Natural Potent NAAA Inhibitor Atractylodin Counteracts LPS-Induced Microglial Activation.

ABSTRACT: N-acylethanolamine-hydrolyzing acid amidase (NAAA) is a lysosomal enzyme that inhibits the degradation of palmitoylethanolamide (PEA), an endogenous lipid that induces analgesic, anti-inflammation, and anti-multiple sclerosis through PPARα activation. Only a few potent NAAA inhibitors have been reported to date, which is mainly due to the restricted substrate-binding site of NAAA. Here, we established a high-throughput fluorescence-based assay for NAAA inhibitor screening. Several new classes of NAAA inhibitors were discovered from a small library of natural products. One of these is atractylodin, a polyethylene alkyne compound from the root of Atractylodes lancea (Thunb) DC., which significantly inhibits NAAA activity and has an IC₅₀ of 2.81 µM. Kinetic analyses a

SUBMITTER: Yang L 

PROVIDER: S-EPMC7565389 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature