Elucidation of the antipyretic and anti-inflammatory effect of 8-O-Acetyl Shanzhiside methyl ester based on intestinal flora and metabolomics analysis

Results show that 8-<i>O</i>aS treatment reduced pyrogenic cytokines (such as IL-6, IL-1β), and down-regulated the level of central thermoregulatory mediators (PGE₂), via multiply involved in TLR4/NF-κB and HSP70/NF-κB signaling pathways. Crucially, 8-<i>O</i>aS treatment significantly reduced the relative abundance of <i>Alistipes</i> (<i>P</i> < 0.01), <i>Odoribacter</i> (<i>P</i> < 0.05) and <i>Alistipes_finegoldii</i> (<i>P</i> < 0.05) in the intestinal flora. The correlation analysis demonstrated that 8-<i>O</i>aS treatment significantly correlated with the increasing on the abundance of <i>Alistipes</i> and levels of 5-hydroxytryptamine (<i>P</i> < 0.01), and tryptamine (<i>P</i> < 0.01). Our findings indicate that 8-<i>O</i>aS exhibits significant antipyretic and anti-inflammatory properties, potentially mediated by intestinal flora and metabolites of neurotransmitters. The results of this study may help to elucidate the antipyretic and anti-inflammatory mechanism of 8-<i>O</i>aS based on intestinal flora and metabolomics analysis.