Effect of curdione on the HPA axis and inflammation in post-traumatic stress disorder rats
REN Huan-nan,REN Dang-li,WANG Jia-huan
Abstract:
Objective To explore the effect of curdione on post-traumatic stress disorder (PTSD) and its underlying mechanism. Methods An inflammatory model of microglia was constructed in vitro using lipopolysaccharide (LPS). After treatment with curdione, the expression levels of inflammatory factors in the cell supernatant and the activation levels of p65 and p38 in cellular inflammatory signaling pathways were detected, respectively. For in vivo experiments, a single prolonged stress (SPS) model was constructed to establish a rat PTSD model. Rats were given intraperitoneal injection of low-, medium-, and high-dose curdione, respectively. The effects of curdione on anxiety-and depression-like behaviors in PTSD rats were determined by conditioned fear test and open field test. The serum levels of corticosterone (Cort), corticotropin-releasing hormone (CRH), adrenocorticotrophic hormone (ACTH), TNF-α, IL-1β, and IL-6 were measured. Meanwhile, the changes in 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), norepinephrine (NE), and adrenaline (AD) in the cerebral cortex were examined. Results In vitro results showed that the expression of TNF-α, IL-1β, and IL-6 were significantly decreased in the curdione-treated groups, and the phosphorylation levels of p65 and p38 were also significantly reduced. In vivo behavioral tests confirmed that curdione administration significantly reduced the freezing time of rats in the conditioned fear box. Compared with the PTSD model group, the curdione-treated groups showed significantly increased central zone residence time in the open field test. Serum levels of Cort, CRH, ACTH, and various inflammatory factors related to the hypothalamic-pituitary-adrenal (HPA) axis were correspondingly restored in curdione-treated groups compared with the PTSD group. The contents of monoamine neurotransmitters 5-HT and 5-HIAA in the cerebral cortex were significantly reversed in curdione-treated groups. Conclusion Curdione can effectively alleviate anxiety-and depression-like behaviors in PTSD rats. Its therapeutic mechanism may be closely related to correcting HPA axis dysfunction, inhibiting systemic and neuroinflammatory responses, and regulating the balance of central monoamine neurotransmitters. This study provides experimental evidence for curdione as a potential therapeutic agent for PTSD.
