Rosmarinic acid protects rats against post-stroke depression after transient focal cerebral ischemic injury through enhancing antioxidant response

•Rosmarinic acid (a-O-caffeoyl-3,4-dihydroxyphenyllacticacid, RA) is one of the most potent polyphenols. Which is commercially available with high (>96%) purification and much less expensive compared to other polyphenol compounds.•RA administration alleviated neurological deficits and reduced infarct volume.•The results revealed RA treatment alleviated the post-stroke depressive behaviors. Rosmarinic acid (RA), a natural polyphenol, possesses potent antioxidant and anti-inflammatory activities. To evaluate the ability of RA to cure ischemic stroke and post-stroke depression (PSD), rats were treated with various doses of RA after cerebral ischemia. Neurological deficits and infarct volume of the brain were measured. The activities of superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) were examined at different time points. In addition, a forced swimming test and sucrose preference test were performed to detect the anti-depressive effects of RA. Our results revealed RA administration significantly alleviated neurological deficits and reduced infarct volumes. RA attenuated the decrease of SOD, CAT activities and GSH levels in the ischemic penumbra of the brain. Most importantly, RA treatment alleviated the depression behaviors. Increased expression of Nrf2 was also induced by RA, while down regulation Nrf2 by Nrf2-short-hairpin RNA sequences reversed the increasing activity of SOD and CAT induced by RA, as well as the protection against PSD. The present study indicates that RA exerts a potent neuroprotective effect against stroke and PSD, which could be a promising therapeutic intervention for stroke.