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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>

      • KCI등재
      • 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.

      • 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.

      • 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.

      • SCIESCOPUSKCI등재

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

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

        Background: In the current phytochemical research on ginseng, the differentiation and structural identification of ginsenosides isomers remain challenging. In this paper, a two-dimensional mass spectrometry (2D-MS) method was developed and combined with statistical analysis for the direct differentiation, identification, and relative quantification of protopanaxadiol (PPD)-type ginsenoside isomers. Methods: Collision-induced dissociation was performed at successive collision energy values to produce distinct profiles of the intensity fraction (IF) and ratio of intensity (RI) of the fragment ions. To amplify the 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 were used to evaluate the statistical significance of the differences between these distributions via the unpaired t test. Results: A triplet and two pairs of PPD-type ginsenoside isomers were differentiated and identified by their distinct IF and RI distributions. In addition, the fragmentation preference of PPD-type ginsenosides was determined on the basis of the activation energy. The developed 2D-MS method was also extended to quantitatively determine the molar composition of ginsenoside isomers in mixtures of biotransformation products. Conclusion: In comparison with conventional mass spectrometry methods, 2D-MS provides more direct insights into the subtle structural differences between isomers and can be used as an alternative approach for the differentiation of isomeric ginsenosides and natural products.

      • 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.

      • KCI등재

        Dynamic Response Analysis and Model Test Research on K6 Single-Layer Spherical Reticulated Shells Subjected to Impact Load

        Xiaotong Ma,Xiuli Wang,Chao Bao,Hua Lu,Wenwei Yang 한국강구조학회 2019 International Journal of Steel Structures Vol.19 No.5

        To study the dynamic response characteristics and failure process of single-layer spherical reticulated shells under impact loads at diff erent loading points, impact dynamic analysis and experimental study are conducted on the K6 single-layer reticulated shell structure. First, the basic theory of numerical calculation and the model parameters are described. Then, dynamic response analysis under impact load is done by choosing diff erent impact points. Finally, the impact test is performed on a large-scale shell model, dynamic response data of key members and nodes of shell structure are obtained, and the shell deformation and destruction process is recorded by a high-speed camera. The results show that the structural dynamic response gradually increases farther from the base point under the same impact force. The nearer the impact point is, the earlier the response occurs, and the larger the corresponding amplitude will be. The apex is the most unfavorable impact loading point, and the member at the apex should be strengthened for impact resistant design of the reticulated shell. The transmission time of the impact dynamic response from the impact site to the entire reticulated shell is short.

      • KCI등재

        Preparation and Investigation of Ulex Europaeus Agglutinin IConjugated Liposomes as Potential Oral Vaccine Carriers

        KeXin Li,DaWei Chen,XiuLi Zhao,HaiYang Hu,ChunRong Yang,DaHai Pang 대한약학회 2011 Archives of Pharmacal Research Vol.34 No.11

        We prepared and optimized Ulex europaeus agglutinin I (UEAI)-modified Bovine serum albumin (BSA)-encapsulating liposomes (UEAI-LIP) as oral vaccine carriers and examined the feasibility of inducing systemic and mucosal immune responses by oral administration of UEAILIP. The prepared systems were characterized in vitro for their average size, zeta potential,encapsulation efficiency (EE%) and conjugation efficiency (CE%). In vitro release studies indicated that the presence of UEAI around the optimized liposomes was able to prevent a burst release of loaded BSA and provide sustained release of the encapsulated protein. In vivo immune-stimulating results in KM mice showed that BSA given intramuscularly generated systemic response only but both systemic and mucosal immune responses could be induced simultaneously in the groups in which BSA-loaded liposomes (LIP) and UEAI-LIP were administered intragastrically. Furthermore, the modification of UEAI on the surface of liposomes could further enhance the IgA and IgG levels obviously. In conclusion, this study demonstrated the high potential of lectin-modified liposomes containing the antigen as carriers for oral vaccine.

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