Guoan Luo

Tsinghua University, Beijing, Beijing Shi, China

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Publications (89)279.46 Total impact

  • Article: Cardioprotective effects of the YiQiFuMai injection and isolated compounds on attenuating chronic heart failure via NF-κB inactivation and cytokine suppression.
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    ABSTRACT: ETHNOPHARMACOLOGICAL RELEVANCE: The YiQiFuMai injection (YQFM) is a traditional Chinese medicine for the treatment of chronic heart failure (CHF). AIM OF THE STUDY: The present study not only evaluated the cardioprotective effect and anti-inflammatory mechanism of the YQFM injection in an experimental model of CHF but also investigated its bioactive constituents in vitro. MATERIALS AND METHODS: The left anterior descending coronary artery (LAD) in rats was ligated to make an animal model of CHF. From this, electrocardiographic parameters and exterior signs of rat hearts were recorded. Additionally, the histopathology of heart tissues was examined, and parameters of inflammatory stress were measured. Experiments were performed over two months in LAD-ligation rats treated with YQFM or vehicle. Treatment with Captopril was used as a positive control, which has previously been shown to prevent CHF, and rats without LAD-ligation were used as a negative control. Furthermore, we screened and identified potential anti-inflammatory constituents by ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS) combined with NF-κB activity luciferase reporter assay systems. Further cytokine detection confirmed the anti-inflammatory effects of the potential NF-κB inhibitors from YQFM. RESULTS: The administration of YQFM significantly improved cardiac function and ameliorated the activity level of inflammatory mediators (such as tumor necrosis factor-alpha, interleukin-6, and interleukin-1β) in CHF rats. Eight potential anti-inflammatory ingredients, ginsenosides Rb1, Rg1, Rf, Rh1, Rc, Rb2, Ro, and Rg3, were characterized and confirmed. Among these compounds, ginsenoside Ro was revealed as a new NF-κB inhibitor. CONCLUSION: The results suggested that NF-κB inactivation and cytokine suppression might be one of the main mechanisms of YQFM that caused ameliorative effects in CHF rats, and the major constituents of ginsenosides were identified playing a key role in the treatment of CHF.
    Journal of ethnopharmacology 04/2013; · 2.32 Impact Factor
  • Article: Screening and Evaluation of Traditional Chinese Medicine by Microarray Expression Analysis.
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    ABSTRACT: Object: Salvia miltiorrhiza is a Chinese medicinal herb, which is widely used for the treatment of cardiovascular disorders. In this article, we investigated the effects of Salvia miltiorrhiza and its hydrophilic and lipophilic components (HCS and LCS) on human umbilical vein endothelial cells (HUVECs), and the molecular mechanism was explored by microarray gene expression profiling. MATERIALS AND METHODS: Cell proliferation and migration were used to evaluate the angiogenic effects of HCS, LCS and total extract of Salvia miltiorrhiza (TES). Microarray technology was applied to detect the gene expression of HUVECs treated with TES, HCS and LCS. Besides, quantitative real-time PCR was used to verify the microarray results. RESULTS: Our results showed that LCS inhibited the proliferation and migration of HUVECs, HCS promoted the proliferation and migration of HUVECs, and TES did not affect the viability of HUVECs at the concentration of 5µg/mL. From the result of principle component analysis (PCA) of microarray data, the effect of LCS on HUVECs was significantly different from the other components. Moreover, there were more differentially expression genes in LCS group than in the other groups, which meant LCS had a strong influence on HUVECs. Compared with untreated cells, 511 significantly changed genes had been detected in LCS treated cells and 236 (approximately 46%) of them were up-regulated. The mRNA expression of IL-6 was found to be increased significantly in LCS group. CONCLUSIONS: In Salvia miltiorrhiza, HCS and LCS had opposite effects on HUVECs. LCS showed significantly inhibitory action on HUVECs proliferation and migration. It was proposed that LCS could apply in the diseases caused by vascular anomaly hyperplasia. In the mechanism of action of LCS on HUVECs, the pathways of ErbB, MAPK, p53, oxidative phosphorylation and inflammatory response were involved.
    Journal of ethnopharmacology 04/2013; · 2.32 Impact Factor
  • Article: Classification and analysis of corn steep liquor by UPLC/Q-TOF MS and HPLC.
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    ABSTRACT: Corn steep liquor (CSL), an important raw material with high nutritional value, serves as a nitrogen source in the fermentation industry. The CSL quality directly affects the yield and quality of fermentation products. In this work, a fingerprinting technique was used to identify the potential markers of CSL. Forty-two CSL samples from different manufacturers were profiled by ultra-performance liquid chromatography with tandem quadrupole time-of-flight mass spectrometry. Sixteen compounds, almost all of which were amino acids and their derivatives, were considered as the potential markers. Then, o-phthalaldehyde-9-fluorenylmethyl chloroformate precolumn derivatization by high-performance liquid chromatography was performed to identify the free amino acids in CSL. Principal component analysis (PCA) was used to distinguish among the samples from different manufacturers. The results demonstrated that the fingerprinting technique combined with PCA analysis was a powerful tool for determining the CSL quality.
    Talanta 03/2013; 107C:344-348. · 3.79 Impact Factor
  • Article: Bioactivity-integrated ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry for the identification of nuclear factor-κB inhibitors and β2 adrenergic receptor agonists in Chinese medicinal preparation Chuanbeipipa dropping pills.
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    ABSTRACT: A simple and dual-target method based on ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry combined with dual-bioactive [nuclear factor-κB (NF-κB) and β2 -adrenergic receptor] luciferase reporter assay systems was developed to rapidly characterize the chemical structure of various bioactive compounds of TCM preparations. Chuanbeipipa dropping pills, a traditional Chinese medicine preparation used for the clinical therapy of chronic obstructive lung disease and cough caused by bronchial catarrh, was analyzed with this method. Potential anti-inflammatory and spasmolytic constituents were screened using NF-κB and β2 -adrenergic receptor activity luciferase reporter assay systems and simultaneously identified according to the time-of-flight mass spectrometry data. One β2 -adrenergic receptor agonist (ephedrine) and two structural types of NF-κB inhibitors (platycosides derivatives and ursolic acid derivatives) were characterized. Platycodin D3 and E were considered new NF-κB inhibitors. Further cytokine and chemokine detection confirmed the anti-inflammatory effects of the potential NF-κB inhibitors. Compared with conventional fingerprints, activity-integrated fingerprints that contain both chemical and bioactive details offer a more comprehensive understanding of the chemical makeup of plant materials. This strategy clearly demonstrated that multiple bioactivity-integrated fingerprinting is a powerful tool for the improved screening and identification of potential multi-target lead compounds in complex herbal medicines. Copyright © 2013 John Wiley & Sons, Ltd.
    Biomedical Chromatography 03/2013; · 1.97 Impact Factor
  • Article: Preparation of Functionalized Alkynyl Magnetic Microspheres for the Selective Enrichment of Cell Glycoproteins Based on Click Chemistry.
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    ABSTRACT: Functionalized alkynyl polyvinyl alcohol magnetic microspheres (PVA MMs) were developed for the specific enrichment of sialic acid-rich glycoproteins by click chemistry. The capture capability for proteins was evaluated through a novel dual-labeled bovine serum albumin (BSA) that utilizes fluorescence resonance energy transfer (FRET). The PVA MM parameters, including the size and coverage of functionalized groups, were optimized by response surface methodology. The optimal parameters obtained were 1.25 µm to 6.31 µm in size and 48.53% to 73.05% in coverage. Then, the optimal PVA MMs were synthesized, and the morphology and surface chemical properties were characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FT-IR). To capture glycoproteins from the cell surface, a bioorthogonal chemical method was applied to metabolically label them with an azide group. The functionalized alkynyl PVA MMs showed a high specificity and strong binding capability for glycoproteins through a [3+2] cycloaddition reaction. The results indicated that the functionalized alkynyl PVA MMs could be applied to the enrichment of cell glycoproteins, and the merits of the MMs suggested an attractive and potential way to facilitate glycoprotein research.
    Biomacromolecules 12/2012; · 5.48 Impact Factor
  • Article: A metabonomic approach to the effect evaluation of treatment in patients infected with influenza A (H1N1).
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    ABSTRACT: The pandemic influenza A virus (H1N1) was transmitted to the human population since 2009, resulting in some consequences of viral pneumonia, respiratory failure, multiple organ failure and, most severely, death. In clinical practice, Chinese medicine possessed extensive experience for prevention and treatment of influenza, but its mechanism still remain unclear. In addition, the efficacy of combination therapy of Chinese and Western medicine was attractive, but not yet clear. In the present study, 131 patients from Guangzhou China referred for H1N1 virus mRNA testing for the evaluation of possible influenza A-infected were eligible for participation. A metabonomics study was carried out to explore the difference between before and after treatment in patients with H1N1 through Chinese and/or Western medicine. Results from metabolic profiling and biochemical detection indicated significant metabolic change in the arachidonic acid metabolic pathway. In the group of combination therapy of Chinese and western medicine, its efficacy was best and the potential biomarkers were significantly changed compared with untreated state. Those results indicated that the potential metabolic biomarker could be supplemented with biochemical detection to obtain more precise diagnosis for H1N1 infection. Clinical trials registration: Clinical Trials. Gov No. 2008GL-50.
    Talanta 10/2012; 100C:51-56. · 3.79 Impact Factor
  • Article: Controlling gas/liquid exchange using microfluidics for real-time monitoring of flagellar length in living Chlamydomonas at the single-cell level.
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    ABSTRACT: Chlamydomonas reinhardtii is widely used for studying cilia/flagella, organelles important for human health and disease. In situ monitoring of flagellar assembly/disassembly kinetics in single living cells has been difficult with conventional methods because of time-consuming media exchange and the requirement of whole cell fixation. Here, we develop a PDMS/glass hybrid microfluidic device for real-time tracking of flagellar length in single living cells of Chlamydomonas. Media exchange is precisely controlled by sequential gas-liquid plugs and complete medium replacement occurs within seconds. Rapid medium exchange allows the capture of transient flagellar dynamics. We show that Chlamydomonas cells respond to acidic medium exchange and deflagellate. However, the two flagella may shed asynchronously. After subsequent medium exchange, cells regenerate full-length flagella. Cells are also induced to shorten their flagella after being exposed to extracellular stimuli. The long-term kinetics of flagellar regeneration and disassembly for the whole cell population on the chip are comparable to those from conventional methods; however, individual cells display non-uniform response kinetics. We also find that flagellar growth rate is dependent on flagellar length. This device provides a potential platform to continuously monitor molecular activities associated with changes in flagellar length and to capture transient molecular changes upon flagellar loss, and initiation of flagellar assembly/disassembly.
    Lab on a Chip 09/2012; 12(21):4516-22. · 5.67 Impact Factor
  • Article: A simple way to configure on-line two-dimensional liquid chromatography for complex sample analysis: acquisition of four-dimensional data.
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    ABSTRACT: An on-line comprehensive two-dimensional liquid chromatography (HPLC×UPLC-TOF MS) was set up just using the injection valve of the ultra performance liquid chromatography (UPLC) as the interface through which the effluent of high performance liquid chromatography (HPLC) was injected automatically to UPLC coupled to time-of-flight mass spectrometry (TOF MS). As a demonstrative application, a complex sample of Traditional Chinese Medicine, Qingkailing was analyzed. As a result, a four-dimensional (4D) data containing 2D retention times, peak intensity and m/z ratios was plotted, where 398 peaks were counted and low concentration components were distinguished from the high concentration ones with a total peak capacity of 1090. Comparing with traditional 3D data acquired by HPLC×HPLC, the 4D data generated by HPLC×UPLC-TOF MS can increase the number of recognized components by three times, reduce the analysis time by 75%. Such a configuration of HPLC×UPLC-TOF MS can realize easily upon commercial chromatographs while exhibited enhanced separation efficiency, high sensitivity, huge peak capacity and great potential in complex sample analysis.
    Talanta 08/2012; 97:150-6. · 3.79 Impact Factor
  • Article: Antifungal activity in plants from Chinese traditional and folk medicine.
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    ABSTRACT: From over 100 Chinese clinical trial publications, we retrieved 22 commercial preparations and 17 clinical prescriptions used as Traditional Chinese Medicine (TCM) for treating mycotic vaginitis, typically caused by Candida albicans. The 8 most frequently used plants as well as another 7 TCM and 18 folk medicinal plants used in the South of China for antifungal therapy were investigated for in vitro antifungal activity. For each plant we tested 4 extracts prepared with different solvents (water, ethanol, acetone, and n-hexane) for inhibition of Candida albicans and Saccharomyces cerevisiae growth in liquid culture. Some plants have quite strong antifungal activity, such as Tujinpi (Pseudolarix kaempferi Gord.), of which each extract could significantly inhibit the growth of both tested fungi. In addition, the acetone extract of Kushen (Sophora flavescens Ait.), the ethanol, acetone, and hexane extracts of Guanghuoxiang (Pogostemon cablin (Blanco) Benth.) and Gaoliangjiang (Alpinia officinarum Hance), the hexane extract of Dingxiang (Eugenia caryophyllata Thunb.), and the ethanol and acetone extracts of Kulianpi (Melia toosendan Sieb. et Zucc.) and Laliao (Polygonum hydropiper L.), all inhibited Candida albicans growth by more than 50%. In some cases growth inhibition was even comparable to that by the clinically used antifungal miconazole, which we used as our positive control. The majority of plants, whose clinical use for antifungal treatment is well supported within TCM or Chinese folk medicine, show in vitro antifungal activity against Candida albicans. Since Candida species represent the most common fungal pathogen of humans, these results provide more scientific evidence supporting the clinical application of these plants, and can serve as a starting point for new drug discovery from TCM and Chinese folk medicine.
    Journal of ethnopharmacology 07/2012; 143(3):772-8. · 2.32 Impact Factor
  • Article: Steaming-induced chemical transformations and holistic quality assessment of red ginseng derived from Panax ginseng by means of HPLC-ESI-MS/MS(n)-based multicomponent quantification fingerprint.
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    ABSTRACT: The purpose of this study is to evaluate the steaming-induced chemical transformation of red ginseng manufactured from fresh ginseng by means of simultaneous quantitative and qualitative analyses with a combinative high-performance liquid chromatography-electrospray tandem mass spectrometry (HPLC-ESI-MS/MS(n)) technique. Thirty-six ginsenosides were identified in red ginseng and white ginseng by comparing the mass spectrum and/or matching the empirical molecular formula with that of known published compounds, and 11 of them were determined to be newly generated during the red ginseng preparatory process. The mechanisms involved were further deduced to be hydrolysis, dehydration, isomerization, and decarboxylation at C-20, and hydrolysis also occurs at C-3 or C-6 of the original ginsenosides through the mimic process of steaming and heating in laboratory. The multicomponent quantification fingerprint of ginseng was also established by HPLC-UV method, and the contents of 12 ginsenosides in red and white ginsengs from different sources were determined simultaneously. The ratio of the total content of determined malonyl ginsenosides to the corresponding neutral ginsenosides (T(m-PPD)/T(PPD)) in white ginseng ranged from 0.46 to 0.62 and from 0 to 0.19 in red ginseng. The validated method is expected to provide an effective approach to standardize the processing procedures of ginseng products and regulate the usage of ginseng in Traditional Chinese Medical prescription.
    Journal of Agricultural and Food Chemistry 07/2012; 60(33):8213-24. · 2.82 Impact Factor
  • Article: Determination of main categories of components in corn steep liquor by near-infrared spectroscopy and partial least-squares regression.
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    ABSTRACT: Corn steep liquor (CSL) is an important raw material that has a high nutritional value and serves as a nitrogen source. This study aimed to develop a fast, versatile, cheap, and environmentally safe analytical method of quantifying the total acidity (TA) of CSL as well as its contents of dry matter (DM), total sugars (TS), total reducing sugars (TRS), total free amino acids (TFAA), total nitrogen (TN), and total sulfite (TSu). The near-infrared (NIR) spectroscopy measurements of 66 samples (22 batches) of CSL were analyzed by partial least-squares regression using several spectral preprocessing methods. Multivariate models developed in the NIR area showed good predictive abilities for DM, TA, TS, TRS, TFAA, TN, and TSu determination. These results confirm the feasibility of the multivariate spectroscopic approach as a replacement for expensive and time-consuming conventional chemical methods. Thus, a convenient and feasible method for the quality control of fermentation raw materials for food additives and fine chemicals, especially in CSL, is established.
    Journal of Agricultural and Food Chemistry 07/2012; 60(32):7830-5. · 2.82 Impact Factor
  • Article: Selectively modified microfluidic chip for solvent extraction of Radix Salvia Miltiorrhiza using three-phase laminar flow to provide double liquid–liquid interface area
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    ABSTRACT: Radix Salvia Miltiorrhiza, a famous herb medicine is widely used in China and limitedly used in USA, Japan, and other countries for the treatment of cardiovascular and cerebrovascular diseases. This herb medicine has two groups (non-polar and polar) of active ingredients with distinct clinical effects, and thus theses ingredients should be separately used to enhance therapeutic efficacy and reduce side effect. In this article, as an alternative of conventional mechanical shaking and separatory funnel, laminar flow extraction in microfluidic chip is proposed to separate the two kinds of herb ingredients. Compared with conventional methods, microfluidic chip provides continuous extraction, less labor intensity, and better performance. Furthermore, we employ three-phase laminar flow to provide double liquid–liquid interface area, circumventing the low efficiency of two-phase laminar flow. Therefore, the extraction ratio is dramatically improved to 92% (tanshinone IIA). To predict the extraction ratio, a straightforward theoretical model is also established and agrees well with the experimental results. This microfluidic chip would be a powerful technical platform for handling complicated natural products. KeywordsLaminar flow-Microfluidics-Hydrophobic modification-Solvent extraction-Radix Salvia Miltiorrhiza
    Microfluidics and Nanofluidics 04/2012; 9(2):365-373. · 3.37 Impact Factor
  • Article: Simultaneous LC–UV–MS–MS Analysis of Nine Pivotal Metabolites in Human Serum: Application to Studies of Impaired Glucose Tolerance
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    ABSTRACT: A rapid, sensitive, and selective LC–UV–MS–MS method for simultaneous quantification of uric acid, creatinine, xanthine, creatine, hypoxanthine, adenosine, inosine, thymidine, and uridine in serum from patients with impaired glucose tolerance (IGT) has been developed and validated. After precipitation of protein in the serum with methanol samples were evaporated with a stream of nitrogen then reconstituted with aqueous ammonia (0.002molL−1). Chromatographic separation was performed on a C18 column with methanol–buffer (8mmolL−1 ammonium acetate adjusted to pH 6.1 with glacial acetic acid) as mobile phase at a flow rate of 0.8mLmin−1. UV and MS–MS detection were used to quantify the metabolites on the basis of different concentrations and detector response. Linearity was excellent, with r 2 no <0.998. Recovery, and intra-day and inter-day relative standard deviation (RSD) were >85, <10, and <10%, respectively. This reliable bioanalytical method enables evaluation of the levels of purines and pyrimidines in serum for IGT studies and diagnosis. KeywordsColumn liquid chromatography–Tandem mass spectrometry–Human serum–Purines and pyrimidines–Impaired glucose tolerance
    Chromatographia 04/2012; 73(1):149-155. · 1.20 Impact Factor
  • Article: Improved GC for Isosorbide-5-mononitrate Determination in Dog Plasma and Its Application in Pharmacokinetics
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    ABSTRACT: The existing methods for the extraction and determination of isosorbide-5-mononitrate (5-ISMN) in biological samples are too complicated, poorly reproducible, and time-consuming. Therefore a procedure is described for the extraction of 5-ISMN from plasma with ethyl acetate and saturated potassium carbonate solution. The procedure of extraction is simple, and has a high recovery. At the same time, an improved, simple, rapid, and specific analytical method for the determination of 5-ISMN in dog plasma by capillary gas chromatography with electron-capture detection was developed. O-Dinitrobenzene was used as an internal standard. This method was successfully applied to a pharmacokinetic study on 5-ISMN.
    Chromatographia 04/2012; 69(7):799-802. · 1.20 Impact Factor
  • Article: Simultaneous RP-LC Analysis of the Prodrug Scu-PEG and its Metabolite Scutellarin in Rat Plasma
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    ABSTRACT: Scutellarin is released from the prodrug Scu-PEG after i.v. administration to rats. To investigate changes in the amount of the prodrug in vivo, a liquid chromatographic method for simultaneous analysis of Scu-PEG and scutellarin in rat plasma was developed and validated. A C18 column was used with a binary mobile phase gradient prepared from acetonitrile and 0.3% aqueous formic acid solution. The detection wavelength was 334nm and the column temperature 40°C. Linearity was excellent, with R 2 no less than 0.999. Intra-assay and inter-assay precision, as RSD, were less than 6.4 and 4.7%, respectively, for scutellarin and less than 2.8 and 2.9% for Scu-PEG. The method is applicable to pharmacokinetic study the prodrug and its metabolite in rats after i.v. administration. KeywordsColumn liquid chromatography-Simultaneous analysis and method validation-Scutellarin-Scu-PEG prodrug
    Chromatographia 04/2012; 71(5):511-515. · 1.20 Impact Factor
  • Article: A modified microfluidic chip for fabrication of paclitaxel-loaded poly(l-lactic acid) microspheres
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    ABSTRACT: In this article, we present a simple PDMS surface modification method based on poly(vinyl alcohol)/glycerol (PVA/Gly) solution immersion, self-assembled absorption, and heat treatment. The results of contact angle and ATR-FTIR demonstrate the superhydrophilic surface in modified PDMS. It can allow for the stable production of monodisperse droplet in a highly reproducible manner. In addition, we demonstrate the fabrication of monodisperse paclitaxel (PTX) loaded poly(l-lactic acid) (PLLA) microspheres on this kind of modification chip with solvent evaporation. The PLLA microspheres can be adjusted to a range of different sizes depending on the system flow rate. Determination of microsphere size is carried out by optical microscopy and image analysis to reveal less than 4% variation in microsphere size. Compared with the results of published papers, the presented data demonstrate that PTX-loaded PLLA microspheres show good physical properties (spherical and discrete), high-drug loading, encapsulation efficiency, a small initial burst, and sustained-release behavior due to outstanding monodispersity. With the characteristic to prepare high-quality, monodisperse, biodegradable microspheres, the versatile and simple microfluidic method facilitates the development of more reliable and reproducible drug delivery systems, which have great potential to benefit pharmaceutical and biological applications. KeywordsMicrofluidic–Droplets–Poly(l-lactic acid) microsphere–Paclitaxel–Drug delivery–Monodisperse
    Microfluidics and Nanofluidics 04/2012; 10(6):1289-1298. · 3.37 Impact Factor
  • Article: Study on Interactions of Phenolic Acid-Like Drug Candidates with Bovine Serum Albumin by Capillary Electrophoresis and Fluorescence Spectroscopy
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    ABSTRACT: The interactions of the phenolic acids cinnamic acid (CNA), ferulic acid (FA), caffeic acid (CA) and chlorogenic acid (CLA) with bovine serum albumin (BSA) were investigated and compared using affinity capillary electrophoresis (ACE) and the fluorescence quenching methods. ACE gives binding constants (K b) and thermodynamic parameters. The thermodynamic parameters show that each of four phenolic acids bind to BSA mainly by hydrogen bonds, electrostatic and hydrophobic interactions. The fluorescence quenching method provided quenching constant K sv, binding site number n and K b. The fluorescence results indicate that BSA fluorescence quenching is mainly a static quenching process. The binding constants (K b) of CNA, FA, CA and CLA were from 2.52×104 to 7.90×104L⋅mol−1 from ACE experiments and 1.19×104 to 5.21×104L⋅mol−1 from fluorescence, their increase corresponded to the increase in the number of hydroxyl groups. These results imply that molecular structure and the number of hydroxyl groups of phenolic acids play act key roles in the affinity of natural phenolic acids towards BSA. KeywordsInteraction-Phenolic acids-Bovine serum albumin-Capillary electrophoresis-Fluorescence quenching
    Journal of Solution Chemistry 04/2012; 39(11):1653-1664. · 1.41 Impact Factor
  • Article: Apolipoprotein A-I mimetic peptide inhibits atherosclerosis by altering plasma metabolites in hypercholesterolemia.
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    ABSTRACT: An apolipoprotein A-I mimetic peptide, D-4F, has been shown to improve vasodilation and inhibit atherosclerosis in hypercholesterolemic low-density lipoprotein receptor-null (LDLr(-/-)) mice. To study the metabolic variations of D-4F ininhibiting atherosclerosis, metabonomics, a novel system biological strategy to investigate the pathogenesis, was developed. Female LDLr(-/-) mice were fed a Western diet and injected with or without D-4F intraperitoneally. Atherosclerotic lesion formation was measured, whereas plasma metabolic profiling was obtained on the basis of ultra-high-performance liquid chromatography in tandem with time-of-flight mass spectrometry operating in both positive and negative ion modes. Data were processed by multivariate statistical analysis to graphically demonstrate metabolic changes. The partial least-squares discriminate analysis model was validated with cross-validation and permutation tests to ensure the model's reliability. D-4F significantly inhibited the formation of atherosclerosis in a time-dependent manner. The metabolic profiling was altered dramatically in hypercholesterolemic LDLr(-/-) mice, and a significant metabolic profiling change in response to D-4F treatment was observed in both positive and negative ion modes. Thirty-six significantly changed metabolites were identified as potential biomarkers. A series of phospholipid metabolites, including lysophosphatidylcholine (LysoPC), lysophosphatidylethanolamine (LysoPE), phosphatidylcholine (PC), phatidylethanolamine (PE), sphingomyelin (SM), and diacylglycerol (DG), particularly the long-chain LysoPC, was elevated dramatically in hypercholesterolemic LDLr(-/-) mice but reduced by D-4F in a time-dependent manner. Quantitative analysis of LysoPC, LysoPE, PC, and DG using HPLC was chosen to validate the variation of these potential biomarkers, and the results were consistent with the metabonomics findings. Our findings demonstrated that D-4F may inhibit atherosclerosis by regulating phospholipid metabolites specifically by decreasing plasma long-chain LysoPC.
    AJP Endocrinology and Metabolism 04/2012; 303(6):E683-94. · 4.75 Impact Factor
  • Article: A gravity-actuated technique for flexible and portable microfluidic droplet manipulation
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    ABSTRACT: In this study, an inexpensive and robust microfluidic droplet manipulation device based on gravity-actuated technique is described. The device is mainly composed of a turntable and some disposable infusion sets. The movement of oil-phase and water-phase in the microchannel is controllable. Droplet volume of different sizes is precisely generated by controlling droplet length using the turntable. A series of essential functional units have been demonstrated including on-demand sampling, droplets generation of controllable size and controllable number, droplets fusion of different sizes and contents, even droplets-stopping. These functions can well meet the requirements of routine droplet-based microfluidic biological/chemical assays, cell research, and high content drug screening. The presented technique shows unique advantages in inexpensiveness, flexibility, and portability when compared with general droplet manipulation systems containing precision syringe pump and complicated micromechanical/pneumatic valve. Furthermore, this device can be used as a portable droplet manipulation tool in outdoor and remote areas, because it does not need electrical source and is very facile to set up in any place. KeywordsMicrofluidic-Droplet-Gravity-Manipulation-Technique
    Microfluidics and Nanofluidics 04/2012; 9(4):995-1001. · 3.37 Impact Factor
  • Article: Ligustrazine phosphate ethosomes for treatment of Alzheimer's disease, in vitro and in animal model studies.
    Jun Shi, Yiming Wang, Guoan Luo
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    ABSTRACT: In the present study, we have investigated transdermal administration of ligustrazine phosphate (LP), as an antioxidant, for the treatment of Alzheimer's disease (AD). The LP transdermal ethosomal system was designed and characterized. Franz-type diffusion cells and confocal laser scanning microscopy were used for the in vitro permeation studies. Furthermore, the effect of LP transdermal ethosomal system on AD was evaluated in the scopolamine-induced amnesia rats by evaluating the behavioral performance in the Morris water maze test. The activities of the antioxidant enzymes and the levels of the lipid peroxidation product malondialdehyde (MDA) in the brain of rats were also determined. The results showed that both the penetration ability and the drug deposition in skin of the LP ethosomal system were significantly higher than the aqueous one. The LP transdermal ethosomal system could recover the activities of the antioxidant enzymes and the levels of MDA in the brain of the amnesic rats to the similar status of the normal rats, which was also indirectly reflected by the improvement in the behavioral performance. In conclusion, LP might offer a potential alternative therapeutic drug in the fight against AD, and ethosomes could be vesicles of choice for transdermal delivery of LP.
    AAPS PharmSciTech 03/2012; 13(2):485-92. · 1.43 Impact Factor

Institutions

  • 2003–2013
    • Tsinghua University
      • • Department of Chemistry
      • • School of Medicine
      Beijing, Beijing Shi, China
    • Qingdao University
      • Department of Chemistry
      Qingdao, Shandong Sheng, China
  • 2012
    • Shanghai University of Traditional Chinese Medicine
      Shanghai, Shanghai Shi, China
    • Sun Yat-Sen University
      Guangzhou, Guangdong Sheng, China
    • Nankai University
      • College of Pharmacy
      Tianjin, Tianjin Shi, China
  • 2007–2012
    • East China University of Science and Technology
      • School of Pharmacy
      Shanghai, Shanghai Shi, China
  • 2011
    • Jiangxi University of Traditional Chinese Medicine
      Nanchang, Jiangxi Sheng, China
  • 2009–2011
    • University of Science and Technology of China
      Hefei, Anhui Sheng, China
  • 2008
    • Hubei University of Technology
      Wuhan, Hubei, China
  • 2007–2008
    • Shenyang Pharmaceutical University
      • School of Pharmaceutics
      Shenyang, Liaoning, China
  • 2006
    • Zhejiang University
      • College of Pharmaceutical Sciences
      Hangzhou, Zhejiang Sheng, China