Abstract
Pro‐inflammatory cytokines have been detected in Alzheimer's disease (AD) brain suggesting that neuroinflammation also plays a role in the pathogenesis of AD. PC‐12 cells in culture respond to LPS stimuli by upregulating the levels of cytokines TNF‐alpha, IL‐1beta, nitric oxide (NO), and caspase activation thereby causing neuronal cell death. The present study investigated the neuroprotective effects of flavonoids such as fisetin, diosmetin and robinetin when administered alone and in combination, on the proinflammatory responses and apoptosis induced in LPS‐stimulated PC‐12 cells. Our studies showed that all the flavonoids alone and in combination markedly suppressed the production of TNF‐alpha, interleukin (IL)‐1beta, and nitric oxide (NO) in a dose –dependent manner, respectively. In parallel, cell apoptosis triggered by LPS and characterized with caspase‐3 activity, pro‐apoptotic gene Bad and anti‐apoptotic gene Bcl‐2 expressions were also significantly inhibited by these flavonoids. The results indicate that the inhibitory activity of flavonoids was greater when taken in combinations compared to those when taken alone. The present study suggests that flavonoids alone and in combination, might offer therapeutic opportunities to delay the progression of neuroinflammatory diseases such as AD.
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