KEY RESULTS
Piperine was identified as a natural inhibitor of human DHODH with an
IC50 value of 0.88 ± 0.04 μM. In addition, we resolved
the co-complex crystal structure of DHODH and piperine at 1.98 Å
resolution and found that Tyr356 residue of DHODH is critical for
piperine binding. Moreover, piperine can markedly suppress T cell
overactivation via a DHODH dependent-manner. Finally, we found that
piperine exhibits strong preventive and therapeutic effect in the
MOG-induced EAE by restricting
inflammatory cells infiltration into the CNS and by preventing myelin
destruction and blood–brain barrier (BBB) disruption.