Eriodictyol, a natural
flavonoid compound identified in numerous medicinal plants, has been reported to have anti-inflammatory, antioxidative and antiproliferative activities and exert protective effects on the neurons, thus drawing attention to its therapeutic potential. However, the effect of
eriodictyol on depression remains unclear. In the present study, we investigated the behavioral effects of chronic
eriodictyol treatment in rat models of depression induced by
lipopolysaccharide (LPS, 1 mg/kg) challenge and chronic unpredictable mild stress (CUMS). We found that chronic
eriodictyol (10, 30, and 100 mg/kg) treatment by oral gavage once daily for 14 days dose-dependently produced
antidepressant effect in the forced swim test (FST), but did not alter locomotor activity in the open field test. Moreover,
oral administration with
eriodictyol (100 mg/kg) for 28 days reversed the depressive- and anxiety-like behaviors induced by LPS or CUMS, as evidenced by significantly increased
sucrose preference in the
sucrose preference test, reduced immobility time in the FST, and reduced latency to feeding in the novelty-suppressed feeding test. In addition, co-administration of subthreshold doses of
eriodictyol (30 mg/kg) and transient potential vanilloid 1 receptor antagonist
capsazepine (1.5 mg/kg) produced a synergistic effect in these tests. Chronic
eriodictyol administration at a dose of 100 mg/kg also rescued the
memory deficits induced by CUMS as indicated by the increased exploration index in the novel object recognition test. Altogether, these results demonstrate that
eriodictyol attenuates depressive- and anxiety-like behaviors and
cognitive impairments in rats, and might be a potential therapeutic avenue for depression.