Integrative SystemsEriodictyol produces antidepressant-like effects and ameliorates cognitive impairments induced by chronic stressZhang, Leia; Liu, Chenb; Yuan, MeiaAuthor Information Departments of aNeurology bUltrasound, Second Affiliated Hospital, University of South China, Hengyang, Hunan, China Received 7 July 2020 Accepted 18 August 2020 Correspondence to Mei Yuan, PhD, Department of Neurology, Second Affiliated Hospital, University of South China, No. 35, JieFang Road, Hengyang, Hunan 421001, China, Tel: +18684571188; e-mail: firstname.lastname@example.org NeuroReport: October 14, 2020 - Volume 31 - Issue 15 - p 1111-1120 doi: 10.1097/WNR.0000000000001525 Buy Metrics Abstract 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. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.