Mechanisms of LouDan LiFei granule attenuate inflammatory injury in AECOPD:A network pharmacology and experimental validation.

BACKGROUND

Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) significantly contributes to the high mortality rate associated with chronic obstructive pulmonary disease (COPD). It leads to a decline in health status, increased rates of readmission, and accelerated disease progression. LouDan LiFei granule (LDLF), a Traditional Chinese Medicine (TCM) granule, has demonstrated efficacy in treating AECOPD patients. However, its underlying regulatory mechanisms remain to be fully elucidated.

PURPOSE

To investigate the pharmacodynamic components and regulatory mechanisms of LDLF in the treatment of AECOPD, and to provide a scientific basis for the further clinical application of subsequent drugs.

METHODS

This study focused on identifying the pharmacodynamic components and regulatory mechanisms of LDLF. In vivo experiments, we established a rat model of AECOPD and systematically evaluated the therapeutic effect by monitoring the body weight, lung function and pathological changes in lung tissue. UPLC-MS/MS was employed to detect the components of LDLF medicated serum. Network pharmacology and molecular docking were utilized to determine the therapeutic targets and pathways of LDLF in AECOPD treatment. Finally, we further verified the research results by establishing AECOPD moded in rat and BEAS-2B.

RESULTS

Our study revealed that LDLF significantly reduced inflammation and pathological damage in lung tissue of AECOPD model rats and improved pulmonary function. UPLC-MS/MS analysis identified 1502 compounds in LDLF medicated serum, primarily comprising flavonoids, terpenoids, alkaloids, ketones, and aldehydes acids. Network pharmacology results suggested that LDLF may treat AECOPD by modulating Th17 cell differentiation and signaling pathways related to IL-17, T cell receptor, and NOD-like receptor. Molecular docking confirmed stable interactions between core compounds and their targets. In vivo validation showed that LDLF redused the proportion of Th17 cells and increased Treg cells proportion in peripheral blood of rat model. Protein expression levels of FOXP3 were elevated, and RORγ and STAT3 were reduced in lung tissue. Inflammatory markers (IL-6, IL-1β, IL-8, IL-17, TNF-α, IL-10, and TGF-β1) in serum and balf were improved after LDLF treatment. Additionally, LDLF significantly inhibited the NLRP3 inflammasome pathway at protein and mRNA levels in lung. In vitro experiments demonstrated that LDLF enhanced the BEAS-2B cells viability and inhibited inflammatory markers IL-6 and TNF-α as well as key targets of NLRP3, STAT3, CASP3, and AKT1.

CONCLUSIONS

This research highlights the potential for LDLF in the treatment of AECOPD and enhances our understanding of its pathogenic and therapeutic mechanisms.