[Essential oil of Cinnamomum camphora mitigates depression-like behavior in mice by regulating Nrf2/HO-1 pathway and inhibiting inflammatory cytokines].

This study aims to investigate the essential oil(EOL) of Cinnamomum camphora regarding its anti-depression effect and mechanism in regulating inflammatory cytokines and the nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase-1(HO-1) pathway. A mouse model of depression was established by intraperitoneal injection of lipopolysaccharide(LPS). Open field, elevated plus maze, and forced swimming tests were carried out to examine mouse behaviors. Western blot and qRT-PCR were employed to determine the expression of proteins and genes in the Nrf2/HO-1 pathway in the hippocampus. The levels of tumor necrosis factor(TNF)-α, interleukin(IL)-6, and IL-1ß in the serum were measured by enzyme-linked immunosorbent assay(ELISA). The changes of apoptosis in mouse brain were detected by Tunel staining. Compared with the blank control group, the model group showed shortened distance travelled and time spent in the central zone and reduced number of entries in the central zone in the open field test. In the elevated plus maze test, the model group showed reduced open arm time(OT%) and open arm entries(OE%). In the force swimming test, the model group showed extended duration of immobility compared with the blank control group. Compared with the model group, the treatment with EOL significantly increased the distance travelled and time spent in the central zone and increased the number of entries in the central zone in the open field test. In addition, EOL significantly increased the OT% and OE% in the elevated plus maze and shor-tened the immobility duration in the forced swimming test. The model group showed lower expression levels of Nrf2 and HO-1 and hig-her levels of TNF-α, IL-6, and IL-1ß than the blank control group. Compared with the model group, the treatment with EOL up-regulated the expression levels of Nrf2 and HO-1 and lowered the levels of TNF-α, IL-6, and IL-1ß. The Tunel staining results showed that the apoptosis rate in the brain tissue of mice decreased significantly after the treatment with EOL. To sum up, EOL can mitigate the depression-like behaviors of mice by up-regulating the expression of Nrf2 and HO-1 and preventing hippocampal inflammatory damage. The findings provide empirical support for the application of EOL and aromatherapy in the treatment of depression.

11-Ethoxyviburtinal improves chronic restraint stress-induced anxiety-like behaviors in gender-specific mice via PI3K/Akt and E2 /ERß signaling pathways.

Anxiety disorder is a chronic and disabling psychiatric disorder that is more prevalent in females than in males. 11-Ethoxyviburtinal is an iridoid extracted from Valeriana jatamansi Jones, which has anxiolytic potential. The aim of the present work was to study the anxiolytic efficacy and mechanism of 11-ethoxyviburtinal in gender-specific mice. We first evaluated the anxiolytic-like efficacy of 11-ethoxyviburtinal in chronic restraint stress (CRS) mice of different sexes through behavioral experiments and biochemical indexes. In addition, network pharmacology and molecular docking were used to predict potential targets and important pathways for the treatment of anxiety disorder with 11-ethoxyviburtinal. Finally, the influence of 11-ethoxyviburtinal on phosphoinositide-3-kinase (PI3K)/protein kinase B (Akt) signaling pathway, estrogen receptor ß (ERß) expression, and anxiety-like behavior in mice was verified by western blotting, immunohistochemistry staining, antagonist intervention methods, and behavioral experiments. 11-ethoxyviburtinal alleviated the anxiety-like behaviors induced by CRS and inhibited neurotransmitter dysregulation and HPA axis hyperactivity. It inhibited the abnormal activation of the PI3K/Akt signaling pathway, modulated estrogen production, and promoted ERß expression in mice. In addition, the female mice may be more sensitive to the pharmacological effects of 11-ethoxyviburtinal. 11-ethoxyviburtinal may exert its anxiolytic-like effects through PI3K/Akt and E2/ERß signaling pathways. Meanwhile, by comparing the male and female mice, gender differences may affect the therapy and development of anxiety disorder.

Nardostachys jatamansi and levodopa combination alleviates Parkinson's disease symptoms in rats through activation of Nrf2 and inhibition of NLRP3 signaling pathways.

CONTEXT: Levodopa combined with traditional Chinese medicine has a synergistic effect on Parkinson's disease (PD). Recently, we demonstrated that Nardostachys jatamansi (D. Don) DC. [syn. Patrinia jatamansi D.Don, N. grandiflora DC.] (Valerianaceae) (NJ) can alleviate PD. OBJECTIVE: To explore the synergistic effect of NJ combined with levodopa against PD. MATERIALS AND METHODS: The PD model was established by injecting rotenone. Eighty-four Sprague-Dawley rats were randomly divided into seven groups: sham, model, different doses of NJ (0.31, 0.62, or 1.24 g/kg) combined with levodopa (25 mg/kg), and levodopa alone (25 and 50 mg/kg) groups. The synergistic effect of the combination was investigated by pharmacodynamic investigation and detection of expression of nuclear factor erythro2-related factor 2 (Nrf2) and NLR family proteins containing Pyrin-related domain 3 (NLRP3) pathways. RESULTS: Compared with the model group, NJ + levodopa (1.24 g/kg + 25 mg/kg) increased the moving distance of PD rats in the open field (2395.34 ± 668.73 vs. 1501.41 ± 870.23, p < 0.01), enhanced the stay time on the rotating rod (84.86 ± 18.15 vs. 71.36 ± 17.53, p < 0.01) and the combination was superior to other treatments. The synergistic effects were related to NJ + levodopa (1.24 g/kg + 25 mg/kg) increasing the neurotransmitter levels by 38.80%-88.67% in PD rats, and inhibiting oxidative stress and NLRP3 pathway by activating Nrf2 pathway. DISCUSSION AND CONCLUSIONS: NJ combined with levodopa is a promising therapeutic candidate for PD, which provides a scientific basis for the subsequent clinical combination therapy of levodopa to enhance the anti-PD effect.

[Effect of Ganmai Dazao Decoction on ethology of rats with PTSD and its mechanism].

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.

Parvalbumin interneuron in the ventral hippocampus functions as a discriminator in social memory.

The ability to identify strange conspecifics in societies is supported by social memory, which is vital for gregarious animals and humans. The function of hippocampal principal neurons in social memory has been extensively investigated; however, the nonprincipal neuronal mechanism underlying social memory remains unclear. Here, we first observed parallel changes in the ability for social recognition and the number of parvalbumin interneurons (PVIs) in the ventral CA1 (vCA1) after social isolation. Then, using tetanus toxin-mediated neuronal lesion and optogenetic stimulation approaches, we revealed that vCA1-PVIs specifically engaged in the retrieval stage of social memory. Finally, through the in vivo Ca2+ imaging technique, we demonstrated that vCA1-PVIs exhibited higher activities when subjected mice approached a novel mouse than to a familiar one. These results highlight the crucial role of vCA1-PVIs for distinguishing novel conspecifics from other individuals and contribute to our understanding of the neuropathology of mental diseases with social memory deficits.

Nootkatone alleviates rotenone-induced Parkinson's disease symptoms through activation of the PI3K/Akt signaling pathway.

Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. Nootkatone (NKT) has been shown to have neuroprotective, anti-inflammatory, and antioxidant effects and in this study, we systematically studied the efficacy and mechanism of action of NKT in rotenone (ROT)-induced PD rats. Firstly, through behavioral experiments and brain tissue staining, we found that NKT alleviated behavioral dysfunction and protected dopaminergic neurons associated with ROT-induced PD rats. Next, target prediction, protein-protein interaction (PPI), Gene Ontology (GO), and pathway enrichment analyses were used to obtain potential targets, specific biological processes, and molecular mechanisms of NKT for the potential treatment of PD. Furthermore, we also applied molecular docking to predict the binding capacity of NKT and related targets. Additionally, in vivo experiments confirmed that NKT could inhibit the expression of Mitogen-activated protein kinase 3 (MAPK3) by activating the PI3K/Akt signaling pathway, reducing neuroinflammation, and ultimately ameliorating ROT-induced PD symptoms. Taken together, the results of the study provide a clear explanation for the remission of PD symptoms by NKT, suggesting that it may be a promising candidate for the treatment of PD.

[Effect of Danzhi Xiaoyao Powder on behavior and mitochondrial morphology and function of anxiety model rats].

Danzhi Xiaoyao Powder is a classical prescription for anxiety. This study aims to analyze the effect of this medicine on mitochondrial morphology and function of anxiety rats and explore the mechanism of it against anxiety. Specifically, uncertain empty bottle drinking water stimulation(21 days) was employed to induce anxiety in rats. The elevated plus-maze test and open field test were respectively performed on the 7 th, the 14 th, and the 21 st days of the stimulation, so as to detect the anxiety-related protein index brain-derived neurotrophic factor(BDNF) and evaluate the anxiety level of animals. On this basis, the effect of this prescription on anxiety rats was preliminarily evaluated. After the behavioral test on the 21 st day, rats were killed and the brain tissues were separated for the observation of the mitochondrial morphology and the determination of mitochondrial function-related indicators and the adenosine 5'-monophosphate-activated protein kinase(AMPK) level. The results showed that Danzhi Xiaoxiao Powder could alleviate the anxiety-like behavior of rats, significantly increase the percentage of time in open arm in elevated plus-maze test and the ration of activity time in the central area of the field, dose-dependently raise the activity levels of respiratory chain complex Ⅰ,Ⅱ,Ⅲ and Ⅳ and the adenosine triphosphate(ATP) content, and elevate the levels of BDNF and phosphorylated AMPK(p-AMPK). Clear structure and intact morphology of mitochondrial cristae in medial prefrontal cortex cells and amygdala were observed in the Danzhi Xiaoyao Powder group. In summary, Danzhi Xiaoyao Powder exerts therapeutic effect on anxiety, and the mechanism is the likelihood that p-AMPK protects the structure and maintains the function of mitochondria.

[Study on mechanism of Valerianae Jatamansi Rhizoma et Radix against post-traumatic stress disorder based on molecular docking and network pharmacology].

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.

Identification of Bioactive Chemical Markers in Zhi zhu xiang Improving Anxiety in Rat by Fingerprint-Efficacy Study.

Zhi zhu xiang (ZZX for short) is the root and rhizome of Valeriana jatamansi Jones, which is a Traditional Chinese Medicine (TCM) used to treat various mood disorders for more than 2000 years, especially anxiety. The aim of the present work was to identify the bioactive chemical markers in Zhi zhu xiang improving anxiety in rats by a fingerprint-efficacy study. More specifically, the chemical fingerprint of ZZX samples collected from 10 different regions was determined by High Performance Liquid Chromatography (HPLC) and the similarity analyses were calculated based on 10 common characteristic peaks. The anti-anxiety effect of ZZX on empty bottle stimulated rats was examined through the Open Field Test (OFT) and the Elevated Plus Maze Test (EPM). Then we measured the concentration of CRF, ACTH, and CORT in rat's plasma by the enzyme-linked immune sorbent assay (ELISA) kit, while the concentration of monoamine and metabolites (NE, DA, DOPAC, HVA, 5-HT, 5-HIAA) in the rat's cerebral cortex and hippocampus was analysed by HPLC coupled with an Electrochemical Detector. At last, the fingerprint-efficacy study between chemical fingerprint and anti-anxiety effect of ZZX was accomplished by partial least squares regression (PLSR). As a result, we screened out four compounds (hesperidin, isochlorogenic acid A, isochlorogenic acid B and isochlorogenic acid C) as the bioactive chemical markers for the anti-anxiety effect of ZZX. The fingerprint-efficacy study we established might provide a feasible way and some elicitation for the identification of the bioactive chemical markers for TCM.

Anticancer activity of safranal against colon carcinoma is due to induction of apoptosis and G2/M cell cycle arrest mediated by suppression of mTOR/PI3K/Akt pathway.

PURPOSE: Colon cancer is among the deadliest malignancies and is responsible for a significant number of deaths across the globe. The treatment options for colon cancer are limited and with lot of side effects. In this study we evaluated the potential anticancer effects of safranal against colo-205 colon cancer cells along with evaluation of its effects on apoptosis, cell cycle phase distribution, reactive oxygene species (ROS) and PI3K/AKT/m-TOR signalling pathway. METHODS: Cell viability was examined by MTT assay. Apoptosis was checked by DAPI staining, comet assay and annexin V/propidium iodide (PI) staining involving the use of fluorescence microscopy and flow cytometry. ROS, mitochondrial membrane potential (MMP) and cell cycle phase distribution were checked by flow cytometry using different fluorescent probes. Effects of safranal on the protein expression of PI3K/AKT/m-TOR were studied by western blot assay. RESULTS: The results revealed that safranal suppressed the proliferation of colo-205 cancer cells with an IC50 of 20 µM. Furthermore, the anticancer effects of safranal were found to be due to accretion of ROS and decrease in the MMP, ultimately leading to apoptosis of colo-205 cancer cells. In addition, safranal caused increase in the expression of Bax in parallel with concomitant reduction in the expression of Bcl-2. Safranal also triggered G2/M cell cycle arrest and inhibition of PI3K/AKT/mTOR signalling pathway. CONCLUSION: In conclusion, the above results indicate that safranal could prove a potential lead molecule in the treatment of colon cancer, provided further in vivo studies are carried out.

Effect of XingPiJieYu decoction on spatial learning and memory and cAMP-PKA-CREB-BDNF pathway in rat model of depression through chronic unpredictable stress.

BACKGROUND: Depression is a mental disorder characterized by a pervasive low mood and loss of pleasure or interest in usual activities, and often results in cognitive dysfunction. The disturbance of cognitive processes associated with depression, especially the impairment of learning and memory, exacerbates illness and increases recurrence of depression. XingPiJieYu (XPJY) is one of the most widely clinical formulas of traditional Chinese medicine (TCM) and can improve the symptoms of depression, including learning and memory. However, its regulatory effects haven't been comprehensively studied so far. Recently, some animal tests have indicated that the cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA)-cAMP response element-binding protein (CREB)-brain derived neurotrophic factor (BDNF) signaling pathway in hippocampus is closely related to depression and the pathogenesis of cognitive function impairments. The present study was performed to investigate the effect and mechanism of XPJY on depression and learning and memory in animal model. MATERIALS: The rat model of depression was established by chronic unpredictable stress (CUS) for 21 days. The rats were randomly divided into six groups: control group, CUS group, CUS + XPJY (1.4 g/kg, 0.7 g/kg and 0.35 g/kg) groups, and CUS + sertraline (10 mg/kg) group. The sucrose preference, open field exploration and Morris water maze (MWM) were tested. The expression of cAMP, CREB, PKA and BDNF protein in hippocampus was examined with Elisa and Western Blot. The mRNA level of CREB and BDNF in hippocampus was measured with PCR. RESULTS: The results demonstrated that rats subjected to CUS exhibited decreases in sucrose preference, total ambulation, percentage of central ambulation, rearing in the open field test and spatial performance in the MWM. CUS reduced the expression of cAMP, PKA, CREB and BDNF in hippocampus of model rats. These effects could be reversed by XPJY. CONCLUSION: The results indicated that XPJY can improve depression and related learning and memory and the effect of XPJY is partly exerted through the cAMP-PKA-CREB-BDNF signaling pathway.

Anti-Anxiety Effect of (-)-Syringaresnol-4-O-ß-d-apiofuranosyl-(1→2)-ß-d-glucopyranoside from Albizzia julibrissin Durazz (Leguminosae).

Albizzia julibrissin Durazz, a Chinese Medicine, is commonly used for its anti-anxiety effects. (-)-syringaresnol-4-O-ß-d-apiofuranosyl-(1→2)-ß-d-glucopyranoside (SAG) is the main ingredient of Albizzia julibrissin Durazz. The present study investigated the anxiolytic effect and potential mechanisms on the HPA axis and monoaminergic systems of SAG on acute restraint-stressed rats. The anxiolytic effect of SAG was examined through an open field test and an elevated plus maze test. The concentration of CRF, ACTH, and CORT in plasma was examined by an enzyme-linked immune sorbent assay (ELISA) kit while neurotransmitters in the cerebral cortex and hippocampus of the brain were examined by High Performance Liquid Chromatography (HPLC). We show that repeated treatment with SAG (3.6 mg/kg, p.o.) significantly increased the number and time spent on the central entries in the open-field test when compared to the vehicle/stressed group. In the elevated plus maze test, 3.6 mg/kg SAG could increase the percentage of entries into and time spent on the open arms of the elevated plus maze. In addition, the concentration of CRF, ACTH, and CORT in plasma and neurotransmitters (NE, 5-HT, DA and their metabolites 5-HIAA, DOPAC, and HVA) in the cerebral cortex and hippocampus of the brain were decreased after SAG treatment, as compared to the repeated acute restraint-stressed rats. These results suggest that SAG is a potential anti-anxiety drug candidate.

[Clinical study on compound prescription with Valerianae Jatamansi Rhizoma et Radix in treatment of generalized anxiety disorder].

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).

Probing Resonances of the Dirac Equation with Complex Momentum Representation.

Resonance plays critical roles in the formation of many physical phenomena, and several methods have been developed for the exploration of resonance. In this work, we propose a new scheme for resonance by solving the Dirac equation in the complex momentum representation, in which the resonant states are exposed clearly in the complex momentum plane and the resonance parameters can be determined precisely without imposing unphysical parameters. Combined with the relativistic mean-field theory, this method is applied to probe the resonances in ^{120}Sn with the energies, widths, and wave functions being obtained. Compared to other methods, this method is not only very effective for narrow resonances, but also can be reliably applied to broad resonances.

[Advanced in studies on anxiolytic effects of natural flavonoids].

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.

Association of the TLR4 signaling pathway in the retina of streptozotocin-induced diabetic rats.

BACKGROUND: Diabetic retinopathy is severe damage to the retina caused by complications of diabetes, and is the prevailing cause of blindness. Accumulating evidence from both animal models and humans suggests that the inflammatory process plays a key role in the development of diabetic retinopathy and is facilitated by innate immune response. The aim of this study was to examine whether the TLR4 signaling pathway was involved in the streptozotocin-induced diabetic rat retina. METHODS: Diabetes was induced by a single intraperitoneal injection of streptozotocin, and rat diabetic retinopathy was examined at 4 weeks of diabetes duration. Then the accumulated leukocytes were counted in vivo by acridine orange leukocyte fluorography, and the retinal vascular permeability was measured by the Evans blue assay. The expressions of TLR4 and its downstream signaling molecules were measured by RT-PCR or Western blot respectively. To evaluate the effect of blocking TLR4 on diabetic retinopathy, TAK-242, a selective TLR4 antagonist, was administered by intraperitoneal injection. RESULTS: Our results showed that the retina of diabetic rats demonstrated accumulated leukocytes and retinal vascular permeability. The mRNA and protein expressions of TLR4 were upregulated in streptozotocin-treated diabetic rat retina. Furthermore, the protein levels of TLR4 downstream signaling molecules were significantly increased in streptozotocin-treated animals. In addition, the protein levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and interferon (IFN)-ß, three downstream proinflammatory cytokines of TLR4 signal transduction pathway, were also markedly increased in diabetic rats. Administration of TAK-242 attenuated leukocytes accumulated and retinal vascular permeability, and decreased TLR4 downstream signaling molecules and proinflammatory cytokines in streptozotocin-induced animals. CONCLUSIONS: Together, these data have demonstrated that TLR4 has a critical role in streptozotocin-induced diabetic retinopathy at the level of inflammatory cytokine induction, in both the MyD88-dependent and MyD88-independent pathways. TLR4 may become a new potential pharmacological target for treating diabetic retinopathy.

A transferable anxiolytic placebo effect from noise to negative effect.

BACKGROUND: The placebo effect in relieving negative emotion arousal is poorly understood. AIMS: We examined whether placebo expectation established with noise stimuli could have a transferable anxiolytic effect on negative emotion arousal. METHODS: In Experiment 1, noise intensity was surreptitiously lowered during placebo condition in the preconditioning phase to reinforce placebo expectation, and the noise-relieving placebo effect was assessed in the testing phase. In Experiment 2, the same manipulation as in Experiment 1 was administered in the preconditioning phase, but the anxiolytic placebo effect was assessed in the testing phase using negative pictures. RESULTS: Intensity and annoyance by the noise in Experiment 1 were significantly reduced, and unpleasantness in Experiment 2 was also significantly reduced in the placebo condition. CONCLUSION: Direct noise-relieving placebo effects and transferred anxiolytic placebo effects were found. The present study provides evidence that the placebo effect can be transferred from noise to emotion.

[Effects of Lycii Cortex on express of PI3K/PKB in PCOS rats].

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.

Probing the symmetries of the Dirac Hamiltonian with axially deformed scalar and vector potentials by similarity renormalization group.

Symmetry is an important and basic topic in physics. The similarity renormalization group theory provides a novel view to study the symmetries hidden in the Dirac Hamiltonian, especially for the deformed system. Based on the similarity renormalization group theory, the contributions from the nonrelativistic term, the spin-orbit term, the dynamical term, the relativistic modification of kinetic energy, and the Darwin term are self-consistently extracted from a general Dirac Hamiltonian and, hence, we get an accurate description for their dependence on the deformation. Taking an axially deformed nucleus as an example, we find that the self-consistent description of the nonrelativistic term, spin-orbit term, and dynamical term is crucial for understanding the relativistic symmetries and their breaking in a deformed nuclear system.

Effects of ginsenoside Rg1 on the expression of toll-like receptor 3, 4 and their signalling transduction factors in the NG108-15 murine neuroglial cell line.

As one of the most important components of Panax ginseng, ginsenoside Rg1 has certain anti-aging effects, improving the activity of learning and memory. Studies have showed that ginsenoside Rg1 improves the memory impairment associated with Alzheimer's disease (AD). In this study, the effects of ginsenoside Rg1 were investigated through the activity of toll-like receptor (TLR) 3, TLR4 and their signaling transduction pathways in amyloid ß peptide 25-35 (Aß25-35) induced AD cell model. Thus we investigated several critical components of the TLR pathway. The neuroglial cell line NG108-15 was stimulated with or without Aß25-35, while different concentrations of ginsenoside Rg1 were administered. After 24 h, tumor necrosis factor-α (TNF-α), interferon-ß (IFN-ß) in cell supernatant and inducible nitric oxide synthase (iNOS) in cell lysate supernatant were measured with enzyme-linked immunosorbent assays (ELISAs). The mRNA and protein expression of TLR3, TLR4, nuclear factor kappa B (NF-κB) and tumor necrosis factor receptor-associated factor-6 (TRAF-6) were detected by real-time PCR and western blot methods, respectively. The experimental results showed that Aß25-35 could markedly raise the level of TNF-α, IFN-ß and iNOS, and increase the expressions of mRNA and TLR3, TLR4, NF-κB and TRAF-6 protein in the NG108-15 cells. At the same time, the ginsenoside Rg1 significantly reduced the expressions of proteins and mRNA of TLR3, TLR4, NF-κB and TRAF-6, and down-regulated the levels of TNF-α, IFN-ß of cell supernatant and iNOS of cell lysate supernatant in a concentration-dependent manner. In conclusion, ginsenoside Rg1 has good activity for suppressing the signaling transduction pathway of TLR3 and TLR4, and decreasing the inflammation factors induced by Aß25-35 in NG108-15 cells, and this may be the mechanism of ginsenoside Rg1 action in AD treatment, but more studies are needed to identify its specificity.