Reduced Prefrontal-Thalamic Theta Flow During Working Memory Retrieval in APP/PS1 Mice.

Background: Working memory deficits in Alzheimer's disease (AD) are linked to impairments in the retrieval of stored memory information. However, research on the mechanism of impaired working memory retrieval in Alzheimer's disease is still lacking. Objective: The medial prefrontal cortex (mPFC) and mediodorsal thalamus (MD) are involved in memory retrieval. The purpose of this study is to investigate the functional interactions and information transmission between mPFC and MD in the AD model. Methods: We recorded local field potentials from mPFC and MD while the mice (APP/PS1 transgenic model and control) performed a T-maze spatial working memory task. The temporal dynamics of oscillatory activity and bidirectional information flow between mPFC and MD were assessed during the task phases. Results: We mainly found a significant decrease in theta flow from mPFC to MD in APP/PS1 mice during retrieval. Conclusions: Our results indicate an important role of the mPFC-MD input for retrieval and the disrupted information transfer from mPFC to MD may be the underlying mechanism of working memory deficits in APP/PS1 mice.

Enhanced permanganate oxidation of phenolic pollutants by alumina and potential industrial application.

In this study, we found that alumina (Al2O3) may improve the degradation of phenolic pollutants by KMnO4 oxidation. In KMnO4/Al2O3 system, the removal efficiency of 2,4-Dibromophenol (2,4-DBP) was increased by 26.5%, and the apparent activation energy was decreased from 44.5 kJ/mol to 30.9 kJ/mol. The mechanism of Al2O3-catalytic was elucidated by electrochemical processes, X-ray photoelectron spectroscopy (XPS) characterization and theoretical analysis that the oxidation potential of MnO4- was improved from 0.46 V to 0.49 V. The improvement was attributed to the formation of coordination bonds between the O atoms in MnO4- and the empty P orbitals of the Al atoms in Al2O3 crystal leading to the even-more electron deficient state of MnO4-. The excellent reusability of Al2O3, the good performance on degradation of 2,4-DBP in real water, the satisfactory degradation of fixed-bed reactor, and the enhanced removal of 6 other phenolic pollutants demonstrated that the KMnO4/Al2O3 system has satisfactory potential industrial application value. This study offers evidence for the improvement of highly-efficient MnO4- oxidation systems.

Taxifolin inhibits melanoma proliferation/migration impeding USP18/Rac1/JNK/ß-catenin oncogenic signaling.

BACKGROUND: Metastatic melanoma is a fatal cancer. Despite the advances in targeted therapy and immunotherapy for patients with melanoma, drug resistance and low response rates pose a considerable challenge. Taxifolin is a multifunctional natural compound with emerging antitumor potentials. However, its utility in melanoma treatment remains unclear. PURPOSE: The study aimed to investigate the effect of purified Taxifolin from Larix olgensis roots (Changbai Mountain, China) on melanoma and explore the underlying mechanism. METHODS: Purified Taxifolin from Larix olgensis roots was evaluated for its antimelanoma effects in vitro and in vivo settings. RNA-seq analysis was performed to explore the underlying mechanism. RESULTS: Purified Taxifolin (> 99 %) from Larix olgensis roots inhibited the proliferation and migration of B16F10 melanoma cells at 200 and 400 µM, and of A375 cells at 100 and 200 µM. Taxifolin administered at 60 mg/kg suppressed tumor growth and metastasis in mouse models without causing significant toxicity. Taxifolin modulated USP18/Rac1/JNK/ß-catenin axis to exert its antitumor effect. CONCLUSION: These findings indicate that Taxifolin derived from Larix olgensis roots may be a promising antimelanoma therapy.

Interleukin 6 (IL-6) Regulates GABAA Receptors in the Dorsomedial Hypothalamus Nucleus (DMH) through Activation of the JAK/STAT Pathway to Affect Heart Rate Variability in Stressed Rats.

The dorsomedial hypothalamus nucleus (DMH) is an important component of the autonomic nervous system and plays a critical role in regulating the sympathetic outputs of the heart. Stress alters the neuronal activity of the DMH, affecting sympathetic outputs and triggering heart rate variability. However, the specific molecular mechanisms behind stress leading to abnormal DMH neuronal activity have still not been fully elucidated. Therefore, in the present study, we successfully constructed a stressed rat model and used it to investigate the potential molecular mechanisms by which IL-6 regulates GABAA receptors in the DMH through activation of the JAK/STAT pathway and thus affects heart rate variability in rats. By detecting the c-Fos expression of neurons in the DMH and electrocardiogram (ECG) changes in rats, we clarified the relationship between abnormal DMH neuronal activity and heart rate variability in stressed rats. Then, using ELISA, immunohistochemical staining, Western blotting, RT-qPCR, and RNAscope, we further explored the correlation between the IL-6/JAK/STAT signaling pathway and GABAA receptors. The data showed that an increase in IL-6 induced by stress inhibited GABAA receptors in DMH neurons by activating the JAK/STAT signaling pathway, while specific inhibition of the JAK/STAT signaling pathway using AG490 obviously reduced DMH neuronal activity and improved heart rate variability in rats. These findings suggest that IL-6 regulates the expression of GABAA receptors via the activation of the JAK/STAT pathway in the DMH, which may be an important cause of heart rate variability in stressed rats.

Ephedrine and pseudoephedrine in Ephedra saxatilis on the vertical altitude gradient changed in southern Tibet Plateau, China.

Ephedra is one of the world's most important plants, used in medicine, plants and ecology. Most Ephedra grows in plain areas and is stable. But the plateau environment is special, with the change of altitude, the variety difference of plateau Ephedra saxatilis is very obvious. E. saxatilis metabolism on the Tibetan Plateau is not only affected by altitude, but also environmental conditions such as climate conditions and different soil components. However, the change mechanism of E. saxatilis alkaloids in special ecological environment is still unclear. Therefore, we analyzed the metabolic and altitude of E. saxatilis species in the Tibetan Plateau. Through the functional analysis of Kyoto Metabolism and Metabolomic Encyclopedia (KEGG), we can determine that the number of E. saxatilis metabolites decreases with the increase of altitude, and there are differences in metabolism among the three mountains. This was confirmed by univariate analysis of the top five metabolic pathways. Based on the analysis of soil and metabolomics, it was found that soil water content was also a factor affecting E. saxatilis metabolism. According to the difference of vertical height gradient, ephedrine and pseudephedrine showed the same change in vertical altitude under different mountains. Ephedrine increased as the altitude gradient increased, and pseudoephedrine decreased as the altitude gradient decreased. Our results provide valuable information for further study of metabolic mechanism and efficacy stability. It provides useful reference for the research of E. saxatilis planting in special area.

Dietary intake of household cadmium-contaminated rice caused genome-wide DNA methylation changes on gene/hubs related to metabolic disorders and cancers.

Cadmium (Cd) contamination in food has raised broad concerns in food safety and human health. The toxicity of Cd to animals/humans have been widely reported, yet little is known about the health risk of dietary Cd intake at the epigenetic level. Here, we investigated the effect of a household Cd-contaminated rice (Cd-rice) on genome-wide DNA methylation (DNAm) changes in the model mouse. Feeding Cd-rice increased kidney Cd and urinary Cd concentrations compared with the Control rice (low-Cd rice), whereas supplementation of ethylenediamine tetraacetic acid iron sodium salt (NaFeEDTA) in the diet significantly increased urinary Cd and consequently decreased kidney Cd concentrations. Genome-wide DNAm sequencing revealed that dietary Cd-rice exposure caused the differentially methylated sites (DMSs), which were mainly located in the promoter (32.5%), downstream (32.5%), and intron (26.1%) regions of genes. Notably, Cd-rice exposure induced hypermethylation at the promoter sites of genes Caspase-8 and interleukin-1ß (Il-1ß), and consequently, their expressions were down-regulated. The two genes are critical in apoptosis and inflammation, respectively. In contrast, Cd-rice induced hypomethylation of the gene midline 1 (Mid1), which is vital to neurodevelopment. Furthermore, 'pathways in cancer' was significantly enriched as the leading canonical pathway. Supplementation of NaFeEDTA partly alleviated the toxic symptoms and DNAm alternations induced by Cd-rice exposure. These results highlight the broad effects of elevated dietary Cd intake on the level of DNAm, providing epigenetic evidence on the specific endpoints of health risks induced by Cd-rice exposure.

Eucommia ulmoides Oliver's Multitarget Mechanism for Treatment of Ankylosing Spondylitis: A Study Based on Network Pharmacology and Molecular Docking.

Background: Eucommia ulmoides Oliver (EU) is a plant used in Chinese medicine as a medicinal herb to treat autoimmune and inflammatory conditions. We used network pharmacology to examine the active ingredients and estimate the main targets and pathways affected by EU when it is used to treat ankylosing spondylitis (AS). Materials and Methods: The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform was used to search for active ingredients in EU and their target proteins. The GeneCards Database was used to find AS-related targets. The targets from the EU and AS searches that coincided were selected by constructing a Venn diagram. Then, a STRING network platform and Cytoscape software were used to analyse the protein-protein interaction (PPI) network and key targets. The strong affinity between EU and its targets was confirmed using molecular docking techniques. The Gene Ontology and the Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analysis of overlapping targets was performed using the database for annotation, visualization, and integrated discovery online tool. Results: The number of active ingredients against AS in EU was discovered to be 28. Major targets against AS in the PPI network and core targets analyses were identified as IL-1B, PTGS2, IL-8, nMMP-9, CCL2, MYC, and IL-2. Furthermore, molecular docking studies showed the strong affinity between EU's bioactive molecules and their AS targets. Enrichment analysis revealed that active ingredients from EU were involved in a variety of biological processes, including the response to molecules derived from bacteria, extracellular stimuli, nutrient levels, and the regulation of reactive oxygen species, all of which are mediated by interleukin-17, TNF-α, and other signalling pathways. Conclusion: The therapy for AS using EU involves a multitarget, multipathway, and multiselection mechanism that includes anti-inflammatory and analgesic effects. This study provides a theoretical basis for future research into targeted molecular therapies for AS.

Platycodon grandiflorum (Jacq.) A. DC.: A review of phytochemistry, pharmacology, toxicology and traditional use.

BACKGROUND: The traditional Chinese medicine Platycodon grandiflorum (Jacq.) A. DC. (PG, balloon flower) has medicinal and culinary value. It consists of a variety of chemical components including triterpenoid saponins, polysaccharides, flavonoids, polyphenols, polyethylene glycols, volatile oils and mineral components, which have medicinal and edible value. PURPOSE: The ultimate goal of this review is to summarize the phytochemistry, pharmacological activities, safety and uses of PG in local and traditional medicine. METHODS: A comprehensive search of published literature up to March 2022 was conducted using the PubMed, China Knowledge Network and Web of Science databases to identify original research related to PG, its active ingredients and pharmacological activities. RESULTS: Triterpene saponins are the primary bioactive compounds of PG. To date, 76 triterpene saponin compounds have been isolated and identified from PG. In addition, there are other biological components, such as flavonoids, polyacetylene and phenolic acids. These extracts possess antitussive, immunostimulatory, anti-inflammatory, antioxidant, antitumor, antiobesity, antidepressant, and cardiovascular system activities. The mechanisms of expression of these pharmacological effects include inhibition of the expression of proteins such as MDM and p53, inhibition of the activation of enzymes, such as AKT, the secretion of inflammatory factors, such as IFN-γ, TNF-α, IL-2 and IL-1ß, and activation of the AMPK pathway. CONCLUSION: This review summarizes the chemical composition, pharmacological activities, molecular mechanism, toxicity and uses of PG in local and traditional medicine over the last 12 years. PG contains a wide range of chemical components, among which triterpene saponins, especially platycoside D (PD), play a strong role in pharmacological activity, representing a natural phytomedicine with low toxicity that has applications in food, animal feed and cosmetics. Therefore, PG has value for exploitation and is an excellent choice for treating various diseases.

[Effect of Chelating Agents and Organic Acids on Remediation of Cadmium and Arsenic Complex Contaminated Soil Using Xanthium sibiricum].

In order to improve the phytoextraction efficiency of Xanthium sibiricum on farmland soil that had been contaminated by Cd and As, this study explored the effects of chelating agents and organic acids (EDTA, SAP, CA, and MA) on the extraction of Cd and As heavy metals using X. sibiricum. The results showed that the four different chelating agents and organic acids had little effect on the biomass of the roots, stems, and leaves of X. sibiricum. However, they had different effects on the concentrations and accumulation of Cd and As in various organs of X. sibiricum. Compared with the those in the CK treatment, EDTA, SAP, CA, and MA significantly increased the Cd concentrations in the leaves of X. sibiricum by 44.1%, 32.4%, 41.2%, and 38.2% and the As concentrations in the roots of X. sibiricum by 89.6%, 7.4%, 94.8%, and 61.5%, respectively. The four treatments (EDTA, SAP, CA, and MA) improved the total Cd accumulation of X. sibiricum, with increasing ranges, respectively, of 70.2%, 29.4%, 28.9%, and 33.1%, and the As accumulation increased by 67.0%, 19.6%, 81.9%, and 40.8%, respectively, compared with that of the CK treatment. The four chelating agents and organic acids had different effects on the Cd and As bioconcentration factor and transfer factor of various organs of X. sibiricum. Treatments with EDTA, SAP, CA, and MA resulted in a decrease of 32.7%-38.2% in soil Cd concentrations and a decrease of 14.6%-20.5% in soil As concentrations. These four chelating agents can be used for enhancing the efficiency of extraction Cd and As heavy metals by X. sibiricum.

Perfluorohexanoic acid caused disruption of the hypothalamus-pituitary-thyroid axis in zebrafish larvae.

Perfluorohexanoic acid (PFHxA) has been recognized as an alternative to the wide usage of perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) in the fluoropolymer industry for years. PFHxA has been frequently detected in the environment due to its wide application. However, the ecological safety of PFHxA, especially its toxicological effects on aquatic organisms, remains obscure. In the present study, PFHxA at different concentrations (0, 0.48, 2.4, and 12 mg/L) was added to the culture medium for zebrafish embryo/larval exposure at 96 h postfertilization (hpf). Zebrafish larvae showed a slow body growth trend and changes in thyroid hormone levels (THs) upon PFHxA exposure, indicating the interference effect of PFHxA on fish larval development. Moreover, the transcription levels of genes related to the hypothalamic-pituitary-thyroid (HPT) axis were also analyzed. The gene expression level of thyroid hormone receptor ß (trß) was upregulated in a dose-dependent manner. Exposure to 0.48 mg/L PFHxA increased the expression levels of the thyrotrophic-releasing hormone (trh) and thyroid hormone receptor α (trα). Significant increases in corticotrophin-releasing hormone (crh) and transthyretin (ttr) gene expression were also observed when the zebrafish larvae were treated with 12 mg/L PFHxA, except iodothyronine deiodinases (dio1), which decreased obviously at that point. There were significant declines in the transcription of both thyroid-stimulating hormone ß (tshß) and uridinediphosphate-glucuronosyltransferase (ugt1ab) upon exposure to 2.4 mg/L PFHxA. In addition, PFHxA induced a dose-related inhibitory effect on the transcription of sodium/iodide symporter (nis). Finally, the thyroid status will be destroyed after exposure to PFHxA, thus leading to growth impairment in zebrafish larvae.

Pd-Cu nanoalloy for dual stimuli-responsive chemo-photothermal therapy against pathogenic biofilm bacteria.

Photothermal therapy (PTT) is a promising strategy for antimicrobial therapy. However, the application of PTT to treat bacterial infections remains a challenge as the high temperature required for bacterial elimination can partly damage healthy tissues. Selecting the appropriate treatment temperature is therefore a key factor for PTT. In this work, we designed a near-infrared/pH dual stimuli-responsive activated procedural antibacterial system based on zeolitic imidazolate framework-8 (ZIF-8), which was bottom-up synthesized and utilized to encapsulate both Pd-Cu nanoalloy (PC) and the antibiotic amoxicillin (AMO). This procedural antibacterial therapy comprises chemotherapy (CT) and PTT. The former disrupts the bacterial cell wall by releasing AMO in an acidic environment, which depends on the sensitive response of ZIF-8 to pH value change. With the progression in time, the AMO release rate decreased gradually. The latter can then significantly stimulate drug release and further complete the antibacterial effect. This impactful attack consisted of two waves that constitute the procedural therapy for bacterial infection. Accordingly, the treatment temperature required for antibacterial therapy can be significantly lowered under this mode of treatment. This antibacterial system has a significant therapeutic effect on planktonic bacteria (G+/G-) and their biofilms and also has good biocompatibility; thus, it provides a promising strategy to develop an effective and safe treatment against bacterial infections. STATEMENT OF SIGNIFICANCE: We have developed a near infrared/pH dual stimuli-responsive activated procedural antibacterial system that combines enhanced antibiotic delivery with photothermal therapy and has highly efficient antimicrobial activity. The antibacterial effect of this therapy was based on two mechanisms of action: chemotherapy, in which the bacterial cell wall was first destroyed, followed by photothermal therapy. After exposure to irradiation with an 808 nm laser, the inhibition rates were 99.8% and 99.1% for Staphylococcus aureus and Pseudomonas aeruginosa, respectively, and the clearance rates for their established biofilms were 75.3% and 74.8%, respectively. Thus, this procedural antibacterial therapy has shown great potentiality for use in the photothermal therapy of bacterial infectious diseases, including biofilm elimination.

Disentangling drivers of soil microbial nutrient limitation in intensive agricultural and natural ecosystems.

Characterized by continuous chemical fertilization, intensive agriculture generally reduces soil ecoenzymatic activities and nutrient mineralization, as well as alters the biomass production and microbial community composition. Soil acidification poses serious threats to the sustainable development of intensive agriculture. However, the mechanism of nutrient cycling and metabolism of soil microorganisms in response to soil acidification in intensive agriculture remains unclear. Herein, we studied the variations in ecoenzymatic stoichiometry of soil ß-glucosidase (BG), cellobiohydrolase (CBH), N-acetylglucosaminidase (NAG) and acid phosphatase (AP) under different land use types and pH gradients of tea garden soils. The results revealed that natural forest and cropland soils had significantly higher BG and CBH activities than tea garden soils. Soil BG and CBH activities displayed significant positive correlations with soil pH, total nitrogen (TN) and phosphorus (TP), while soil NAG activity was significantly associated with nitrate nitrogen, total carbon (TC), TN, carbon: phosphorus (C:P) and nitrogen: phosphorus (N:P) ratios. Soil AP activity showed significant negative associations with pH, TP and C:N ratio, but was significantly positively correlated with TC, TN, C:P and N:P ratios. Enzyme vector model revealed that soil microorganisms are limited by P (enzyme vector angle >45°) regardless of land use types. Compared to natural forest soils, the P limitation of microorganisms in tea garden soils became increasingly serious with a decreasing pH gradient, as indicated by the significant increase in enzyme vector angle. Thus, the overall ecoenzymatic stoichiometry was shifted by soil pH. In summary, higher pH increased BG activity and decreased AP activity, but had no significant effect on NAG activity, suggesting co-limitation of soil microorganisms by C and P in this area. This study provides novel insights into the effect of soil acidification on ecoenzymatic stoichiometry, and also highlights the stoichiometric and energy limitations on the metabolism of soil microorganisms in agricultural ecosystems.

Efficient Eradication of Bacterial Biofilms with Highly Specific Graphene-Based Nanocomposite Sheets.

Bacterial biofilms are usually resistant to antibiotics, thus powerful methods are required for removal. Nanomaterial involving a combination of treatment modalities recently has been recognized as an effective alternative to combat biofilm. However, its targeted and controlled release in bacterial infection is still a major challenge. Here, we present an intelligent phototherapeutic nanoplatform consisting of an aptamer (Apt), indocyanine green (ICG), and carboxyl-functionalized graphene oxide (GO-COOH), namely, ICG@GO-Apt, for targeted treatment of the biofilm formed by Salmonella Typhimurium. Since Apt-conjugated nanosheets (NSs) can specifically accumulate near abscess caused by the pathogens, they enhance greatly the local drug molecule concentration and promote their precise delivery. They can simultaneously generate heat and reactive oxygen species under near-infrared irradiation for photothermal/photodynamic therapy, thereby significantly enhancing biofilm elimination. The phototherapeutic ICG@GO-Apt also displays a good biocompatibility. More importantly, the multifunction phototherapeutic platform shows an efficient biofilm elimination with an efficiency of greater than 99.99% in an abscess formation model. Therefore, ICG@GO-Apt NSs with bacteria-targeting capability provide a reliable tool for clinical bacterial infection that circumvents antibiotic resistance.

Gold-Platinum Nanodots with High-Peroxidase-like Activity and Photothermal Conversion Efficiency for Antibacterial Therapy.

Combined therapeutic strategies for bacterial infection have attracted worldwide attention owing to their faster and more effective therapy with fewer side effects compared with monotherapy. In this work, gold-platinum nanodots (AuPtNDs) are simply and quickly synthesized by a one-step method. They not only exhibit powerful peroxidase-like activity but also confer a higher affinity for hydrogen peroxide (H2O2), which is 3.4 times that of horseradish peroxidase. Under 808 nm laser irradiation, AuPtNDs also have excellent photothermal conversion efficiency (50.53%) and strong photothermal stability. Excitingly, they can combat bacterial infection through the combination of chemodynamic and photothermal therapy. In vitro antibacterial results show that the combined antibacterial strategy has a broad-spectrum antibacterial property against both Escherichia coli (Gram negative, 97.1%) and Staphylococcus aureus (Gram positive, 99.3%). Animal experiments further show that nanodots can effectively promote the healing of bacterial infection wounds. In addition, owing to good biocompatibility and low toxicity, they are hardly traceable in the main organs of mice, which indicates that they can be well excreted through metabolism. These results reveal the application potential of AuPtNDs as a simple and magic multifunctional nanoparticle in antibacterial therapy and open up new applications for clinical anti-infective therapy in the near future.

Potential anti-diabetic isoprenoids and a long-chain δ-lactone from frangipani (Plumeria rubra).

A decoction of Plumeria rubra flowers has been used traditionally for the treatment of diabetes in China and Mexico. Chemical investigations on the bioactive constituents of these flowers led to the isolation of 30 compounds, including the four new compounds, one iridoiod (1), two triterpenoids (4, 5), and a long-chain δ-lactone (16). In addition, 26 known compounds (2, 3, 6-15, 17-30) are also reported. All of these compounds were identified on the basis of spectroscopic data interpretation and the absolute configurations of compound 4, 5, 16 were determined by Mosher's method. Compounds 1-4, 7, 8 and 16 showed moderate to significant inhibitory activities against α-glucosidase and protein tyrosine phosphatase 1B, with 4 having IC50 values of 19.45 µM and 0.21 µM, respectively.

Exposure to PFDoA causes disruption of the hypothalamus-pituitary-thyroid axis in zebrafish larvae.

Perfluorododecanoic acid (PFDoA), a kind of perfluorinated carboxylic acid (PFCA) with 12 carbon atoms, has an extensive industrial utilization and is widespread in both wildlife and the water environment, and was reported to have the potential to cause a disruption in the thyroid hormone system homeostasis. In this study, zebrafish embryos/larvae were exposed to different concentrations of PFDoA (0, 0.24, 1.2, 6 mg/L) for 96 h post-fertilization (hpf). PFDoA exposure caused obvious growth restriction connected with the reduced thyroid hormones (THs) contents in zebrafish larvae, strengthening the interference effect on the growth of fish larvae. The transcriptional level of genes within the hypothalamic-pituitary-thyroid (HPT) axis was analyzed. The gene expression levels of thyrotropin-releasing hormone (trh) and corticotrophin-releasing hormone (crh) were upregulated upon exposure to 6 mg/L of PFDoA, and iodothyronine deiodinases (dio2) was upregulated in the 1.2 mg/L PFDoA group. The transcription of thyroglobulin (tg) and thyroid receptor (trß) were significantly downregulated upon exposure to 1.2 mg/L and 6 mg/L of PFDoA. PFDoA could also decrease the levels of sodium/iodide symporter (nis) and transthyretin (ttr) gene expression in a concentration-dependent manner after exposure. A significant decrease in thyroid-stimulating hormoneß (tshß), uridinediphosphate-glucuronosyltransferase (ugt1ab) and thyroid receptor (trα) gene expression were observed at 6 mg/L PFDoA exposure. Upregulation and downregulation of iodothyronine deiodinases (dio1) gene expression were observed upon the treatment of 1.2 mg/L and 6 mg/L PFDoA, respectively. All the data demonstrated that gene expression in the HPT axis altered after different PFDoA treatment and the potential mechanisms of the disruption of thyroid status could occur at several steps in the process of synthesis, regulation, and action of thyroid hormones.

Antidiabetic activities of entagenic acid in type 2 diabetic db/db mice and L6 myotubes via AMPK/GLUT4 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Entada phaseoloides (L.) Merr., a traditional Chinese folk medicine, has been used in treating diabetes and other inflammatory disorders. Our previous study revealed that the triterpene saponins in E.Phaseoloides possessed an antidiabetic effect in type 2 diabetic rats by activating AMP-activated protein kinase (AMPK). Entagenic acid, the principal aglycon, isolated from the seed kernels of E. phaseoloides, has been proposed to possess a significant role in the antidiabetic effect, however, its actual effect and pertinent mechanisms are still unknown. AIM OF THE STUDY: The aim of the present study was to investigate the antidiabetic effect of entagenic acid in a type 2 diabetic animal model (C57BIKsj db/db mice) and its role in the regulation of glucose uptake in L6 myotubes, and to explore the possible molecular mechanisms. MATERIALS AND METHODS: In vivo, average weekly body weight, daily water, food intake and postprandial blood glucose levels, the intraperitoneal insulin tolerance test, glucose tolerance test, serum lipid profiles and pancreatic histopathological changes in db/db mice treated with entagenic acid orally at different doses (5, 10 and 20mg/kg) were assessed and compared with wild-type littermates or vehicle- and metformin-treated db/db mice. In vitro, effects of entagenic acid on the glucose consumption and the phosphorylation of protein kinase B (AKT) and AMPK in L6 myotubes were evaluated. RESULTS: In vivo, entagenic acid significantly lowered postprandial blood glucose levels but not the body weight, normalized the serum lipid imbalance, improved the impaired glucose tolerance, insulin resistance, as well as the pathological changes in pancreatic islets. In vitro, entagenic acid dose-dependently promoted glucose utilization and enhanced the translocation and expression of glucose transporter 4 (GLUT4), and phosphorylation of AMPK but not AKT. CONCLUSIONS: The present study demonstrated that entagenic acid can markedly maintain the glucose homeostasis, improve insulin resistance and ameliorate dyslipidemia. Its antihyperglycemic effect could be caused by promoting AMPK mediated cellular signaling and GLUT4 translocation in muscles.

Production, identification, and field evaluation of sex pheromone from calling females in Diaphania angustalis (Lepidoptera: Crambidae).

Insect sex pheromones play a crucial role in the mate finding and calling behavior of Lepidoptera pests. Currently, little is known about the chemical ecology of Diaphania angustalis Snellen (Lepidoptera: Crambidae), a severe and important defoliator attacking the medicinal plant, Alstonia scholaris. In the present study, the pheromone components of D. angustalis females were investigated using electrophysiological and behavioral methods. Distilled hexane extracts of female pheromone glands were analyzed through electroantennogram (EAG) and gas chromatography-electroantennogram detector (GC-EAD), and the active compounds were identified through gas chromatography-mass spectrometry (GC-MS). Production peak of female sex pheromone occurred on the third day of age at 5 h into the scotophase with the EAG test, and the hexane extracts were attractive to males in the wind tunnel test. GC-EAD analysis of virgin males to gland extracts that were subsequently evaluated showed two active compounds, (E,E)-10,12-hexadecadienal (E10E12-16:Ald) and (E,E)-10,12-hexadecadien-1-ol (E10E12-16:OH), based on comparison of retention time and mass spectrum, with suitable synthetic compounds. Under laboratory conditions, the blend of E10E12-16:Ald and E10E12-16:OH in a ratio of 9:1 elicited a stronger EAG response than other treatments or a single component. In the field, more male moths were captured by traps baited with the mixture of E10E2-16:Ald and E10E2-16:OH in a ratio of 9:1, whereas a mixture of 8:1 and 10:1 also caught males. Accordingly, E10E2-16:Ald and E10E2-16:OH were regarded as the major sex pheromone components in D. angustalis females.

Paeoniflorin, a Monoterpene Glycoside, Protects the Brain from Cerebral Ischemic Injury via Inhibition of Apoptosis.

Paeoniflorin (PF) is a principal bioactive component, which exhibits many pharmacological effects, including protection against ischemic injury. This paper aimed to investigate the protective effect of PF both in vivo and in vitro. Middle cerebral artery occlusion (MCAO) was performed on male Sprague-Dawley (SD) rat for 2 h, and different doses of PF or vehicle were administered 2 h after reperfusion. Rats were sacrificed after 7 days treatment of PF/vehicle. PF treatment for 7 days ameliorated MCAO-induced neurological deficit and decreased the infarct area. Further study demonstrated that PF inhibited the over-activation of astrocytes and apoptosis of neurons, and PF promoted up-regulation of neuronal specific marker neuron-specific nuclear (NeuN) and microtubule-associated protein 2 (MAP-2) in brain. Moreover, NMDA-induced neuron apoptosis was employed. The in vitro study revealed that PF treatment protected against NMDA-induced cell apoptosis and neuronal loss via up-regulation of neuronal specific marker NeuN, MAP-2 and Bcl-2 and the down-regulation Bax. Taken together, the present study demonstrates that PF produces its protective effect by inhibiting the over-activation of astrocytes, apoptosis of neurons and up-regulation of neuronal specific marker NeuN, MAP-2, and B-cell lymphoma-2 (Bcl-2), and down-regulation Bax. Our study reveals that PF may be a potential neuroprotective agent for stroke and can provide basic data for clinical use.

Ameliorative effects of Gualou Guizhi decoction on inflammation in focal cerebral ischemic-reperfusion injury.

Gualou Guizhi decoction (GLGZD) is a well-established Traditional Chinese Medicinal formulation which has long been used to treat stroke in a clinical setting in China. The present study investigated the ameliorative effects of GLGZD on inflammation in focal cerebral ischemic-reperfusion injury. A rat model of middle cerebral artery occlusion (MCAO) was employed. Rats were administrated GLGZD (7.2 and 14.4 g/kg per day) or saline as control 2 h after reperfusion and daily over the following seven days. Neurological deficit score and screen test were evaluated at 1, 3, 5 and 7 days after MCAO. Brain infarct size and brain histological changes were observed via 2,3,5-triphenyltetrazolium chloride staining and regular hematoxylin & eosin staining. Furthermore, inflammation mediators and nuclear factor-κB (NF-κB) were investigated using ELISA and immunohistochemistry. GLGZD treatment significantly improved neurological function, ameliorated histological changes to the brain and decreased infarct size in focal cerebral ischemic-reperfusion injury. GLGZD was found to significantly reduce interleukin (IL)-1, tumor necrosis factor-α and NF-κB levels, while increasing levels of IL-10. In conclusion, the present study suggested that GLGZD has a neuroprotective effect on focal cerebral ischemic-reperfusion injury and this effect is likely to be associated with the anti-inflammatory function of GLGZD.