Resveratrol Ameliorates the Anxiety- and Depression-Like Behavior of Subclinical Hypothyroidism Rat: Possible Involvement of the HPT Axis, HPA Axis, and Wnt/ß-Catenin Pathway.

Metabolic disease subclinical hypothyroidism (SCH) is closely associated with depression-like behavior both in human and animal studies, and our previous studies have identified the antidepressant effect of resveratrol (RES) in stressed rat model. The aim of this study was to investigate whether RES would manifest an antidepressant effect in SCH rat model and explore the possible mechanism. A SCH rat model was induced by hemi-thyroid electrocauterization, after which the model rats in the RES and LT4 groups received a daily intragastric injection of RES at the dose of 15 mg/kg or LT4 at the dose of 60 µg/kg for 16 days. The rats' plasma concentrations of thyroid hormones were measured. Behavioral performance and hypothalamic-pituitary-adrenal (HPA) activity were evaluated. The protein expression levels of the Wnt/ß-catenin in the hippocampus were detected by western blot. The results showed that RES treatment downregulated the elevated plasma thyroid-stimulating hormone concentration and the hypothalamic mRNA expression of thyrotropin-releasing hormone in the SCH rats. RES-treated rats showed increased rearing frequency and distance in the open-field test, increased sucrose preference in the sucrose preference test, and decreased immobility in the forced swimming test compared with SCH rats. The ratio of the adrenal gland weight to body weight, the plasma corticosterone levels, and the hypothalamic corticotrophin-releasing hormone mRNA expression were reduced in the RES-treated rats. Moreover, RES treatment upregulated the relative ratio of phosphorylated-GSK3ß (p-GSK3ß)/GSK3ß and protein levels of p-GSK3ß, cyclin D1, and c-myc, while downregulating the relative ratio of phosphorylated-ß-catenin (p-ß-catenin)/ß-catenin and expression of GSK3ß in the hippocampus. These findings suggest that RES exerts anxiolytic- and antidepressant-like effect in SCH rats by downregulating hyperactivity of the HPA axis and regulating both the HPT axis and the Wnt/ß-catenin pathway.

Oxazole: A Promising Building Block for the Development of Potent Antitumor Agents.

Oxazole derivatives are found to have a variety of biological activities. A large number of studies have revealed their outstanding anticancer activities. Here we review four different types of oxazole derivatives with anticancer potential reported over the last ten years. We focus our discussion on their activity, selectivity in different cancer cell lines, mechanisms of action, and their structural evolution.

Nesfatin-1, a potent anorexic agent, decreases exploration and induces anxiety-like behavior in rats without altering learning or memory.

The anorectic neuropeptide nesfatin-1 has recently been characterized as a potential mood regulator, but the accurate effect of nesfatin-1 on anxiety and learning and memory behavior and the possible mechanisms remains unknown. In the present study, to test the hypothesis that nesfatin-1 might affect the anxiety-like and learning and memory behaviors in rats via ERK/CREB/BDNF pathway, nesfatin-1 was administered intraperitoneally to rats with the doses (10, 20, 40µg/kg), and the behavioral performance was tested using the open field task, the Morris water maze (MWM), and the Y maze. Moreover, the protein expression of brain-derived neurotrophic factor (BDNF), total and phosphorylated-ERK in the hippocampus and the prefrontal cortex (PFC) were evaluated. The results showed that chronic administration of nesfatin-1 could decrease the moving distance, the duration in the center, and the frequencies of rearing and grooming in the open field task, decrease the moving distance, frequency, and the preference index of new arm in the Y maze, although there was no significant difference of the performance in the MWM task among groups. Furthermore, 3 weeks' consecutive administration of nesfatin-1 resulted in the decrease of protein expression of BDNF and phosphorylated-ERK in the hippocampus and the PFC. These results provided evidence that exogenous nesfatin-1 could decrease exploration and induce anxiety-like behavior in rats, the mechanism of which might be related to the reduced protein expression of BDNF and phosphorylated-ERK in the hippocampus and the PFC.

Antidepressant-like effect of resveratrol: involvement of antioxidant effect and peripheral regulation on HPA axis.

This study focused on exploring the antidepressant potential of resveratrol (RES) and its possible mechanisms of action. Cell injury was induced by corticosterone (CORT) and detected through cell viability and contents of lactate dehydrogenase (LDH) and malonaldehyde (MDA). A rat model of depression was established through 3weeks of consecutive chronic unpredictable mild stress (CUMS), and both the depression-like behaviors and the activity of the hypothalamic-pituitary-adrenal (HPA) axis were tested. Apart from the inhibitory effect on MDA production in vitro and in vivo, the results showed that RES (10(-10)mol/L to 10(-5)mol/L) could significantly increase the cell viability and decrease the LDH activity and that RES (15mg/kg) treatment could alleviate the depression-like behavior of CUMS rats, as indicated by increased sucrose preference and decreased immobility in forced swimming test and tail suspension test. Rats that received RES treatment displayed a reduction of serum CORT, suggesting that RES affected the hyperactivity of the HPA axis in CUMS rats. However, RES did not affect the expression of corticotropin-releasing hormone (CRH) mRNA in the hypothalamus of CUMS rats. In summary, our results demonstrated that in addition to its widely known antioxidant properties, RES also has antidepressant-like effects, and suggested that the underlying mechanism might involve its peripheral effect on the regulation of the HPA axis.