Chlorogenic acid-based combinations alleviate Streptococcus pneumoniae-induced injury in canine lung epithelium by...

Streptococcus pneumoniae (SP) infection frequently results in acute lung injury and post-infectious respiratory syndrome (PIRS), characterized by persistent epithelial dysfunction despite bacterial clearance. However, effective therapeutic strategies to restore epithelial function during the post-antibiotic phase are currently lacking, and the need for safe alternatives is increasingly urgent. To mimic clinical recovery, we established a canine alveolar epithelial (CAE) cell model by infecting cells with SP followed by doxycycline treatment. Cells were subsequently exposed to chlorogenic acid (CA), fish collagen peptides (FP), and sodium houttuyfonate (HC), administered individually or in combination. Cytotoxicity, apoptosis, oxidative stress, and cytokine release were measured, and integrated transcriptomic-metabolomic analyses were performed to elucidate mechanisms. Compared to untreated controls, the SP + antibiotic group exhibited marked cytotoxicity, including increased lactate dehydrogenase (LDH) release, apoptosis, oxidative stress, and inflammatory cytokines. Mechanistically, SP activated integrin-extracellular matrix (ECM) interaction, IL-17 signaling, glycerophospholipid metabolism. The CA, CA/FP, and CA/FP/HC combination significantly suppressed LDH release and mitigated apoptosis, oxidative imbalance, and inflammation. These effects were associated with inhibition of the integrin-ECM axis and restoration of ABC transporter function. The CA also modulated fatty acid and purine metabolism. Notably, CA/FP and CA/FP/HC downregulated lysophosphatidylcholine and phosphatidylcholine accumulation, thereby attenuating SP-induced lipid remodeling. These findings could highlight the multi-layered protective mechanisms of CA-based combinations and offer mechanistic insight into functional compound-mediated epithelial repair during PIRS.