Mechanism of barley malt-dependent DRD2 to treat hyperprolactinemia based on UPLC-Q-TOF/MS and network pharmacology

Abstract

IntroductionBarley malt (Hordeum vulgare L.) is a traditional Chinese herbal medicine that has a favorable therapeutic effect against hyperprolactinemia (HPRL), but information about its active components and mechanism of action is still lacking. Therefore, we explored the underlying pharmacological properties and possible application of barley malt for the treatment of HPRL using UPLC-Q-TOF/MS and a network pharmacology method. MethodsThe chemical composition of barley malt was identified by UPLC-Q-TOF/MS. The main chemical components of barley malt were selected by searching the literature and TCMSP database, and the active components and targets of barley malt were screened and collected by evaluating the oral bioavailability (OB) and drug-likeness (DL). The HPRL-related targets were searched in OMIM and GeneCards databases and intersected with barley malt targets to give the key targets, which were analyzed using the STRING database to construct their protein-protein interaction (PPI) network. The GO function and KEGG signaling pathway enrichment analysis of key targets were performed with the DAVID database, and the active barley malt component-target pathway model was established using Cytoscape 3.6.0 software. The molecular mechanism of dopamine receptor D2 (DRD2, a key target) in HPRL treatment with total alkaloids (effective substances) of barley malt was validated in a cell experiment. ResultsAfter removing the recurrent products by additional screening, 18 chemical components and 268 targets of barley malt were obtained. There were 221 HPRL-related targets, of which 22 were targets of malt for treating HPRL. PPI network analysis indicated that the 22 targets (e.g., DRD1, DRD2, and DRD3) might be the key targets of barley malt for treating HPRL. DRD2 was validated as a key target of barley malt for treating HPRL using cell-based experiments. ConclusionIn this study, DRD2 was identified as the major target of barley malt-related HPRL treatment by network pharmacology. Malt might upregulate DRD2 in MMQ cells via its total alkaloids to achieve an anti-HPRL effect. This study provides a substantial foundation and scientific basis underlying the mechanism of barley malt and its use in the treatment of HPRL and other relevant diseases.