Discovery of a sugar-based nanoparticle universally existing in boiling herbal water extracts and their immunostimulant effect

Herbal medicine is mainly prepared from boiling herbal water extracts. Many epoch-making immunosuppressant drugs, such as glycyrrhizic acid (old example) and FTY720 (current example), were developed from herbal secondary metabolites in the boiling water extract by partition with organic solvents. Ho...

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Main Authors: Hirofumi Iitsuka, Keiichi Koizumi, Akiko Inujima, Mikiko Suzaki, Yusuke Mizuno, Yoshiki Takeshita, Takeshi Eto, Yoshiki Otsuka, Ryo Shimada, Mengxin Liu, Keisuke Ikeda, Minoru Nakano, Ryo Suzuki, Kazuo Maruyama, Yue Zhou, Hiroaki Sakurai, Naotoshi Shibahara
Format: Article
Language:English
Published: Elsevier 2018-12-01
Series:Biochemistry and Biophysics Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S2405580818301766
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author Hirofumi Iitsuka
Keiichi Koizumi
Akiko Inujima
Mikiko Suzaki
Yusuke Mizuno
Yoshiki Takeshita
Takeshi Eto
Yoshiki Otsuka
Ryo Shimada
Mengxin Liu
Keisuke Ikeda
Minoru Nakano
Ryo Suzuki
Kazuo Maruyama
Yue Zhou
Hiroaki Sakurai
Naotoshi Shibahara
author_facet Hirofumi Iitsuka
Keiichi Koizumi
Akiko Inujima
Mikiko Suzaki
Yusuke Mizuno
Yoshiki Takeshita
Takeshi Eto
Yoshiki Otsuka
Ryo Shimada
Mengxin Liu
Keisuke Ikeda
Minoru Nakano
Ryo Suzuki
Kazuo Maruyama
Yue Zhou
Hiroaki Sakurai
Naotoshi Shibahara
author_sort Hirofumi Iitsuka
collection DOAJ
description Herbal medicine is mainly prepared from boiling herbal water extracts. Many epoch-making immunosuppressant drugs, such as glycyrrhizic acid (old example) and FTY720 (current example), were developed from herbal secondary metabolites in the boiling water extract by partition with organic solvents. However, few immunostimulants have been discovered by this method. Instead of the usual method, we aimed to find a novel immunostimulant component by two unique methods in the research of herbal medicine: ultracentrifugation and electron microscopy. The immunostimulant was not a secondary metabolite, as expected, but the structure was a nanoparticle formed by a polysaccharide. In addition, we clarified the immune effect of the nanoparticle. Intake of the nanoparticle by phagocytosis resulted in immunostimulant effects by increasing the genes and proteins of inflammatory cytokines in macrophage cells. The immunostimulant effects were inhibited by a phagocytosis inhibitor, cytochalasin D. To the best of our knowledge, this study is the first to describe the discovery of a nanoparticle in boiling herbal water extracts and its immunostimulant properties. This study will provide additional understanding of the efficacy of herbal medicine, in that the immunostimulant nanoparticle universally exists in boiling herbal water extracts. Thus, traditional herbal medicine may be an oldest known nanomedicine. Furthermore, this study suggests that the immunostimulant nanoparticle simply can be obtained from herbal medicine only by ultracentrifugation. We hope that this simple strategy will substantially contribute to drug development, including vaccine adjuvant, in the future. Keywords: Boiling herbal water extracts, Sugar-based nanoparticle, Immunostimulant effect
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spelling doaj.art-344afe62762b4c58ac35e551547b72e92022-12-22T03:50:53ZengElsevierBiochemistry and Biophysics Reports2405-58082018-12-01166268Discovery of a sugar-based nanoparticle universally existing in boiling herbal water extracts and their immunostimulant effectHirofumi Iitsuka0Keiichi Koizumi1Akiko Inujima2Mikiko Suzaki3Yusuke Mizuno4Yoshiki Takeshita5Takeshi Eto6Yoshiki Otsuka7Ryo Shimada8Mengxin Liu9Keisuke Ikeda10Minoru Nakano11Ryo Suzuki12Kazuo Maruyama13Yue Zhou14Hiroaki Sakurai15Naotoshi Shibahara16Division of Kampo Diagnostics, Institute of Natural Medicine, University of Toyama, Toyama 930-0194, JapanDivision of Kampo Diagnostics, Institute of Natural Medicine, University of Toyama, Toyama 930-0194, Japan; Corresponding author.Division of Kampo Diagnostics, Institute of Natural Medicine, University of Toyama, Toyama 930-0194, JapanDivision of Kampo Diagnostics, Institute of Natural Medicine, University of Toyama, Toyama 930-0194, JapanDivision of Kampo Diagnostics, Institute of Natural Medicine, University of Toyama, Toyama 930-0194, JapanDivision of Kampo Diagnostics, Institute of Natural Medicine, University of Toyama, Toyama 930-0194, JapanDivision of Kampo Diagnostics, Institute of Natural Medicine, University of Toyama, Toyama 930-0194, JapanDivision of Kampo Diagnostics, Institute of Natural Medicine, University of Toyama, Toyama 930-0194, JapanDivision of Kampo Diagnostics, Institute of Natural Medicine, University of Toyama, Toyama 930-0194, JapanDivision of Kampo Diagnostics, Institute of Natural Medicine, University of Toyama, Toyama 930-0194, JapanGraduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, JapanGraduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, JapanLaboratory of Drug Delivery System, Faculty of Pharma-Science, Teikyo University, Tokyo 173-8605, JapanLaboratory of Drug Delivery System, Faculty of Pharma-Science, Teikyo University, Tokyo 173-8605, JapanDepartment of Cancer Cell Biology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, JapanDepartment of Cancer Cell Biology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, JapanDivision of Kampo Diagnostics, Institute of Natural Medicine, University of Toyama, Toyama 930-0194, JapanHerbal medicine is mainly prepared from boiling herbal water extracts. Many epoch-making immunosuppressant drugs, such as glycyrrhizic acid (old example) and FTY720 (current example), were developed from herbal secondary metabolites in the boiling water extract by partition with organic solvents. However, few immunostimulants have been discovered by this method. Instead of the usual method, we aimed to find a novel immunostimulant component by two unique methods in the research of herbal medicine: ultracentrifugation and electron microscopy. The immunostimulant was not a secondary metabolite, as expected, but the structure was a nanoparticle formed by a polysaccharide. In addition, we clarified the immune effect of the nanoparticle. Intake of the nanoparticle by phagocytosis resulted in immunostimulant effects by increasing the genes and proteins of inflammatory cytokines in macrophage cells. The immunostimulant effects were inhibited by a phagocytosis inhibitor, cytochalasin D. To the best of our knowledge, this study is the first to describe the discovery of a nanoparticle in boiling herbal water extracts and its immunostimulant properties. This study will provide additional understanding of the efficacy of herbal medicine, in that the immunostimulant nanoparticle universally exists in boiling herbal water extracts. Thus, traditional herbal medicine may be an oldest known nanomedicine. Furthermore, this study suggests that the immunostimulant nanoparticle simply can be obtained from herbal medicine only by ultracentrifugation. We hope that this simple strategy will substantially contribute to drug development, including vaccine adjuvant, in the future. Keywords: Boiling herbal water extracts, Sugar-based nanoparticle, Immunostimulant effecthttp://www.sciencedirect.com/science/article/pii/S2405580818301766
spellingShingle Hirofumi Iitsuka
Keiichi Koizumi
Akiko Inujima
Mikiko Suzaki
Yusuke Mizuno
Yoshiki Takeshita
Takeshi Eto
Yoshiki Otsuka
Ryo Shimada
Mengxin Liu
Keisuke Ikeda
Minoru Nakano
Ryo Suzuki
Kazuo Maruyama
Yue Zhou
Hiroaki Sakurai
Naotoshi Shibahara
Discovery of a sugar-based nanoparticle universally existing in boiling herbal water extracts and their immunostimulant effect
Biochemistry and Biophysics Reports
title Discovery of a sugar-based nanoparticle universally existing in boiling herbal water extracts and their immunostimulant effect
title_full Discovery of a sugar-based nanoparticle universally existing in boiling herbal water extracts and their immunostimulant effect
title_fullStr Discovery of a sugar-based nanoparticle universally existing in boiling herbal water extracts and their immunostimulant effect
title_full_unstemmed Discovery of a sugar-based nanoparticle universally existing in boiling herbal water extracts and their immunostimulant effect
title_short Discovery of a sugar-based nanoparticle universally existing in boiling herbal water extracts and their immunostimulant effect
title_sort discovery of a sugar based nanoparticle universally existing in boiling herbal water extracts and their immunostimulant effect
url http://www.sciencedirect.com/science/article/pii/S2405580818301766
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