1: Brain Res. 2006 Oct 2; [Epub ahead of print]

Curcumin reverses the effects of chronic stress on behavior, the HPA axis, BDNF
expression and phosphorylation of CREB.

Xu Y, Ku B, Tie L, Yao H, Jiang W, Ma X, Li X.

Department of Pharmacology, School of Basic Medical Science, Peking University,
38 Xueyuan Road, Beijing, 100083, PR China.

Curcuma longa is a major constituent of the traditional Chinese medicine
Xiaoyao-san, which has been used to effectively manage stress and
depression-related disorders in China. Curcumin is the active component of
curcuma longa, and its antidepressant effects were described in our prior
studies in mouse models of behavioral despair. We hypothesized that curcumin may
also alleviate stress-induced depressive-like behaviors and
hypothalamic-pituitary-adrenal (HPA) axis dysfunction. Thus in present study we
assessed whether curcumin treatment (2.5, 5 and 10 mg/kg, p.o.) affects behavior
in a chronic unpredictable stress model of depression in rats and examined what
its molecular targets may be. We found that subjecting animals to the chronic
stress protocol for 20days resulted in performance deficits in the shuttle-box
task and several physiological effects, such as an abnormal adrenal gland weight
to body weight (AG/B) ratio and increased thickness of the adrenal cortex as
well as elevated serum corticosterone levels and reduced glucocorticoid receptor
(GR) mRNA expression. These changes were reversed by chronic curcumin
administration (5 or 10 mg/kg, p.o.). In addition, we also found that the
chronic stress procedure induced a down-regulation of brain-derived neurotrophic
factor (BDNF) protein levels and reduced the ratio of phosphorylated cAMP
response element-binding protein (pCREB) to CREB levels (pCREB/CREB) in the
hippocampus and frontal cortex of stressed rats. Furthermore, these
stress-induced decreases in BDNF and pCREB/CREB were also blocked by chronic
curcumin administration (5 or 10 mg/kg, p.o.). These results provide compelling
evidence that the behavioral effects of curcumin in chronically stressed
animals, and by extension humans, may be related to their modulating effects on
the HPA axis and neurotrophin factor expressions.

PMID: 17022948 [PubMed - as supplied by publisher]