Huashi Baidu granules alleviates LPS-induced acute lung injury by targeting TACE-mediated inflammatory signaling and stress granules disassembly.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE: Acute lung injury (ALI) is a severe health issue characterized by high morbidity and mortality, driven by excessive inflammatory responses. The traditional Chinese medicine Huashi Baidu Granules (HBG) demonstrated clinical efficacy in treating severe ALI, yet its mechanisms remain unclear. AIM OF THE STUDY: This research aimed to examine the efficacy and underlying mechanisms of HBG in a lipopolysaccharide (LPS)-induced ALI model, identify core herbal constituents, active compounds, and therapeutic targets, providing a foundation for optimizing HBG-based treatments. MATERIALS AND METHODS: Structure-based molecular docking identified core herbs and targets. A LPS-induced ALI model was established, with HBG's effects assessed via histopathology, RNA-Seq, RT-qPCR, ELISA, and flow cytometry. Key pathways and targets, including TNF-α-converting enzyme (TACE), were validated. Licorice-derived compounds were analyzed for anti-inflammatory and stress granules (SGs)-modulating effects. RESULTS: Molecular docking indicated 7 herbal constituents influenced 7 of 8 potential therapeutic targets. These targets (sPLA2, TACE, AMPK, CCR2, P38 MAPK, VEGFR2, and ALK5) were validated by RT-qPCR, demonstrating significant regulation in lung tissues. RNA-Seq revealed HBG-induced gene expression changes were highly consistent with the established multi-target network. HBG (2.5 g/kg, 7 d) alleviated lung inflammation and oxidative stress by inhibiting TACE expression, suppressing NF-κB signaling, and reducing pro-inflammatory cytokine release. Licorice (0.06 g/kg, 7d) emerged as a core herb, with its active component licochalcone B significantly inhibiting TACE, mediating autophagy promoting SGs disassembly and potentially clearing residual mRNA. CONCLUSION: HBG, with licorice as its pivotal herb, mitigates ALI by targeting TACE-mediated inflammatory cascades and modulating SGs. The licorice-derived licochalcone B exerts a pivotal effect in this mechanism, offering insights for optimizing traditional formulations and developing novel therapies.