Immunomodulatory, Anti-Inflammatory and Wound Healing Properties of Echinacea Species Zili Zhai Iowa State University
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Iowa State University Capstones, Theses and Retrospective Theses and Dissertations Dissertations 2008 Immunomodulatory, anti-inflammatory and wound healing properties of Echinacea species Zili Zhai Iowa State University Follow this and additional works at: https://lib.dr.iastate.edu/rtd Part of the Agriculture Commons, Allergy and Immunology Commons, Food Science Commons, and the Medical Immunology Commons Recommended Citation Zhai, Zili, "Immunomodulatory, anti-inflammatory and wound healing properties of Echinacea species" (2008). Retrospective Theses and Dissertations. 15689. https://lib.dr.iastate.edu/rtd/15689 This Dissertation is brought to you for free and open access by the Iowa State University Capstones, Theses and Dissertations at Iowa State University Digital Repository. It has been accepted for inclusion in Retrospective Theses and Dissertations by an authorized administrator of Iowa State University Digital Repository. For more information, please contact [email protected]. Immunomodulatory, anti-inflammatory and wound healing properties of Echinacea species by Zili Zhai A dissertation submitted to the graduate faculty in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY Major: Neuroscience Program of Study Committee: Joan E. Cunnick, Major Professor Tim A. Day Walter H. Hsu Marian L. Kohut Patricia A. Murphy Iowa State University Ames, Iowa 2008 Copyright © Zili Zhai, 2008. All rights reserved. 3316206 3316206 2008 ii TABLE OF CONTENTS LIST OF FIGURES ................................................................................................................. iv LIST OF TABLES................................................................................................................... vi LIST OF ABBREVIATIONS................................................................................................. vii ABSTRACT............................................................................................................................. ix CHAPTER 1. GENERAL INTRODUCTION ......................................................................... 1 Introduction................................................................................................................... 1 Dissertation Organization ............................................................................................. 3 Literature Review.......................................................................................................... 4 References................................................................................................................... 20 CHAPTER 2. ENHANCEMENT OF INNATE AND ADAPTIVE IMMUNE FUNCTIONS BY MULTIPLE ECHINACEA SPECIES ................................................. 31 Abstract....................................................................................................................... 31 Introduction................................................................................................................. 32 Materials and Methods................................................................................................ 34 Results......................................................................................................................... 41 Discussion................................................................................................................... 46 Acknowledgements..................................................................................................... 52 References................................................................................................................... 52 CHAPTER 3. ALCOHOL EXTRACTS OF ECHINACEA INHIBIT PRODUCTION OF NITRIC OXIDE AND TUMOUR NECROSIS FACTOR-ALPHA BY MACROPHAGES IN VITRO ........................................................................................... 66 Abstract....................................................................................................................... 66 Introduction................................................................................................................. 67 Materials and Methods................................................................................................ 69 Results......................................................................................................................... 73 Discussion................................................................................................................... 76 Acknowledgements..................................................................................................... 80 References................................................................................................................... 81 CHAPTER 4. ECHINACEA INCREASES ARGINASE ACTIVITY AND HAS ANTI-INFLAMMATORY PROPERTIES IN RAW 264.7 MACROPHAGE CELLS INDICATIVE OF ALTERNATIVE MACROPHAGE ACTIVATION............. 92 Abstract....................................................................................................................... 92 Introduction................................................................................................................. 93 Materials and Methods................................................................................................ 96 Results....................................................................................................................... 102 Discussion................................................................................................................. 106 Acknowledgements................................................................................................... 111 References................................................................................................................. 111 iii CHAPTER 5. ALCOHOL EXTRACT OF ECHINACEA PALLIDA REVERSES STRESS-DELAYED WOUND HEALING IN MICE .................................................. 126 Abstract..................................................................................................................... 126 Introduction............................................................................................................... 127 Materials and Methods.............................................................................................. 130 Results....................................................................................................................... 134 Discussion................................................................................................................. 137 Acknowledgements................................................................................................... 142 References................................................................................................................. 143 CHAPTER 6. GENERAL CONCLUSIONS ...................................................................... 154 General Discussion ................................................................................................... 154 Recommendations for Future Research.................................................................... 156 References................................................................................................................. 158 ACKNOWLEDGEMENTS.................................................................................................. 160 iv LIST OF FIGURES Figure 2.1. HPLC chromatograms of the lipophilic amides and hydrophilic caffeic acid derivatives in Echinacea preparations .................................................................. 57 Figure 2.2. Effect of Echinacea preparations on the percentages of (A) splenic CD49+ subset and (B) CD19+ subset.................................................................................59 Figure 2.3. Effect of Echinacea preparations on NK cytotoxity after covarying for the percentage of CD49+ splenocytes in each animal. ............................................... 60 Figure 2.4. Effect of Echinacea preparations on splenic plaque forming cell (PFC) response after covariance for the percentage of CD19+ splenocytes in each animal.....................................................................................................................61 Figure 2.5. Effect of Echinacea preparations on (A) splenic lymphocyte proliferation and (B) blood lymphocyte proliferation ................................................................62 Figure 2.6. Effect of Echinacea preparations on T H2 cytokine production by mouse splenocytes stimulated in vitro without or with mitogen...................................... 63 Figure 2.7. Effect of Echinacea preparations on T H1 cytokine production by mouse splenocytes stimulated in vitro without or with mitogen...................................... 64 Figure 2.8. Effect of Echinacea preparations on macrophage cytokine production in vitro without or with mitogen ............................................................................... 65 Figure 3.1. Viability of RAW 264.7 cells exposed to Echinacea alcohol extracts................. 86 Figure 3.2. Effect of Echinacea alcohol extracts on NO production and TNF-α secretion in LPS-activated RAW 264.7 cells. ...................................................................... 87 Figure 3.3. Survival of Salmonella within RAW 264.7 cells pretreated with indicated concentrations of Echinacea alcohol extracts....................................................... 88 Figure