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

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.