Exploration of the mechanism of Qi-Xian decoction in asthmatic mice using metabolomics combined with network pharmacology

Yuhua Lin; Yue Wu; Fuqi Ma; Cuiting Shan; Jialu Ma; Wenguan Li; Huayang Pan; Xiayi Miao; Jinjin Liu; Xiongbiao Wang; Zhenhua Ni

doi:10.3389/fmolb.2023.1263962

Exploration of the mechanism of Qi-Xian decoction in asthmatic mice using metabolomics combined with network pharmacology

Front Mol Biosci. 2023 Dec 13:10:1263962. doi: 10.3389/fmolb.2023.1263962. eCollection 2023.

Authors

Yuhua Lin^#¹, Yue Wu^#¹, Fuqi Ma^#¹, Cuiting Shan¹, Jialu Ma¹, Wenguan Li¹, Huayang Pan¹, Xiayi Miao¹, Jinjin Liu¹, Xiongbiao Wang¹, Zhenhua Ni²

Affiliations

¹ Department of Respiratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
² Central Lab, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

^# Contributed equally.

Abstract

Introduction: Qi-Xian Decoction (QXD), a traditional Chinese medicine (TCM) formula consisting of eight herbs, has been clinically used to treat asthma. However, the underlying mechanisms have not been completely elucidated. This study aimed to combine metabolomics and network pharmacology to reveal the mechanism of action of QXD in asthma treatment. Methods: An ovalbumin (OVA)-induced asthma mouse model was constructed to evaluate the therapeutic effects of QXD. Serum metabolomics and network pharmacology were combined to study the mechanism of anti-asthma action as well as the potential target, and related biological functions were validated. Results: The QXD treatment has demonstrated significant protective effects in OVA-induced asthmatic mice, as evidenced by its ability to inhibit inflammation, IgE, mucus overproduction, and airway hyperreactivity (AHR). Metabolomic analysis has revealed a total of 140 differential metabolites associated with QXD treatment. In addition, network pharmacology has identified 126 genes that are linked to the effects of QXD, including TNF, IL-6, IL1β, STAT3, MMP9, EGFR, JUN, CCL2, TLR4, MAPK3 and MAPK8. Through comprehensive gene-metabolite interaction network analysis, seven key metabolites have been identified and associated with the potential anti-asthmatic effect of QXD, with palmitic acid (PA) being the most notable among them. In vitro validation studies have confirmed the gene-metabolite interaction involving PA, IL-6, and MAPK8. Furthermore, our research has demonstrated that QXD treatment can effectively inhibit PA-promoted IL-6 expression in MH-S cells and reduce PA concentration in OVA-induced asthmatic mice. Conclusion: The regulation of metabolic pathways by QXD was found to be associated with its anti-asthmatic action, which provides insight into the mechanism of QXD in treating asthma.

Keywords: Qi-Xian decoction; asthma; metabolomics; network pharmacology; palmitic acid.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Plan of Clinical Specialty Construction in Shanghai Putuo District Health System (2020tszk02), the Shanghai Science and Technology Committee (20ZR1450400), the Scientific Innovation Foundation of Putuo District (ptkwws202111).