Kolaviron ameliorates chronic unpredictable mild stress-induced anxiety and depression: involvement of the HPA axis, antioxidant defense system, cholinergic, and BDNF signaling.

Objectives: This study sought to investigate the beneficial effect of kolaviron (KV) (a biflavonoid) isolated from seed on chronic unpredictable mild stress (CUMS)-induced anxiety- and depressive-like behavior.

Methods: Male albino mice were randomly divided into six groups (n=8) as follows; Group I: vehicle-control unstressed; Group II: CUMS-control; Group III-V: CUMS + KV 1, 5 or 50 mg/kg, respectively, Group VI: KV (50 mg/kg, p.o.) unstressed mice. Animals were subjected to CUMS for 14 days, followed by estimation of depressive- and anxiety-like behavior from days 14-16. This was followed by biochemical assays for oxidative stress, hypothalamo-pituitary axis, cholinergic, and BDNF signaling.

Results: CUMS caused significant reduction in time spent in open arms of elevated plus maze test (EPM) and increase in immobility time in tail suspension test (TST) and forced swim test (FST) ameliorated by KV treatments. KV administration also attenuated CUMS-induced malondialdehyde/nitrite generation and decrease in antioxidant enzymes activities in the prefrontal cortex and hippocampus. CUMS increased serum corticosterone, acetylcholinesterase activity, and reduced BDNF level in the PFC and hippocampus were attenuated by KV administration.

Conclusions: KV prevented CUMS induced anxiety- and depression-like behavior in mice through enhancement of antioxidant defense mechanisms, neurotrophic factors, and cholinergic systems.