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

Xing Zhang; Jiacheng Lin; Dongliang Zuo; Xuan Chen; Guihua Xu; Jie Su; Wei Zhang

doi:10.1016/j.gene.2024.149001

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

Gene. 2024 Oct 12:149001. doi: 10.1016/j.gene.2024.149001. Online ahead of print.

Authors

Xing Zhang¹, Jiacheng Lin², Dongliang Zuo³, Xuan Chen⁴, Guihua Xu⁵, Jie Su⁶, Wei Zhang⁷

Affiliations

¹ Department of Respiratory Disease, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Division of Pulmonary, Critical Care, Allergy, and Sleep, Department of Medicine, University of California, San Francisco, CA 94143, USA. Electronic address: zhangxing2012@shutcm.edu.cn.
² Central Laboratory, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address: linjc_sh@shutcm.edu.cn.
³ Shanghai Institute for Advanced Immunochemical Studies, Shanghai Tech University, Shanghai 201210, China. Electronic address: zuodl@shanghaitech.edu.cn.
⁴ Department of Respiratory Disease, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address: zuodl@shanghaitech.edu.cn.
⁵ Department of Respiratory Disease, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
⁶ School of Life Sciences and Biotechnology and State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, National Research Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China. Electronic address: su.jie@sjtu.edu.cn.
⁷ Department of Respiratory Disease, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address: zhangw1190a@sina.com.

PMID: 39401735
DOI: 10.1016/j.gene.2024.149001

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.

Keywords: Acute lung injury; Diarrhea; Macrophage; Systems pharmacology; Tan-Re-Qing Capsule.