Combination of Geniposide and Eleutheroside B Exerts Antidepressant-like Effect on Lipopolysaccharide-Induced Depression Mice Model.

OBJECTIVE: To study the antidepressant-like effect and action mechanism of geniposide and eleutheroside B combination treatment on the lipopolysaccharide (LPS)-induced depression mice model. METHODS: Depression mice model was established by lipopolysaccharide (LPS) injection. Totally 48 mice were randomly divided into 6 groups (8 rats per group) according to a random number table, including normal, model, fluoxetine (20 mg/kg), geniposide (100 mg/kg) + eleutheroside B (100 mg/kg), geniposide + eleutheroside B + WAY 100635 (0.03 mg/kg), geniposide + eleutheroside B+ N-methyl-D-aspartic acid receptor (NMDA, 75 mg/kg) groups, respectively. After continuous administration for 10 days, autonomic activity tests after 30 min of administration were performed on the 10th day. On the 11th day, except for the normal group, the mice in the other groups were intraperitoneally injected with LPS (1 mg/kg), and the behavioral tests were performed 4 h later. Enzyme linked immunosorbent assay was used to detect tumor necrosis factor alpha (TNF- α) and interleukin-1 ß (IL-1 ß) levels in mice serum. The mRNA expression of indoleamine 2,3-dioxygenase (IDO) and nuclear transcription factor (NF- κB) were detected by real-time quantitative polymerase chain reaction. Western-blot analysis was used to detect IDO and NF- κB protein expressions in hippocampus tissue. RESULTS: Compared with the normal group, a single administration of LPS increased the immobility time in the forced swimming test (FST) and tail suspension test (TST, P<0.01), without affecting autonomous activity. Compared with the model group, fluoxetine and geniposide + eleutheroside B administration significantly improved the immobility time of depressed mice in the FST and TST, decreased serum IL-1 ß content, inhibited the expression levels of NF- κ B gene and protein in hippocampus tissues (P<0.05 or P<0.01). Compared with the model group, geniposide + eleutheroside B treatment significantly reduced serum TNF-α content and inhibited IDO mRNA and protein expressions in hippocampus (P<0.05 or P<0.01). In addition, NMDA partly prevented the inhibition of IDO mRNA expression by geniposide + eleutheroside B; NMDA and WAY-100635 also partly prevented the reduction of IL-1 ß content induced by geniposide + eleutheroside B treatment (P<0.05 or P<0.01). CONCLUSIONS: The combination of geniposide and eleutheroside B showed a certain antidepression-like effect. Its main mechanism of action may be contributed to inhibiting the activation of NF- κB, decreasing the proinflammatory cytokines such as TNF-α, IL-1 ß, and inhibiting in the neuroinflammatory reaction. Additionally, it also affects tryptophan metabolism, reduces the expression of a key enzyme of tryptophan metabolism, IDO. And this antidepressant-like effect may be mediated by 5-hydroxytryptamine and glutamate systems.

Antidepressant-like mechanism of honokiol in a rodent model of corticosterone-induced depression.

Depression is closely linked to hypothalamus-pituitary-adrenal axis hyperactivity. Honokiol, a biphenolic lignan compound obtained from the traditional Chinese medicine Magnolia officinalis, can reduce the activity of the hypothalamus-pituitary-adrenal axis and improve depression-like behavior caused by hypothalamus-pituitary-adrenal axis hyperactivity. The current study investigated the specific mechanism of action of this effect. A depression model was established by repeated injections of corticosterone to study the antidepressant-like effect of honokiol and its potential mechanism. Honokiol prevented the elevated activity of the hypothalamus-pituitary-adrenal axis and the depression-like behavior induced by corticosterone. Treatment with honokiol resulted in greater glucocorticoid receptor mRNA expression, greater glucocorticoid receptor-positive expression, and a greater ratio of glucocorticoid receptor to the mineralocorticoid receptor in the hippocampus. Moreover, honokiol treatment led to lower levels of interleukin-1ß in serum and the positive expression of the interleukin-1ß receptor in the hippocampus. These results demonstrate that the antidepressant-like mechanism of honokiol, which has effects on inflammatory factors, may act through restoring the typical activity of the hypothalamus-pituitary-adrenal axis by regulating the glucocorticoid receptor-mediated negative feedback mechanism and the balance between glucocorticoid and mineralocorticoid receptors.

The Traditional Chinese Medicine Fuyou Formula Alleviates Precocious Puberty by Inhibiting GPR54/GnRH in the Hypothalamus.

The purpose of this study was to explore the effect of the traditional Chinese medicine Fuyou formula on precocious puberty (PP). The Fy formula may exert an effect in female rats with PP and GT-7 cells through the GPR54/GnRH signaling pathway. To confirm the effect of the Fy formula on PP through the GPR54/GnRH signaling pathway, we first treated GT1-7 cells with the Fy formula and observed changes in the expression of related genes and proteins and in GnRH secretion. Then, we randomly divided young female Sprague-Dawley rats into the control group, model group, leuprorelin group and the Fy formula group. A PP model was established by injection of danazol on postnatal day 5, and the Fy formula was administered on PND15. The time of vaginal opening, the wet weights of the ovary and uterus, serum hormone levels and the expression of hypothalamic-related genes were observed. We found that the Fy formula delayed vaginal opening, decreased the wet weights and coefficients of the ovary and uterus, decreased the levels of serum hormones (E2, follicle-stimulating hormone and luteinizing hormone) and the cellular GnRH level, and downregulated the gene expression of Kiss1, GPR54 and GnRH in the hypothalamus and the gene and protein expression of GPR54 and GnRH in GT1-7 cells. In conclusion, the Fy formula may alleviate PP via the GPR54/GnRH signaling pathway.

Cynomorium songaricum Extract Alleviates Memory Impairment through Increasing CREB/BDNF via Suppression of p38MAPK/ERK Pathway in Ovariectomized Rats.

Cynomorium songaricum Rupr is a very important traditional Chinese medicine for tonifying the kidney, which has a significant effect on improving estrogen level on the long term. In many studies, it can improve the learning and memory function of ovariectomized (OVX) model animals. 10 of the 50 rats received only bilateral back surgery and were harvested with the same amount of fat as the ovaries without removing the ovaries as sham group; remains underwent bilateral ovariectomy and equally randomized into five groups: sham group, with OVX as model group, estradiol valerate (EV, 0.2 mg/kg) as positive control, with 3.3 and 33 mg/kg body weight/day of ethyl acetate extract of Cynomorium songaricum extract (CSE) as low and high dosage groups, respectively. The orally administered CSE to ovariectomized rats exerted an ameliorative effect on learning and memory in the Morris water maze tests. All rats were sacrificed after 8 weeks of treatment, and tissue was analyzed using histopathology and electron microscopy. To comprehensively examine the mechanism, brain derived neurotrophic factor (BDNF), p-p38 mitogen-activated protein kinase (p-p38MAPK), extracellular regulated protein kinases (ERK), p-extracellular regulated protein kinases (p-ERK), and p-cAMP-response element binding protein (p-CREB) were detected by Western blotting. Using histopathology and electron microscopy, it was clearly observed that the pyramidal neurons of the hippocampal CA1 area were reduced in the OVX groups, indicating that CSE could attenuate the loss of pyramidal neurons in hippocampal CA1 and revert the synaptic morphological variations produced by ovariectomy. Mechanistically, the expressions of p-p38MAPK and p-ERK levels were significantly downregulated by CSE intervention, whereas the BDNF and p-CREB were significantly upregulated by CSE as compared to the control. Concisely, Cynomorium songaricum Rupr exhibited potential therapeutic effect on Neuroprotection of ovariectomized rats, and its effect was possibly exerted by p-CREB/BDNF mediated down regulation of ERK/p38MAPK.

Antidepressant-Like Effect and Mechanism of Action of Honokiol on the Mouse Lipopolysaccharide (LPS) Depression Model.

There is growing evidence that neuroinflammation is closely linked to depression. Honokiol, a biologically active substance extracted from Magnolia officinalis, which is widely used in traditional Chinese medicine, has been shown to exert significant anti-inflammatory effects and improve depression-like behavior caused by inflammation. However, the specific mechanism of action of this activity is still unclear. In this study, the lipopolysaccharide (LPS) mouse model was used to study the effect of honokiol on depression-like behavior induced by LPS in mice and its potential mechanism. A single administration of LPS (1 mg/kg, intraperitoneal injection) increased the immobility time in the forced swimming test (FST) and tail suspension test (TST), without affecting autonomous activity. Pretreatment with honokiol (10 mg/kg, oral administration) for 11 consecutive days significantly improved the immobility time of depressed mice in the FST and TST experiments. Moreover, honokiol ameliorated LPS-induced NF-κB activation in the hippocampus and significantly reduced the levels of the pro-inflammatory cytokines; tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß), and interferon γ (IFN-γ). In addition, honokiol inhibited LPS-induced indoleamine 2,3-dioxygenase (IDO) activation and quinolinic acid (a toxic product) increase and reduced the level of free calcium in brain tissue, thereby inhibiting calcium overload. In summary, our results indicate that the anti-depressant-like effects of honokiol are mediated by its anti-inflammatory effects. Honokiol may inhibit the LPS-induced neuroinflammatory response through the NF-κB signaling pathway, reducing the levels of related pro-inflammatory cytokines, and furthermore, this may affect tryptophan metabolism and increase neuroprotective metabolites.

[Effect of acupuncture on quality of life in post-ischemic stroke patients with dysphagia].

OBJECTIVE: To observe the effect of acupuncture on quality of life (QOL) in post-ischemic stroke patients with dysphagia. METHODS: Sixty-six patients with dysphagia were randomly assigned to 3 groups, the 23 patients in the electro-acupuncture (EA) group treated by EA, 18 in the control group received rehabilitation training combined with acupoint percutaneous electric stimulation, and 25 in the acupoint token puncturing (TP) group received rehabilitation training combined with acupoint TP, once every day for 20 days in total. Changes in QOL scale specified for dysphagia of patients before and after treatment were compared. RESULTS: The total effective rate was 69.6% in the EA group, 50.0% in the control group and 64.0% in the TP group with insignificant difference among them (P > 0.05), but the improvements dealing with patients' general condition, time for taking food, frequency of uneasiness, emotion, appetite, social intercourse ability, fatigue, sleep and mental health, etc. in the EA group were superior to those in the other two groups (P < 0.05). CONCLUSION: Acupuncture could improve the QOL of patients with dysphagia after ischemic stroke.

[Experimental studies on treatment of depression with YJ-XCC1Z3 in mouse models].

OBJECTIVE: To evaluate the pre-clinical effect of YJ-XCC1Z3 on the treatment of depression with the mice mouse. METHOD: YJ-XCC1Z3 was administered at the dose of 405 mg x kg(-1) and 135 mg x kg(-1) to observe the locomotor activity with the mouse locomotor activity recorder apparatus, to observe the effect of YJ-XCC1Z3 on the duration of immohility in the mouse forced swimming test and tail suspension test, to observe the effect of YJ-XCC1Z3 on the body temperature and the metabolism of monoamine neurotransmitters in mouse brain in the mouse model of reserpine induced hypothermia, and to observe the effect of YJ-XCC1 Z3 on the times of 5-HTP induced head-twitches in mice. RESULT: There were no significant changes in the locomotor activity, but a significant reduction in the immobility time was observed in the mice treated with YJ-XCC1Z3 405 mg x kg(-1) and imipramine in the forced swimming test and the tail suspension test. YJ-XCC1Z3 135 mg x kg(-1) and 405 mg x kg(-1) could improve the range of reserpine induced hypothermia in mice, and the latter could also enhance the times of 5-HTP induced head-twitches in mice. YJ-XCC1Z3 405 mg x kg(-1) and 135 mg x kg(-1) could increase the content of 5-HT and NE and decrease the ratio of 5-HIAA/5-HT in mouse brain, but the dose of 405 mg x kg(-1) could decrease the content of DA. The dose of 405 mg x kg(-1) could increase the content of 5-HIAA and had no obvious effect on the content of HVA and DOPAC. CONCLUSION: YJ-XCC1Z3 shows potent antidepressant effect by improving the behaviour of the mouse in depression and not inducing hyperlocomotion in the mice. This effect results in the increase of the content of 5-HT and NE in the mouse brain. YJ-XCC1Z3 can decrease the metabolism of 5-HT to effect the content of 5-HT.