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Objective: To investigate the effects of cembrane-type diterpenes extracted from Sinularia flexibilis on the proliferation of PC12 cells and their protective effects on PC12 cells exposed to glutamate., Methods: Methyl thiazolyl tetrazolium (MTT) method was adopted to observe the effects of cembrane-type diterpenes (compound 1, compound 2 and compound 3) on the proliferation of PC12 cells. And the protective effects of the three compounds on PC12 cells exposed to glutamate were also detected by MTT. Furthermore, the influence of compound 1 on intracellular concentration of calcium in PC12 cells exposed to glutamate was detected by laser confocal microscopy., Results: After 72-hour PC12 cell culture, OD values in the 2, 10 and 50 micromol/L compound 1 groups were significantly higher than that in the normal group (P<0.05, P<0.01). After 24-hour glutamate damage, OD values in the 0.4, 2 and 50 micromol/L compound 1 groups, the 0.4, 2 and 100 micromol/L compound 2 groups and the 2 micromol/L compound 3 group were obviously increased as compared with the untreated group (P<0.01, P<0.05). After 48-hour glutamate damage, OD values in the compound 1 group were approximate to those in the normal control and the positive control group while were significantly higher than that in the untreated group (P<0.01, P<0.05), but no dose-dependent effect was observed. Compound 1 of 0.4, 2, 50 micromol/L could significantly reduce the intracellular concentration of calcium in PC12 cells exposed to glutamate (P<0.05, P<0.01), which was also approximate to the effect of nimodipine (positive control drug)., Conclusion: Cembrane-type diterpenes (compound 1, compound 2 and compound 3) extracted from Sinularia flexibilis have obvious protective effects on PC12 cells damaged by glutamate, and compound 1 has the best neuroprotective effect. The mechanism of the neuroprotective effect of compound 1 may lie in reducing the intracellular concentration of calcium in PC12 cells exposed to glutamate and relieving the calcium overload.

3,6'-Disinapoyl sucrose (DISS) is the active oligosaccharide ester component from roots of Polygala tenuifolia, and its antidepressant effects was found in the forced swimming test (FST) and tail suspension test (TST). We aimed to study the antidepressant effects of DISS in the chronic unpredictable mild stress (CMS) model in rats and explore the underlying mechanisms in the hypothalamic-pituitary-adrenal (HPA) axis. We found that when subjected to the chronic stress protocol for 28 days, animals showed reduced sensitivity to reward and abnormality in the HPA axis. DISS (10 or 20 mg/kg, i.g.) improved the reward reaction as measured by increasing sucrose consumption, remarkably reduced serum CORT, ACTH and CRH levels in the CMS-treated rats. In addition, DISS enhanced the expression of glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) mRNA. These results indicated that the antidepressant effects of DISS in chronically stressed animals might relate to the modulating effects on the HPA axis, which might be an important mechanism for its antidepressant effect.

Objective: To study the antidepressant effects of piperine in chronic unpredictable mild stress (CUMS) rats and to explore the underlying mechanisms in the hypothalamic-pituitary-adrenal (HPA) axis., Methods: Fifty rats were housed alone and exposed to an unpredicted sequence of mild stressors to induce CUMS, and then were divided into untreated group, desipramine group and low-, medium- and high-dose piperine groups. Another 10 normal rats were used as normal control. The behavior of the rats was detected by body weight and sucrose preference test, and the serum levels of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and corticosterone (CORT) in different groups were observed by radioimmunoassay., Results: The results indicated that after 21-day administration, piperine at concentrations of 10 and 20 mg/kg could significantly improve the behavioral disorder by increasing sucrose consumption. Piperione at concentrations of 5, 10 and 20 mg/kg could remarkably reduce serum ACTH and CRH levels in the CUMS rats, but had little effect on the content of CORT., Conclusion: Piperine can relieve depression in CUMS rats by modulating the function of HPA axis.

Objective: To investigate the antidepressant components of Polygala tenuifolia., Method: The chromatographic method was used to isolate and purify the chemical constituents, their structures were identified by spectral analysis, MTT method was applied to investigate their cytotoxic activities., Result: Nine compounds were isolated from the roots of P. tenuifolia. Their structures were identified as sibiricose A, (1), sibiricose A5 (2), tenuifoliside A (3) and 3', 6-disinapoyl sucrose (4), sibiricose A6 (5), 3, 4, 5-trimethoxycinnamate (6), polygalaxanthone III (7), tenuifolioses A (8), tenuifolioses H (9) and some compounds' activities to PC12 were observed., Conclusion: Compound 1 was isolated from this plant for the first time. Compounds 2,3 could protect PC12 cells damage induced by P. tenuifolia.