Molecular mechanisms of An-Chuan Granule for the treatment of asthma based on a network pharmacology approach and experimental validation.

Abstract

An-Chuan Granule (ACG), a traditional Chinese medicine (TCM) formula, is an effective treatment for asthma but its pharmacological mechanism remains poorly understood. In the present study, network pharmacology was applied to explore the potential mechanism of ACG in the treatment of asthma. The tumor necrosis factor (TNF), Toll-like receptor (TLR), and Th17 cell differentiation-related, nucleotide-binding oligomerization domain (NOD)-like receptor, and NF-kappaB pathways were identified as the most significant signaling pathways involved in the therapeutic effect of ACG on asthma. A mouse asthma model was established using ovalbumin (OVA) to verify the effect of ACG and the underlying mechanism. The results showed that ACG treatment not only attenuated the clinical symptoms, but also reduced inflammatory cell infiltration, mucus secretion and MUC5AC production in lung tissue of asthmatic mice. In addition, ACG treatment notably decreased the inflammatory cell numbers in bronchoalveolar lavage fluid (BALF) and the levels of pro-inflammatory cytokines (including IL-6, IL-17, IL-23, TNF-alpha, IL-1beta and TGF-beta) in lung tissue of asthmatic mice. In addition, ACG treatment remarkably down-regulated the expression of TLR4, p-P65, NLRP3, Caspase-1 and adenosquamous carcinoma (ASC) in lung tissue. Further, ACG treatment decreased the expression of receptor-related orphan receptor (RORγt) in lung tissue but increased that of Forkhead box (Foxp3). In conclusion, the above results demonstrate that ACG alleviates the severity of asthma in a ´multi-compound and multi-target' manner, which provides a basis for better understanding of the application of ACG in the treatment of asthma.

• Authors: Xiao-Li Chen, Qing-Ling Xiao, Zhong-Hua Pang, Cheng Tang, Qi-Yong Zhu
• Journal: Bioscience reports (Biosci Rep) Vol. 41 Issue 3 (03 26 2021) ISSN: 1573-4935 [Electronic] England
• PMID: 33645621 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 The Author(s).

Chemical References

• Drugs, Chinese Herbal
• Forkhead Transcription Factors
• Foxp3 protein, mouse
• Interleukins
• Muc5ac protein, mouse
• Mucin 5AC
• NF-kappa B
• NLR Family, Pyrin Domain-Containing 3 Protein
• Nlrp3 protein, mouse
• Nuclear Receptor Subfamily 1, Group F, Member 3
• Toll-Like Receptors
• Tumor Necrosis Factor-alpha

Topics

• Animals
• Asthma (drug therapy, immunology)
• Drugs, Chinese Herbal (pharmacology, therapeutic use)
• Forkhead Transcription Factors (metabolism)
• Interleukins (metabolism)
• Lung (drug effects, metabolism)
• Male
• Mice
• Mice, Inbred BALB C
• Mucin 5AC (metabolism)
• NF-kappa B (metabolism)
• NLR Family, Pyrin Domain-Containing 3 Protein (metabolism)
• Nuclear Receptor Subfamily 1, Group F, Member 3 (metabolism)
• T-Lymphocytes, Regulatory (drug effects, immunology)
• Th17 Cells (drug effects, immunology)
• Toll-Like Receptors (metabolism)
• Tumor Necrosis Factor-alpha (metabolism)