Title : Neuroprotective Role of Sodium Butyrate through Suppressing Inflammation and Modulating Antioxidant Enzymes in vitro and High Fat Diet-fed Mice
Abstract:
The discovery of effective therapeutic agents against neurodegenerative diseases (NDDs) remains challenging. Neurotoxicity, inflammations, and oxidative stress are associating factors of NDDs. Sodium butyrate (NaB) is a short-chain fatty acid found in diet and produced in the gut that reportedly protects against cancer, inflammation, obesity, and so on. We have investigated the neuroprotective effects of NaB in SH-SY5Y cells stimulated with TNF-α. We also used four-week-old male C57Bl/6NTac mice were divided into three groups; the control group, the High Fat Diet (HFD) group, and the HFD + NaB group where mice received 11 mg/kg body weight of NaB with HFD. Our results showed that NaB attenuated cell death and inhibited the NO production and decreased the expression of iNOS and COX-2. NaB notably ameliorated apoptotic regulatory proteins p-53, Caspase-3 and caspase-1 level, and reversed phosphorylation of extracellular signal-regulated kinases and p-38 proteins. We found that NaB restored bodyweight and attenuated P-53, Bcl-2-associated X protein (BAX), and caspase cascades in the brains of HFD-fed mice. NaB ameliorated Glucocorticoid receptor and NLRP3 inflammasome expressions in SH-SY5Y cells and brains of HFD-fed mice. On the other hand, NaB treatment upregulated the expression of the growth factor-related factors PPARγ, CREB, and BDNF in the brain tissues of HFD-fed mice. NaB also suppressed the BAX activation and modulated Nrf-2, HO-1 and MnSOD expression in neuroblastoma cells and in the cerebral cortex of HFD-fed mice. In addition, NaB substantially reversed the Amyloid-beta and Tau activation in SH-SY5Y and BV-2 cells. Altogether, our results suggest that sodium butyrate has potential therapeutic effects against NDDs.
