The flavonoids of Rosa roxburghii Tratt alleviate endotoxemia progression by inhibiting the proinflammatory effects of neutrophil and macrophage via ROS/NLRP3 signaling pathway.

Endotoxemia and sepsis secondary to pathogen invasion constitute the major cause of hospital death in the surgical intensive care unit, which are mainly presented with systemic inflammation and multiple organ dysfunction. Although specific agents were designed to interrupt the proinflammatory cytokine cascade, few strategies have so far shown efficacy. Rosa roxburghii Tratt (RRT) is a special medicinal and edible resource from southwestern China rich in antioxidant and anti-inflammatory compounds. Here, we reveal that Rosa roxburghii Tratt flavonoids (RF), the major bioactive component in RRT, shows robust effect against LPS-induced endotoxemia mice by alleviating cytokine storm and tissue damage. Treatment with RF at low concentration can reduce IL-6, IL-1β, TNF-α expression in neutrophils and macrophages triggered by LPS and diminishes neutrophil extracellular traps (NETs) release as well as macrophage pyroptosis in vivo and in vitro, with a more pronounced effect when using high-dose RF. Further investigation indicates that low or high dose of RF can effectively inhibit NOD-like receptor protein 3 (NLRP3) inflammasome activation in both myeloid cells via suppressing reactive oxygen species (ROS) and mitochondrial ROS (mtROS) production, thereby abating the improper immune response of endotoxemia. Taken together, our study extends the current understanding of the RRT function by showing that RF improves the prognosis of endotoxemia in versatile manners, and highlights the pharmacological potential of such characteristic fruit in treating clinical inflammatory diseases with lower toxicity.