Tanreqing injection regulates Sema7a/Plxnc1 signaling pathway mediated neutrophil extracellular trap formation to alleviate lipopolysaccharide-induced acute lung injury.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE: Tanreqing Injection (TRQ) is derived from the traditional Chinese herbal formula Qing-Jin-Hua-Tan Decoction, which exhibits properties of heat-clearing, detoxification, phlegm-resolution, and cough alleviation. Historically, it has been employed in the treatment of respiratory system diseases. Recent studies have demonstrated TRQ's significant efficacy in mitigating acute lung injury (ALI), underscoring its potential role in pulmonary inflammation management. AIM OF THE STUDY: This study aims to evaluate the therapeutic effects of TRQ on ALI and elucidate its molecular mechanisms. MATERIALS AND METHODS: An ALI rat model was established via intratracheal injection of lipopolysaccharide. The key components of TRQ were identified using ultra-high-performance liquid chromatography-quadrupole-electrospray mass spectrometry (UHPLC-QE-MS). Differentially expressed genes and related pathways were analyzed through integrated metabolomics, RNA sequencing, and single-cell sequencing. The mechanisms were validated via molecular docking and in vitro/in vivo experiments. RESULTS: TRQ significantly reduced the formation of neutrophil extracellular traps (NETs) and the secretion of inflammatory cytokines in ALI rats. Its protective effect is primarily mediated through inhibition of the Sema7a/Plxnc1 signaling pathway. In vivo experiments confirmed that TRQ treatment reduced NETs accumulation and downregulated the expression of Sema7a and Plxnc1. Moreover, molecular docking and in vitro experiments revealed that baicalin, an active component of TRQ, competitively inhibits the binding of Sema7a to Plxnc1, thereby significantly suppressing NETs formation. CONCLUSION: This study provides novel molecular insights into the potential mechanisms of TRQ in the treatment of ALI, highlighting its therapeutic promise in pulmonary inflammation management.