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        Pretreatment with low-dose fimasartan ameliorates NLRP3 inflammasome-mediated neuroinflammation and brain injury after intracerebral hemorrhage

        Yang, Xiuli,Sun, Jing,Kim, Tae Jung,Kim, Young-Ju,Ko, Sang-Bae,Kim, Chi Kyung,Jia, Xiaofeng,Yoon, Byung-Woo Elsevier 2018 Experimental neurology Vol.310 No.-

        <P><B>Abstract</B></P> <P>Nucleotide-binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, which is composed of an NLRP3 domain, the adaptor molecule apoptosis-associated speck-like protein containing a CARD (ASC) domain, and procaspase-1, plays an important role in the immune pathophysiology of the secondary damage induced by intracerebral hemorrhage (ICH). This study aims to investigate whether pre-stroke treatment with fimasartan, an angiotensin II receptor blocker, has anti-inflammatory effects on ICH by inhibiting the activation of the NLRP3 inflammasome. Sprague-Dawley rats were divided into five groups: sham, vehicle, low-dose (0.5 mg/kg) and regular-doses (1.0 and 3.0 mg/kg) fimasartan. These rats were treated for 30 days before the induction of collagenase-induced ICH and continuously 3 days after surgery. The mean blood pressure (BP) in the low-dose fimasartan group was not significantly different from that of control, and BP in the regular-dose groups was decreased in a dose-dependent manner. Pretreatment with low-dose fimasartan attenuated ICH-induced edema and improved neurological functions. Activation of the NLRP3/ASC/caspase-1 and the NF-κB pathways after ICH was markedly reduced by low-dose fimasartan. The double immunofluorescence staining of brain cells showed a significant decrease in the co-localization of NLRP3 with Iba1 (microglia marker) positive cells by fimasartan treatment. Cultured microglia cells stimulated by hemolysate demonstrated significant activation of the inflammasome, which was reduced by fimasartan. Pretreatment with a low-dose fimasartan alleviated brain damage after acute ICH by inhibiting the NLRP3 inflammasome without lowering MBP. Our study suggests pre-stroke administration of fimasartan could potentially attenuate ICH-induced secondary brain injury by targeting the inflammasome.</P> <P><B>Highlights</B></P> <P> <UL> <LI> NLRP3 inflammasome activation is involved in the secondary brain damage after ICH. </LI> <LI> Pre-stroke treatment with low-dose fimasartan has favorable effects on acute ICH injury. </LI> <LI> Fimasartan could potentially target the NLRP3 inflammasome to protect ICH injury independent of its effect on BP. </LI> </UL> </P>

      • SCIESCOPUSKCI등재

        Torque Ripple Suppression Method for BLDCM Drive Based on Four-Switch Three-Phase Inverter

        Pan, Lei,Sun, Hexu,Wang, Beibei,Su, Gang,Wang, Xiuli,Peng, Guili The Korean Institute of Power Electronics 2015 JOURNAL OF POWER ELECTRONICS Vol.15 No.4

        A novel inverter fault-tolerant control scheme is proposed to drive brushless DC motor. A fault-tolerant inverter and its three fault-tolerant schemes (i.e., phase A fault-tolerant, phase B fault-tolerant, and phase C fault-tolerant) are analyzed. Eight voltage vectors are summarized and a voltage vector selection table is used in the control scheme to improve the midpoint current of the split capacitors. A stator flux observer is proposed. The observer can improve flux estimation, which does not require any speed adaptation mechanism and is immune to speed estimation error. Global stability of the flux observer is guaranteed by the Lyapunov stability analysis. A novel stator resistance estimator is incorporated into the sensorless drive to compensate for the effects of stator resistance variation. DC offset effects are mitigated by introducing an integral component in the observer gains. Finally, a control system based on the control scheme is established. Simulation and experiment results show that the method is correct and feasible.

      • SCIESCOPUSKCI등재

        Simultaneous determination and difference evaluation of 14 ginsenosides in Panax ginseng roots cultivated in different areas and ages by high-performance liquid chromatography coupled with triple quadrupole mass spectrometer in the multiple reaction-monitoring mode combined with multivariate statistical analysis

        Yang Xiu,Xue Li,Xiuli Sun,Dan Xiao,Rui Miao,Huanxi Zhao,Shuying Liu 고려인삼학회 2019 Journal of Ginseng Research Vol.43 No.4

        Background: Ginsenosides are not only the principal bioactive components but also the important indexes to the quality assessment of Panax ginseng Meyer. Their contents in cultivated ginseng vary with the growth environment and age. The present study aimed at evaluating the significant difference between 36 cultivated ginseng of different cultivation areas and ages based on the simultaneously determined contents of 14 ginsenosides. Methods: A high-performance liquid chromatography (HPLC) coupled with triple quadrupole mass spectrometer (MS) method was developed and used in the multiple reaction-monitoring (MRM) mode (HPLC-MRM/MS) for the quantitative analysis of ginsenosides. Multivariate statistical analysis, such as principal component analysis and partial least squares-discriminant analysis, was applied to discriminate ginseng samples of various cultivation areas and ages and to discover the differentially accumulated ginsenoside markers. Results: The developed HPLC-MRM/MS method was validated to be precise, accurate, stable, sensitive, and repeatable for the simultaneous determination of 14 ginsenosides. It was found that the 3- and 5-yrold ginseng samples were differentiated distinctly by all means of multivariate statistical analysis, whereas the 4-yr-old samples exhibited similarity to either 3- or 5-yr-old samples in the contents of ginsenosides. Among the 14 detected ginsenosides, Rg1, Rb1, Rb2, Rc, 20(S)-Rf, 20(S)-Rh1, and Rb3 were identified as potential markers for the differentiation of cultivation ages. In addition, the 5-yr-old samples were able to be classified in cultivation area based on the contents of ginsenosides, whereas the 3- and 4-yr-old samples showed little differences in cultivation area. Conclusion: This study demonstrated that the HPLC-MRM/MS method combined with multivariate statistical analysis provides deep insight into the accumulation characteristics of ginsenosides and could be used to differentiate ginseng that are cultivated in different areas and ages.

      • KCI등재

        Torque Ripple Suppression Method for BLDCM Drive Based on Four-Switch Three-Phase Inverter

        Lei Pan,Hexu Sun,Beibei Wang,Gang Su,Xiuli Wang,Guili Peng 전력전자학회 2015 JOURNAL OF POWER ELECTRONICS Vol.15 No.4

        A novel inverter fault-tolerant control scheme is proposed to drive brushless DC motor. A fault-tolerant inverter and its three fault-tolerant schemes (i.e., phase A fault-tolerant, phase B fault-tolerant, and phase C fault-tolerant) are analyzed. Eight voltage vectors are summarized and a voltage vector selection table is used in the control scheme to improve the midpoint current of the split capacitors. A stator flux observer is proposed. The observer can improve flux estimation, which does not require any speed adaptation mechanism and is immune to speed estimation error. Global stability of the flux observer is guaranteed by the Lyapunov stability analysis. A novel stator resistance estimator is incorporated into the sensorless drive to compensate for the effects of stator resistance variation. DC offset effects are mitigated by introducing an integral component in the observer gains. Finally, a control system based on the control scheme is established. Simulation and experiment results show that the method is correct and feasible.

      • SCIESCOPUSKCI등재

        Simultaneous determination and difference evaluation of 14 ginsenosides in Panax ginseng roots cultivated in different areas and ages by high-performance liquid chromatography coupled with triple quadrupole mass spectrometer in the multiple reaction-moni

        Xiu, Yang,Li, Xue,Sun, Xiuli,Xiao, Dan,Miao, Rui,Zhao, Huanxi,Liu, Shuying The Korean Society of Ginseng 2019 Journal of Ginseng Research Vol.43 No.4

        Background: Ginsenosides are not only the principal bioactive components but also the important indexes to the quality assessment of Panax ginseng Meyer. Their contents in cultivated ginseng vary with the growth environment and age. The present study aimed at evaluating the significant difference between 36 cultivated ginseng of different cultivation areas and ages based on the simultaneously determined contents of 14 ginsenosides. Methods: A high-performance liquid chromatography (HPLC) coupled with triple quadrupole mass spectrometer (MS) method was developed and used in the multiple reaction-monitoring (MRM) mode (HPLC-MRM/MS) for the quantitative analysis of ginsenosides. Multivariate statistical analysis, such as principal component analysis and partial least squares-discriminant analysis, was applied to discriminate ginseng samples of various cultivation areas and ages and to discover the differentially accumulated ginsenoside markers. Results: The developed HPLC-MRM/MS method was validated to be precise, accurate, stable, sensitive, and repeatable for the simultaneous determination of 14 ginsenosides. It was found that the 3- and 5-yr-old ginseng samples were differentiated distinctly by all means of multivariate statistical analysis, whereas the 4-yr-old samples exhibited similarity to either 3- or 5-yr-old samples in the contents of ginsenosides. Among the 14 detected ginsenosides, Rg1, Rb1, Rb2, Rc, 20(S)-Rf, 20(S)-Rh1, and Rb3 were identified as potential markers for the differentiation of cultivation ages. In addition, the 5-yr-old samples were able to be classified in cultivation area based on the contents of ginsenosides, whereas the 3- and 4-yr-old samples showed little differences in cultivation area. Conclusion: This study demonstrated that the HPLC-MRM/MS method combined with multivariate statistical analysis provides deep insight into the accumulation characteristics of ginsenosides and could be used to differentiate ginseng that are cultivated in different areas and ages.

      • KCI등재

        Differentiation and identification of ginsenoside structural isomers by two-dimensional mass spectrometry combined with statistical analysis

        Yang Xiu,Huanxi Zhao,Xiuli Sun,Xue Li,Shuying Liu 고려인삼학회 2019 Journal of Ginseng Research Vol.43 No.3

        Background: In the current phytochemical research on ginseng, the differentiation and structural identificationof ginsenosides isomers remain challenging. In this paper, a two-dimensional mass spectrometry(2D-MS) method was developed and combined with statistical analysis for the directdifferentiation, identification, and relative quantification of protopanaxadiol (PPD)-type ginsenosideisomers. Methods: Collision-induced dissociation was performed at successive collision energy values to producedistinct profiles of the intensity fraction (IF) and ratio of intensity (RI) of the fragment ions. To amplifythe differences in tandem mass spectra between isomers, IF and RI were plotted against collision energy. The resulting data distributions were then used to obtain the parameters of the fitted curves, which wereused to evaluate the statistical significance of the differences between these distributions via the unpairedt test. Results: A triplet and two pairs of PPD-type ginsenoside isomers were differentiated and identified bytheir distinct IF and RI distributions. In addition, the fragmentation preference of PPD-type ginsenosideswas determined on the basis of the activation energy. The developed 2D-MS method was also extendedto quantitatively determine the molar composition of ginsenoside isomers in mixtures of biotransformationproducts. Conclusion: In comparison with conventional mass spectrometry methods, 2D-MS provides more directinsights into the subtle structural differences between isomers and can be used as an alternativeapproach for the differentiation of isomeric ginsenosides and natural products.

      • KCI등재

        Accumulation characteristics and correlation analysis of five ginsenosides with different cultivation ages from different regions

        Dan Xiao,Hao Yue,Yang Xiu,Xiuli Sun,YiBo Wang,Shuying Liu 고려인삼학회 2015 Journal of Ginseng Research Vol.39 No.4

        Background: Ginseng (the roots of Panax ginseng Meyer) is a well-known traditional Oriental medicine and is now widely used as a health food. It contains several types of ginsenosides, which are considered the major active medicinal components of ginseng. It has recently been reported that the qualitative and quantitative properties of ginsenosides found in ginseng may differ, depending on cultivation regions, ages, species, and so on. Therefore, it is necessary to study these variations with respect to cultivation ages and regions. Methods: In this study, 3e6-yr-old roots of P. ginseng were collected from three different cultivation regions. The contents of five ginsenosides (Rb1, Rd, Rc, Re, and Rgl) were measured by rapid resolution liquid chromatography coupled with quadrupleetime-of-flight mass spectrometry. The KruskaleWallis Rank sum test and multiple t test were used for comparative analysis of the data to evaluate the dynamic changes in the accumulation of these ginsenosides affected by cultivation regions and ages. Results: The content and composition of ginsenosides varied significantly among specimens collected from different cultivation regions and having different cultivation ages. For all samples, the content of Rg1 and Re ginsenosides increases with age and this rate of increase is different for each sample. The contents of Rb1, Rc, and Rd varied with cultivation ages in samples from different cultivation regions; especially, Rb1 from a 6-yr-old root showed approximately twofold variation among the samples from three cultivation regions. Furthermore, the content of Rb1 highly correlated with that of Rd (r ¼ 0.89 across all locations and ages). Conclusion: In our study, only the contents of ginsenosides Rg1 and Re were affected by the root age. Ginsenosides Rb1, Rc, and Rd varied widely with ages in samples from different cultivation regions.

      • SCIESCOPUSKCI등재

        Accumulation characteristics and correlation analysis of five ginsenosides with different cultivation ages from different regions

        Xiao, Dan,Yue, Hao,Xiu, Yang,Sun, Xiuli,Wang, YiBo,Liu, ShuYing The Korean Society of Ginseng 2015 Journal of Ginseng Research Vol.39 No.4

        Background: Ginseng (the roots of Panax ginseng Meyer) is a well-known traditional Oriental medicine and is now widely used as a health food. It contains several types of ginsenosides, which are considered the major active medicinal components of ginseng. It has recently been reported that the qualitative and quantitative properties of ginsenosides found in ginseng may differ, depending on cultivation regions, ages, species, and so on. Therefore, it is necessary to study these variations with respect to cultivation ages and regions. Methods: In this study, 3-6-yr-old roots of P. ginseng were collected from three different cultivation regions. The contents of five ginsenosides (Rb1, Rd, Rc, Re, and Rgl) were measured by rapid resolution liquid chromatography coupled with quadruple-time-of-flight mass spectrometry. The Kruskal-Wallis Rank sum test and multiple t test were used for comparative analysis of the data to evaluate the dynamic changes in the accumulation of these ginsenosides affected by cultivation regions and ages. Results: The content and composition of ginsenosides varied significantly among specimens collected from different cultivation regions and having different cultivation ages. For all samples, the content of Rg1 and Re ginsenosides increases with age and this rate of increase is different for each sample. The contents of Rb1, Rc, and Rd varied with cultivation ages in samples from different cultivation regions; especially, Rb1 from a 6-yr-old root showed approximately twofold variation among the samples from three cultivation regions. Furthermore, the content of Rb1 highly correlated with that of Rd (r = 0.89 across all locations and ages). Conclusion: In our study, only the contents of ginsenosides Rg1 and Re were affected by the root age. Ginsenosides Rb1, Rc, and Rd varied widely with ages in samples from different cultivation regions.

      • KCI등재

        A comparative study on chemical composition of total saponins extracted from fermented and white ginseng under the effect of macrophage phagocytotic function

        Dan Xiao,Yang Xiu,Hao Yue,Xiuli Sun,Huanxi Zhao,Shuying Liu 고려인삼학회 2017 Journal of Ginseng Research Vol.41 No.3

        In this study, white ginseng was used as the raw material, which was fermented with Paecilomyces hepiali through solid culture medium, to produce ginsenosides with modified chemical composition. The characteristic chemical markers of the products thus produced were investigated using rapid resolution liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (RRLCeQTOFeMS). Chemical profiling data were obtained, which were then subjected to multivariate statistical analysis for the systematic comparison of active ingredients in white ginseng and fermented ginseng to understand the beneficial properties of ginsenoside metabolites. In addition, the effects of these components on biological activity were investigated to understand the improvements in the phagocytic function of macrophages in zebrafish. According to the established RRLCeQTOFeMS chemical profiling, the contents in ginsenosides of high molecular weight, especially malonylated protopanaxadiol ginsenosides, were slightly reduced due to the fermentation, which were hydrolyzed into rare and minor ginsenosides. Moreover, the facilitation of macrophage phagocytic function in zebrafish following treatment with different ginseng extracts confirmed that the fermented ginseng is superior to white ginseng. Our results prove that there is a profound change in chemical constituents of ginsenosides during the fermentation process, which has a significant effect on the biological activity of these compounds.

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