Tricyclic Neovibsanin Scaffold (TCNS) as an Effective Antidepressant Agent.

Neovibsanin type natural products were found to display neurite outgrowth activity in PC12 cells. This suggests that such type of compounds could be promising candidates for the development of novel therapeutic agents to treat neurological diseases. In the present study rats after chronic mild stress (CMS) were treated with tricyclic neovibsanin scaffold (TCNS) to study its effect on depression. The results revealed that 15 mg/kg doses of TCNS reduced the duration of immobility in CMS model of depression. It led to a significant increase in neurite outgrowths which increased the synaptic and structural plasticity of neurons. Treatment with TCNS decreased the levels of MAO-A and caspase-3 expression both of which were found to be higher in CMS. TCNS also led to an increase in expression of heat shock protein 70 (Hsp70) in the hippocampus. These findings suggest that TCNS possesses antidepressant activity in CMS model of depression. Therefore the relief in depression by TCNS may be due to suppression of MAO-A expression and the apoptosis cascade by increased expression of Hsp70.