Network pharmacology and molecular docking analysis on molecular targets and mechanisms of Huayan Capsules in the treatment of osteosarcoma (Preprint)

Abstract

BACKGROUND Huayan Capsules (HYCA) has adjuvant therapeutic effect to the patients with OS in China, which is based on our hospital long-term clinical practice. Network pharmacology is a theory based on systems biology that helps to reveal the underlying mechanisms of action between drugs and disease development. OBJECTIVE Osteosarcoma (OS) is the most frequent primary bone sarcomas. It is commonly found in the long bones of the limbs of the human body. The purpose of study was to explore the active ingredients, targets and mechanism of HYCA in the treatment of OS through network pharmacology and molecular docking technology. METHODS TCMSP and TCMID database were used to obtain the active ingredients and targets of HYCA. Targets related to OS were obtained by GeneCards, TTD and OMIM. The related target protein network was constructed and analyzed for Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. The compound was molecularly docked with proteins associated with OS by using AutoDock Vina. RESULTS In this study, we searched that HYCA has 239 active compounds, 1703 targets and of HYCA. Meanwhile, there was 220 intersection targets of OS and HYCA. Construction of protein-protein interactions (PPI) network analysis showed that there were 25 key targets of HYCA in the treatment of OS including TP53, AKT1, etc. GO enrichment analysis mainly including cell response to hormones and other compounds. KEGG enrichment analysis obtained 196 signaling pathways, which mainly including pathways in cancer, PI3K-Aktsignaling pathway, MAPK signaling pathway. Molecular docking showed that quercetin, kamanol and luteolin have strong binding ability with AKT1, TP53. CONCLUSIONS HYCA may treat OS by regulating the pathways in cancer, PI3K-Akt and MAPK signaling pathway. We will demonstrate the relationship among the active compounds of HYCA, TCM classification of OS and signal pathway, so as to provide a systematic TCM treatment plan for the clinical treatment of OS.