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Neuroprotective Effects of Sodium Butyrate through Suppressing Neuroinflammation and Modulating Antioxidant Enzymes

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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 cancer, inflammation, obesity and so on. Previously, SH-SY5Y cells were studied as in vitro models of cerebral diseases. We have investigated the neuroprotective effects of NaB in SH-SY5Y cells stimulated with TNF-α. The expression of inflammatory mediators, including iNOS, COX-2, and mitogen-activated protein kinases (MAPK) and the apoptotic regulators, including P-53, Bcl-2 associated X (BAX) Protein, and caspase-3 were analyzed by western blot analysis. The anti-apoptotic gene Bcl-2 and the pro-apoptotic gene BAX translocation were also investigated. Our results showed that NaB attenuated cell death and inhibited the NO production and decreased the expression of iNOS and COX-2 in TNF-α-stimulated SH-SY5Y cells. 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. NaB ameliorated Glucocorticoid receptor and NLRP3 inflammasome expressions. NaB also suppressed the BAX nuclear translocation and modulated Nrf-2, HO-1 and MnSOD expression in neuroblastoma cells. In addition, NaB substantially reversed the reactive oxygen species in H2O2 induced SH-SY5Y cells. Altogether, our results suggest that sodium butyrate has potential therapeutic effects against NDDs.

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Acknowledgements

This research was financially supported by the Ministry of Trade, Industry, and Energy (MOTIE), Korea, under the “Regional Specialized Industry Development Program” supervised by the Korea Institute for Advancement of Technology (KIAT).

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Authors and Affiliations

  1. Department of Integrated Biosciences, Graduate School of Konkuk University, Chungju, 27478, Korea

    Al Borhan Bayazid & Beong Ou Lim

  2. Convergence Research Center for Smart Healthcare, R&DB Foundation of Kyungsung University, Busan, Korea

    Young Ah Jang

  3. Bio-Nano Technology Co, Daegu, Korea

    Yu Mi Kim

  4. BK21 FOUR, GLOCAL Education Program for Nutraceutical and Biopharmaceutical Research, Konkuk University, Chungju, 27478, Korea

    Jae Gon Kim

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  1. Al Borhan Bayazid
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Contributions

ABB designed the study, carried out the experiments, and wrote the manuscript. ABB, YAJ, YMK and JGK analyzed the data and reviewed the manuscript. BOL reviewed and supervised the study.

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Correspondence to Beong Ou Lim.

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Bayazid, A., Jang, Y.A., Kim, Y.M. et al. Neuroprotective Effects of Sodium Butyrate through Suppressing Neuroinflammation and Modulating Antioxidant Enzymes. Neurochem Res 46, 2348–2358 (2021). https://doi.org/10.1007/s11064-021-03369-z

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