Effects of Baicalein on Cortical Proinflammatory Cytokines and the Intestinal Microbiome in Senescence Accelerated Mouse Prone 8

Baicalein, a flavonoid derived from the roots of Scutellariae baicalensis Georgi, has shown health benefits for an array of human diseases including dementia. The senescence-accelerated mouse prone 8 (SAMP8) strain is extensively used as a senile dementia model. To further investigate the effects of baicalein in SAMP8 mice, behavioral testing, biochemical detection, and gut microbiota analysis were performed. The results demonstrated that treatment with baicalein ameliorated the senescence status of the SAMP8 mice, as manifested by reducing the grading score of senescence. Additionally, baicalein improved the cognitive functions of the SAMP8 mice, including spatial learning and memory abilities, object recognition memory, and olfactory memory. Furthermore, baicalein significantly inhibited the release of proinflammatory cytokines such as interleukin-6 (IL-6), interleukin-1 beta (IL-1 beta), and tumor necrosis factor-alpha (TNF-alpha) in the brain cortex of SAMP8 mice. Gut microbiota analysis revealed that treatment with baicalein markedly altered the abundance of six genera in SAMP8 mice. Correlation analysis indicated that the abundances of Mucispirillum, Bacteroides, and Sutterella were negatively correlated with cognitive abilities and that Christensenellaceae was positively correlated with cognition. Furthermore, the abundance of Christensenellaceae was negatively correlated with the levels of IL-6 and TNF-alpha, while [Prevotella] was positively correlated with the levels of IL-1 beta and IL-6. In addition, Mucispirillum and Bacteroides were positively correlated with the level of IL-6 in the brain cortex. These data indicated that baicalein ameliorates senescence status and improves cognitive function in SAMP8 mice and that this effect might be attributable to suppression of cortical proinflammatory cytokines and modulation of the intestinal microbiome.