A novel dual-model photoelectrochemical/electrochemical sensor based on Z-scheme TiO2 disks/methylene blue for kanamycin detection.

Herein, a new dual-model photoelectrochemical (PEC)/electrochemical (EC) sensor based on Z-scheme titanium dioxide (TiO2) disk/methylene blue (MB) sensibilization for the detection of kanamycin (Kana) was developed. Metal-organic framework-derived porous TiO2 disks were synthesized and exhibited excellent anodic photocurrent under visible light excitation. Subsequently, amino-labeled double-stranded DNA (dsDNA) was introduced into the modified electrode. Photocurrent was enhanced with MB embedded in dsDNA to form Z-scheme TiO2/MB sensibilization. When the target, Kana, was present, it specifically bound to the aptamer in the dsDNA, leading to the disruption of the dsDNA structure and the release of MB. This release of MB and the increase in target spatial resistance resulted in a significant weakening of PEC signal and a decreased oxidation peak current of MB. The PEC sensor successfully detected Kana in the range of 2-1000 pM with an LOD of 0.17 pM. Meanwhile, the EC sensor for Kana detection showed a linear range of 5-500 pM with an LOD of 1.8 pM. Additionally, the sensor exhibited excellent selectivity, reproducibility, stability, and good recoveries when applied to milk and honey samples. As a result, this method has the potential for application in ensuring food safety through the rapid determination of antibiotics in food.

Dioscin Ameliorates Experimental Autoimmune Thyroiditis via the mTOR and TLR4/NF-κB Signaling.

Background: Autoimmune thyroiditis (AIT) is a common autoimmune disease that causes thyroid dysfunction. Clinical symptoms in Hashimoto thyroiditis patients were improved after oral administration of dioscin. However, the mechanisms involved in the therapeutic effect remain unclear. Methods: The protective effects and potential mechanisms of dioscin for autoimmune thyroiditis were explored in a rat model of thyroglobulin-induced autoimmune thyroiditis. Firstly, the rat model of AIT was obtained by subcutaneous injection of thyroglobulin and drinking the sodium iodide solution, followed by gavage administration for 8 weeks. Rats were sacrificed after anaesthesia, serum and thyroid samples were preserved. Serum triiodothyronine (T3), thyroxine (T4), free triiodothyronine (FT3), free thyroxine (FT4), thyrotropin (TSH), thyroglobulin antibody (TgAb), thyroid peroxidase antibody (TPOAb), and thyrotropin receptor antibody (TRAb) expressions were measured by enzyme-linked immunosorbent assay (ELISA). Morphological changes were observed by H&E staining. Next, we used transcriptomics techniques to find the potential therapeutic target of dioscin. Finally, we validated the transcriptomic results by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC-P), respectively. Results: Animal experiments showed that dioscin regulated T3, T4, FT3, TSH, TgAb, TPOAb, and TRAb and alleviated the pathological process in a dose-dependent manner, with the high-dose group showing optimal efficacy. In the transcriptome, the nuclear factor kappa B (NF-κB) pathway was identified by KEGG enrichment analysis and validated by RT-PCR and IHC-P. The relative expression of NF-κB, mechanistic target of rapamycin (mTOR), and toll-like receptor 4 (TLR4) mRNA and protein were decreased in the dioscin-treated group compared to the AIT model group. Conclusion: Our results suggest that dioscin treatment improved thyroid function and downregulated TGAb, TPOAb and TRAb levels in rat models of AIT, which may alleviate the pathological process and suppress the inflammatory response by inhibiting mTOR and TLR4/NF-κB pathways.

[Safety evaluation of Tibetan medicine Qishiwei Zhenzhu Pills based on serum pharmacochemistry and network pharmacology].

To explore the mechanism of the active ingredients of Qishiwei Zhenzhu Pills in inhibiting the hepatorenal toxicity of the zogta component based on serum pharmacochemistry and network pharmacology, thereby providing references for the clinical safety application of Qishiwei Zhenzhu Pills. The small molecular compounds in the serum containing Qishiwei Zhenzhu Pills of mice were identified by high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS). Then, by comprehensively using Traditional Chinese Medicines Systems Pharmacology(TCMSP), High-throughput Experiment-and Reference-guided Database(HERB), PubChem, GeneCards, SuperPred, and other databases, the active compounds in the serum containing Qishiwei Zhenzhu Pills were retrieved and their action targets were predicted. The predicted targets were compared with the targets of liver and kidney injury related to mercury toxicity retrieved from the database, and the action targets of Qishiwei Zhenzhu Pills to inhibit the potential mercury toxicity of zogta were screened out. Cytoscape was used to construct the active ingredient in Qishiwei Zhenzhu Pills-containing serum-action target network, and STRING database was used to construct the protein-protein interaction(PPI) network of intersection targets. The Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were carried out on the target genes by the DAVID database. The active ingredient-target-pathway network was constructed, and the key ingredients and targets were screened out for molecular docking verification. The results showed that 44 active compounds were identified from the serum containing Qishiwei Zhenzhu Pills, including 13 possible prototype drug ingredients, and 70 potential targets for mercury toxicity in liver and kidney were identified. Through PPI network topology analysis, 12 key target genes(HSP90AA1, MAPK3, STAT3, EGFR, MAPK1, APP, MMP9, NOS3, PRKCA, TLR4, PTGS2, and PARP1) and 6 subnetworks were obtained. Through GO and KEGG analysis of 4 subnetworks containing key target genes, the interaction network diagram of active ingredient-action target-key pathway was constructed and verified by molecular docking. It was found that taurodeoxycholic acid, N-acetyl-L-leucine, D-pantothenic acid hemicalcium, and other active ingredients may regulate biological functions and pathways related to metabolism, immunity, inflammation, and oxidative stress by acting on major targets such as MAPK1, STAT3, and TLR4, so as to inhibit the potential mercury toxicity of zogta in Qishiwei Zhenzhu Pills. In conclusion, the active ingredients of Qishiwei Zhenzhu Pills may have a certain detoxification effect, thus inhibiting the potential mercury toxicity of zogta and playing a role of reducing toxicity and enhancing effect.

Targeted Lipidomics and Inflammation Response to Six Weeks of Sprint Interval Training in Male Adolescents.

Lipids play an important role in coordinating and regulating metabolic and inflammatory processes. Sprint interval training (SIT) is widely used to improve sports performance and health outcomes, but the current understanding of SIT-induced lipid metabolism and the corresponding systemic inflammatory status modification remains controversial and limited, especially in male adolescents. To answer these questions, twelve untrained male adolescents were recruited and underwent 6 weeks of SIT. The pre- and post-training testing included analyses of peak oxygen consumption (VO2peak), biometric data (weight and body composition), serum biochemical parameters (fasting blood glucose, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triacylglycerol, testosterone, and cortisol), inflammatory markers, and targeted lipidomics. After the 6-week SIT, the serum C-reactive protein (CRP), interleukin (IL)-1ß, IL-2, IL-4, IL-10, tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-ß significantly decreased (p < 0.05), whereas IL-6 and IL-10/TNF-α significantly increased (p < 0.05). In addition, the targeted lipidomics revealed changes in 296 lipids, of which 33 changed significantly (p < 0.05, fold change > 1.2 or <1/1.2). The correlation analysis revealed that the changes in the inflammatory markers were closely correlated with the changes in some of the lipids, such as LPC, HexCer, and FFA. In conclusion, the 6-week SIT induced significant changes in the inflammatory markers and circulating lipid composition, offering health benefits to the population.

Microstructure and Properties of Densified Gd2O3 Bulk.

In this work, Gd2O3 bulks were sintered at temperatures ranging from 1400 °C to 1600 °C for times from 6 h to 24 h, and their microstructure and properties were studied for a wider application of materials in thermal barrier coatings. The densification of the Gd2O3 bulk reached 96.16% when it was sintered at 1600 °C for 24 h. The elastic modulus, hardness, fracture toughness and thermal conductivity of the bulks all increased with the rise in sintering temperature and extension of sintering time, while the coefficient of thermal expansion decreased. When the Gd2O3 bulk was sintered at 1600 °C for 24 h, it had the greatest elastic modulus, hardness, fracture toughness and thermal conductivity of 201.15 GPa, 9.13 GPa, 15.03 MPa·m0.5 and 2.75 W/(m·k) (at 1100 °C), respectively, as well as the smallest thermal expansion coefficients of 6.69 × 10-6/°C (at 1100 °C).

Exploring the role of Tibetan medicinal formula Qishiwei Zhenzhu Pills (Ranasampel) against diabetes mellitus-linked cognitive impairment of db/db mice through serum pharmacochemistry and microarray data analysis.

Background: Diabetes cognitive impairment (DCI) is a common diabetic central nervous system disorder that severely affects the quality of life of patients. Qishiwei Zhenzhu Pills (Ranasampel) is a valuable Tibetan medicine formula with the ability to improve cerebral blood vessels, protect nerves and improve learning and memory, which has also been widely verified in clinical and basic research. Currently, the prevention and treatment of DCI are still in the exploratory research stage, and the use of Ranasampel will provide new ideas and insights for its treatment. Objective: This study is to explore the absorbed components in serum derived from Ranasampel using serum pharmacochemistry, then identify the potential mechanism of Ranasampel for the treatment of DCI through bioinformatics and microarray data validation. Methods: The UPLC-Q-Exactive MS/MS-based serum pharmacochemistry method was conducted to identify the main active components in serum containing Ranasampel. Then, these components were used to predict the possible biological targets of Ranasampel and explore the potential targets in treating DCI by overlapping with differentially expressed genes (DEGs) screened from Gene Expression Omnibus datasets. Afterward, the protein-protein interaction network, enrichment analyses, hub gene identification, and co-expression analysis were used to study the potential mechanism of Ranasampel. Particularly, the hub genes and co-expression transcription factors were further validated using hippocampal expression profiles of db/db mice treated with Ranasampel, while the Morris water-maze test and H&E staining were used to assess the spatial learning and memory behaviors and histopathological changes. Results: Totally, 40 compounds derived from Ranasampel had been identified by serum sample analysis, and 477 genes related to these identified compounds in Ranasampel, 110 overlapping genes were collected by the intersection of Ranasampel target genes and DEGs. Further comprehensive analysis and verification emphasized that the mechanism of Ranasampel treatment of DCI may be related to the improvement of learning and memory function as well as insulin resistance, hyperglycemia-induced neuronal damage, and neuroinflammation. Conclusion: This study provided useful strategies to explore the potential material basis for compound prescriptions such as Ranasampel. These hub genes and common pathways also provided new ideas for further study of therapeutic targets of DCI and the pharmacological mechanism of Ranasampel.

Antidepressant Mechanism of Traditional Chinese Medicine Formula Xiaoyaosan in CUMS-Induced Depressed Mouse Model via RIPK1-RIPK3-MLKL Mediated Necroptosis Based on Network Pharmacology Analysis.

Background: Depression is a stress-related disorder that seriously threatens people's physical and mental health. Xiaoyaosan is a classical traditional Chinese medicine formula, which has been used to treat mental depression since ancient times. More and more notice has been given to the relationship between the occurrence of necroptosis and the pathogenesis of mental disorders. Objective: The purpose of present study is to explore the potential mechanism of Xiaoyaosan for the treatment of depression using network pharmacology and experimental research, and identify the potential targets of necroptosis underlying the antidepressant mechanism of Xiaoyaosan. Methods: The mice model of depression was induced by chronic unpredictable mild stress (CUMS) for 6 weeks. Adult C57BL/6 mice were randomly divided into five groups, including control group, chronic unpredictable mild stress group, Xiaoyaosan treatment group, necrostatin-1 (Nec-1) group and solvent group. Drug intervention performed from 4th to 6th week of modeling. The mice in Xiaoyaosan treatment group received Xiaoyaosan by intragastric administration (0.254 g/kg/d), and mice in CUMS group received 0.5 ml physiological saline. Meanwhile, the mice in Nec-1 group were injected intraperitoneally (i.p.) with Nec-1 (10 mg/kg/d), and the equivalent volume of DMSO/PBS (8.3%) was injected into solvent group mice. The behavior tests such as sucrose preference test, forced swimming test and novelty-suppressed feeding test were measured to evaluate depressive-like behaviors of model mice. Then, the active ingredients in Xiaoyaosan and the related targets of depression and necroptosis were compiled through appropriate databases, while the "botanical drugs-active ingredients-target genes" network was constructed by network pharmacology analysis. The expressions of RIPK1, RIPK3, MLKL, p-MLKL were detected as critical target genes of necroptosis and the potential therapeutic target compounds of Xiaoyaosan. Furthermore, the levels of neuroinflammation and microglial activation of hippocampus were measured by detecting the expressions of IL-1ß, Lipocalin-2 and IBA1, and the hematoxylin and eosin (H&E) stained was used to observe the morphology in hippocampus sections. Results: After 6-weeks of modeling, the behavioral data showed that mice in CUMS group and solvent group had obvious depressive-like behaviors, and the medication of Xiaoyaosan or Nec-1 could improve these behavioral changes. A total of 96 active ingredients in Xiaoyaosan which could regulate the 23 key target genes were selected from databases. Xiaoyaosan could alleviate the core target genes in necroptosis and improve the hippocampal function and neuroinflammation in depressed mice. Conclusion: The activation of necroptosis existed in the hippocampus of CUMS-induced mice, which was closely related to the pathogenesis of depression. The antidepressant mechanism of Xiaoyaosan included the regulation of multiple targets in necroptosis. It also suggested that necroptosis could be a new potential target for the treatment of depression.

Traditional Chinese Formula Xiaoyaosan Alleviates Depressive-Like Behavior in CUMS Mice by Regulating PEBP1-GPX4-Mediated Ferroptosis in the Hippocampus.

BACKGROUND: At present, the pathogenesis of depression is not fully understood, and nearly half of depression patients experience no obvious effects during treatment. This study aimed to establish a depression mouse model to explore the possible role of ferroptosis in the pathogenesis of depression, and observe the effects of Xiaoyaosan on PEBP1-GPX4-mediated ferroptosis in the hippocampus. METHODS: Forty-eight male C57BL/6 mice were randomly divided into a control group, CUMS group, Xiaoyaosan group and fluoxetine group, and the model was established by chronic unpredictable mild stress (CUMS) for a successive 6 weeks. The medication procedure was performed from the 4th to the 6th week of modeling. The behavioral evaluations were measured to evaluate depressive-like behaviors. The expressions of GPX4, FTH1, ACSL4 and COX2 were detected as ferroptosis-related indicators. Then, the total iron and ferrous content in the hippocampus were measured. The levels of PEBP1 and ERK1/2 were observed, and the expressions of GFAP and IBA1 were also detected to measure the functions of astrocytes and microglia in the hippocampus. RESULTS: Eight herbs of Xiaoyaosan had 133 active ingredients which could regulate the 43 ferroptosis-related genes in depression. After 6 weeks of modeling, the data showed that mice in the CUMS group had obvious depressive-like behaviors, and medication with Xiaoyaosan or fluoxetine could significantly improve the behavioral changes. The expressions of GPX4, FTH1, ACSL4, COX2, PEBP1, ERK1/2, GFAP and IBA1 changed in the CUMS group mice, while the total iron and ferrous content also changed. Xiaoyaosan and fluoxetine had obvious curative effects that could significantly alleviate the above changes in the hippocampus. CONCLUSION: Our results revealed that the activation of ferroptosis might exist in the hippocampi of CUMS-induced mice. The PEBP1-GPX4-mediated ferroptosis could be involved in the antidepressant mechanism of Xiaoyaosan. It also implied that ferroptosis could become a new target for research into the depression mechanism and antidepressant drugs.

Effects of Xiaoyaosan on Depressive-Like Behaviors in Rats With Chronic Unpredictable Mild Stress Through HPA Axis Induced Astrocytic Activities.

ABSTRACT: Astrocytes in the hippocampus are immediately relevant to depressive-like behavior. By regulating their activities, Xiaoyaosan (XYS), a traditional Chinese medicine compound, works in the treatment of depression. OBJECTIVE: Chronic unpredictable mild stress (CUMS) rat model was established to observe the regulation of XYS. We investigated the behavioral changes of CUMS, the expression of corticosterone (CORT) of the hypothalamo-pituitary-adrenal (HPA) axis, the expression of Glu-NMDA receptor and astrocytes glial fibrillary acidic protein (GFAP) in the hippocampus. We also investigated whether these changes were linked to XYS. METHODS: 80 adult SD rats were randomly divided into four groups, control group, CUMS group, XYS group, and fluoxetine group. The rats in the control group and the CUMS group received 0.5 ml of deionized water once a day by intragastrically administration. Rats in the two treatment groups received XYS (2.224g/kg/d) and fluoxetine (2.0mg/kg/d) once a day, respectively. Rat hippocampus GFAP and Glu-NMDA receptor were respectively detected by real-time fluorescent quantitative PCR and western blot. The CORT of HPA axis was detected by Elisa. Body weight, food intake, and behavioral tests, such as open field tests, the sucrose preference test, and exhaustive swimming test, were used to assess depressive-like behavior in rats. RESULTS: In this work, significant behavioral changes and differences in expression of the CORT of HPA axis and hippocampal GFAP and Glu-NMDA receptor were presented in CUMS-exposed rats. Like fluoxetine, XYS improved CUMS-induced rat's body weight, food intake, and depressive-like behavior. The study also proved that XYS could reverse the CUMS-induced changes of the CORT of HPA axis and affect the astrocytic activities and down-regulate the NR2B subunit of NMDA receptor (NR2B) level in the hippocampus. CONCLUSION: Changes in the hippocampus GFAP and Glu-NMDA receptor may be an essential mechanism of depression. Besides, XYS may be critical to the treatment of depression by intervention the HPA axis, GFAP and Glu-NMDA receptor.

Study on urinary metabolomics of premenstrual dysphoric disorder patients with liver-qi depression syndrome treated with Xiaoyaosan: Study Protocol Clinical Trial (SPIRIT Compliant).

INTRODUCTION: Premenstrual dysphoric disorder (PMDD) is a serious form of premenstrual syndrome with mental symptoms as its main manifestation, which seriously affects women's health and daily life. Some basic research and clinical studies have shown that the Chinese herbal medicine of Xiaoyaosan can relieve the symptoms of mental disorders with few side effects. The aim of this study is to evaluate the clinical efficacy of Xiaoyaosan for treating PMDD with liver-qi depression syndrome. In addition, metabonomics and small molecular marker compounds closely related to the pathogenesis of PMDD are expected to be found, and mechanism of Xiaoyaosan is further explored from the metabolic level. METHODS AND ANALYSIS: This study is a clinical pilot trial. Thirty PMDD patients with liver-qi depression syndrome and thirty healthy participants will be recruited. Study participants will be assigned in a 1:1 ratio to 2 groups: a normal control group and Xiaoyaosan treatment group. The treatment group will receive the Chinese patent medicine of Xiaoyaosan for 3 menstrual cycles. The primary outcome is the syndrome change in the Daily Record of Severity of Problems (DRSP). The secondary outcome is improvement in TCM syndrome, which will be measured with TCM symptom score scale. Urine metabolism profiles of participants by liquid chromatograph-mass spectrometer (LC-MS) method will be measured to explore the mechanism of PMDD pathogenesis and action of Xiaoyaosan on PMDD. DISCUSSION: This trial will evaluate the effectiveness and the therapeutic mechanism from the metabolomics level of Xiaoyaosan in individuals with PMDD. If successful, the outcome of this trial will provide a viable treatment option for PMDD patients and objective evidence on the efficacy of Xiaoyaosan for PMDD. ETHICS AND DISSEMINATION: The trial has been approved by the Institutional Ethics Committee of Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine (file number: DZMEC-KY-2019-73). Written informed consent will be obtained from all participants. The results of the study will be published in peer-reviewed journals or communicated via yearly reports to funding bodies. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900026296.

Xiaoyaosan regulates depression-related behaviors with physical symptoms by modulating Orexin A/OxR1 in the hypothalamus.

The functional regulation of the orexin system in the central nervous system is closely related to the occurrence and development of psychotic disorders. Abnormal changes in the lateral region of the hypothalamus are associated with the comorbidity of depression and physical symptoms, and how the traditional Chinese formula Xiaoyaosan regulates these changes may reveal aspects of the pathogenesis of depression. This study aimed to establish a rat model of depression in order to examine changes in Orexin A/OxR1 expression in the lateral region of the hypothalamus and the effects of Xiaoyaosan. Sixty specific pathogen-free (SPF) male healthy Sprague-Dawley (SD) rats were used in the experiment and randomly divided into the control group, the model group, the Xiaoyaosan group and the fluoxetine group. The depression model was established by 21-day chronic immobilization stress (CIS). Food intake and body weight were recorded, and the sucrose preference test (SPT) and open field test (OFT) were used to evaluate the model. Then, the expression of Orexin A/OxR1 in the hypothalamus was measured by ELISA, Western blot and quantitative real-time polymerase chain reaction (qRT-PCR) analysis. The expression of Orexin A and OxR1 in the lateral hypothalamic area was significantly down regulated in the model group, compared with the control group. Xiaoyaosan significantly reversed these changes with obvious curative effects. Abnormal changes in Orexin A/OxR1 in the lateral hypothalamic area of rats with depression caused by chronic stress are closely related to the pathogenesis of depression accompanied by physical symptoms. Xiaoyaosan can improve depression accompanied by physical symptoms by regulating Orexin A/OxR1.

Xiaoyaosan Produces Antidepressant Effects in Rats via the JNK Signaling Pathway.

BACKGROUND: Xiaoyaosan (XYS) has achieved definite curative effects in clinic. However, the mechanism is not clear. Previous studies of our team indicated XYS improved anxiety-like behaviors through inhibiting c-Jun N-terminal kinase (JNK) signaling pathway of hippocampus. OBJECTIVES: In the study, we explored whether the JNK signaling pathway is involved in the mechanism of XYS treating depression. METHOD: Forty-eight rats were divided randomly into 4 groups (n = 12): the control group (deionized water, p.o.), the model group (deionized water, p.o.), the fluoxetine group (2.08 mg/kg/day, p.o.), and the XYS group (3.9 g/kg/day, p.o.). All rats except for the control group were given continuous 21 days of chronic immobilization stress (CIS; 3 h/day). On day 29, the body weights and the behavioral tests, including the novelty suppressed feeding test, the open field test, and the elevated plus maze test, were measured. On day 30, all the rats were sacrificed, and three indices of the JNK signaling pathway were tested by Western blot. RESULTS: The body weight and behavioral tests of all groups indicated that 21 days of CIS induced depression-like behaviors. After 21 days of treatment with fluoxetine and XYS, changes were seen in body weight, behaviors, and JNK, phosphorylated JNK (P-JNK), and phosphorylated c-Jun (P-c-Jun) levels in the hippocampus. CONCLUSIONS: XYS ameliorated the depression-like behaviors, potentially through affecting the JNK signaling pathway in the hippocampus.

Effects of Moxibustion and Moxa Smoke on Behavior Changes and Energy Metabolism in APP/PS1 Mice.

OBJECTIVE: To investigate the antiaging effects of moxibustion and moxa smoke on APP/PS1 mice and to illustrate the mechanism of moxibustion improving Alzheimer's disease (AD). METHODS: 36 male APP/PS1 mice were randomly assigned into three groups (n = 12), including a model control group, a moxibustion group, and a moxa smoke group. In addition, 12 C57BL/6 normal mice served as a normal (negative) control group. Mice in the moxibustion group received moxibustion intervention using Guanyuan (RN4) acupoint. Mice in the moxa smoke group received moxa smoke exposure with the same frequency as the moxibustion group. Behavioral tests were implemented in the 9th week, 3 days after the completion of the intervention. Tricarboxylic acid cycle and fatty acid metabolomics assessments of the mice were determined after behavioral tests. RESULTS: In this study, relative to normal mice, we found that AD mice showed altered tricarboxylic and fatty acid metabolism and showed behavioral changes consistent with the onset of AD. However, both the moxibustion and moxa smoke interventions were able to mitigate these effects to some degree in AD mice. CONCLUSIONS: The data suggest that tricarboxylic acid cycle and unsaturated fatty acid metabolomics changes may be a target of AD, and the beneficial effects of moxibustion on cognitive behaviors may be mediated by the energy metabolism system.

Evaluating the Anti-depression Effect of Xiaoyaosan on Chronically-stressed Mice.

In addition to the standardized use of antidepressant medications and psychotherapy, the usage of traditional Chinese medicine has lead to an overall improvement of patients with major depressive disorder (MDD). Therefore, the purpose of this study was to establish the mouse depressive model, observe the behavior changes associated with chronic unpredictable mild stress (CUMS), and then evaluate the anti-depression effect of Xiaoyaosan. Mice were randomly divided into four groups: a control group, a model group, a treatment group with Xiaoyaosan, and a treatment group with fluoxetine. All mice were individually kept in cages, and depression was induced in the mice by exposing them to several designed manipulations of CUMS for 21 days, as described in the protocol. Mice in the control group and model group received 0.5 mL of distilled water, while mice in the treatment groups received either Xiaoyaosan (0.25 g/kg/day) or fluoxetine (2.6 mg/kg/day). The drugs used in the study were given intragastrically daily during the entire three weeks. To estimate the depressive-like behaviors, a series of parameters including the coat state, body weight, open field test score, and sucrose preference test score were recorded. Data analysis showed that behaviors of model mice were significantly changed compared to behaviors of mice in the control group, which were improved by the treatment of Xiaoyaosan and fluoxetine. The current findings demonstrated the anti-depression effects of Xiaoyaosan on the behaviors of CUMS-induced mice and revealed that compounds from the Xiaoyaosan prescription may be worthwhile for treating depression, considering their beneficial effects on depressive-like behaviors.

Xiaoyaosan Ameliorates Chronic Immobilization Stress-Induced Depression-Like Behaviors and Anorexia in Rats: The Role of the Nesfatin-1-Oxytocin-Proopiomelanocortin Neural Pathway in the Hypothalamus.

Background: Chronic stress is an important risk factor for depression. The nesfatin-1 (NES1)-oxytocin (OT)-proopiomelanocortin (POMC) neural pathway, which is involved in the stress response, was recently shown to have an anorectic effect in the hypothalamus. Our previous study showed that Xiaoyaosan, a well-known antidepressant used in traditional Chinese medicine, effectively relieved appetite loss induced by chronic immobilization stress (CIS). However, whether Xiaoyaosan ameliorates depression-like behaviors and anorexia by regulating the NES1-OT-POMC neural pathway remains unclear. Objective: To investigate whether the antidepressant-like and anti-anorexia effects of Xiaoyaosan are related to the NES1-OT-POMC neural pathway in the hypothalamus. Methods: Rats were randomly divided into control, CIS, Xiaoyaosan treatment, and fluoxetine treatment groups. The rats in the CIS, Xiaoyaosan treatment, and fluoxetine treatment groups were subjected to CIS for 21 consecutive days, during which they were administered distilled water, a Xiaoyaosan decoction [3.854 g/(kg·d)] or fluoxetine [1.76 mg/(kg·d)], respectively, by gavage, and their body weights and food intake were monitored daily. The rats were subsequently subjected to the open field test and sucrose preference test. Then, the expression levels of corticosterone and NES1 in the serum and the expression levels of NES1, OT, POMC, and melanocortin-4 receptor (MC4R) in the hypothalamus were determined by real-time fluorescence quantitative polymerase chain reaction, Western blot analysis, and immunochemistry. Furthermore, immunofluorescence double staining was used to determine whether related proteins in the hypothalamic NES1-OT-POMC neural pathway were co-expressed. Results: Compared to control rats, rats exposed to CIS exhibited gradually less food intake and lower body weights and significantly increased concentrations of NES1 in the serum and paraventricular nucleus. Moreover, the expression levels of POMC, OT, and MC4R in the hypothalamus were significantly higher in the CIS group than those in the control group. However, these changes were reversed by pretreatment with Xiaoyaosan and fluoxetine. Specifically, the expression levels of members of the NES1-OT-POMC neural pathway were lower in the Xiaoyaosan-treated group than in the CIS group. Conclusion: Xiaoyaosan ameliorates CIS-induced depression-like behaviors and anorexia by regulating the NES1-OT-POMC neural pathway in the hypothalamus.

Influence of Xiaoyaosan on depressive-like behaviors in chronic stress-depressed rats through regulating tryptophan metabolism in hippocampus.

BACKGROUND: Tryptophan metabolism has always been considered to play a vital role in mental disorder diseases, and how traditional Chinese formula Xiaoyaosan regulates the tryptophan metabolism is a complement to the pathogenesis of depression. This study established a depression rat model by the chronic immobilization stress (CIS) method and observed the change in tryptophan metabolism in hippocampus and the effects of Xiaoyaosan. METHODS: Forty-eight male Sprague Dawley (SD) rats were randomly divided into the following four groups: control group, CIS group, Xiaoyaosan group, and fluoxetine group. The depression model was established by the 21-day CIS. The food intake and body weight were recorded, and the sucrose preference test (SPT), novelty suppressed feeding (NSF) test and open field test (OFT) were also used to evaluate the model. Then, the contents of tryptophan and 5-hydroxytryptamine (5-HT) in hippocampus were detected by the ELISA method, and the expression levels of tryptophan hydrogenase 2 (TPH2) and indoleamine 2,3-dioxygenase 1 (IDO1) in hippocampus were determined by quantitative reverse transcriptase polymerase chain reaction reaction (qRT-PCR) and Western blot methods. RESULTS: The behavioral data showed a significant difference between the model group and the normal group. The 5-HT content in the hippocampi of CIS rats was significantly reduced, whereas the tryptophan content in the hippocampi of model rats was significantly increased. The TPH2 level in hippocampus of the model group was significantly decreased, and the IDO1 level was significantly increased. Xiaoyaosan and fluoxetine could significantly reverse these changes and had obvious curative effects. CONCLUSION: The abnormal tryptophan metabolism existed in the hippocampi of chronic stress-depressed rats, which was closely related to the pathogenesis of depression. Xiaoyaosan could improve the tryptophan metabolism by regulating the expression levels of TPH2 and IDO1, thus exerting an antidepressant-like effect.

Xiaoyaosan Improves Depressive-Like Behaviors in Mice through Regulating Apelin-APJ System in Hypothalamus.

Background: The apelin-APJ system has been considered to play a crucial role in HPA axis function, and how the traditional Chinese compound prescription Xiaoyaosan regulates the apelin-APJ system as a supplement to treat depressive disorders. Objective: To investigate the depression-like behaviors and expression of apelin and APJ in hypothalamus of chronic unpredictable mild stress (CUMS) mice and study whether these changes related to the regulation of Xiaoyaosan. Methods: 60 adult C57BL/6J mice were randomly divided into four groups, including control group, CUMS group, Xiaoyaosan treatment group and fluoxetine treatment group. Mice in the control group and CUMS group received 0.5 mL physiological saline once a day by intragastric administration. Mice in two treatment groups received Xiaoyaosan (0.25 g/kg/d) and fluoxetine (2.6 mg/kg/d), respectively. After 21 days of modeling with CUMS, the expression of apelin and APJ in hypothalamus were measured by real-time fluorescence quantitative PCR, western blot and immunohistochemical staining. The physical condition, body weight, food intake and behavior tests such as open field test, sucrose preference test and force swimming test were measured to evaluate depressive-like behaviors. Results: In this study, significant behavioral changes were found in CUMS-induced mice, meanwhile the expressions of apelin and APJ in the hypothalamus were changed after modeling. The body weight, food-intake and depressive-like behaviors in CUMS-induced mice could be improved by Xiaoyaosan treatment which is similar with the efficacy of fluoxetine, while the expressions of apelin and APJ in hypothalamus were modified by Xiaoyaosan. Conclusions: The data suggest that apelin-APJ system changes in the hypothalamus may be a target of depressive disorders, and the beneficial effects of Chinese compound prescription Xiaoyaosan on depressive-like behaviors may be mediated by the apelin-APJ system.

Desulfurization of Model Oil by Selective Adsorption over Porous Boron Nitride Fibers with Tailored Microstructures.

We report on the controllable synthesis of porous BN microfibers and explore their applications as adsorbent for removing dibenzothiophene (DBT) in model oil. The growth evolution of porous BN microfibers has been carefully investigated by correlating their structural characteristics with their synthesis conditions. The as-prepared BN microfibers exhibit very high adsorption capacity for DBT (86 mg S g-1 according to the Langmuir isotherm model), showing excellent adsorptive desulfurization performance. The porous BN after adsorption can be regenerated by a simply heat treatment. After four times recycling, the regenerated adsorption capacity still remains more than 83% of that at the first adsorption. The superb oxidation resistance and chemical inertness, high sulfur adsorption capacity, as well as excellent regeneration performance render the developed porous BN microfibers to be a decent adsorbent for sulfur removal from fuels.

Involvement of Normalized Glial Fibrillary Acidic Protein Expression in the Hippocampi in Antidepressant-Like Effects of Xiaoyaosan on Chronically Stressed Mice.

The research has only yielded a partial comprehension of MDD and the mechanisms underlying the antidepressant-like effects of XYS. Therefore, in this study, we aimed to explore the effects of XYS on chronic unpredictable mild stress- (CUMS-) induced changes in the neuronal and the astrocytic markers in the mouse hippocampus. The physical states and depressive-like behaviors in mice with CUMS were recorded. The serum contents of brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) were measured. The protein and mRNA expressions and the immunoreactivities of glial fibrillary acidic protein (GFAP) and neuronal nuclei (NeuN) in mouse hippocampus were detected using a Western blot, qRT-PCR, and immunohistochemical staining, respectively. XYS treatment markedly improved the physical state and depressive-like behaviors in mice subjected to CUMS compared with the model group, and the serum contents of BDNF and GDNF were significantly upregulated. XYS treatment also elevated the protein and mRNA levels, as well as the immunoreactivity of GFAP in the hippocampus. However, CUMS did not influence NeuN expression. In conclusion, these results reveal that chronic administration of XYS elicits antidepressant-like effects in a mouse model of depression and may normalize glial fibrillary acidic protein expression in the hippocampi of mice with CUMS.

Xiaoyaosan exerts anxiolytic-like effects by down-regulating the TNF-α/JAK2-STAT3 pathway in the rat hippocampus.

Although the anxiolytic-like effects of Xiaoyaosan, a Chinese herbal formula, have been described in many previous studies, its underlying mechanism remains undefined. The cytokine tumour necrosis factor-α (TNF-α) and its closely associated janus kinase 2 (JAK2)-signal transducer and activator of transcription (STAT3) signalling pathway regulate the neuro-inflammatory response in the brain, thus participating in the development of anxiety. Our purpose was to investigate whether the anxiolytic-like effects of Xiaoyaosan are related to the TNF-α/JAK2-STAT3 pathway in the hippocampus. We examined the effects of Xiaoyaosan on behaviours exhibited in the elevated plus maze test, open field test and novelty-suppressed feeding test as well as hippocampal neuron damage and changes in the TNF-α/JAK2-STAT3 pathway in a rat model of chronic immobilization stress (CIS)-induced anxiety. Xiaoyaosan exerts anxiolytic-like effects on CIS-induced anxiety, with a significant alleviation of anxiety-like behaviours, an attenuation of hippocampal neuron damage, and a reversal of the activation of the TNF-α/JAK2-STAT3 pathway in the hippocampus that are similar to the effects of the JAK2 antagonist AG490. However, Xiaoyaosan and AG490 failed to effectively regulate apoptosis-related factors, including Bax and Caspase-3. These results suggest that Xiaoyaosan attenuates stress-induced anxiety behaviours by down-regulating the TNF-α/JAK2-STAT3 pathway in the rat hippocampus.