Chicoric Acid Effectively Mitigated Dextran Sulfate Sodium (DSS)-Induced Colitis in BALB/c Mice by Modulating the Gut Microbiota and Fecal Metabolites.

Chicoric acid (CA) has been reported to exhibit biological activities; it remains unclear, however, whether CA could regulate colitis via modulation of the gut microbiota and metabolites. This study aimed to assess CA's impact on dextran sulfate sodium (DSS)-induced colitis, the gut microbiota, and metabolites. Mice were induced with 2.5% DSS to develop colitis over a 7-day period. CA was administered intragastrically one week prior to DSS treatment and continued for 14 days. The microbial composition in the stool was determined using 16S rRNA sequencing, while non-targeted metabolomics was employed to analyze the metabolic profiles of each mouse group. The results show that CA effectively alleviated colitis, as evidenced by an increased colon length, lowered disease activity index (DAI) and histological scores, and decreased tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) expression levels. CA intervention restored the structure of gut microbiota. Specifically, it decreased the abundance of Bacteroidetes and Cyanobacteria at the phylum level and Bacteroides, Rosiarcus, and unclassified Xanthobacteraceae at the genus level, and increased the abundance of unclassified Lachnospiraceae at the genus level. Metabolomic analysis revealed that CA supplementation reversed the up-regulation of asymmetric dimethylarginine, N-glycolylneuraminic acid, and N-acetylneuraminic acid, as well as the down-regulation of phloroglucinol, thiamine, 4-methyl-5-thiazoleethanol, lithocholic acid, and oxymatrine induced by DSS. Our current research provides scientific evidence for developing CA into an anti-colitis functional food ingredient. Further clinical trials are warranted to elucidate the efficacy and mechanism of CA in treating human inflammatory bowel disease (IBD).

The antioxidant, anti-inflammatory and analgesic activity effect of ethyl acetate extract from the flowers of Syringa pubescens Turcz.

ETHNOPHARMACOLOGICAL RELEVANCE: Syringa Pubescens Turcz. (SP), a member of the Oleaceae family, is a species of plant known as Syringa. Flowers, as the medicinal part, are commonly used in the treatment of hepatitis and tonsillitis. AIM OF THE STUDY: The research was the first to assess the antioxidant and anti-inflammatory potential of different parts of SP flowers (SPF) in vitro. The most promising fraction was ethyl acetate fraction of SP flower (SPFEA). The antioxidant, anti-inflammatory and analgesic activities of SPFEA were further studied, and the chemical components were identified. METHODS: HPLC was used to identify the major components in various fraction of SPF. DPPH and ABTS + radical scavenging assays as well as FRAP test and ß-carotene bleaching test were employed to assess the antioxidant potential of SPF fraction in vitro. The inhibitory effect on NO production in LPS-treated RAW264.7 cells and heat-induced protein denaturation test were used to evaluate the anti-inflammatory potential of SPF fraction. Further analysis of the biological activity of SPFEA was performed. Acute toxicity test was conducted to assess the toxicity of SPFEA. The anti-inflammatory effect was assessed by utilizing xylene induced ear edema model, carrageenan-induced foot edema model and peritonitis model in vivo. The analgesic effect of SPFEA was evaluated using hot plate test, tail immersion test, formaldehyde test as well as acetic acid-induced abdominal writhing pain experiment in vivo. In carrageenan induced foot edema model, ELISA kits were employed to measure levels of inflammation factors (NO, TNF-α, IL-6, COX-2, IL-1ß) in foot tissue as well as MDA, CAT, SOD, GSH-PX levels in liver tissue. RESULTS: HPLC results showed that there were significant differences in bioactive substances among different fractions of SPF, and SPFEA was rich in bioacitve components. Compared with other fractions of SPF, SPFEA exhibited better antioxidant and anti-inflammatory abilities. The 3000 mg/kg SPFEA group in mice had no obvious side effects. The xylene-induced ear edema model, carrageenan-induced foot edema and peritonitis models demonstrated that the SPFEA had significant anti-inflammatory effect. Moreover, inflammation factors including NO, TNF-α, IL-6, COX-2, IL-1ß were significantly reduced in SPFEA groups in foot tissue induced by carrageenan. Additionally, SPFEA effectively decreased liver tissue oxidative stress levels (MDA, SOD, GSH-PX and CAT). The bioactivities of SPFEA demonstrated a clear dose-dependent relationship. The results of the hot plate test, tail immersion test, formaldehyde test and acetic acid-induced abdominal writhing pain experiments indicated the SPFEA possessed an excellent analgesic effect, and this effect was in dose-dependent manner. CONCLUSION: The study provides a scientific foundation for understanding the pharmacological action of SPFEA. It has been indicated that SPFEA has excellent antioxidant, analgesic and anti-inflammatory effects.

Influence of Five Drying Methods on Active Compound Contents and Bioactivities of Fresh Flowers from Syringa pubescens Turcz.

The flower of Syringa pubescens Turcz. is used in Chinese folk medicine and also as a flower tea for healthcare. The effects of five drying methods on the active compound contents, the antioxidant abilities, anti-inflammatory properties and enzyme inhibitory activities were evaluated. The plant materials were treated using shade-drying, microwave-drying, sun-drying, infrared-drying and oven-drying. The seven active compounds were simultaneously determined using an HPLC method. Furthermore, the chemical profile was assessed using scanning electron microscopy, ultraviolet spectroscopy and infrared spectroscopy. The antioxidant capacities and protective effects on L02 cells induced with hydrogen peroxide were measured. The anti-inflammatory effects on lipopolysaccharide-induced RAW264.7 cells were investigated. The enzyme inhibitory activities were determined against α-amylase, α-glucosidase cholinesterases and tyrosinase. The results indicated that drying methods had significant influences on the active compound contents and biological properties. Compared with other samples, the OD samples possessed low IC50 values with 0.118 ± 0.004 mg/mL for DPPH radical, 1.538 ± 0.0972 for hydroxyl radical and 0.886 ± 0.199 mg/mL for superoxide radical, while the SHD samples had stronger reducing power compared with other samples. The SHD samples could be effective against H2O2-induced injury on L02 cells by the promoting of T-AOC, GSH-PX, SOD and CAT activities and the reducing of MDA content compared with other samples. Furthermore, SPF samples, especially the SHD sample, could evidently ameliorate inflammation through the inhibition of IL-6, IL-1ß and TNF-α expression. All the studied SPF samples exhibited evidently inhibitory effects on the four enzymes. The IC50 values of inhibitory activity on α-glucosidase and α-amylase from SHD sample were 2.516 ± 0.024 and 0.734 ± 0.034 mg/mL, respectively. SD samples had potential inhibitory effects on cholinesterases and tyrosinase with IC50 values of 3.443 ± 0.060 and 1.732 ± 0.058 mg/mL. In consideration of active compound contents and biological activities, it was recommended that SHD and SD be applied for drying SPF at an industrial scale.

Fabrication of multifunctional materials based on chitosan/gelatin incorporating curcumin-clove oil emulsion for meat freshness monitoring and shelf-life extension.

A new multifunctional film with active and intelligent effects was developed by incorporating curcumin-clove oil emulsion into natural materials. The basic properties, functional characteristics, and pH/NH3-sensitivity of films were investigated, and then these films were applied to extend shelf-life and monitor freshness of meat. Curcumin solution and emulsion illustrated significant color variations at different pH values. The incorporation of emulsion improved the UV-vis barrier and water resistance properties of films, which blocked most of UV-light and its water contact angle reached 100.03°. Meanwhile, the films had stronger mechanical strength and higher thermal stability, with elongation at break reaching 79.18 % and the maximum degradation temperature rising to 316 °C. Moreover, emulsion made films have a slow-release effect on clove oil, which not only enhanced the antioxidant property but also significantly improved their antibacterial activity. Additionally, the multifunctional films presented a significant color response to acidic/alkaline environments over a short time interval and could be easily identified by naked eyes. Finally, the films effectively extended the shelf-life of fresh meat by 3 days at 4 °C and visually monitored freshness through color changes in real-time. This knowledge provides insights and ideas for the development of novel food packaging with both active and intelligent functions.

Traditional Chinese medicine Tongxie Yaofang treating irritable bowel syndrome with diarrhea and type 2 diabetes mellitus in rats with liver-depression and spleen-deficiency: A preliminary study.

Tongxie Yaofang (TXYF), a Traditional Chinese Medicine (TCM) with four components as follows: Rhizoma Atractylodis Macrocephalae (baizhu), Radix Paeoniae Alba (baishao), Pericarpium Citri Reticulatae (chenpi) and Radix Saposhnikovia Divaricata (fangfeng), benefits irritable bowel syndrome (IBS). Nonetheless, proofs of this formula ameliorating D-IBS and T2DM are required. This research aimed at investigating the efficacy of TXYF in treating inflammation in rats with D-IBS and T2DM using animal models. In this study, gavage with high-fat diet, fasciculation, and senna was given to develop rat models with target diseases. To determine intestinal inflammations, major inflammatory factors, and intestinal permeability proteins, H&E staining, ELISA, and immunohistochemistry methods were employed, respectively. This study also utilized Western blot to discover potential inflammatory targets. Results of this research illustrates that TXYF treatment reduced the level of TNF-α, IL-1ß, and IL-6, and raised the IL-10 concentration in liver-depressed spleende ficient rats with D-IBS and T2DM, indicating controlled inflammatory reactions. Staining analysis also showed improved disease states of animal models. Furthermore, efficient rebounds of claudin-1, an intestinal permeability-associated protein, were detected. Moreover, TXYF may treat D-IBS and T2DM in rats via the rage pathway.

Corn peptides improved obesity-induced non-alcoholic fatty liver disease through relieving lipid metabolism, insulin resistance and oxidative stress.

Non-alcoholic fatty liver disease (NAFLD) is increasingly threatening human health. The remarkable effects of corn peptides (CPs) as bioactive peptides on liver protection have attracted much attention. Nevertheless, the specific effect of CPs on NAFLD remains unclear. The present study was designed to investigate the efficacy of CPs in the prevention and auxiliary treatment of high-fat diet (HFD)-induced NAFLD in SD rats, and puerarin was used as the positive control. SD rats were fed a high-fat diet to establish the NAFLD rat model, and LO2 cells were treated with a high concentration of fructose to simulate the NAFLD cell model. NAFLD was comprehensively examined in terms of body weight, liver function markers, serum biochemistry and liver histology. Protein expression was determined using western blot analysis. The results of animal experiments showed that CPs could effectively inhibit the rate of weight gain, reduce the blood lipid level and liver index, and enhance glucose tolerance. The results of cell experiments showed that CPs could effectively reduce the accumulation of lipids in LO2 cells and inhibit the accumulation of reactive oxygen species (ROS). In addition, CPs could markedly reduce liver lipid accumulation in the liver cell and liver tissue, as further evidenced by the reduced expression of SREBP-1c in human non-tumour hepatic (LO2) cells. Meanwhile, the increased expression of SIRT1/PPAR-α and Nrf2/HO-1 pathways under the pretreatment of CPs in LO2 cells indicated that CPs could markedly relieve high fat-induced fatty liver injury, regulate insulin sensitivity, and reduce production of ROS. The results of in vivo and in vitro experiments demonstrated that CPs provided potential prevention and auxiliary treatment for NAFLD through reducing lipid accumulation, alleviating insulin resistance, and inhibiting oxidative stress. This study investigated the biological activity of CPs and laid the theoretical basis for the development of CP-based functional foods and dietary supplements.

SiNiSan alleviates liver injury by promoting hepatic stem cell differentiation via Wnt/ß-catenin signaling pathway.

BACKGROUND: SiNiSan, a Traditional Chinese Medicine containing Radix Bupleuri, Radix Paeoniae Alba, Fructus Aurantii Immaturus, and Radix Glycyrrhizae, has been shown to be clinically effective in treating liver damage, its underlying molecular mechanisms however remains unclear. PURPOSE: The aim of the current study was to understand the molecular mechanisms of SiNiSan in the treatment of liver damage utilizing mice and cell culture models. METHODS: Here, mice were gavaged with 0.2% CCl4 to obtain acute liver injury model and with alcohol to obtain chronic liver injury model. H&E staining was performed to detect liver histomorphology. HPLC-MS was performed to analyze the composition of SiNiSan decoction and SiNiSan-medicated serum (SMS). In addition, western blots were done to analyze the representative protein expression in Wnt/ß-catenin signaling. Immunofluorescence staining was done to analyze the protein levels in WB-F344 cells. Finally, in an attempt to measure the influence of SiNiSan on liver regeneration in rats, we constructed a rats partial hepatectomy models. RESULTS: We demonstrated that SiNiSan treatment mitigated liver damage in mice, as evidenced by the decrease in serum AST and ALT levels, as well as improved liver tissue morphology. HPLC-MS results showed that SMS contained a variety of components from the SiNiSan decoction. Next, our results showed that SMS reduced the expression of α-fetoprotein (AFP) and enhanced the expression of albumin (ALB) and cytokeratin 19 (CK19) in WB-F344 cells. Further, SMS treatment induced the accumulation of ß-catenin. After 14 days of SMS treatment, ß-catenin protein underwent nuclear translocation and bound to the LEF1 receptor in the nucleus, which regulated c-Myc and Cyclin D1 factors to activate Wnt/ß-catenin signaling and promoted differentiation of WB-F344 cells. In addition, we demonstrated that SiNiSan increased liver regeneration in rat hepatectomy. CONCLUSION: Collectively, the current study revealed that SiNiSan alleviated the acute liver injury induced by CCl4 as well as the chronic liver damage triggered by alcohol and sucrose in vitro. Concurrently, SMS treatment induced hepatic stem cell differentiation by activating Wnt/ß-catenin signaling in vivo. Further study showed that SiNiSan promoted the regeneration of rats liver. The current study provides a theoretical basis for the clinical treatment of liver-related diseases with SiNiSan.

Hepatoprotective effects of Di Wu Yang Gan: A medicinal food against CCl4-induced hepatotoxicity in vivo and in vitro.

The development of functional foods based on medicinal food ingredients has become a hot topic in China. Di Wu Yang Gan (DWYG) is a Chinese medicinal food that contains five dietary plants. Various health benefits, including anti-inflammation, liver regeneration regulation, have been reported, though the mechanism is not clear. This study aimed to investigate the protective effect of DWYG on carbon tetrachloride-induced acute liver injury (ALI) in embryonic liver L-02 cells and mice model. DWYG-medicated serum protected L-02 cells from carbon tetrachloride-induced damage, reduced the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the culture medium, decreased the expression of Bax and increased the expression of Bcl-2. Mice study suggested that DWYG decreased the levels of malondialdehyde, ALT and AST. Together, these results suggest the hepatoprotective effects of DWYG against ALI and provide an experimental basis for the utilization of DWYG to treat liver damage.

Determination of tea polyphenols in green tea by homemade color sensitive sensor combined with multivariate analysis.

Tea polyphenols content in green tea has an indirect relationship with the aroma quality of tea. This study innovatively proposed a method for quantitative determination of tea polyphenols in green tea based on the self-developed color sensitive sensor. Firstly, the color sensitive sensor was prepared to acquire the aroma information of green tea. Secondly, color components were extracted and then optimized using ant colony optimization (ACO) algorithm. Finally, extreme learning machine (ELM) model was built using the optimized color feature components for quantitative determination of tea polyphenols content in green tea. Results showed that the correlation coefficient (RP) of the best ELM model is 0.8035, and the root mean square error prediction (RMSEP) is 1.6003% in the validation set. The overall results sufficiently demonstrate that it is feasible to quantitative detect tea polyphenols content in green tea by the homemade color sensitive sensor combined with appropriate chemometrics methods.

Evaluating aroma quality of black tea by an olfactory visualization system: Selection of feature sensor using particle swarm optimization.

Aroma is an important index to evaluate the quality and grade of black tea. This work innovatively proposed the sensory evaluation of black tea aroma quality based on an olfactory visual sensor system. Firstly, the olfactory visualization system, which can visually represent the aroma quality of black tea, was assembled using a lab-made color sensitive sensor array including eleven porphyrins and one pH indicator for data acquisition and color components extraction. Then, the color components from different color sensitive spots were optimized using the particle swarm optimization (PSO) algorithm. Finally, the back propagation neural network (BPNN) model was developed using the optimized characteristic color components for the sensory evaluation of black tea aroma quality. Results demonstrated that the BPNN models, which were developed using three color components from FTPPFeCl (component G), MTPPTE (component B) and BTB (component B), can get better results based on comprehensive consideration of the generalization performance of the model and the fabrication cost of the sensor. In the validation set, the average of correlation coefficient (RP) value was 0.8843 and the variance was 0.0362. The average of root mean square error of prediction (RMSEP) was 0.3811 and the variance was 0.0525. The overall results sufficiently reveal that the optimized sensor array has promising applications for the sensory evaluation of black tea products in the process of practical production.

Autophagy inhibition enhances Matrine derivative MASM induced apoptosis in cancer cells via a mechanism involving reactive oxygen species-mediated PI3K/Akt/mTOR and Erk/p38 signaling.

BACKGROUND: In the quest for new anti-cancer drugs, the drug discovery process has shifted to screening of active ingredients in traditional eastern medicine. Matrine is an active alkaloid isolated from plants of the Sophora genus used in traditional Chinese herbal medicine that exhibits a wide spectrum of biological properties and has a potential as an anti-proliferative agent. In this study, we investigated the anticancer property of MASM, ([(6aS, 10S, 11aR, 11bR, 11cS)210-Methylamino-dodecahydro-3a, 7a-diaza-benzo (de)anthracene-8-thione]), a potent derivative of matrine. METHODS: Four epithelial cancer cell lines representing the dominant cancers, namely: A549 (non-small-cell lung cancer cell line), MCF-7 and MDA-MB-231 (breast cancer cell lines), and Hela (cervical cancer cell line) were employed, and the mechanistic underpinning of MASM-induced apoptosis was investigated using flow cytometry, western blot and immunofluorescence. RESULTS: MASM, induced apoptosis via caspase 3 dependent and independent pathways, and autophagy in all the four cancer cell lines, but post-EMT (epithelial mesenchymal transition) cells showed greater sensitivity to MASM. Scavenging reactive oxygen species using N-acetylcysteine rescued all cancer cell lines from apoptosis and autophagy. Mechanistic analysis revealed that MASM induced autophagy involves inhibition of Akt signaling and the activation of Erk and p38 signaling, and inhibition of autophagy further enhanced the apoptosis induced by MASM. CONCLUSIONS: These results indicate that MASM possesses potency against cancer cells and modulating autophagy during MASM administration could be used to further enhance its therapeutic effects.

Reno-Protective Effect of Realgar Nanoparticles on Lupus Nephritis of MRL/Lpr Mice through STAT1.

BACKGROUND: Realgar, an arsenic tetrasulfide compound, is a highly recognized traditional Chinese medicinal prescription that has been widely used to treat various diseases such as inflammatory diseases. However, there are still some problems in the clinical treatment of Realgar, such as large oral dose and high potential toxicity. OBJECTIVE: To evaluate effects of Realgar nanoparticles on lupus nephritis (LN) in vivo in MRL/lpr mice. METHODS: Ten-week mice were orally administered every day for eight consecutive weeks except the mice of normal model groups. The serum levels of anti-ds-DNA antibody IgG, IgM, IFN-γ, Creatinine (Cr), and blood urea nitrogen (BUN) were determined, and 24-hour urine protein was also measured. Renal inflammatory pathology analysis was assessed by hematoxylin-eosin (H&E) staining. The expression of phosphorylated signal transducer and activator of transcription 1 (p-STAT 1) and Janus Kinase 1 (JAK 1) in kidney tissue was determined by direct reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC). RESULTS: The mice treated with Realgar nanoparticle in the high dose-treated (Realgar HD, 0.03 g/kg/d) group exhibited significantly reduced serum levels of anti-dsDNA (p<0.01), IgG (p<0.01), IgM (p<0.01), BUN (p<0.01), Cr (p<0.01), and inflammatory cytokine IFN-γ (p<0.01) as well as proteinuria (p<0.01) compared to the untreated model MRL/lpr mice. Additionally, high doses of Realgar nanoparticles significantly suppressed the phosphorylations of STAT 1(p<0.01) and the renal pathological changes. CONCLUSIONS: The study indicates that Realgar nanoparticles may be a potential agent to treat LN, and the down-regulated p-STAT1 expression suggests that it may be one of the LN treatment targets for Realgar nanoparticles.

Music reduces panic: an initial study of listening to preferred music improves male patient discomfort and anxiety during flexible cystoscopy.

PURPOSE: To assess the impact of listening to preferred music on relieving male patients' pain and anxiety during flexible cystoscopy. PATIENTS AND METHODS: A total of 124 male patients were admitted to our hospital for flexile cystoscopy by a single urologist between January 2013 and September 2013 and randomized to two equal groups. Group 2 included 62 patients who could select and listen to their preferred music during flexible cystoscopy. Group 1 included 62 patients who were unable to listen to the music. All patients were administered the same amount of lidocaine (10 mL) for 3 minutes for local anesthesia before flexible cystoscopy. A visual analog scale (VAS) ranging from 0 to 10 was used to assess patients' pain feeling after the cystoscopy procedure. Anxiety levels were calculated according to the State Instrument of State-Trait Anxiety Inventory (STAI-S), and the pulse rate were recorded 5 minutes before and immediately after the procedure. The duration of the procedure of each group were also analyzed. RESULTS: Statistically significant differences were detected between group 1 and group 2 in the mean pain score on VAS (2.53 ± 1.34 vs 1.63 ± 1.09, P=0.002, Mann-Whitney U test), mean postprocedural State Anxiety Inventory pain score (39.4 ± 6.5 vs 34.5 ± 5.8), and postprocedural pulse rate (79.8 ± 5.5 vs 76.0 ± 7.3) (P<0.001 for both, t test). Patients who listened to their preferred music experienced less discomfort and lower anxiety at cystoscopy. Patient age, duration of the procedure, preprocedural STAI-S, and preprocedural pulse rate of each group were comparable. CONCLUSION: Listening to preferred music during flexible cystoscopy is an easy way to improves male patients' comfort and reduce their anxiety. It could be recommended for male patients.

Emodin inhibits tumor necrosis factor-α-induced migration and inflammatory responses in rat aortic smooth muscle cells.

Emodin, a naturally occurring anthraquinone derivative in oriental herbal medicine, has been shown to exert a variety of pharmacological activities. The goal of this study was to determine the effects of emodin on the modulation of cell proliferation, migration, inflammatory responses, and matrix metalloproteinase (MMP)-2 and MMP-9 expression in tumor necrosis factor (TNF)-α-induced rat aortic smooth muscle cells (RASMCs). Cell proliferation and migration were measured using the MTT assay and the transwell chamber assay, respectively. Quantitative real-time PCR and western blot analysis were used to detect MMP expression. Gel shift was used for analysis of nuclear factor (NF)-κB activation. In addition, the expression of several inflammatory genes was also analyzed. Treatment of RASMCs with emodin significantly and dose-dependently attenuated TNF-α-induced proliferation, migration, mRNA and protein expression of MMP-2 and MMP-9, and NF-κB activation. Furthermore, emodin significantly inhibited TNF-α-evoked inflammatory responses, as demonstrated by the reduction in the expression of inflammatory genes. These results suggest that emodin inhibits TNF-α-induced proliferation, migration, MMP-2 and MMP-9 expression as well as inflammatory responses in cultured RASMCs, supporting the notion that emodin may have potential application in clinical atherosclerosis disease.

Anti-hyperglycemic activity of chromium(III) malate complex in alloxan-induced diabetic rats.

The synthesis, characterization, anti-hyperglycemic activity, oxidative DNA damage capacity, and acute toxicity of chromium(III) malate complex [Cr2(LMA)3] were described. [Cr2(LMA)3] was synthesized in a single-step reaction by chelating chromium(III) with L-malic acid in aqueous solution. Based on elemental analysis, thermodynamic analysis, and spectroscopy studies, the molecular formula of [Cr2(LMA)3] was inferred as Cr2(C4H4O5)3·5H2O. Daily treatment with 2.85-17.10 mg/kg body mass of [Cr2(LMA)3] in alloxan-induced diabetic rats for 2 weeks indicated that low-molecular-weight organic chromium complex [Cr2(LMA)3] had better bioavailability and more beneficial influences on the improvement of controlling blood glucose, serum lipid, and liver glycogen levels compared with CrCl3·6H2O. [Cr2(LMA)3] did not cause oxidative DNA damage under physiologically relevant conditions. Acute toxicity studies revealed no-measurable toxicity of the [Cr2(LMA)3]. Collectively, these results suggest that [Cr2(LMA)3] may represent a novel, proper chromium supplement with potential therapeutic value to control blood glucose and serum lipid in diabetes.

Subthalamic nucleus stimulation modulates thalamic neuronal activity.

Deep brain stimulation (DBS) in the subthalamic nucleus (STN) is an effective tool for the treatment of advanced Parkinson's disease. The mechanism by which STN DBS elicits its beneficial effect, however, remains unclear. We previously reported STN stimulation increased the rate and produced a more regular and periodic pattern of neuronal activity in the internal segment of the globus pallidus (GPi). Here we extend our observations to neurons in the pallidal [ventralis lateralis pars oralis (VLo) and ventralis anterior (VA)] and cerebellar [ventralis lateralis posterior pars oralis (VPLo)] receiving areas of the motor thalamus during STN DBS. Stimulation parameters that produced improvement in rigidity and bradykinesia resulted in changes in the pattern and power of oscillatory activity of neuronal activity that were similar in both regions of the motor thalamus. Neurons in both VA/VLo and VPLo tended to become more periodic and regular with a shift in oscillatory activity from low to high frequencies. Burst activity was reduced in VA/VLo, but was not significantly changed in VPLo. There was also a significant shift in the population of VA/VLo neurons that were inhibited during STN DBS, whereas VPLo neurons tended to be activated. These data are consistent with the hypothesis that STN DBS increases output from the nucleus and produces a change in the pattern and periodicity of neuronal activity in the basal ganglia thalamic network, and that these changes include cerebellar pathways likely via activation of adjacent cerebello-thalamic fiber bundles.

Deep brain stimulation reduces neuronal entropy in the MPTP-primate model of Parkinson's disease.

High-frequency stimulation (HFS) of the subthalamic nucleus (STN) or internal segment of the globus pallidus is a clinically successful treatment for the motor symptoms of Parkinson's disease. However, the mechanisms by which HFS alleviates these symptoms are not understood. Whereas initial studies focused on HFS-induced changes in neuronal firing rates, recent studies suggest that changes in patterns of neuronal activity may correlate with symptom alleviation. We hypothesized that effective STN HFS reduces the disorder of neuronal firing patterns in the basal ganglia thalamic circuit, minimizing the pathological activity associated with parkinsonism. Stimulating leads were implanted in the STN of two rhesus monkeys rendered parkinsonian by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Action potentials were recorded from neurons of the internal and external globus pallidus and the motor thalamus (ventralis anterior, ventralis lateralis pars oralis, and ventralis posterior lateralis pars oralis) during HFS that reduced motor symptoms and during clinically ineffective low-frequency stimulation (LFS). Firing pattern entropy was calculated from the recorded spike times to quantify the disorder of the neuronal activity. The firing pattern entropy of neurons within each region of the pallidum and motor thalamus decreased in response to HFS (n > or = 18 and P < or = 0.02 in each region), whereas firing rate changes were specific to pallidal neurons only. In response to LFS, firing rates were unchanged, but firing pattern entropy increased throughout the circuit (n > or = 24 and P < or = 10(-4) in each region). These data suggest that the clinical effectiveness of HFS is correlated with, and potentially mediated by, a regularization of the pattern of neuronal activity throughout the basal ganglia thalamic circuit.

[Determination of 1-deoxynojirimycin in leaves of Morus alba by high performance liquid chromatography with fluorescence detection].

OBJECTIVE: To develop a high performance liquid chromatographic method for the determination of DNJ in Morus alba leaves with fluorimetric detection after precolumn derivatization with 9-fluorenylmnethyl chlorformate (FMOC-Cl). METHOD: DNJ in Morus alba leaves was extracted with 0.05 mol x L(-1) HCl, reacted with FMOC-Cl, and separated on a HiQSiL C18 column at 250 degrees C. Mobile phase consisted of acetonitrile-0.1% aqueous acetic acid (55:45) with a flow rate of 1.0 mL x min. The fluorescence detector was operated at lambdaEX = 254 nm, lambdaEM = 322 nm. RESULT: A satisfactory separation between DNJ and impurity was obtained. The calibration curve was linear over the concentration range from 0.567 microg x mL(-1) to 34 microg mL(-1), r = 0.9998. The average recovery was 97.2%. The contents of DNJ in M. alba collected in different seasons and grown in different environment were determined. CONCLUSION: The quantity of DNJ in leaves of M. alba is related to the environment factor, temperature and growing period. The method can be used for qualioy control of the medicinal material.

A C-fiber reflex inhibition induced by electroacupuncture with different intensities applied at homotopic and heterotopic acupoints in rats selectively destructive effects on myelinated and unmyelinated afferent fibers.

The aims of this study were to explore the C-fiber reflex inhibition induced by electroacupuncture with different intensities applied at homotopic or heterotopic acupoints, and to determine the influence selectively destroyed myelinated and unmyelinated afferent fibers on the C-fiber reflex inhibition. In the ipsilateral local acupoint, the general behavior of the C-fiber reflex can be depressed by electroacupuncture below the threshold of Adelta-fiber activation. Electroacupuncture stimulation within the intensity of Adelta-fiber activation applied to the ipsilateral limb pretreated with cobra venom did not elicit inhibition of C-fiber reflex in rats with demyelinated sciatic nerve. However, heterotopic electroacupuncture below the threshold of Adelta-fiber activation was totally ineffective. In contralateral heterotopic acupoints, the C-fiber reflex can be depressed only by electroacupuncture with stimulating intensities exceeding thresholds of Adelta and C-fiber activation. Electroacupuncture stimuli applied to capsaicin-pretreated limb in the intensities of threshold of Adelta-fiber and treble thresholds of C-fiber activation produced only a little inhibition of C-fiber reflex. Inhibitory intensity was roughly similar to that induced by the stimulation with intensity for the activation of Adelta-fiber in normal animal. In the spinalized animals transections at T6-T7 segments, regardless of intensities, the homotopic electroacupuncture stimulation only induced moderate depression of C-fiber reflex similar to that of Adelta-fiber activation; whereas, no matter what intensities of application, the inhibitory effects of C-fiber reflex disappeared totally by using heterotopic noxious electroacupuncture in these animals.