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

Mingsheng Lyu; Jingbo Qin; Shuaiyang Huang; Dongmei Shao; Guirui Huang; Fan Yang; Xuefeng Gong; Shiyu Zhang; Zhijie Zhang; Ji Wang; Hongsheng Cui

doi:10.2147/DDDT.S406483

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

Drug Des Devel Ther. 2023 Jun 2:17:1613-1630. doi: 10.2147/DDDT.S406483. eCollection 2023.

Authors

Mingsheng Lyu^{1

2}, Jingbo Qin³, Shuaiyang Huang², Dongmei Shao⁴, Guirui Huang², Fan Yang^{5

6}, Xuefeng Gong⁷, Shiyu Zhang², Zhijie Zhang², Ji Wang⁶, Hongsheng Cui²

Affiliations

¹ Center of Respiratory Disease, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, People's Republic of China.
² Department of Respiratory, The Third Affiliated Hospital, Beijing University of Chinese Medicine, Beijing, People's Republic of China.
³ Department of Geratology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People's Republic of China.
⁴ Department of Infectious Disease, Shunyi Hospital, Beijing Hospital of Traditional Chinese Medicine, Beijing, People's Republic of China.
⁵ College of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, People's Republic of China.
⁶ National Institute of Traditional Chinese Medicine (TCM) Constitution and Preventive Medicine, Beijing University of Chinese Medicine, Beijing, People's Republic of China.
⁷ Department of Traditional Chinese Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People's Republic of China.

Abstract

Background: 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: NLRP3; TLR4; Tuo-Min-Ding-Chuan Decoction; allergic asthma; network pharmacology; pyroptosis; traditional Chinese medicine.

MeSH terms

Animals
Asthma* / drug therapy
Disease Models, Animal
Drugs, Chinese Herbal* / pharmacology
Inflammation
Mice
Molecular Docking Simulation
NLR Family, Pyrin Domain-Containing 3 Protein
Network Pharmacology
Pyroptosis
Toll-Like Receptor 4

Substances

NLR Family, Pyrin Domain-Containing 3 Protein
Toll-Like Receptor 4
Drugs, Chinese Herbal

Grants and funding

This work was supported by Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine [No: ZYYCXTD-C-202001].