| Summary: | Mingsheng Lyu,1,2 Jingbo Qin,3 Shuaiyang Huang,2 Dongmei Shao,4 Guirui Huang,2 Fan Yang,5,6 Xuefeng Gong,7 Shiyu Zhang,2 Zhijie Zhang,2 Ji Wang,6 Hongsheng Cui2 1Center of Respiratory Disease, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Department of Respiratory, The Third Affiliated Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 3Department of Geratology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 4Department of Infectious Disease, Shunyi Hospital, Beijing Hospital of Traditional Chinese Medicine, Beijing, People’s Republic of China; 5College of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 6National Institute of Traditional Chinese Medicine (TCM) Constitution and Preventive Medicine, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 7Department of Traditional Chinese Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Hongsheng Cui, Department of Respiratory, The Third Affiliated Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China, Email hshcui@sina.com; Ji Wang, National Institute of Traditional Chinese Medicine Constitution and Preventive Medicine, Beijing University of Chinese Medicine, Beijing, People’s Republic of China, Email doctorwang2009@126.comBackground: Tuo-Min-Ding-Chuan Decoction (TMDCD) is an effective traditional Chinese medicine (TCM) formula granule for allergic asthma (AA). Previous studies proved its effects on controlling airway inflammations, while the specific mechanism was not clear.Methods: We conducted a network pharmacology study to explore the molecular mechanism of TMDCD against AA with the public databases of TCMSP. Then, HUB genes were screened with the STRING database. DAVID database performed GO annotation and KEGG functional enrichment analysis of HUB genes, and it was verified with molecular docking by Autodock. Then, we built a classic ovalbumin-induced allergic asthma mice model to explore the mechanism of anti-inflammation effects of TMDCD.Results: In the network pharmacology study, we found out that the potential mechanism of TMDCD against AA might be related to NOD-like receptor (NLR) signaling pathway and Toll-like receptor (TLR) signaling pathway. In the experiment, TMDCD showed remarkable effects on alleviating airway inflammations, airway hyperresponsiveness (AHR), and airway remodeling in the asthmatic mice model. Further molecular biology and immunohistochemistry experiments suggested TMDCD could repress TLR4-NLRP3 pathway-mediated pyroptosis-related gene transcriptions to inhibit expressions of target proteins.Conclusion: TMDCD could alleviate asthmatic mice model airway inflammations by regulating TLR4-NLRP3 pathway-mediated pyroptosis.Keywords: Tuo-Min-Ding-Chuan Decoction, allergic asthma, TLR4, NLRP3, pyroptosis, network pharmacology, traditional Chinese medicine
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