College of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, People's Republic of China.
Chengdu Public Health Clinical Medical Center & Public Health Clinical Center of Chengdu University of Traditional Chinese Medicine, Chengdu, 610021, People's Republic of China.
J Ethnopharmacol. 2025 Jan 30;337(Pt 3):118976. doi: 10.1016/j.jep.2024.118976. Epub 2024 Oct 22.
Modified Ma-Xing-Shi-Gan decoction (MMXSGD), a classic prescription from Treatise on Febrile Disease in China, is commonly used to treat Klebsiella pneumoniae (KP) infections in clinical settings.
The aim of this study is to assess the efficacy of MMXSGD in the treatment of pneumonia and investigate its underlying mechanism of action. UHPLC-MS/MS was established to identify the main chemical components of serum after intragastric administration with MMXSGD. A mouse model of pneumonia caused by KP was used to evaluate the therapeutic potential of MMXSGD. The macrophage polarization was analyzed by immunohistochemistry. The cytokine profile was assessed using Luminex assay. Lung transcript and metabolite levels were assessed by transcriptomics and non-targeted metabolomics to analyze potential anti-pneumonia mechanisms and targets.
22 major blood-entry components and 274 MMXSGD-pneumonia-related targets were identified. Compared with the model group, the mortality rate of mice in different dosage groups of MMXSGD was significantly reduced, and pathological lung damage was significantly alleviated. Among them, the low dose of MMXSGD treatment had the best protective effect. Further, MMXSGD treatment could regulates M1/M2 polarization in macrophages and inhibits the production of pro-inflammatory cytokines. The data from transcriptome and metabolome analysis indicate that MMXSGD could regulate inflammation-related pathways (PI3K/AKT, HIF-1, NF-κB pathway) and metabolites to modulate pulmonary inflammation. The results demonstrate that MMXSGD enhances the antibacterial effect in vivo by suppressing inflammation and regulating immunity rather than directly antibacterial effect.
These findings provide a further assessment of MMXSGD, suggesting that MMXSGD has good therapeutic efficacy in bacterial infectious diseases.
改良麻杏石甘汤（MMXSGD）是《伤寒论》中的经典方剂，常用于临床治疗肺炎克雷伯菌（KP）感染。
本研究旨在评估 MMXSGD 治疗肺炎的疗效，并探讨其作用机制。采用 UHPLC-MS/MS 法鉴定 MMXSGD 灌胃后血清中的主要化学成分。采用肺炎克雷伯菌致肺炎小鼠模型评价 MMXSGD 的治疗潜力。采用免疫组化法分析巨噬细胞极化。采用 Luminex assay 检测细胞因子谱。采用转录组学和非靶向代谢组学分析肺转录物和代谢物水平，以分析潜在的抗肺炎机制和靶点。
鉴定出 22 种主要血中成分和 274 种 MMXSGD-肺炎相关靶点。与模型组相比，不同剂量 MMXSGD 组小鼠的死亡率明显降低，肺部病理损伤明显减轻。其中，低剂量 MMXSGD 治疗效果最佳。此外，MMXSGD 治疗可调节巨噬细胞 M1/M2 极化，抑制促炎细胞因子的产生。转录组和代谢组学数据分析表明，MMXSGD 可通过调节炎症相关通路（PI3K/AKT、HIF-1、NF-κB 通路）和代谢物来调节肺部炎症。结果表明，MMXSGD 通过抑制炎症和调节免疫而不是直接抗菌作用来增强体内的抗菌作用。
这些发现进一步评估了 MMXSGD，表明 MMXSGD 在细菌性传染病中具有良好的治疗效果。
