Kurarinone alleviated Parkinson’s disease via stabilization of epoxyeicosatrienoic acids in animal model
Parkinson’s disease (PD) is among the most typical neurodegenerative disorders and it is characterised by lack of dopaminergic neurons within the substantia nigra (SN), causing bradykinesia and rest tremors. Even though the molecular mechanism of PD continues to be not fully understood, neuroinflammation includes a key role within the harm to dopaminergic neurons. Herein, we discovered that kurarinone, a distinctive natural product from Sophora flavescens, alleviated the fir-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-caused behavior deficits and dopaminergic neurotoxicity, such as the losses of neurotransmitters and tyrosine hydroxylase (TH)-positive cells (SN and striatum [STR]). In addition, kurarinone attenuated the MPTP-mediated neuroinflammation via suppressing the activation of microglia active in the nuclear factor kappa B signaling path. The proteomics consequence of the solvent-caused protein precipitation and thermal proteome profiling claim that the soluble epoxide hydrolase (sEH) enzyme, that is connected using the neuroinflammation of PD, is really a promising target of kurarinone. This really is based on the rise of plasma epoxyeicosatrienoic acids (sEH substrates) and also the loss of dihydroxyeicosatrienoic acids (sEH products), and also the outcomes of in vitro inhibition kinetics, surface plasmon resonance, and cocrystallization of kurarinone with sEH says this natural compound is MPTP definitely an uncompetitive inhibitor. Additionally, sEH knockout (KO) attenuated the advancement of PD, and sEH KO plus kurarinone didn’t further lessen the protection of PD in MPTP-caused PD rodents. These bits of information claim that kurarinone might be a potential natural candidate to treat PD, possibly through sEH inhibition.