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

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.

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