Beta-Glucuronidase Inhibition by Constituents of Mulberry Bark

• DOI: 10.1055/a-1402-6431
• Publication Date: 2021-03-18T00:04:22Z
• Authors: Yue Bai; Lu Chen; Yun-Feng Cao; Xu-Dong Hou; Shou-Ning Jia; Qi Zhou; Yu-Qi He; Jie Hou
• Keywords: Aglycone; Glucuronidase

Abstract Intestinal bacterial β-glucuronidases, the key enzymes responsible for hydrolysis of various glucuronides into free aglycone, have been recognized as targets treating intestinal diseases. This study aimed to investigate inhibitory effects and mechanisms Mulberry bark constituents on E. coli β-glucuronidase (EcGUS), most abundant β-glucuronidases produced by bacteria. The results showed that flavonoids isolated from could strongly inhibit β-glucuronidase, with IC50 values ranging 1.12 µM 10.63 µM, which were more potent than D-glucaric acid-1,4-lactone. Furthermore, mode inhibition 5 strong activity (IC50 ≤ µM) was carefully investigated a set kinetic assays in silico analyses. demonstrated these noncompetitive inhibitors against β-glucuronidase-catalyzed 4-nitrophenyl β-D-glucuronide hydrolysis, Ki 0.97 2.71 3.74 3.35 4.03 morin (1), sanggenon C (2), kuwanon G (3), sanggenol A (4), (5), respectively. Additionally, molecular docking simulations all identified flavonoid-type be well-docked at nonsubstrate binding sites, highly consistent agentsʼ mode. Collectively, our findings displayed activity, suggesting might promising dietary supplement ameliorating β-glucuronidase-mediated toxicity.