Relinqing Granules inhibiting lipopolysaccharide-induced pneumonia injury through modulation of the PI3K/AKT/mTOR signaling pathway

ETHNOPHARMACOLOGICAL RELEVANCE: Relinqing Granules (RLQ), a single-herb formulation derived from Polygonum capitatum Buch.-Ham. ex D. Don (THL), possesses diverse pharmacological properties-including antimicrobial, anti-inflammatory, and antioxidant activities-which suggest their potential utility in treating pneumonia. This study seeks to elucidate the underlying mechanisms of RLQ to support its future clinical application in managing inflammatory lung diseases. AIM OF THE STUDY: This study aimed to investigate the therapeutic effects of RLQ on pneumonia and elucidate its underlying mechanisms, with a particular focus on the phosphoinositide 3-kinase/protein kinase B/mechanistic target of rapamycin (PI3K/AKT/mTOR) signaling pathway. MATERIALS AND METHODS: Pneumonia was induced in mice via lipopolysaccharide (LPS) administration, while A549 cells were similarly stimulated with LPS to establish an in vitro inflammation model. Mice received RLQ treatment by oral gavage for seven consecutive days. Subsequently, lung tissues were collected for hematoxylin-eosin (H&E) staining, enzyme-linked immunosorbent assay (ELISA), Western blotting, and quantitative real-time polymerase chain reaction (qPCR). In vitro, RLQ-treated A549 cells were evaluated through ELISA, Cell Counting Kit-8 (CCK-8), flow cytometry, Western blotting, and qPCR. To further elucidate the underlying mechanism, A549 cell models with mTOR knockdown and overexpression (OE) were constructed to assess the regulatory role of mTOR in inflammation and apoptosis. RESULTS: RLQ alleviated LPS-induced lung inflammation by shifting the regulatory T cell/T helper 17 cell (Treg/Th17) balance toward an immunoregulatory state and modulating pro-inflammatory cytokine expression, potentially through the PI3K/AKT/mTOR signaling pathway. In vitro, RLQ treatment reduced cytokine levels, improved cell viability, and inhibited apoptosis in LPS-injured A549 cells by regulating this pathway and its downstream apoptotic proteins. Furthermore, in mTOR knockdown and OE models, RLQ significantly mitigated LPS-induced cellular damage, enhanced cell viability, and suppressed apoptosis, which correlated with the downregulation of mTOR pathway activation. CONCLUSION: RLQ effectively protected against LPS-induced lung and alveolar epithelial cell injury by inhibiting PI3K/AKT/mTOR pathway phosphorylation, restoring the Treg/Th17 immune balance, and suppressing apoptosis. These findings provide new mechanistic insights into the therapeutic potential of RLQ in the treatment of pneumonia.