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Oridonin, commonly used in Traditional Chinese Medicine (TCM), exhibits significant anti\u2010inflammation activity. To explore the protective mechanisms of oridonin against the pathophysiological changes, the authors conducted single\u2010cell transcriptome (scRNA\u2010seq) analysis on septic liver models induced by cecal ligation and puncture (CLP). They obtained a total of 63,486 cells, distributed across 11 major cell clusters, and concentrated their analysis on four specific clusters (hepatocytes\/Heps, macrophages, endothelial\/Endos and T\/NK) based on their changes in proportion during sepsis and under oridonin treatment. Firstly, biological changes in Hep, which are related to metabolic dysregulation and pro\u2010inflammatory signaling, are observed during sepsis. Secondly, they uncovered the dynamic profiles of macrophage's phenotype, indicating that a substantial number of macrophages exhibited a M1\u2010skewed phenotype associated with pro\u2010inflammatory characteristics in septic model. Thirdly, they detected an upregulation of both inflammatory cytokines and transcriptomic factor <jats:italic>Nfkb1<\/jats:italic> expression within Endo, along with slight capillarization during sepsis. Moreover, excessive accumulation of cytotoxic NK led to an immune imbalance. Though, oridonin ameliorated inflammatory\u2010related responses and improved the liver dysfunction in septic mice. 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