Open AccessKurarinone alleviated Parkinson's disease via stabilization of epoxyeicosatrienoic acids in animal model
Author(s) -
ChengPeng Sun,
Jiren Zhou,
Zhenlong Yu,
Xiaokui Huo,
Juan Zhang,
Christophe Morisseau,
Bruce D. Hammock,
Xiaochi Ma
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2118818119
Subject(s) - neuroinflammation , mptp , chemistry , dopaminergic , pharmacology , substantia nigra , epoxide hydrolase 2 , microglia , neuroprotection , dopamine , biochemistry , neuroscience , medicine , biology , enzyme , inflammation
Significance To date, no cure or preventative treatment for Parkinson’s disease (PD) has yet been developed. Here, we show that kurarinone, a natural flavonoid, alleviated parkinsonism-like symptoms induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice. Using a proteomics approach, we identified the soluble epoxide hydrolase (sEH) as a possible target of kurarinone’s reduction of neuroinflammation. This was supported using complementary biochemical approaches, which demonstrated that kurarinone is a high nanomolar uncompetitive inhibitor of sEH. Our findings suggest that natural products could attenuate the development of PD through inhibition of sEH.