Tuo-Min-Ding-Chuan Decoction Alleviates Airway Inflammations in the Allergic Asthmatic Mice Model by Regulating TLR4-NLRP3 Pathway-Mediated Pyroptosis: A Network Pharmacology and Experimental Verification Study

• Published in: Drug design, development and therapy Vol. 17; pp. 1613 - 1630
• Main Authors: Lyu, Mingsheng, Qin, Jingbo, Huang, Shuaiyang, Shao, Dongmei, Huang, Guirui, Yang, Fan, Gong, Xuefeng, Zhang, Shiyu, Zhang, Zhijie, Wang, Ji, Cui, Hongsheng
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01-01-2023; Dove; Dove Medical Press
• Subjects: Albumin; allergic asthma; Animal experimentation; Animals; Asthma; Asthma - drug therapy; Disease Models, Animal; Drugs, Chinese Herbal - pharmacology; Genetic transcription; Inflammation; Medicine, Chinese; Mice; Molecular biology; Molecular Docking Simulation; Network Pharmacology; NLR Family, Pyrin Domain-Containing 3 Protein; nlrp3; Original Research; Pharmacology; Pyroptosis; tlr4; Toll-Like Receptor 4; traditional chinese medicine; tuo-min-ding-chuan decoction; China; pyroptosis; allergic asthma; network pharmacology; NLRP3; Tuo-Min-Ding-Chuan Decoction; traditional Chinese medicine; TLR4
• ISSN: 1177-8881; 1177-8881
• DOI: 10.2147/DDDT.S406483

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.
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.
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.
TMDCD could alleviate asthmatic mice model airway inflammations by regulating TLR4-NLRP3 pathway-mediated pyroptosis.