Evaluation of the toxicological properties and anti-inflammatory mechanism of Hemerocallis citrina in LPS-induced depressive-like mice.

Hemerocallis citrina Baroni (Liliaceae), a Liliaceae plant, has been widely used in food and traditional medicine. This study investigated the safety of ethanol extracts from Hemerocallis citrina (HCE) after oral treatment (p.o.) and evaluating the anti-inflammatory mechanism of HCE in a lipopolysaccharide (LPS)-induced depressive-like model. First, in an 8-week experimental procedure, blood and tissue samples collected from mice were used for biochemical and histopathological analysis every two weeks. Neither the body weight nor relative organ weights were affected by HCE administration. Only the total cholesterol levels were decreased by HCE administration. Histopathological analysis showed no significant liver and kidney changes caused by HCE. In addition, in an LPS-induced mouse depressive-like model, HCE significantly reversed the reduction of sucrose preference with LPS. The results also indicated that LPS activated the nuclear factor-κB (NF-κB), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression in the prefrontal cortex. In contrast, these activations were normalized by HCE pretreatment. In summary, our study provided essential evidence for the safety of Hemerocallis citrina in both food and medicine. The results also demonstrated that HCE exhibited antidepressant-like effects that might be related to inhibition of the NF-κB signaling pathway.

Antidepressant-like effects of standardized gypenosides: involvement of brain-derived neurotrophic factor signaling in hippocampus.

RATIONALE: Gypenosides have been reported to produce neuroprotective effects and increase monoamine neurotransmitter levels in the brain. OBJECTIVE: Considering that depression is involved in monoamine reduction, this study evaluated the antidepressant-like effects of gypenosides in mice exposed to chronic unpredictable mild stress (CUMS). METHODS: The sucrose preference test and forced swimming test were performed after administration of gypenosides (at 25, 50, or 100 mg/kg) for 4 weeks. Hippocampal brain-derived neurotrophic factor (BDNF) and its downstream targets were analyzed by western blot. Additionally, hippocampal neuronal proliferation was measured by immunohistochemistry. RESULTS: Four-week treatment with fluoxetine (20 mg/kg) and gypenosides (at either 50 or 100 mg/kg) increased sucrose preference and decreased the immobility time in mice exposed to CUMS. In addition, gypenosides (at either 50 or 100 mg/kg) also increased BDNF expression and neuronal proliferation in the hippocampus of CUMS animals. Further, we showed that treating CUMS mice with K252a, which is an inhibitor of the BDNF receptor TrkB, blocked the effects of gypenosides (100 mg/kg), including behavioral improvements, neuronal proliferation, and up-regulation of p-TrkB, p-ERK, and p-Akt proteins. CONCLUSIONS: This study demonstrates that gypenosides exhibit antidepressant-like effects in mice, which may be mediated by activation of the BDNF-ERK/Akt signaling pathway in the hippocampus.

Activation of hippocampal BDNF signaling is involved in the antidepressant-like effect of the NMDA receptor antagonist 7-chlorokynurenic acid.

Previous studies showed that acute 7-chlorokynurenic acid treatment produced a rapid antidepressant-like action in depression-like animal models. However, the underlying mechanism involved in neurotrophin system about 7-chlorokynurenic acid is unclear. Our present study aimed to verify whether chronic 7-chlorokynurenic acid treatment produced an antidepressant-like effect through the activation of brain-derived neurotrophic factor (BDNF) signaling in mice exposed to chronic unpredictable mild stress (CUMS). In addition, we performed an oral toxicological evaluation of chronic 7-chlorokynurenic acid administration in mice. The results showed that a two-week administration with 7-chlorokynurenic acid reversed the decreased sucrose preference and prolonged first feeding latency. In addition, 7-chlorokynurenic acid significantly reversed the CUMS-induced down-regulation of BDNF, p-ERK, p-Akt, PSD-95, synapsin I and cell proliferation in the hippocampus. In contrast, K252a, an inhibitor of BDNF receptor tropomyosin-related kinase receptor B (TrkB), blocked the antidepressant-like effect and the improvement of 7-chlorokynurenic acid. Furthermore, we found that 7-chlorokynurenic acid did not produce any toxicological effect in mice. In conclusion, our findings suggest that the antidepressant-like effect of 7-chlorokynurenic acid may be mediated, at least in part, by activating BDNF signaling in the hippocampus.

Essential oil of Syzygium aromaticum reverses the deficits of stress-induced behaviors and hippocampal p-ERK/p-CREB/brain-derived neurotrophic factor expression.

Syzygium aromaticum has been widely used in traditional medicine. Our study investigated the safety and antidepressant-like effects of the essential oil of S. aromaticum after acute or long-term treatment. Using GC-MS, a total of eight volatile constituents were identified in the essential oil of S. aromaticum. The single LD50 was approximately 4500 mg/kg based on a 24-h acute oral toxicity study. In a long-term repeated toxicity study of this essential oil (100, 200, and 400 mg/kg, p. o.), only 400 mg/kg induced a significant decrease in body weight. In addition, no significant changes in relative organ weights and histopathological analysis were observed in all doses of essential oil-treated mice compared with the control group. Furthermore, acute S. aromaticum essential oil administration by gavage exerted antidepressant-like effects in the forced swimming test (200 mg/kg, p < 0.05) and tail suspension test (100 and 200 mg/kg, p < 0.05). Long-term S. aromaticum essential oil treatment via gavage significantly increased sucrose preference (50 mg/kg, p < 0.05; 100 and 200 mg/kg, p < 0.01) as well as elevated the protein levels of hippocampal p-ERK, p-CREB, and brain-derived neurotrophic factor in mice exposed to chronic unpredictable mild stress. These results confirmed the safety of the essential oil of S. aromaticum and suggested that its potent antidepressant-like property might be attributed to the improvement in the hippocampal pERK1/2-pCREB-BDNF pathway in rats exposed to chronic unpredictable mild stress.

[Postmenopausal osteoporosis and blood stasis].

OBJECTIVE: To investigate whether blood stasis is one of the main causes in the pathogenesis of postmenopausal osteoporosis. METHODS: The clinical manifestation of blood stasis syndrome were comprehensively scored in sixty postmenopausal osteoporosis patients, their vascular endothelial function and platelet activating capacity were also detected, and compared with those in 30 healthy women as control. RESULTS: The molecular indexes as vascular endothelial function and platelet activating capacity, as well as comprehensive scores of clinical manifestation of blood stasis syndrome in postmenopausal osteoporosis patients were significantly different to those of healthy women (P < 0.05, P < 0.01). CONCLUSION: There is objective molecular pathologic change of blood stasis syndrome in postmenopausal osteoporosis. Blood stasis plays an important role in pathogenesis of postmenopausal osteoporosis.