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Artemisia annua Prospects, Applications and Therapeutic Uses Artemisia annua Prospects, Applications and Therapeutic Uses Edited by Tariq Aftab M. Naeem M. Masroor A. Khan CRC Press Taylor & Francis Group 6000 Broken Sound Parkway NW, Suite 300 Boca Raton, FL 33487-2742 © 2018 by Taylor & Francis Group, LLC CRC Press is an imprint of Taylor & Francis Group, an Informa business No claim to original U.S. Government works Printed on acid-free paper International Standard Book Number-13: 978-1-138-63210-3 (Hardback) This book contains information obtained from authentic and highly regarded sources. Reasonable efforts have been made to publish reliable data and information, but the author and publisher cannot assume responsibility for the validity of all materials or the consequences of their use. The authors and publishers have attempted to trace the copyright holders of all material reproduced in this publication and apologize to copyright holders if permission to publish in this form has not been obtained. If any copyright material has not been acknowledged please write and let us know so we may rectify in any future reprint. Except as permitted under U.S. Copyright Law, no part of this book may be reprinted, reproduced, transmit- ted, or utilized in any form by any electronic, mechanical, or other means, now known or hereafter invented, including photocopying, microfilming, and recording, or in any information storage or retrieval system, with- out written permission from the publishers. For permission to photocopy or use material electronically from this work, please access www.copyright.com (http://www.copyright.com/) or contact the Copyright Clearance Center, Inc. (CCC), 222 Rosewood Drive, Danvers, MA 01923, 978-750-8400. CCC is a not-for-profit organization that provides licenses and registration for a variety of users. For organizations that have been granted a photocopy license by the CCC, a separate system of payment has been arranged. Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for identification and explanation without intent to infringe. Library of Congress Cataloging- in- Publication Data Names: Aftab, Tariq, author. Title: Artemisia annua : prospects, applications and therapeutic uses / Tariq Aftab, M. Naeem, and M. Masroor A. Khan. Description: Boca Raton : Taylor & Francis, 2018. | “A CRC title, part of the Taylor & Francis imprint, a member of the Taylor & Francis Group, the academic division of T&F Informa plc.” | Includes bibliographical references. Identifiers: LCCN 2017034216 | ISBN 9781138632103 (hardback : alk. paper) Subjects: LCSH: Artemisinin--Therapeutic use. | Artemisia annua. Classification: LCC RC159.A7 A38 2018 | DDC 616.9/362061--dc23 LC record available at https://lccn.loc.gov/2017034216 Visit the Taylor & Francis Web site at http://www.taylorandfrancis.com and the CRC Press Web site at http://www.crcpress.com Contents Preface......................................................................................................................vii About the Editors ......................................................................................................ix Contributors ..............................................................................................................xi Chapter 1 Diverse Biologies and Experiential Continuities: A Physiognomic Reading of the Many Faces of Malaria in the Chinese Materia Medica .....................................1 Elisabeth Hsu Chapter 2 Artemisia annua and Grassroots Responses to Health Crises in Rural Tanzania ...17 Caroline Meier zu Biesen Chapter 3 Use of Artemisia annua L. in the Treatment of Diseases—An Update ..................41 M. Naeem, Tariq Aftab, Asfia Shabbir, and M. Masroor A. Khan Chapter 4 Current Perspectives and Future Prospects in the Use of Artemisia annua for Pharmacological and Agricultural Purposes ...........................................................57 Ebiamadon Andi Brisibe Chapter 5 Artemisia annua and Its Bioactive Compounds as Anti-Inflammatory Agents ......83 Bianca Ivanescu and Andreia Corciova Chapter 6 Biosynthetic Pathway of Artemisinin ....................................................................115 Bushra Hafeez Kiani Chapter 7 Cultivation of Artemisia annua—The Environmental Perspective .......................131 Karina Knudsmark Sjøholm (nee Jessing), Bjarne W. Strobel, and Nina Cedergreen v vi Contents Chapter 8 Therapeutics of Artemisia annua: Current Trends ................................................155 Shilpi Paul Chapter 9 Various Applications of Artemisia Annua L. (Qinghao) .......................................183 Himanshu Misra, Mauji Ram, Ashish Bharillya, Darshana Mehta, Bhupendra Kumar Mehta, and Dharam Chand Jain Chapter 10 Impact of Integrated Omics Technologies for Identification of Key Genes and Enhanced Artemisinin Production in Artemisia annua L. ....................................221 Shashi Pandey-Rai, Neha Pandey, Anjana Kumari, Deepika Tripathi, and Sanjay Kumar Rai Chapter 11 Engineering the Plant Cell Factory for Artemisinin Production ...........................245 Mauji Ram, Himanshu Misra, Ashish Bharillya, and Dharam Chand Jain Chapter 12 Use of Nanocarriers to Enhance Artemisinin Activity .........................................271 Anna Rita Bilia Chapter 13 In Situ Cultivation of Artemisia annua ..................................................................295 Salisu Muhammad Tahir Chapter 14 Mode of Action of Artemisinin: An Update ..........................................................323 Athar Ali, Abdul Qadir, Mather Ali Khan, Parul Saxena, and Malik Zainul Abdin Index ......................................................................................................................335 Preface Internationally, scientists are making unstinted efforts to improve the under- standing of malarial biology and to develop more effective malaria treatments. Malaria remained the major scourge of mankind until the Chinese introduced arte- misinin to the world as a remedy. The antimalarial drug artemisinin was discovered by Tu Youyou, a Chinese scientist, who was awarded half of the 2015 Nobel Prize in Medicine for her discovery. Since the discovery of artemisinin, treatments con- taining artemisinin derivatives (artemisinin combination therapies, or ACTs), have been standardized for the treatment of Plasmodium falciparum malaria worldwide. Artemisinin is certainly one of the most promising natural products investigated in the past couple of decades. The plant has potent therapeutic potential beyond its antimalarial activity, including anticancer, immunosuppressive, anti-inflammatory, antihypertensive, antioxidative, antimicrobial, antiparasitic, and antiviral activities. However, artemisinin-derived drugs are not available to millions of the world’s poor- est people because of the low yield (0.1%–0.5% of dry weight) of artemisinin in naturally grown Artemisia plants. The present demand for artemisinin far outstrips supply; therefore, researchers around the world are working toward improving the artemisinin content of the plant by various means. The editors’ efforts, in the form of this comprehensive volume, detail recent updates to the applications, current research, and future prospects of Artemisia annua. Since the intact plant contains artemisinin in very low concentrations, its commercial extraction requires huge amounts of plant biomass to be processed. Massive demand and low yield of artemisinin from the plant has led to exploration of alternative means of production, including the cultivation of A. annua on scien- tific lines. Considering the significant benefits of various properties of the plant to human health, we present this exclusive volume entitled Artemisia annua: Prospects, Applications and Therapeutic Uses. As per the rationale, this volume focuses on various scientific approaches, namely, agricultural, pharmacological, and pharma- ceutical aspects, in vitro technology, and nutrient management strategies, as well as omics technologies for the regulation of artemisinin biosynthesis in A. annua. The book also contains a plethora of information about various scientific approaches to the cultivation of this medicinal plant. Also, it includes information about the plant’s survival under conditions of environmental stress. The book comprises 14 chapters, most of them being reviewed articles written by experts from around the globe. We are hopeful that this volume will meet the needs of all researchers who are working or have interest in this particular field. Undoubtedly, this book will be helpful to research students, teachers, ethnobotanists, oncologists, pharmacologists, herbal growers, and anyone else with an interest in this plant of paramount importance. We are greatly thankful to the CRC Press, Taylor & Francis Group, USA, for their expeditious acceptance and compilation of this scientific work. Sincere thanks are expressed to the team members of the Taylor & Francis Group for their dedication, sincerity, and friendly cooperation in producing this volume. With great pleasure, we vii viii PrefaCe extend our sincere thanks to all the contributors for their timely response, outstand- ing and up-to-date research contributions, support, and consistent patience. Lastly, thanks are also due to the well-wishers, research students, and authors’ family members for their moral support, blessings, and inspiration in the compila- tion of this book. Tariq Aftab M. Naeem M. Masroor A. Khan Aligarh Muslim University, Aligarh, India About the Editors Tariq Aftab received his PhD from the Department of Botany at Aligarh Muslim University, India, and is currently an assistant professor there. He is the recipient of the pres- tigious Leibniz-DAAD Fellowship from Germany, Raman Fellowship from the Government of India, and Young Scientist Awards from the State Government of Uttar Pradesh (India) and Government of India. He has worked as a visiting sci- entist at IPK, Gaterleben, Germany, and in the Department of Plant Biology at Michigan State University, United States. He is also a member of various scientific associations in India and abroad. He has published research articles in several peer-reviewed national and international journals and is the lead editor of the book Artemisia annua: Pharmacology and Biotechnology. His research interests include physiological, pro- teomic, and molecular studies on medicinal and aromatic plants. M. Naeem is an assistant professor in the Department of Botany at Aligarh Muslim University, India. For more than a decade, he has devoted his research to improving the yield and quality of commercially important medicinal and aromatic plants (MAPs). His research focuses on escalating the produc- tion of MAPs and their active principles using a novel and safe technique involving radiation-processed polysaccharides (RPPs) as well as the application of potent plant growth regu- lators (PGRs). To date, he has successfully run three major research projects as principal investigator, two of which were sanctioned by the Department of Science & Technology, New Delhi, while another was awarded by the Council of Science and Technology, Uttar Pradesh, Lucknow. Dr. Naeem has published 7 books and more than 80 research papers in reputable national and international journals. He has also participated in various national and international conferences and acquired life memberships to various scientific bodies in India and abroad. Based on his research contributions, Dr. Naeem has been awarded a Research Associateship from the Council of Scientific & Industrial Research, New Delhi; a Young Scientist Award (2011) from the State Government of Uttar Pradesh; a Fast Track Young Scientist Award from the Department of Science & Technology, India; a Young Scientist of the Year Award (2015) from the Scientific and Environmental Research Institute, Kolkata; a Rashtriya Gaurav Award (2016) from the International Friendship Society, New Delhi; and a Distinguished Young Scientist of the Year Award (2016) from the International Foundation for Environment and Ecology, Kolkata. ix

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