Effect of Ganmai Dazao Decoction on ethology of rats with PTSD and its mechanism / 中国中药杂志

This study aimed to explore the effect of Ganmai Dazao Decoction on the ethology of rats with posttraumatic stress disorder(PTSD) and study the related mechanism through the changes in magnetic resonance imaging and protein expression. Sixty rats were randomly divided into 6 groups, namely the normal group, the model group, the low(1 g·kg~(-1)), medium(2 g·kg~(-1)), and high-dose Ganmai Dazao Decoction groups(4 g·kg~(-1)), and the positive control group(intragastric administration with 10.8 mg·kg~(-1) of fluoxetine), with 10 rats in each group. Two weeks after inducing PTSD by single-prolonged stress(SPS) in rats, the positive control group was given fluoxetine hydrochloride capsule by gavage, the low, medium, and high-dose groups were given Ganmai Dazao Decoction by gavage, and both the normal group and the model group were given the same volume of normal saline by gavage, each for 7 days. The open field experiment, elevated cross elevated maze, forced swimming experiment, and new object recognition test were carried out for the behavioral test. Three rats in each group were selected to detect the expression of neuropeptide receptor Y1(NPY1R) protein in the hippocampus by Western blot. Then, the other three rats in each group were selected to use the 9.4T magnetic resonance imaging experiment to observe the overall structural changes in the brain region and the anisotropy fraction of the hippocampus. The results of the open field experiment showed that the total distance and central distance of rats in the model group were significantly lower than those in the normal group, and the total distance and central distance of rats in the middle and high-dose Ganmai Dazao Decoction groups were higher than those in the model group. The results of the elevated cross maze test showed that medium and high-dose Ganmai Dazao Decoction remarkably increased the number of open arm entries and the residence time of open arm of rats with PTSD. The results of the forced swimming experiment showed that the immobility time in the water of the model group rats was significantly higher than that of the normal group, and Ganmai Dazao Decoction hugely reduced the immobility time in the water of rats with PTSD. The results of the new object recognition test showed that Ganmai Dazao Decoction significantly increased the exploration time of new objects and familiar objects in rats with PTSD. The results of Western blot showed that Ganmai Dazao Decoction significantly reduced the expression of NYP1R protein in the hippocampus of rats with PTSD. The 9.4T magnetic resonance examination found that there was no significant difference in the structural image among the groups. In the functional image, the fractional anisotropy(FA value) of the hippocampus in the model group was significantly lower than that in the normal group. The FA value of the hippocampus in the middle and high-dose Ganmai Dazao Decoction groups was higher than that in the model group. Ganmai Dazao Decoction reduces the injury of hippocampal neurons by inhibiting the expression of NYP1R in the hippocampus of rats with PTSD, thereby improving the nerve function injury of rats with PTSD and playing a neuroprotective role.

Study on mechanism of Valerianae Jatamansi Rhizoma et Radix against post-traumatic stress disorder based on molecular docking and network pharmacology / 中国中药杂志

This paper aims to investigate the active components and mechanism of Valerianae Jatamansi Rhizoma et Radix against post-traumatic stress disorder(PTSD) based on network pharmacology and molecular docking. The main components and targets of Valerianae Jatamansi Rhizoma et Radix were obtained by literature mining methods, SwissTargetPrediction, BATMAN and ETCM database. PTSD-related genes were collected from DrugBank, TTD and CTD databases. The protein-protein interaction(PPI) network was constructed based on STRING, and the core targets of Valerianae Jatamansi Rhizoma et Radix in the treatment of PTSD were selected according to the topological parameters. Cytoscape 3.7.2 was used to construct the compound-target network. DAVID database was used for GO enrichment analysis and KEGG enrichment analysis. The relationship network of "compound-target-pathway" was constructed through Cytoscape 3.7.2 to analyze and obtain the key targets and their corresponding components in the network, and their results were verified by molecular docking. The results showed that a total of 47 components(such as valeraldehyde, dihydrovalerin, valerate, chlorovaltrate K, 8-hydroxypinoresinol, 6-hydroxyluteolin, apigenin, farnesin, vanillin, luteolin, kaempferol, glycosmisic acid and pogostemon) of Valerianae Jatamansi Rhizoma et Radix may act on 94 key targets such as CNR1, MAOA, NR3 C1, MAPK14, MAPK8, HTR2 C and DRD2. Totally 29 GO terms were obtained by GO functional enrichment analysis(P<0.05), and 20 signaling pathways were obtained from KEGG pathway enrichment, mainly involving neuroactive ligand-receptor interaction, serotonergic synapse, calcium signaling pathway, cAMP signaling pathway, dopaminergic synapse, retrograde endocannabinoid signaling, neurotrophin signaling pathway, gap junction, cholinergic synapse, estrogen signaling pathway, glutamatergic synapse and long-term potentiation. Molecular docking analysis showed that hydrogen bonding, π-π interaction and hydrophobic effecting may be the main forms of interaction. This study used the network of compound-target-pathway and molecular docking technology to screen the effective components of Valerianae Jatamansi Rhizoma et Radix against PTSD, and explore its anti-PTSD mechanism, so as to provide scientific basis for exploring the anti-PTSD drugs from traditional Chinese medicine and clarifying its mechanism of action.

Effect of Traditional Chinese Medicines in Treatment of Post-traumatic Stress Disorder / 中国实验方剂学杂志

Post-traumatic stress disorder (PTSD) is a mental disorder characterized by restitution of trauma and emotional irritability and avoidance caused by sudden, threatening or catastrophic life events. PTSD occurs not only abnormal behavioral indicators but also abnormal neurobiological indicators. Studies on the pathogenesis of PTSD have focused on neuroendocrine system, central nervous system and immune system, mainly finding abnormal levels of stress hormones, pro-inflammatory cytokines, neurotransmitters and neuroprotective factors. Traditional Chinese medicines(TCM) have many advantages in the treatment of PTSD due to their multi-target, multi-component and multi-pathway characteristics. Current studies have showed that a variety of TCM can improve the abnormal behaviors of animals in the models of post-traumatic stress disorder and reverse the neurobiological indicators. As many of these TCM compounds have been used in clinic and have good efficacy, TCM treatment of PTSD has a broad application prospect. However, there is no specific medicine for PTSD, and its mechanisms have not been fully understood. Therefore, this paper reviews the current studies on the treatment of PTSD with TCM, and focuses on the occurrence and treatment progress of PTSD in terms of TCM, mechanisms of action and animal models, so as to provide references for the treatment of PTSD.

Clinical study on compound prescription with Valerianae Jatamansi Rhizoma et Radix in treatment of generalized anxiety disorder / 中国中药杂志

This study was aimed to observe the clinical efficacy of anxiolytic compound prescription with Valerianae Jatamansi Rhizoma et Radix (ACPV) in treating liver Qi stagnation and feel ill at ease type generalized anxiety disorder (GAD). Sixty-seven patients diagnosed as GAD with stagnation of liver Qi and feel ill at ease were randomly divided into treatment group and control group. Patients in treatment group (n=34) was treated with ACPV decoction, and patients in control group (n=33) were treated with deanxit. Both groups were treated with respective drugs for 4 weeks. HAMA scale, traditional Chinese medicine (TCM) symptom scale (liver Qi stagnation and feel ill at ease type) and salivary cortisol levels were measured before and 2 weeks and 4 weeks after drug treatment. The life events scale (LES) and drug safety evaluation were performed before and after 4 weeks treatment. Two patients were excluded according to LES, and 5 patients were discontinued. Sixty patients were enrolled in the study finally (30 cases in each group). As compared with baseline, HAMA scores in both groups were significantly decreased at 2 weeks and 4 weeks (P<0.05, P<0.01). After 2 weeks and 4 weeks treatment, the TCM syndrome score in both group was also significantly improved (P<0.01). Moreover, the salivary cortisol levels in both groups were also decreased at 2 weeks and 4 weeks (P<0.05, P<0.01). The total efficiency between two groups had no statistically significant difference after 2 weeks treatment and 4 weeks treatment; moreover, no statistically significant differences were observed between two groups in HAMA scores, TCM syndrome scale scores and salivary cortisol levels between two groups. The incidence of adverse reactions in the treatment group was significantly lower than that in the control group (P<0.01), and there were no obvious side effects in general physical examination during the period of treatment. Thus, anxiolytic compound prescription with Valerianae Jatamansi Rhizoma et Radix is effective for GAD (stagnation of liver Qi and feel ill at ease type).

Advanced in studies on anxiolytic effects of natural flavonoids / 中国中药杂志

Anxiety is one of the most common diseases endangering human health. Its pathogenesis is complex, the studies on the mechanisms of anxiety disorder are concentrated on neurotransmitter, neuroendocrine, immunologic system. Flavonoids are a kind of compounds which possess a variety of physiological activity, used in plenty of diseases. In recent years, researches of natural flavonoids on anti-anxiety were increasing, but contents were incomplete. It was just involved several neurotransmitters in research area. This paper is based on different anxiolytic effect mechanisms and structure-activity relationships of natural flavonoids, summarizing the researches of domestic and foreign, which can serve as a reference for further studies on anxiolytic effects of natural flavonoids.

Effects of Lycii Cortex on express of PI3K/PKB in PCOS rats / 中国中药杂志

The effect of Lycii Cortex on the PCOS rat model and the mechanism of action were investigated in the present study. The PCOS rat model was induced with Poretsky methods. Then the rats were randomly divided into four groups: the model group, melbine group (0.45 g x kg(-1)), low (2.5 g x kg(-1) and high (10 g x kg(-1)) dosage group of Lycii Cortex. The animals were orally administrated with the drugs for 14 days. In addition, another control group was added in this study. The rats were weighted before and after drug treatment. After 14 days treatment, oestrous cycle of rats were detected; blood serum was separated to determine T and FINS and rat's uteri were isolated. The mRNA and protein (total and phosphorylated) expressions of PI3K and PKB in uteri were measured with Real-time RT-PCR and Western blot, respectively. Compared with the control rats, the body weight gain and serum level of T and FINS were significantly increased. While, the mRNA and protein (phosphorylated) levels of PI3K and PKB were markedly decreased in PCOS group. Lycii Cortex treatment significantly decreased the body weight gain and serum level of T and FINS in a dose-dependant manner. It also markedly increased the mRNA and protein (phosphorylated) expressions of PI3K and PKB. Meanwhile, the melbine treatment also showed the curative effect. Lycii Cortex can relieve the symptoms of PCOS and the mechanism might be related to PI3K/PKB pathway.

Study on effect of astragali radix polysaccharides in improving learning and memory functions in aged rats and its mechanism / 中国中药杂志

To observe the effect of Astragali Radix polysaccharides (APS) on the learning and memory functions of aged rats, in order to explore its mechanism for improving the learning and memory functions. Natural aging female SD rats were selected in the animal model and randomly divided into the control group, the APS low-dose group (50 mg x kg(-1)), the APS high-dose group (150 mg x kg(-1)) and the piracetam-treated group (560 mg x kg(-1)). They were orally administered with the corresponding drugs for consecutively 60 days. Besides, a young control group was set. The learning and memory functions of the rats were tested by the open-field test and the Morris water maze task. The Western-blot method was used to observe the levels of relevant neural plasticity protein N-methyl-D-aspartate receptor (NMDA receptor) in hippocampus, calcium/calmodulin dependent protein kinase II (CaMK II), protein kinase (PKA), the phosphorylation level of CAMP response element binding protein (CREB) and the protein expression of brain derived neurotrophic factor(BDNF). In this study, the authors found that the learning and memory functions and the hippocampus neural plasticity protein expression of the aged rat group were much lower than that of the young control group (P < 0.01). Compared with the aged rat group, the APS group showed the significant improvement in the impaired learning and memory functions of aged rats and the up-regulation in the hippocampus neural plasticity protein expression. The results showed that APS may improve the learning and memory functions of aged rats by increasing the expressions of relevant neural plasticity proteins.

Effect of ginsenoside Rg1 on behaviors and hippocampal amino acids in depressive-like rats / 中国中药杂志

<p><b>OBJECTIVE</b>To observe the effect of ginsenoside Rg1 on behavior and hippocampal amino acids in depressive-like rats.</p><p><b>METHOD</b>SD rats were randomly divided into 5 groups: control, model, fluxetine, low dose ginsenoside Rg1 and high dose of ginsenoside Rg1. The chronic unpredictable mild stress (CUMS) was performed to induce depressive-like animal model. Fluxetine group was orally given fluxetine in dose of 10 mg x kg(-1) for 21 days, low dose ginsenoside Rg1 group was orally given ginsenoside Rg1 in dose of 20 mg x kg(-1) for 21 days, high dose ginsenoside Rg1 group was orally given ginsenoside Rg1 in dose of 40 mg x kg(-1) for 21 days. The control and model group was orally given saline for 21 days. The sucrose consumption was detected before and after the CUMS procedure. The horizontal and vertical activities of rats were determined by open-field test. HPLC was adopted to detect the contents of amino acids in hippocampus.</p><p><b>RESULT</b>The sucrose consumption, horizontal and vertical activities in CUMS rats were decreased compared with those in control group. Compared with control group, the contents of glutamate (Glu) and aspartate (Asp) in hippocampus of CUMS group were increased, while the gamma amino butyric acid (GABA) and taurine (Tau) were decreased. Ginsenoside Rg1 treatment significantly increased the CUMS-induced decrease in sucrose consumption, horizontal and vertical activities. Administrated with ginsenoside Rg1 also decreased Glu and Asp and increased the GABA and Tau in hippocampus in a dose dependent manner.</p><p><b>CONCLUSION</b>Ginsenoside Rg1 could alleviate the behavior changes of depressive-like rats, which might be related to regulate the levels of amino acids in hippocampus during CUMS and prevent the neuro-toxicity of excitatory amino acids.</p>

Effects of volatie oil of Schizonepeta tenuifolia Briq herb and Saposhnikovia divaricata Schischke root on proinflammatory cytokine expression and regulation / 中国中药杂志

<p><b>OBJECTIVE</b>To study the effects of volatie oil of Schizonepeta tenuifolia Briq herb and Saposhnikovia divaricata Schischke root (OSS) on proinflammatory cytokine expression and regulation in rats.</p><p><b>METHOD</b>OA and LPS were injected intravenously to rats to develop acute lung injury (ALI). The rats were treated with OSS (45.19 microL kg(-1)). The pathological sections of lung tissue were prepared and observed in acute lung injury rats. The expression of nuclear factor-kappa B p65 (NF-kappaB p65), intercellar adhesion molecule CD54, and NF-kappaB p65 mRNA were determined in lung cells.</p><p><b>RESULT</b>volatie oil of Schizonepeta tenuifolia Briq herb and Saposhnikovia divaricata Schischke root significantly inhibited the expression of CD54, the activation of NF-kappaB p65, and the transcription of NF-kappaB p65 mRNA.</p><p><b>CONCLUSION</b>OSS can reduce the expression of CD54 and NF-kappaB p65 protein synthesis, which may be its anti-inflammatory molecular mechanisms.</p>

Effect of 2-methoxycinnamaldehyde on activity of COX and PGE2 release in cerebral microvascular endothelial cells stimulated by IL-1 / 中国中药杂志

<p><b>OBJECTIVE</b>To observe the effect of 2-methoxycinnamaldehyde (isolated from fraction A of Guizhi Tang) on activity of COX and PGE2 release in rat cerebral microvascular endothelial cells (rCMEC) stimulated by IL-1.</p><p><b>METHOD</b>rCMEC were cultured, and identified by immunohistochemistry for von Willebrand factor (VIII factor, a marker for all endothelial cells) in cytoplasm of the cells. Different concentrations of 2-methoxycinnamaldehyde were added respectively and incubated for 3 hours, then stimulated for another 12 hours by IL-1. Activities of COX-1 and COX-2 in rCMEC, and production of PGE2 in the conditioned media were measured by ELISA.</p><p><b>RESULT</b>Positive immunostaining for VIII factor was present diffusely in the cytoplasm of > 90% rCMEC. After being exposed to 30 ng x mL(-1) IL, the activity of COX-2 in rCMEC and the production of PGE2 in conditioned media were higher than those of control group, while there was no difference on activity of COX-1 in the two groups. 2-methoxycinnamaldehyde could down-regulate them in concentration-dependently, and significant differences on the activity of COX-2 and amount of PGE2 were showed in 200 microg x mL(-1) concentration.</p><p><b>CONCLUSION</b>2-methoxycinnamaldehyde can affect the PGE2 release in rCMEC induced by IL-1, which might be related with its inhibition on the activity of COX-2.</p>