Helicid Ameliorates Learning and Cognitive Ability and Activities cAMP/PKA/CREB Signaling in Chronic Unpredictable Mild Stress Rats.

Helicid (4-formylphenyl-O-ß-D-allopyranoside), an active component found in seeds from the Chinese herb Helicia nilagirica, has been reported to exert sedative, analgesic, hypnotic and antidepressant effects. The present study was designed to evaluate the antidepressant, learning and cognitive improvement effects of helicid in a chronic unpredictable mild stress (CUMS) model of depression in rats and to explore cAMP/protein kinase A (PKA)/cAMP response element-binding (CREB) signaling pathway. Sprague-Dawley rats were randomly assigned to six groups (n = 10): control; CUMS; CUMS + fluoxetine (5 mg/kg) and CUMS + helicid at 8, 16 and 32 mg/kg. All rats were subjected to 12 weeks of CUMS protocols and drug administration during the last 6 weeks of CUMS. Our results showed that helicid, at a dose of 32 mg/kg, significantly reversed decreases in body weight and sucrose consumption, increased the distance and number of crossings in the open-field test (OFT), reduced immobility times in the forced swimming test (FST) and improved spatial memory in the Morris water maze (MWM); all of these effects had been induced by CUMS paradigm. Immunohistochemistry showed that administration of helicid could promoted the proliferation of neurons in the hippocampal CA1 and dentate gyrus (DG) regions. CUMS rats treated with helicid had dramatically decreased protein levels of serotonin transporters (SERTs). In addition, CUMS resulted in a significant reduction in the expression of cAMP, PKA C-α and p-CREB, each of which were partially attenuated by helicid administration. These results indicated that helicid could improve depressive behaviors, learning and cognitive deficits and increase hippocampal neurogenesis, which may be mediated by the regulation of SERTs, activation of the cAMP/PKA/CREB signaling pathway and upregulation of p-CREB levels in hippocampal.

Antidepressant effect of helicid in chronic unpredictable mild stress model in rats.

Helicid (4-formylphenyl-ß-D-allopyranoside) is a bioactive constituent of Helicid nilgirica Bedd that has been used in Chinese traditional herbal medicine to treat headache, insomnia, and depression. However, the underlying mechanisms of these effects are unclear. We have now investigated the effect of helicid on depression-related behaviors in rats exposed to chronic unpredictable mild stress (CUMS) and have also explored possible underlying mechanisms that involve neurotrophin expression. After 6 weeks isolation, body weight and sucrose preference were significantly reduced in rats with CUMS-induced depression compared with controls. The CUMS rats also showed significant inhibition of locomotory parameters in open field tests (involving behavioral assays). Helicid significantly regulated levels of corticosterone (CORT), inflammatory cytokines and 5-hydroxytryptamine (5-HT). Helicid also reversed CUMS-induced decreases of 5-HT1A receptor expression and promoted brain derived neurotrophic factor (BDNF) expression in the hippocampus The significant reversal of depressive-like behaviors by helicid is similar to that achieved by fluoxetine. The antidepressive effects are likely attributable to the promotion of hippocampal neurotrophin expression through activation of the serotonergic system. Helicid thus has potential for treating depressive disorders.