Integration of network pharmacology, bioinformatics and experimental verification strategy to discover the pharmacological mechanisms of mogroside acts against pharyngitis.

Abstract

Ethnopharmacological relevance: Siraitia grosvenorii (Swingle) C. Jeffrey ex Lu & Zhang, a popular herb in traditional Chinese materials, has been broadly employed in food and medicine homology. According to TCM, S. grosvenorii is an essential medicine for clearing the throat and relieving the lungs (Qingyanlifei). However, the bioactive effects of S. grosvenorii on pharyngitis targets remain unclear.

Aim: To determine the active compounds, prospective targets, and the associated molecular mechanisms of S. grosvenorii acts healing pharyngitis. The present study integrated network pharmacology, bioinformatics, molecular docking strategies, and in vitro verification for analysis.

Methods: The active components and potential targets of S. grosvenorii and pharyngitis-related disease targets were sourced from open databases available to the public using network pharmacology approach. The key active components, anti-pharyngitis core targets and pathways were predicted to be obtained by PPI network, GO and KEGG pathway enrichment and bioinformatics analysis. Afterward, molecular docking was executed to estimate the binding interactions of the active constituents with the primary targets. Finally, the key targets predicted via network pharmacology were retrieved from the HPA database, WGCNA, and in vitro trials were performed to further substantiate the outcomes.

Results: A total of 23 bioactive components in S. grosvenorii and 568 herb targets were screened, producing 82 mutual targets in combination with 756 disease targets. GO enrichment analysis incorporated 1708 BP, 49 CC, and 91 MF. KEGG enrichment analysis indicated that the anti-inflammatory effect of mogroside where possessed through a variety of different pathways, including PI3K/AKT and TLR4/NFκB/MyD88 signaling pathway. Probably, the PI3K/AKT signaling pathway has a key impact in S. grosvenorii against pharyngitis. Cell experiments demonstrated that mogroside, the most crucial ingredients on S. grosvenorii, regulated the release of inflammatory cytokines, as well as PI3K/AKT and TLR4/NFκB/MyD88 signaling pathway in LPS-activated RAW264.7 cells, this evidence reinforced the predictions suggested by network pharmacology and molecular docking.

Conclusion: The study extensively identified the biological activities, potential targets and molecular mechanisms of S. grosvenorii in combating pharyngitis through the application of network pharmacology and in vitro assessment. A perspective strategy is provided to offer the scientific foundations and healing mechanism of TCM for pharyngitis treatment.