Neferine exerts anti-inflammatory activity in BV-2 microglial cells and protects mice with MPTP-induced Parkinson's disease by inhibiting NF-κB activation

Abstract

Abnormal activation of microglia and the production of proinflammatory cytokines can lead to chronic neuroinflammation, which is an important pathological characteristic of Parkinson's disease (PD). Neferine is a chemical compound extracted from lotus seed which has previously been reported to exert protective effects on the development of several types of cancer, myocardial injury and hypoxic-ischemic encephalopathy. However, its effect on microglial functions in neuroinflammation remains to be clarified. The present study used network pharmacology and screening in a lipopolysaccharide (LPS) model to demonstrate that neferine suppresses the production of inducible nitric oxide synthase, interleukin-6 and tumor necrosis factor α in LPS-treated BV-2 cells. The working concentration of neferine did not exert cytotoxic effects on BV-2 cells. Mechanistically, neferine attenuated inflammation by inhibiting the phosphorylation and nuclear translocation of the NF-κB p65 subunit. In vivo, neferine protected mice from the inflammatory response in the substantia nigra and inhibited the development of nervous disorders in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced PD model. The present study demonstrated that neferine inhibited LPS-mediated activation of microglia by inhibiting NF-κB signaling. These findings may provide a new reference for the prevention and future treatment of PD.