β-Glucuronidase Acts as a Novel Nonantioxidative Target for Vitamin E

Inhibition of gut β-glucuronidase (GUS) protects the gastrointestinal tract by reducing local exposure to toxic aglycones from inactive glucuronides. Development of highly safe GUS inhibitors has attracted extensive attentions. The current study demonstrates that natural and synthetic vitamin E (VE) analogues all display potent inhibition toward GUS. dl-α-tocopherol acts as the most potent inhibitor with the K_i value of 0.14 μM, while the other analogues have K_i values below 15.1 μM. Docking analysis indicates that the amino residues in the active pocket of GUS form various hydrophobic interactions with both the chromanol ring and side chain of VE, as well as hydrogen bonds with the hydroxyl group. It is predicted that GUS inhibition readily occurs owing to the daily intake of common plant foods. The current study offers highly safe inhibitors for GUS, as well demonstrates a novel nonantioxidant target for VE providing new insights into the vitamin's gastrointestinal protection.