Investigation of the Active Ingredients and Mechanism of Polygonum cuspidatum in Asthma Based on Network Pharmacology and Experimental Verification

Abstract

Background Polygonum cuspidatum is a Chinese medicine commonly used to treat phlegm-heat asthma. However, its anti-asthmatic active ingredients and mechanism are still unknown. The aim of this study was to predict the active ingredients and pathways of Polygonum cuspidatum and to further explore the potential molecular mechanism in asthma by using network pharmacology. Methods The active ingredients and their targets related to Polygonum cuspidatum were seeked out with the TCM systematic pharmacology analysis platform (TCMSP), and the ingredient-target network was constructed. The GeneCards, DrugBank and OMIM databases were used to collect and screen asthma targets, and then the drug-target-disease interaction network was constructed with Cytoscape software. A target protein-protein interaction (PPI) network was constructed using the STRING database to screen key targets. Finally, GO and KEGG analyses were used to identify biological processes and signaling pathways. The anti-asthmatic effects of Polygonum cuspidatum and its active ingredients were tested in vitro for regulating airway smooth muscle (ASM) cells proliferation and MUC5AC expression, two main symptoms of asthma, by using Real-time PCR, Western blotting, CCK-8 assays and annexin V-FITC staining. Results Twelve active ingredients in Polygonum cuspidatum and 479 related target proteins were screened in the relevant databases. Among these target proteins, 191 genes had been found to be differentially expressed in asthma. PPI network analysis and KEGG pathway enrichment analysis predicted that the Polygonum cuspidatum could regulate the AKT, MAPK and apoptosis signaling pathways. Consistently, further in vitro experiments demonstrated that Polygonum cuspidatum and resveratrol (one active ingredient of Polygonum cuspidatum ) were shown to inhibit ASM cells proliferation and promoted apoptosis of ASM cells. Furthermore, Polygonum cuspidatum and resveratrol inhibited PDGF-induced AKT/mTOR activation in ASM cells. In addition, Polygonum cuspidatum decreased H 2 O 2 induced MUC5AC overexpression in airway epithelial NCI-H292 cells. Conclusion Polygonum cuspidatum could alleviate the symptoms of asthma including ASM cells proliferation and MUC5AC expression through the mechanisms predicted by network pharmacology, which provides a basis for further understanding of Polygonum cuspidatum in the treatment of asthma.

Revealing the Underlying Mechanism of Acacia Nilotica against Asthma from a Systematic Perspective: A Network Pharmacology and Molecular Docking Study

“…PI3K-AKT signaling pathway was found to be the highly enriched pathway targeting 16 overlapping genes compared to the other screened pathways. AKT pathway has been shown to reduce cell proliferation in airway smooth muscle cells in asthmatic conditions [ 1 ]. PI3K signaling molecule is involved in practically every facet of asthma pathogenesis.…”

“…Airway inflammation, hyperresponsiveness, and remodeling are the prime manifestations of asthma. The recurrence of the disease, along with the high expense of available treatment, make it life-threatening sometimes [ 1 ]. Many treatment options are available for managing asthma, but all are preventive therapies with associated side effects.…”

Luteolin Isolated from Polygonum cuspidatum Is a Potential Compound against Nasopharyngeal Carcinoma

“…Although there have been previous studies on the anticancer activity of luteolin or P. cuspidatum [43][44][45], our study is the first to use network pharmacology and experimental verification to preliminarily analyze the material basis and molecular mechanism of P. cuspidatum against NPC. Our research ideas and analysis methods are different from other studies.…”

Research hotspot and frontier analysis of traditional Chinese medicine in asthma using bibliometric methods from 1991 to 2021

“…A network pharmacology strategy has been adopted for investigating the mechanism of action underlying the effectiveness of Chinese drugs 68 and TCM formulas. 69 , 70 To some extent, the application of network pharmacology will accelerate the research process of TCM in asthma.…”