Lonicerae Japonicae Flos Extract Promotes Sleep in Sleep-Deprived and Lipopolysaccharide-Challenged Mice.

Lonicerae Japonicae Flos (LJF) is commonly used in Chinese herbal medicines and exhibits anti-viral, anti-oxidative, and anti-inflammatory properties. The reciprocal relationship between sleep, the immune system and the central nervous system is well-established in the animal models. In this study, we used the mouse model to analyze the beneficial effects of the LJF on the dysregulated sleep-wakefulness cycle in response to acute sleep deprivation and lipopolysaccharide (LPS)-induced inflammation and the potential underlying mechanisms. Polysomnography data showed that LJF increased the time spent in non-rapid eye movement (NREM) sleep during the day under basal conditions. Furthermore, latency to sleep was reduced and the time spent in rapid eye movement (REM) sleep was increased during recovery from acute sleep deprivation. Furthermore, LJF-treated mice showed increased REM sleep and altered electroencephalogram (EEG) power spectrum in response to intra-peritoneal injection of LPS. LJF significantly reduced the levels of proinflammatory cytokines such as IL-6, TNF-α, and IL-1ß in the blood serum as well as hippocampus, and medial prefrontal cortex (mPFC) tissues in the LPS-challenged mice by inhibiting microglial activation. Moreover, LJF increased the time spent in REM sleep in the LPS-challenged mice compared to the control mice. These results suggested that LJF stimulated the sleep drive in response to acute sleep deprivation and LPS-induced inflammation, thereby increasing REM sleep for recovery and neuroprotection. In conclusion, our findings demonstrate that the clinical potential of LJF in treating sleep disorders related to sleep deprivation and neuro-inflammation.

Compressive and Energy Absorption Properties of Pyramidal Lattice Structures by Various Preparation Methods.

Metallic three-dimensional lattice structures exhibit many favorable mechanical properties including high specific strength, high mechanical efficiency and superior energy absorption capability, being prospective in a variety of engineering fields such as light aerospace and transportation structures as well as impact protection apparatus. In order to further compare the mechanical properties and better understand the energy absorption characteristics of metal lattice structures, enhanced pyramidal lattice structures of three strut materials was prepared by 3D printing combined with investment casting and direct metal additive manufacturing. The compressive behavior and energy absorption property are theoretically analyzed by finite element simulation and verified by experiments. It is shown that the manufacturing method of 3D printing combined with investment casting eliminates stress fluctuations in plateau stages. The relatively ideal structure is given by examination of stress-strain behavior of lattice structures with varied parameters. Moreover, the theoretical equation of compressive strength is established that can predicts equivalent modulus and absorbed energy of lattice structures.

Insulin-loaded hydroxypropyl methyl cellulose-co-polyacrylamide-co-methacrylic acid hydrogels used as rectal suppositories to regulate the blood glucose of diabetic rats.

The purpose of this study was developing a novel hydroxypropyl methyl cellulose-co-polyacrylamide-co-methacrylic acid (HPMC-co-PAM-co-PMAA) hydrogel, which was used as rectal suppository to regulate the blood glucose of diabetes. HPMC-co-PAM-co-PMAA hydrogel was fabricated via free-radical polymerization. Fourier transform infrared spectroscopy (FTIR) and Raman spectra were used to confirm the fabrication of HPMC-co-PAM-co-PMAA hydrogel. Their inner morphology was observed with scanning electron microscope (SEM). The extracts of hydrogel were applied to study their cell viability. The hypoglycemic effects of insulin (INS)-loaded HPMC-co-PAM-co-PMAA hydrogels were investigated by rectal administration. FTIR and Raman spectra confirmed the obtaining of HPMC-co-PAM-co-PMAA hydrogels. Many micro-pores were found in the SEM photograph of HPMC-co-PAM-co-PMAA hydrogels. Cell experiments indicated that HPMC-co-PAM-co-PMAA hydrogel was out of cytotoxicity. In vitro release profiles showed that INS-loaded hydrogel could release INS at a continuous manner in pH 7.4 buffer (rectal conditions). Animal experiments suggested that INS-loaded hydrogel had an obvious hypoglycemic effect. Therefore, as a convenient and economic method of administration, INS-loaded HPMC-co-PAM-co-PMAA hydrogels could be used as rectal suppositories to regulate blood glucose.

Network pharmacology-based prediction of the active ingredients, potential targets, and signaling pathways in compound Lian-Ge granules for treatment of diabetes.

AIMS: Compound Lian-Ge granules (CLGGs) is a traditional Chinese medicine preparation with good hypoglycemic effect and health function. This study was to predict its active ingredients, potential targets, signaling pathways, and investigate its mechanism of "ingredient-targets-pathways." METHODS: Pharmacodynamics studies on diabetic rats showed that CLGGs had an obvious hypoglycemic effect. On this basis, 27 hypoglycemic active ingredients were screened out. Their targets were confirmed by comparing with these hypoglycemic targets in PharmMapper and DrugBank databases via reversed pharmacophore matching approach. The relationships between ingredients and targets were revealed by comparing data in the String database. A network of "ingredient-target-passageway" was constructed. RESULTS: Studies showed that CLGGs had 24 active ingredients, ie, berberine, puerarin, danshinolic acid A, and sinigrin, etc. These ingredients involved nine targets, ie, insulin-like growth factor 1 receptor, insulin-degrading enzyme, ɑ-amylase, and so on, and 111 metabolic pathways, eg, hypoxia-inducible factor 1 signaling pathway, PI3K-Akt signaling pathway, mammalian target of rapamycin signaling pathway, and FoxO signaling pathway. CONCLUSION: Using network pharmacology methods, this study predicted the hypoglycemic active ingredients in CLGGs and revealed their targets, and provided a clue for further exploration of the hypoglycemic mechanism of CLGGs.

Polyelectrolyte Complex Nanoparticles Based on Methoxy Poly(Ethylene Glycol)-B-Poly (ε-Caprolactone) Carboxylates and Chitosan for Delivery of Tolbutamide.

In this study, a novel chitosan (CS)-modified nanoparticles (NPs) were developed to orally deliver tolbutamide (TOL). Methoxy poly(ethylene glycol)- b-poly(ε-caprolactone) carboxylates (mPEG2000-b-PCL4000) was synthesized via an esterification reaction. CS-modified mPEG2000-b-PCL4000-COOH NPs (CS@NPs) were fabricated by injecting mPEG2000-b-PCL4000-COOH NPs suspension (1.0 mg/mL) into CS solution (1.0 mg/mL, pH 5.0). Fourier transform infrared spectroscopy (FTIR) spectra were used to confirm the obtaining of mPEG2000-b-PCL4000-COOH. Transmission electron microscope (TEM) was carried out to observe morphology of all NPs. Nano ZS90 Malvern ParticleSizer were used to monitor the size distribution of obtained NPs. Thermogravimetry analysis (TGA) was performed to investigate the thermostability of CS@NPs. In vitro TOL release profiles were carried out in pH 1.2 and 7.4 buffers. FTIR spectra confirmed the obtaining of mPEG2000-b-PCL4000-COOH. TGA curves indicated that the protection of CS shells improved the thermostability of mPEG2000-b-PCL4000-COOH NPs. Cell tests indicated the CS@NPs had no obvious cytotoxicity, and they were easily taken up by 293T cells. In vitro release profiles showed that 91.0 ± 1.9% of encapsulated TOL were released from TOL-CS@NPs in pH 7.4 buffer. Therefore, the positive potential of CS@NPs could increase their combining capacity with intestinal mucosal cells. Finally, these NPs would improve the bioavailability of hydrophobic drugs.

Methylcellulose and polyacrylate binary hydrogels used as rectal suppository to prevent type I diabetes.

The purpose of this study was to fabricate a novel binary hydrogel, and the insulin-loaded hydrogel was used as rectal suppository to prevent type I diabetes. The binary hydrogel was synthesized via solution polymerization. Its structure was studied by Fourier transform infrared spectroscopy (FTIR) and Raman spectra. The swelling behaviors of binary hydrogels were revealed in pH 1.2, 6.8 and 7.4 buffers, respectively. Their inner morphologies were observed with a scanning electron microscope (SEM). Insulin (INS) was selected as a model drug and encapsulated into the binary hydrogels. INS release study was carried out in pH 7.4 buffer. The hypoglycemic effects of INS-loaded hydrogels were studied by rectal administration. FTIR and Raman spectra confirmed the obtaining of binary hydrogels. The hydrogel showed a high swelling ratio in pH 7.4 (rectum environment). SEM photographs illustrated that many micro-pores in the inner of binary hydrogels, which could accommodate abundant guest molecule (e.g. INS). INS release profile suggested that INS-loaded hydrogels could diffuse INS at a sustained manner. Animal studies proved that INS-loaded binary hydrogel had an obvious hypoglycemic effect. Therefore, it could be speculated that the binary hydrogel had a potential application on treating type I diabetes by rectal administration.

Polyelectrolyte complex nanoparticles based on chitosan and methoxy poly(ethylene glycol) methacrylate-co-poly(methylacrylic acid) for oral delivery of ibuprofen.

In this study, the copolymer of methoxy poly(ethylene glycol) methacrylate-co-poly(methylacrylic acid) [poly(mPEGMA-co-MAA)] was synthesized via radical polymerization. Based on this copolymer, novel chitosan-modified poly(mPEGMA-co-MAA) nanoparticles (CS/NPs) were developed to improve the bio-availability of ibuprofen (IBU). Fourier transform infrared spectroscopy (FTIR) and 1H nuclear magnetic resonance (1H NMR) spectra were used to confirm the synthesis of the copolymers. The morphology of CS/NPs was investigated with transmission electron microscopy (TEM). Thermogravimetric analysis (TGA) was used to reveal the thermodynamic properties of the CS/NPs. The cytotoxicity of CS/NPs was assessed by the cell viability of 293T cells. FTIR and 1H NMR spectra confirmed the synthesis of the novel copolymer. TEM photographs showed that the CS/NPs had a core-shell structure. High cell viability indicated that the CS/NPs were nontoxic. The in vitro release profiles suggested that the CS/NPs released IBU in pH 7.4 buffer in a continuous manner. Furthermore, the IBU-CS/NPs showed a long antifebrile effect. Animal experiments showed that the IBU-CS/NPs had obvious antifebrile effects. Therefore, CS/NPs could reduce the dosing frequency of IBU, and improve its bio-availability.

Surface-modified PLGA nanoparticles with chitosan for oral delivery of tolbutamide.

The main purpose of present study was to develop novel chitosan-modified polylactic-co-glycolicacid nanoparticles (CS@PLGA NPs) for improving the bio-availability of tolbutamide (TOL). The TOL-loaded CS@PLGA NPs (TOL-CS@PLGA NPs) were fabricated with the solvent evaporation method. The cargo-free CS@PLGA NPs showed a diameter of 228.3±2.5nm monitored with a laser light particlesizer, and the transmission electron microscope (TEM) photographs revealed their "core-shell" structures. The Zeta potential of the original PLGA NPs and the cargo-free CS@PLGA NPs was measured to be -20.2±3.21mV and 24.2±1.1mV, respectively. The changes in Zeta potential indicated the CS chains were coated on the surfaces of the original PLGA NPs. The thermal gravity analysis (TGA) curves suggested that the CS chains improved the thermostability of the original PLGA NPs. The results of cells viability indicated the cargo-free CS@PLGA NPs were nontoxicity. The in vitro release profiles suggested that TOL-CS@PLGA NPs could release TOL in pH 7.4 phosphate buffer solution (PBS) at a sustained manner. Streptozotocin (STZ) was employed to build the diabetic rat models. The physiological changes in the islet ß cells confirmed the obtaining of diabetic rats. After treatment by gavage, the TOL-CS@PLGA NPs showed an excellent hypoglycemic effect. Therefore, the TOL-CS@PLGA NPs had a potential application in oral delivery of TOL.

Plant Phenolics Extraction from Flos Chrysanthemi: Response Surface Methodology Based Optimization and the Correlation Between Extracts and Free Radical Scavenging Activity.

Huaiju is one of the most famous and widely used Flos Chrysanthemi (FC) for medicinal purposes in China. Although various investigations aimed at phenolics extraction from other FC have been reported, a thorough optimization of the phenolics extraction conditions from Huaiju has not been achieved. This work applied the widely used response surface methodology (RSM) to investigate the effects of 3 independent variables including ethanol concentration (%), extraction time (min), and solvent-to-material ratio (mL/g) on the ultrasound-assisted extraction (UAE) of phenolics from FC. The data suggested the optimal UAE condition was an ethanol concentration of 75.3% and extraction time of 43.5 min, whereas the ratio of solvent to material has no significant effect. When the free radical scavenging ability was used as an indicator for a successful extraction, a similar optimal extraction was achieved with an ethanol concentration of 72.8%, extraction time of 44.3 min, and the ratio of solvent to material was 29.5 mL/g. Furthermore, a moderate correlation between the antioxidant activity of TP extract and the content of extracted phenolic compounds was observed. Moreover, a well consistent of the experimental values under optimal conditions with those predicted values suggests RSM successfully optimized the UAE conditions for phenolics extraction from FC. PRACTICAL APPLICATION: The work of the research investigated the plant phenolics in Flos Chrysanthemi and antioxidant capacities. These results of this study can support the development of antioxidant additive and relative food.

[The Study of Methodology Validation in Multicomponent Quantitative Analysis of Raman Spectroscopy].

Raman spectroscopy with the help of sophisticated data analysis techniques based on multivariate analysis have made it possible to study the full information of Raman spectra and to draw conclusions about the chemical structure and composition of very complex systems. As Raman spectroscopy has the advantage to provide rich information of the sample, so it was first included in Chinese Pharmacopoeia (2010) as "Annex XIX L Guidelines of Raman spectroscopy". However the validation method for multicomponent quantitative analysis of Raman spectroscopy was not discussed in this pharmacopoeia. The purpose of this study was to develop innovatively the validation method for the Raman model in multicomponent quantitative analysis. Two kinds of samples with different matrix background were used to study the self-performance test of the instrument, linearity, limit of quantitation, accuracy and precision, respectively. As the sample was complex composition in our study, so there is no need to provide sample blank and rupture test for specificity study which was carried out in the traditional method of experiments. As the result showed, we propose a validation method for Raman spectroscopy in multicomponent analysis for the further study and improvement of standards of the method.

Noninvasive measurement of glucose in artificial plasma with near-infrared and Raman spectroscopy.

The goal of this research was to develop a method for noninvasive blood glucose assay. Near-infrared (NIR) spectroscopy and Raman spectroscopy, two more promising techniques compared to other methods, were investigated in two kinds of artificial plasma (AP). Calibration models were generated by performing partial least squares (PLS) regression and optimized individually by considering spectral range, spectral pretreatment methods, and number of model factors. The two spectroscopic models were validated for the determination of glucose, and the results show that the two spectroscopic models established are robust, accurate, and repeatable. Compared to Raman spectroscopy, the performance of NIR spectroscopy was much better, with lower root mean square errors of cross-validation (RMSECV) of 0.128 and 0.094 mg/ml, lower root mean square errors of validation (RMSEP) of 0.061 and 0.046 mg/ml, higher correlation coefficients (R) of 99.15% and 99.55%, and higher residual predictive deviations (RPD) of 10.8 and 15.0 for artificial plasma I and II, respectively.

Profiling the dynamics of abscisic acid and ABA-glucose ester after using the glucosyltransferase UGT71C5 to mediate abscisic acid homeostasis in Arabidopsis thaliana by HPLC-ESI-MS/MS.

The HPLC-MS/MS method was developed to profile the dynamics of abscisic acid (ABA) and ABA-glucose ester (ABA-GE) after cloning glycosyltransferase enzyme family gene AtUGT71C5 into Arabidopsis thaliana. By constructing over-expression lines (OE) and down-expression lines (DN), we acquired mutant strains to analyze the function of AtUGT71C5. The multiple-reaction monitoring (MRM) was used for quantitative determination in negative mode. The transition was m/z 263.1→153.0 for ABA ([M-H]+), m/z 425.1→263.0 for ABA-GE ([M-H]+), and m/z 321.0→152.0 for chloramphenicol. The linear range was 0.8684-217.1 ng/mL for ABA and 0.3920-196.0 ng/mL for ABA-GE. The accuracy was 88.0-109.0% for ABA and 86.6-113.0% for ABA-GE; the inter-day and intra-day precisions were less than 5.4% for ABA and 8.9% for ABA-GE, respectively. This method is simple and sensitive enough for determination of ABA and ABA-GE in A. thaliana leaves. All the evidence confirmed the speculation that AtUGT71C5 can mediate abscisic acid homeostasis.

Effect of acupuncture on rats with acute gouty arthritis inflammation: a metabonomic method for profiling of both urine and plasma metabolic perturbation.

Acute gouty arthritis is a common inflammation model with multiple pathogenic mechanisms seen in clinical practice, for which acupuncture may potentially be an alternative therapy. To investigate the effect of acupuncture on acute gouty arthritis and search for its mechanism, a metabonomic method was developed in this investigation. Acute gouty arthritis model rats were induced by monosodium urate (MSU) crystals. The urine and plasma samples were collected at several time points and the endogenous metabolites were analyzed by an ultra-performance liquid chromatography coupled with a mass spectrometry (UPLC-MS). Data were analyzed using principal components analysis (PCA) and partial least squares (PLS) analysis to compare metabolic profiles of MSU crystal-induced acute gouty arthritis rats with MSU crystal-induced acute gouty arthritis, treated with acupuncture rats. The results showed that acupuncture could restore the metabolite network that disturbed by MSU administration. Our study indicates that UPLC-MS-based metabonomics can be used as a potential tool for the investigation of biological effect of acupuncture on acute gouty arthritis.