Neuroprotective mechanisms of sodium butyrate in Parkinson's disease in preclinical rodent models: a systematic review and meta-analysis.

In this study, we performed a systematic review and meta-analysis to assess existing preclinical evidence and potential sodium butyrate (NaB) mechanisms, specifically focusing on motor function, neuroinflammation, and dopaminergic markers in PD animal models. PubMed, Embase, Scopus, and Web of Science were searched until October 2024. Universal desktop ruler software was used to extract numerical values and the data was analyzed with RevMan 5.3. The SYRCLE risk of bias tool and CAMARADES checklist were used to assess quality assessment and the risk of bias in animal studies. The results of the included studies indicate that NaB administration was associated with improvements in motor function and exploratory behavior, as evidenced by performance on the rotarod, pole, open field, and narrow beam walk tests. Regarding neurochemical and histological markers, this meta-analysis revealed no statistically significant overall effect of NaB on tyrosine hydroxylase-positive (TH +) neuron counts in the substantia nigra pars compacta (SNpc). However, subgroup analyses identified specific conditions under which significant effects emerged: higher dosages (> 300 mg/kg) combined with prolonged treatment duration were associated with a significant increase in TH + neurons in the SNpc. Similarly, while the overall effect on striatal TH expression was significant, this effect was primarily driven by studies using lower dosages (< 300 mg/kg) administered over a long duration. For neuroinflammatory markers, NaB administration was associated with a significant overall reduction in brain levels of tumor necrosis factor-alpha (TNF-α), an effect consistent across various dosages and durations. Brain levels of interleukin-6 (IL-6) also showed a significant overall decrease, with subgroup analyses indicating this effect was most pronounced with lower dosages (< 300 mg/kg) and long-term administration. In contrast, NaB showed no significant overall effect on brain interleukin-1 beta (IL-1β), serum levels of TNF-α or IL-6, or markers of glial activation (allograft inflammatory factor 1 (IBA1), and glial fibrillary acidic protein). Notably, while the overall effect on IBA1 was non-significant, subgroup analysis suggested a potential reduction with lower dosages and short-term treatment. No significant effects were observed for brain-derived neurotrophic factor (BDNF), dopamine, serotonin, or their metabolites (3,4-dihydroxyphenylacetic acid and 5-hydroxyindoleacetic acid). The findings indicate that NaB improve behavioral functions in experimental models of PD and warrant further investigation as a potential therapeutic strategy.