Antidepressant effects of TBE-31 and MCE-1, the novel Nrf2 activators, in an inflammation model of depression.

Antidepressant effects of TBE-31 and MCE-1, the novel Nrf2 activators, in an inflammation model of depression. Eur J Pharmacol. 2016 Nov 1;: Authors: Yao W, Zhang JC, Ishima T, Ren Q, Yang C, Dong C, Ma M, Saito A, Honda T, Hashimoto K Abstract The Nuclear factor (erythroid 2-derived)-like 2 (Nrf2) plays a key role in inflammation which is implicated in the pathophysiology of depression. The Nrf2 activators have antidepressant effects in animal models of depression. The present study was undertaken to examine whether TBE-31 [(±)-(4bS,8aR,10aS)-10a-ethynyl-4b,8,8-trimethyl-3,7-dioxo-3,4b,7,8,8a,9,10,10a-octahydrophenanthrene-2,6-dicarbonitrile] and MCE-1 [(±)-3-ethynyl-3-methyl-6-oxocyclohexa-1,4-dienecarbonitrile], the novel Nrf2 activator, could show antidepressant effects in inflammation model of depression. We found that TBE-31 and MCE-1 significantly potentiated nerve growth factor (NGF)-induced neurite outgrowth in PC12 cells, in a concentration dependent manner. The Nrf2 siRNA, but not negative control of siRNA, significantly blocked the potentiating effects of TBE-31 and MCE-1 on neurite outgrowth in PC12 cells. Furthermore, oral administration of TBE-31 or MCE-1 significantly attenuated an increase in serum levels of tumor necrosis factor-α (TNF-α) after administration of lipopolysaccharide (LPS: 0.5mg/kg). In the tail-suspension test and forced swimming test, oral administration of TBE-31 or MCE-1 significantly attenuate...
Source: European Journal of Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Eur J Pharmacol Source Type: research