The Tan-Re-Qing Capsule mitigates acute lung injury by suppressing the NLRP3 inflammasome and MAPK/NF-κB signaling pathways

Abstract

Objective

The Tan-Re-Qing Capsule (TRQC), a traditional Chinese medicine (TCM) preparation, has been historically utilized in treating acute lung injury (ALI) and COVID-19-induced pulmonary diseases. This study aimed to explore the effect and underlying mechanisms of TRQC in lipopolysaccharide (LPS)-induced ALI models.

Methods

The changes of acute lung injury and inflammatory response were observed after TRQC treatment of the LPS-induced ALI mouse model. Based on active compounds in TRQC and network pharmacology analysis, potential targeting signals were identified. The effects of TRQC on signaling in LPS-stimulated BMDMs were investigated. Additionally, the defecatory status of mice and the mechanism of Cl⁻ secretion in HBE cells and T84 colonic epithelial cells were examined.

Results

TRQC exhibited a notable amelioration of inflammatory injuries in ALI mice. Utilizing a systems-pharmacology approach based on active chemical compounds, TRQC was found to regulate inflammation-related pathways, including NF-κB, NOD-like signaling, and MAPK signaling. In vitro experiments demonstrated that TRQC effectively suppressed LPS-induced activation of macrophages and the assembly of the NLRP3 inflammasome induced by LPS and Nigericin. These effects were attributed to the suppression of NF-κB and NOD-like signaling pathways. Furthermore, TRQC blocked MAPK signaling, thereby mitigating the inhibitory effects of LPS and Nigericin on Ca²⁺-dependent Cl⁻ efflux across colonic epithelial cells. This mechanism generated a cathartic effect, potentially aiding in the removal of harmful substances and pathogenic bacteria.

Conclusion

Our study demonstrates that TRQC significantly mitigates ALI by effectively suppressing the NLRP3 inflammasome and MAPK/NF-κB signaling pathways. These findings suggest that TRQC could serve as a promising therapeutic candidate for inflammatory lung diseases, offering a novel approach to managing conditions like ALI and potentially extending to other inflammatory diseases.