Protective effect of diosmin on LPS-induced apoptosis in PC12 cells and inhibition of TNF-α expression.

Several studies have demonstrated a link between increased pro-inflammatory mediators and apoptosis in neurodegenerative diseases. It has been reported that lipopolysaccharide (LPS) induces apoptosis mostly through the production of TNF-α. In this study, we investigated the possible protective and anti-inflammatory mechanisms of diosmin, a natural flavone glycoside, on LPS-induced PC12 cells death through inhibition of TNF-α production. PC12 Cells were pretreated with diosmin for 2h prior to LPS treatment for 48 h to assess PC12 cells viability, TNF-α expression, and cell death mechanisms. Diosmin significantly increased cells survival and suppressed LPS-induced TNF-α in a concentration-dependent manner. Diosmin also significantly reduced the DNA fragmentation of LPS-induced cells, and its anti-apoptotic effect was confirmed by the decrease in the expression of pro-apoptotic protein Bad and the increase in the expression of anti-apoptotic protein Bcl-2 on Western blot analysis. Furthermore, diosmin inhibited LPS-induced caspase-3 activation further confirming its anti-apoptotic effects. This is the first study to report the anti-inflammatory and anti-apoptotic effects of diosmin via inhibition of TNF-α and a caspase-dependent pathway in neuronal PC12 cells. These results support the potential for diosmin to be investigated as a potential agent for the treatment of neurodegenerative diseases.