Assessment of anti-depressant effect of nelumbinis semen on rats under chronic mild stress and its subchronic oral toxicity in rats and beagle dogs

BACKGROUND Previously, we examined the antidepressant effects of Nelumbinis Semen (NS). In this study, we assessed the anti-depressant effects of NS in the forced swimming test and chronic mild stress (CMS) models of depression and its oral toxicity in rats and dogs. METHODS In the forced swimming test, NS was intraperitoneally injected before 24 h, 5 h and 1 h of forced swimming test. And the rats were forced to swim for 5 min, the duration of immobility was observed. In CMS models, animals were exposed to a variety of CMS for 8 weeks in order to induce depression-like symptoms. They were treated with NS for the last four weeks of the 8-week CMS and then an open field test was conducted. The anti-depression effects were evaluated based on a measured index, which consisted of visiting counts, start latency, rearing number and grooming time. In the toxicological studies, NS was administered to rats by gavages for 13 weeks at doses of 0, 500, 1000, and 2000 mg/kg/day. To assess the toxicity of NS in beagle dogs, NS was administered orally for 28 days at doses of 0, 500, 1000, 2000 and 4000 mg/kg/day. RESULTS 400 mg/kg of NS had the lowest immobility times in forced swimming test. And NS significantly reversed the decreased visiting counts, rearing number and grooming time caused by CMS. In addition, NS treatment significantly decreased the start latency. No treatment-related toxicity was detected during 13 weeks administration in rats and 28 days administration in dogs. CONCLUSIONS Based on the results of this study and previous reports that have examined the anti-depressive effects of NS, NS holds great promise for use in the treatment of depression without causing any adverse effects or toxicities.