Lipopolysaccharide induced anxiety- and depressive-like behaviour in mice are prevented by chronic pre-treatment of esculetin

•ESC pre-treatment attenuated LPS-induced anxiety- & depressive-like behaviour in mice.•LPS-induced elevated brain IL-1β, IL-6, and TNF-α level were reversed by ESC.•Plasma CORT level was also decreased by ESC pre-treatment in LPS challenged mice. Chronic pre-treatment of ESC prevented LPS evoked oxidative stress in mouse brain.•ESC could be effective in psychiatric disorders associated with neuroinflammation.

Inflammation and oxidative stress are involved in the pathophysiology of anxiety and depression. Esculetin (ESC), a coumarin derived potent antioxidant, also possessing anti-inflammatory and neuroprotective activity. This study investigated the effect of ESC in lipopolysaccharide (LPS)-induced anxiety- and depressive-like behaviour in mice. ESC (25 and 50 mg/kg, p.o.) was administered daily for 14 days, and challenged with saline or LPS (0.83 mg/kg; i.p.) on the 15th day. Behavioural paradigms such as elevated plus maze (EPM), open field test (OFT), forced swim test (FST) and tail suspension test (TST) were employed to assess anxiety- and depressive-like behaviour in mice post-LPS injection. Hippocampal cytokines, MDA and GSH level, and plasma corticosterone (CORT) were measured. ESC pre-treatment significantly (P < 0.05) attenuated LPS-induced anxiety-like behaviour by modulating EPM and OFT parameters. Moreover, LPS-induced increase in immobility time in FST and TST were also prevented significantly (P < 0.05) by ESC (50 mg/kg). ESC pre-treatment ameliorated LPS-induced neuroinflammation by attenuating brain IL-1β, IL-6, TNF-α level, and oxidative stress as well as plasma CORT level. In conclusion, the results suggest that ESC prevented LPS-induced anxiety- and depressive-like behaviour which may be governed by inhibition of cytokine production, oxidative stress and plasma CORT level. The results support the potential usefulness of ESC in the treatment of psychiatric disorders associated with inflammation and oxidative stress.

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