Abstract
Yupingfeng San (YPFS) is a representative Traditional Chinese Medicine (TCM) formula with accepted therapeutic effect on Asthma. However, its action mechanism is still obscure. In this study, we used network pharmacology to explore potential mechanism of YPFS on asthma. Nucleotide-binding oligomerization domain (NOD)-like receptor pathway was shown to be the top one shared signaling pathway associated with both YPFS and asthma. In addition, NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome was treated as target protein in the process of YPFS regulating asthma. Further, experimental validation was done by using LPS-stimulated U937 cells and ovalbumin (OVA)-sensitized BALB/c mice model. In vitro experiments showed that YPFS significantly decreased the production of TNF-α and IL-6, as well as both mRNA and protein levels of IL-1β, NLRP3, Caspase-1 and ASC in LPS-stimulated U937 cells. In vivo experiment indicated that YPFS treatment not only attenuated the clinical symptoms, but also reduced inflammatory cell infiltration, mucus secretion and MUC5AC production in lung tissue of asthmatic mice. Moreover, YPFS treatment remarkably decreased the mRNA and protein levels of IL-1β, NLRP3, Caspase-1 and ASC in lung tissue of asthmatic mice. In conclusion, these results demonstrated that YPFS could inhibit NLRP3 inflammasome components to attenuate the inflammatory response in asthma.
Highlights
Asthma is a chronic inflammatory disorder of the airways in which many inflammatory cells play a role
Chemical compounds with OB ≥ 30% or DL ≥ 0.18 in Astragalus membranaceus, Atractylodes macrocephala, and Saposhnikoviae radix were obtained in Traditional Chinese Medicine Systems Pharmacology Database (TCMSP)1
DAVID database pathway enrichment analysis showed that the top five pathways of Yupingfeng San (YPFS) regulating asthma were Nucleotide-binding oligomerization domain (NOD)-like receptor signaling pathway, tumor necrosis factor (TNF) signal pathway, phosphatidylinositol-3kinase (PI3K)-AKT signal pathway, Hypoxia-inducible factor (HIF)-1 signal pathway and nuclear factor-kappaB (NF-κB) signal pathway (Table 1)
Summary
Asthma is a chronic inflammatory disorder of the airways in which many inflammatory cells play a role. Current research showed that Nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain-containing 3 (NLRP3), one of nucleotide-binding domain and leucine-rich repeat containing (NLR) family membranes, had a substantial impact on tissue inflammation including respiratory diseases like asthma and could aggravate the progress of asthma (Kufer and Sansonetti, 2011; Im and Ammit, 2014; Hosseinian et al, 2015) For this reason, NLRP3 inflammasome has been suggested as an important target for inflammatory disease control (Peng et al, 2016). There’s studies proved that NLRP3 mediated IL-1β could lead to a vicious cycle between previous and future exacerbations in asthma (Kim et al, 2017) For this reason, NLRP3 inflammasome and IL-1β have been suggested as important targets for inflammatory disease control (Fu et al, 2015; Peng et al, 2016)
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