Abstract
Isoliquiritigenin (ISL) is a naturally-occurring flavonoid with numerous pharmacological properties such as 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 the lipopolysaccharide (LPS)-stimulated BV-2 microglial cells. Our results showed that ISL had the capability to prevent behavioral deficits and the excessive microglial activation in MPTP-treated mice. Besides that, ISL was able to reduce MPTP-mediated neuronal cell death in the substantia nigra and striatum of mice. In addition, ISL was found to prevent the elevation of nitric oxide synthase (iNOS), 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) as well as inhibitor of NFκB protein ɑ in substantia nigra and striatum of MPTP-treated mice. In LPS-stimulated BV-2 cells, ISL inhibited production of inflammatory mediators such as interleukin (IL)-1β, IL-6 and tumor necrosis factor alpha (TNF-α), suppressed the phosphorylation and nuclear translocation of NFκB, and inhibited the activation of JNK and AKT signaling. Moreover, the agonists of JNK partly abolished the inhibitory effects of ISL in LPS-treated BV-2 cells. ISL inhibits microglia-mediated neuroinflammation in PD models probably through deactivating JNK/NFκB/AKT signaling pathway. The novel findings suggest the therapeutic potential of ISL for microglia-mediated neuroinflammation in PD.
Published Version
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