Mulberry vinegar attenuates lipopolysaccharide and interferon gamma-induced inflammatory responses in C6 glial cells

The present study evaluated the effect of mulberry vinegar (MV) on the regulation of the inflammatory responses using C6 glial cells. Treatment with lipopolysaccharide (LPS) and interferon-γ (IFN-γ) induced the nitric oxide and reactive oxygen species generation, while pre-incubation with MV inhibited these formations in a concentration-dependent manner. MV treatment also decreased the production of pro-inflammatory cytokines, such as interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α in C6 glial cells stimulated by LPS/IFN-γ. Compared to the LPS/IFN-γ-treated control group, the MV-treated group exerts downregulation in the protein expressions of inducible nitric oxide synthase and cyclooxygenase-2, through inhibition of nuclear factor-κB activation. Protein expressions of glial fibrillary acidic protein and ionized calcium-binding adapter molecule 1 were also decreased in the MV-treated group. These findings suggest that MV prevents neuroinflammation by regulating the NF-κB signaling pathway and glial activation. PRACTICAL APPLICATION: Mulberry fruits (Morus alba L.) have been commonly consumed as juice or jam. It is a rich source of anthocyanins that might be associated with beneficial effects on human health, including the anti-oxidant, anti-inflammatory, anti-obesity, and anti-diabetic effects. Mulberry vinegar was produced by alcohol and acetic fermentation of mulberry juice, and they possessed a protective effect against LPS/IFN-γ-stimulated inflammatory responses in glial cells via regulation of glial activation and NF-κB signaling pathway (i.e., downregulation of iNOS, COX-2, TLR4, p-IκB, and NF-κB p65 protein expressions). Although further research especially animal and clinical trials are still necessary, the present study will be helpful to scale-up the production of functional vinegar with neuroprotective and anti-inflammatory properties using mulberry.