Investigation into the mechanistic action of zhuye shigao decoction in acute pneumonia treatment <i>via</i> liquid chromatography-mass spectrometry-based metabolomics combined with network pharmacology analysis

The traditional Chinese medicine (TCM) formulation Zhuye Shigao Decoction (ZSD) has demonstrated therapeutic efficacy in the treatment of acute pneumonia. Nevertheless, the precise mechanisms underlying its pharmacological action remain inadequately elucidated. This study aims to assess the therapeutic efficacy of ZSD in managing acute pneumonia and to elucidate the potential mechanisms driving its effects. A lipopolysaccharide (LPS)-induced murine model of acute pneumonia was established. Histopathological examination and serum biochemical assays were conducted to assess the therapeutic efficacy of ZSD for acute pneumonia. An LC-MS-based metabolomics strategy was employed to explore the impact of ZSD on the serum metabolome. To further elucidate the underlying mechanisms of ZSD’s therapeutic effects, a combined metabolomics and network pharmacology strategy was employed. Compared with the model group, ZSD demonstrated the ability to reduce serum levels of Tumor necrosis factor α (TNF-α), Interleukin-1β (IL-1β), and Interleukin-6 (IL-6), while simultaneously enhancing the expression of IgA and IgM. Histological analysis showed that ZSD could significantly improve lung tissue changes caused by LPS exposure. We selected 74 serum metabolites as metabolic biomarkers for acute pneumonia, of which 67 demonstrated significant recovery following treatment with ZSD, thereby highlighting its therapeutic potential in addressing LPS-induced pneumonia. Network pharmacology analysis identified potential targets, including AKT1, IL-6, IL-1β, TNF, Myc proto-oncogene protein (MYC), and Peroxisome proliferator-activated receptor gamma (PPARG). The joint analysis indicated that the potential therapeutic mechanism of ZSD might associated with sphingolipid metabolism, arachidonic acid metabolism, glycerophospholipid metabolism, PPAR signaling pathway, and Janus kinase-signal transducer and activator of transcription ((JAK-STAT) signaling pathway. This study illustrated the comprehensive regulatory role of ZSD in the treatment of acute pneumonia and, for the first time, elucidated the possible mechanisms of ZSD at both the protein and metabolic levels. Furthermore, it offers a new perspective on the pharmacological effects of Chinese materia medica (CMM) in acute pneumonia treatment, with a particular emphasis on metabolic regulation.