Bridging in silico and in vitro perspectives to unravel molecular mechanisms underlying the inhibition of β-glucuronidase by coumarins from Hibiscus trionum

• DOI: 10.1016/j.bpc.2024.107304
• Publication Date: 2024-07-26T23:27:39Z
• Authors: Emadeldin M. Kamel; Faris F. Aba Alkhayl; Haifa A. Alqhtani; May Bin-Jumah; Hassan A. Rudayni; Al Mokhtar Lamsabhi
• Keywords: Hibiscus

Unraveling the intricacies of β-glucuronidase inhibition is pivotal for developing effective strategies in applications specific to gastrointestinal health and drug metabolism. Our study investigated the efficacy of some Hibiscus trionum phytochemicals as β-glucuronidase inhibitors. The results showed that cleomiscosin A and mansonone H emerged as the most potent inhibitors, with IC50 values of 3.97 ± 0.35 μM and 10.32 ± 1.85 μM, respectively. Mechanistic analysis of β-glucuronidase inhibition indicated that cleomiscosin A and the reference drug EGCG displayed a mixed inhibition mode against β-glucuronidase, while mansonone H exhibited noncompetitive inhibition against β-glucuronidase. Docking studies revealed that cleomiscosin A and mansonone H exhibited the lowest binding affinities, occupying the same site as EGCG, and engaged significant key residues in their binding mechanisms. Using a 30 ns molecular dynamics (MD) simulation, we explored the interaction dynamics of isolated compounds with β-glucuronidase. Analysis of various MD parameters showed that cleomiscosin A and mansonone H exhibited consistent trajectories and significant energy stabilization with β-glucuronidase. These computational insights complemented experimental findings, underscoring the potential of cleomiscosin A and mansonone H as β-glucuronidase inhibitors.