| Summary: | The <i>Ormosia henryi Prain</i> leaf (OHPL) is a new bioactive resource with potential antidepressant activity, but few reports have confirmed its chemical composition or antidepressant effect. To investigate the phytochemical profile of OHPL ethanol extract (OHPLE), six flavone <i>C</i>-glycosides and two flavone <i>O</i>-glycosides were purified by high-speed counter-current chromatography combined with preparative high-performance liquid chromatography (HSCCC-prep-HPLC). The eight isolated compounds were identified by NMR and MS. Forty-six flavonoids, including flavones, flavone <i>C</i>-glycosides, flavone <i>O</i>-glycosides, isoflavones, isoflavone <i>O</i>-glycosides, prenylflavones and polymethoxyflavones were definitively or tentatively identified from OHPLE using ultra-performance liquid chromatography/ electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOF-MS/MS) on the basis of fragment ions that are characteristic of these isolated compounds. The results of the antidepressant assay suggest that OHPLE significantly improved depression-related behaviors of chronic unpredictable mild stress (CUMS) mice. The observed changes in these mice after OHPLE treatment were an increased sucrose preference index, reduced feeding latency, prolonged tail suspension time, and upregulated expression of brain-derived neurotrophic factor (BDNF). The details of the phytochemicals and the antidepressant effect of OHPLE are reported here for the first time. This study indicates that the OHPL, enriched in flavone <i>C</i>-glycosides, is a new resource that might be potentially applied in the field of nutraceuticals (or functional additives) with depression-regulating functions.
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