Identification of antidiabetic constituents in Polygonatum odoratum (Mill.) Druce by UPLC-Orbitrap-MS, network pharmacology and molecular docking

Abstract

Polygonatum odoratum has been known as having therapeutic effects on diabetes. However, due to its complex composition, it is difficult to elucidate the molecular mechanisms of its functions. In this study, we investigated the material basis and molecular mechanisms underlying the antidiabetic activities of methanol extract of P. odoratum (Mill.) Druce by ultra-performance liquid chromatography orbitrap mass spectrometry (UPLC-Orbitrap-MS) and network pharmacology. In specificity, we first constructed a compound-protein interaction network for type 2 diabetes mellitus (T2DM) to identify potential drug targets. Disease Ontology (DO), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were then conducted to discover the pathways involved in the antidiabetic activities of P. odoratum. Among the 334 compounds detected in P. odoratum, 277 active constituents and 897 corresponding targets were identified to be associated with antidiabetic activities. Five compounds and five targets were consequently obtained by analyzing the compound-target-pathway network. The five compounds were 9-Aminocamptothecin, 9-Methoxycamptothecin, 5-Hydroxy-1-tetralone, 5,7,3′-Trihydroxy-6,4′,5′-trimethoxyflavone, and Diacerein, while the five targets were ACTB, JUN, STAT3, HIF1A, and MMP9. In addition, 30 antidiabetic-related pathways were recognized by using KEGG pathway analysis. Moreover, molecular docking was performed with the five essential compounds and the top five targets based on degree ranking. Our study confirms that active components in P. odoratum can exert antidiabetic activities via multi-component, multi-target, and multi-pathway mechanisms of action, which serves as a practical guidance for further experimental investigations into the biological functions of the methanol extract of P. odoratum in the treatment of T2DM.

Keywords

• T2DM
• Polygonatum odoratum
• Network pharmacology
• Mass spectrometry
• Molecular docking