Isoliquiritigenin inhibits microglia-mediated neuroinflammation in models of Parkinson's disease via JNK/AKT/NFκB signaling pathway.

Abstract

Isoliquiritigenin (ISL) is a flavonoid with numerous pharmacological properties, including anti-inflammation, yet its role in Parkinson's disease (PD) with microglia-mediated neuroinflammation remains unknown. In this study, the effects of ISL on inhibiting microglia-mediated neuroinflammation in PD were evaluated in the 1-methyl-4-phenylpyridinium (MPTP)-induced mouse model of PD and in lipopolysaccharide (LPS)-stimulated BV-2 microglia. Our results showed that ISL prevented behavioral deficits and excessive microglial activation in MPTP-treated mice. Moreover, ISL was found to prevent the elevation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and mitigate the phosphorylation of c-Jun N-terminal protein kinase (JNK), protein kinase B (AKT), nuclear factor kappa light-chain enhancer of activated B cells (NFκB), and inhibitor of NFκB protein ɑ (IκBɑ) in the substantia nigra and striatum of MPTP-treated mice and LPS-stimulated BV-2 cells. Meanwhile, in LPS-stimulated BV-2 cells, ISL inhibited the production of inflammatory mediators such as interleukin (IL)-1β, IL-6 and tumor necrosis factor alpha (TNF-α). In addition, the agonist of JNK partly abolished the inhibitory effects of ISL in LPS-treated BV-2 cells. Our results demonstrated that ISL inhibits microglia-mediated neuroinflammation in PD models probably through deactivating JNK/AKT/NFκB signaling pathways. The novel findings suggest the therapeutic potential of ISL for microglia-mediated neuroinflammation in PD.