Ge Fan, Tian Fang, Zhu Yeyan, Yan Qixiang, Sun Qimeng, Lu Jun
Department of Intensive Care Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, People's Republic of China.
Department of Central Laboratory, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, People's Republic of China.
J Inflamm Res. 2025 Apr 13;18:5017-5030. doi: 10.2147/JIR.S509734. eCollection 2025.
Modified Xi-Jiao-Di-Huang decoction (MXJDH) has significant clinical efficacy for the treatment of sepsis; however, its mechanism of action remains unclear. The purpose of this study was to investigate the protective effects of MXJDH in septic mice and explore its mechanism of action.
Utilizing UPLC-Q-TOF-MS, we identified the primary constituents of the compound MXJDH. Subsequently, we created a mouse model for sepsis, observing their overall condition, including specific symptoms and behavior. We also monitored key inflammatory markers and pathological changes in their organs. Flow cytometry was then employed to assess the polarization of macrophages. Transcriptome sequencing was used to identify genes with altered expression patterns. We investigated the connection between MXJDH and the Pim2/NF-κB signaling pathway, a crucial regulatory mechanism in inflammation. Finally, we examined the expression and tissue distribution of macrophages in the sepsis-induced mice.
MXJDH effectively reduces inflammation in sepsis mice, leading to a progressive recovery of organ functions. Moreover, MXJDH facilitates the conversion of macrophages from pro-inflammatory M1 phenotype to anti-inflammatory M2 phenotype. This transformation is potentially mediated through the Pim2/NF-κB signaling pathway. By suppressing Pim2 expression, MXJDH mitigates the nuclear translocation of NF-κB, thereby modulating the expression of downstream inflammatory mediators. The role of MXJDH in regulating macrophage polarization has also been confirmed in sepsis mouse tissues.
MXJDH regulates macrophage polarization, inhibits CRS, and alleviates sepsis by inhibiting the Pim2/NF-κB signaling pathway.
加味犀角地黄汤（MXJDH）在脓毒症治疗中具有显著的临床疗效；然而，其作用机制尚不清楚。本研究旨在探讨MXJDH对脓毒症小鼠的保护作用并探索其作用机制。
利用超高效液相色谱-四极杆飞行时间质谱联用技术（UPLC-Q-TOF-MS），我们鉴定了复方MXJDH的主要成分。随后，我们建立了脓毒症小鼠模型，观察它们的整体状况，包括特定症状和行为。我们还监测了关键炎症标志物以及它们器官中的病理变化。然后采用流式细胞术评估巨噬细胞的极化情况。转录组测序用于鉴定表达模式发生改变的基因。我们研究了MXJDH与Pim2/NF-κB信号通路之间的联系，这是炎症中的一种关键调节机制。最后，我们检测了脓毒症诱导小鼠中巨噬细胞的表达及组织分布。
MXJDH有效减轻脓毒症小鼠的炎症，使器官功能逐渐恢复。此外，MXJDH促进巨噬细胞从促炎M1表型向抗炎M2表型转化。这种转化可能是通过Pim2/NF-κB信号通路介导的。通过抑制Pim2表达，MXJDH减轻了NF-κB的核转位，从而调节下游炎症介质的表达。MXJDH在调节巨噬细胞极化方面的作用也在脓毒症小鼠组织中得到了证实。
MXJDH通过抑制Pim2/NF-κB信号通路调节巨噬细胞极化，抑制细胞因子释放综合征（CRS），减轻脓毒症。
