Antidepressant-like effects of a chlorogenic acid- and cynarine-enriched fraction from Dittrichia viscosa root extract

Dittrichia viscosa is a perennial Mediterranean plant used in traditional medicine for “calming purposes”, pointing at a possible antidepressant activity of the plant. We conducted chromatographic and bioassay-guided fractionation of D. viscosa root extract to isolate a specific fraction (fraction “K”) with antidepressant-like characteristics in vivo and strong antioxidant properties in vitro. A single dose of “K” reduced immobility time in the forced swim test with a mouse model possessing a depressive-like phenotype. Neurochemical profiling for 5-hydroxytryptamine (5-HT) and its primary metabolite, 5-hydroxyindoleacetic acid (5-HIAA), in prefrontal cortex and hippocampus of “K”-treated mice showed reduction in 5-HIAA, indicative of either serotonin uptake transporter or monoamine oxidase-A inhibition, as well as slight increases in 5-HT content. These neurochemical alterations, as well as the behavioral changes observed, were comparable to the effects of paroxetine. “K” also protected PC12 cells in a H₂O₂ cytotoxicity assay, thus demonstrating antioxidant properties, yet paroxetine augmented oxidative damage and cell death. Identification of the main compounds in “K” by high-performance liquid chromatography-tandem mass spectrometry (HPLC–MS/MS) indicated that chlorogenic acid and cynarine comprised 87% of the total components. D. viscosa root extract appears to produce antidepressant and cytoprotective effects and may serve as an attractive alternative to standard therapies for depression.