Pharmacological Mechanism of Sancao Yuyang Decoction in the Treatment of Oral Mucositis Based on Network Pharmacology and Experimental Validation

Abstract

Purpose The network pharmacology analysis, molecular docking and experimental verification were performed to explore the pharmacological mechanisms of Sancao Yuyang Decoction (SCYYD) in the treatment of oral mucositis (OM). Methods Active ingredients in SCYYD and their potential targets, as well as OM-related targets were screened from public databases. The core targets and signaling pathways of SCYYD against OM were determined by protein–protein interaction (PPI) network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The ingredient-target-disease network and target-pathway network were constructed. Subsequently, molecular docking was carried out to predict the binding activity between active ingredients and key targets. Moreover, in vivo experiment was conducted to further verify the core targets predicted by network pharmacology analysis. Results A total of 119 bioactive ingredients were screened from the corresponding databases. One hundred and eighty-six putative targets were retrieved and bioinformatics analysis was performed to reveal the top 5 potential candidate agents and 10 core targets. GO and KEGG enrichment analysis showed that SCYYD exerted excellent therapeutic effects on OM through several pathways, such as HIF-1 and Ras signaling pathway. Subsequently, molecular docking showed that main ingredients in SCYYD had optimal binding activities to the key protein targets. Moreover, the result of in vivo experiment indicated that SCYYD not only inhibited inflammation response and promoted wound healing of oral mucosa in OM rats, but also reversed high expressions of SRC, HSP90AA1, STAT3, HIF1α, mTOR, TLR4, MMP9, and low expression of ESR1. Conclusion This study preliminarily uncovered the multiple compounds and multiple targets of SCYYD against OM using network pharmacology, molecular docking and in vivo verification, which provided a new insight of the pharmacological mechanisms of SCYYD in treatment of OM.

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“…Within this network, nodes were sorted according to the degree value and those with a larger size and more connections were identified as more important. 44 The network calculation results ( Table S4 ) reminded us to pay more attention to T1, M5 and M4 in compounds and KDR, MMP2, and AKT1 in targets.…”