH 7.4, 114 μL) and 4‐MU in the absence or presence of 100 μ m artocarpin.…”

“…Because CYP3A4 is the most abundant CYP isoform expressed in human liver, the half inhibition concentra-.8 | UGTs inhibition experiments 4-MU, the nonspecific probe substrate for UGT isoforms, was used to assess the inhibition of artocarpin against UGT isoforms. Incubations with each UGT isoform have been reported previously(Shan et al, 2014). The reaction system (200 mL total volume) consisted of recombinant UGT isoforms, UDPGA (5 mM, 20 μL), MgCl 2 (5 mM 20 μL),…”

Psoralea corylifolia L: Ethnobotanical, biological, and chemical aspects: A review

“…Additionally, bakuchiol caused the apoptotic cell induction and interrupted membrane potential in mitochondria of MCF‐7 cells via an intrinsic apoptotic pathway. The same compound when tested for in vivo anti‐breast cancer effect in zebrafish xenografts the reduction in MCF‐7 cell mass was significant Bavachalcone and Corylin from P. corylifolia has been investigated against UDP‐Glucuronosyltransferases and showed strong inhibition (Shan et al, ). It also inhibits lipopolysaccharide‐induced endothelial‐mesenchymal transition via down regulation of the NF‐κB‐SNAIL signaling pathway (Jung et al, ).…”