Lan-Qin oral liquid alleviates influenza A virus-induced acute lung injury by regulating monocyte-derived macrophages and TLR4-PI3K-AKT-NF-κB signal pathways.

ETHNOPHARMACOLOGICAL RELEVANCE

Lan-Qin oral liquid (LQ), a combined traditional Chinese medicine preparation originated from Huang-Lian-Jie-Du decoction recorded in classical book of "The Handbook of Prescriptions for Emergencies", possesses remarkable efficacy in treating influenza. However, its pharmacological mechanism against influenza is still unclear, restricting its clinical applications.

AIM OF THE STUDY

This work aimed to explore the effects and mechanism of LQ against influenza virus-induced acute lung injury (ALI).

MATERIALS AND METHODS

The influenza virus A/PR/8/34 (PR8)-induced ALI mouse model was used to investigate the effects of LQ. The survival rate, lung index, lung pathological changes, cytokines in the bronchoalveolar lavage fluid (BALF), and monocyte levels in the blood, spleen, and BALF were detected and analyzed. Meanwhile, alveolar macrophages (AMs) and monocyte-derived macrophages (MDMs) in BALF were also detected by flow cytometry. An AMs-eliminated coupled PR8 infection model was established by using clodronate liposomes (CL) and utilized to evaluate the effects of LQ. The potential anti-ALI mechanism of LQ was explored by in vivo chemical profiling and network pharmacology. Furthermore, western blotting was used to verify the mechanism of action of LQ against influenza.

RESULTS

LQ (66 g crude drug/kg/day) treatment significantly improved the survival rate and lifespan of PR8 infected mice and reduced lung index, lung pathological damage, levels of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, IFN-γ, and MCP-1) in BALF and viral titers in the lung. Meanwhile, LQ treatment significantly reduced monocytes in blood and lung. Subsequent results indicate that MDMs levels were significantly reduced while there was no appreciable impact on AM levels after LQ treatment. In addition, chemical profiling indicated that a total of 241 compounds were identified or tentatively characterized in LQ, and 99 prototypes were presented in the host circle system. Network pharmacology analysis revealed that TNF, IL-6, AKT1, etc. Might be the core targets of LQ in treating ALI, involving in PI3K-AKT signaling pathway, MAPK signaling pathway, TNF signaling pathway, etc. Further, it was found that LQ exerts its anti-PR8-induced ALI effects by reducing MDMs and regulating the TLR4-PI3K-AKT-NF-κB signaling pathway.

CONCLUSIONS

LQ could treat PR8-induced ALI by reducing MDMs and regulating the TLR4-PI3K-AKT-NF-κB signaling pathway. Meanwhile, the chemical information of LQ in vitro and in vivo was also supplied for further pharmacological substance exploration.