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Xijun Yan Editor Dan Shen (Salvia miltiorrhiza) in Medicine Volume 1. Biology and Chemistry Dan Shen (Salvia miltiorrhiza) in Medicine Xijun Yan Editor Dan Shen (Salvia miltiorrhiza) in Medicine Volume 1. Biology and Chemistry 123 Editor Xijun Yan Tianjin China ISBN 978-94-017-9468-8 DOI 10.1007/978-94-017-9469-5 ISBN 978-94-017-9469-5 (eBook) Springer Dordrecht Heidelberg New York London Library of Congress Control Number: 2014950646 © Springer Science+Business Media Dordrecht and People’s Medical Publishing House 2015 This work is subject to copyright. All rights are reserved by the Publishers, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. Exempted from this legal reservation are brief excerpts in connection with reviews or scholarly analysis or material supplied specifically for the purpose of being entered and executed on a computer system, for exclusive use by the purchaser of the work. Duplication of this publication or parts thereof is permitted only under the provisions of the Copyright Law of the Publishers’ locations, in its current version, and permission for use must always be obtained from Springer. Permissions for use may be obtained through RightsLink at the Copyright Clearance Center. Violations are liable to prosecution under the respective Copyright Law. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. While the advice and information in this book are believed to be true and accurate at the date of publication, neither the authors nor the editors nor the publishers can accept any legal responsibility for any errors or omissions that may be made. The publishers make no warranty, express or implied, with respect to the material contained herein. Printed on acid-free paper Springer is part of Springer Science+Business Media (www.springer.com) Preface to Dan Shen (Salvia miltiorrhiza) in Medicine In the 2008 press conference on the publication of the Chinese edition of the Dan Shen (Salvia miltiorrhiza) in Medicine, several volume editors suggested that the book should be translated into English and distributed internationally. They all believed that the medical communities are enthusiastic about TCM research, and that among the studies on single herbs, the study of Danshen has taken the lead. Therefore, it was a worthy undertaking to introduce the study conducted by the Chinese people over the past 1,000 years, and especially in the past 30 years, to the world. Meanwhile, I was asked unanimously to be its editor-in-chief. After several years of hard work by nearly 100 professors and research scientists, the translation is finally complete. The English edition of Dan Shen (Salvia miltiorrhiza) in Medicine is based on its Chinese edition. Modifications include changing the five-volume format to one volume and deleting some duplicated portions in the Chinese edition. Since the chapters in each volume of the Chinese edition were written by many individuals, details such as biological properties and ancient literature reviews were repeated many times, and the duplications were deleted in the English edition. Also, the various names of Danshen were unified. The appendix in the fifth volume, the prescriptions or formulas in ancient China, and the chapter on information management in the fourth volume were also deleted. The introduction to the production region, common names, and phytochemical components had appeared in the first three volumes, while this time only their first appearance was preserved. Some typos and oversights were corrected after consulting with volume editors. New progress in Danshen research was included in this book, such as the development of Salvianolate Lyophilized Injection, which finally came on the market in 2011 after 8 years of strict examination, and it was a landmark event in the development of TCM injections. It is unfortunate that we could not include the data on Qishenyiqi Dripping Pills, as the papers have not been published yet. The drug, developed by academician Boli Zhang, passed large-scale, evidence-based medicine clinical research trials in 2010, the first for a TCM drug, and won the 2011 National Science and Technology Progress Award. In principle, the English edition of Dan Shen (Salvia miltiorrhiza) in Medicine is the translation of the Chinese edition, thus preserving the latter’s framework. Because the Chinese edition was written by more than 100 v vi Preface to Dan Shen (Salvia miltiorrhiza) in Medicine scholars and published in five volumes, the styles and layouts were not identical. For example, some references were listed at the end of the chapter, while some were listed at the end of the section. The English edition did not change the style. Dan Shen (Salvia miltiorrhiza) in Medicine has amassed Danshen research results since the times of ancient China—it is not only a magnificent historical scroll, but also a huge work which shines the light of modern science and technology. I sincerely thank academicians Yongyan Wang and Boli Zhang. They have given me so much substantive guidance and encouragement despite their busy schedules. Without their help, it would have been impossible to finish the work. I also want to thank every author and volume editor who has participated in the writing and editing of both editions of this book; they have solved various problems which arose during the writing and translating processes. Last but not least, I want to thank the comrades working in the office of Dan Shen (Salvia miltiorrhiza) in Medicine, who have worked patiently and diligently over the past 15 years, collecting and organizing data and information. The publication of the English edition of Dan Shen (Salvia miltiorrhiza) in Medicine is a testimony of our sincere desire for the communication and discussion of TCM among international communities. We earnestly welcome suggestions and criticism from our colleagues around the world. Xijun Yan Preface to Volume 1. Biology and Chemistry “Botany of Danshen” systematically introduces the research on and the resource survey for Danshen (Salvia miltiorrhiza). It also describes Danshen’s pharmaceutical and biological characteristics, its identification, distribution and ecological environment, and its planting, in vitro cultivation, and genetic breeding. The content of Part I is based on a large amount of literature research. More importantly, many authors of this section are those who conducted this original research. For example, most of the content from Chaps. 3 to 6 is based on firsthand data; it represents not only the latest research results on Danshen, but also the theoretical foundation for further research. It is worth pointing out that the writing of this part has received support from Tianjin Tasly Group and from a project sponsored by the National High-tech development Program (“863 program”). Special thanks! Since Danshen is currently a hot topic in Chinese medicinal research, it is sure that more and more research data will be released, and that this part will have room for improvement. We welcome any criticism or comments. February 2008 Luqi Huang vii Editing Committee Chief Editor Xijun Yan Chief Reviewers Yongyan Wang Boli Zhang Associate Chief Editors Naifeng Wu Guoguang Zhu Luqi Huang Lianniang Li Houwei Luo Juntian Zhang Guanhua Du Dean Guo Yiyu Cheng Xuewen Zhang Xinde Shi Zhengliang Ye Yonghong Zhu Shuiping Zhou Hanxi Xue Editing Office Director Renshu Li Members Yonghong Zhu Zhengliang Ye Hanxi Xue Ying Zhao ix x Volume 1. Biology and Chemistry Chief Editors Luqi Huang Lianniang Li Houwei Luo Associate Chief Editors Deyou Qiu Zongsuo Liang Min Chen Editors Xuefeng Feng Wenting Liu Xirong He Jingyuan Song Deyou Qiu Min Chen Jinda Hao Lanping Guo Guanghon Cui Zongsuo Liang Luqi Huang Houwei Luo Lianniang Li Volume 2. Pharmacology and Quality Control Chief Editors Juntian Zhang Guanhua Du Dean Guo Associate Chief Editors Xiumei Gao Shen Ji Ming Zhu Rongxia Liu Haibin Qu Editors Lianhua Fang Yitao Wang Editing Committee Editing Committee xi Xiaoying Wang Yuehua Wang Dongxia Wang Xiaoming Wang Yi Wang Jinhua Wang Jie Wang Xiaoying Wang Hongmei Guang Changsuo Liu Ailin Liu Yan Sun Yonghong Zhu Jinglan Xu Guorong He Xiuying Yang Danshen Zhang Tiantai Zhang Ran Zhang Juntian Zhang Li Zhang Lihua Zhang Bin Zhang Chuan Li Guanhua Du Rong Du Ping Chen Yonghong Chen Xiuping Chen Ji Chen Shuiping Zhou Zhiwei Qu Xiaoming Zhu Zhihao Jiang Minke Tang Zhiwen Li Zhixin Guo Xiumei Gao Mei Gao Hongcai Shang Xinrui Cheng Guangliang Han Jingyan Han Yanqiao Zang Ying Dai Linke Ma Hongzhi Wang xii Junquan Wang Yi Wang Zhun Feng Zhengliang Ye Yonghui Liu Yan Liu Rongxia Liu Shunhang Liu Aihua Liu Xuesong Liu Jianghao Sun Guoqing Wu Ling Tong Yongjiang Wu Wanying Wu Xiaoqian Zhang Xuemin Zhang Jinlan Zhang Xian Zhang Yunfei Li Manling Li Min Yang Yuewu Yang Bilian Chen Shen Ji Jianping Lin Dean Guo Guoqiang Fan Xiaohui Fan Qiang Zheng Zhangzhao Jin Ming Zhu Jun Gao Hongfang Cui Fenglan Cao Rixin Liang Shunnan Zhang Qing Gong Haiou Dong Jianping Han Haibin Qu Volume 3. Clinical Research Chief Editors Guoguang Zhu Xuewen Zhang Editing Committee Editing Committee xiii Xinde Shi Associate Chief Editors Yi Zheng Ruizhi Luo Naifeng Wu Editors Xinde Shi Yan Liu Jinping Liu Jia Liu Yonghong Zhu Danyong Wu Naifeng Wu Xuewen Zhang Renshu Li Ruizhi Luo Yi Zheng Guoguang Zhu Jingsheng Zhao Ying Zhao Jiaoli Guo Shunnan Zhang Keqin Han Contents 1 2 3 Materia Medica and Plant Resource . . . . . . . . . Jinda Hao, Xirong He, Luqi Huang and Min Chen 1.1 Nomenclature . . . . . . . . . . . . . . . . . . . . . . 1.1.1 Common Name. . . . . . . . . . . . . . . . 1.1.2 Names in Literature [3] . . . . . . . . . . 1.1.3 Names in Different Regions [3]. . . . . 1.1.4 Commercial Names [3] . . . . . . . . . . 1.1.5 Prescription Names [3]. . . . . . . . . . . 1.2 Etymology . . . . . . . . . . . . . . . . . . . . . . . . 1.3 Materia Medica Studies . . . . . . . . . . . . . . . 1.4 Resource Survey . . . . . . . . . . . . . . . . . . . . 1.4.1 Local Varieties and Original Plant of Danshen [6] . . . . . . . . . . . . . . . . 1.4.2 Species Confused with Danshen [6]. . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . ......... 1 . . . . . . . . . . . . . . . . . . 1 1 1 1 2 2 2 2 3 ......... ......... ......... 4 8 10 ............ 11 . . . . . . . . . . . . . . . . . . . . . . 11 11 12 12 12 12 12 13 13 15 18 ............. 19 ............. ............. ............. 19 19 24 Distribution and Habitat of Danshen. . . . . . Luqi Huang, Min Chen and Lanping Guo 2.1 Geographic Distribution . . . . . . . . . . . . 2.2 Ecological and Biological Characteristics 2.3 Environmental Condition . . . . . . . . . . . 2.3.1 Climatic Conditions . . . . . . . . . . 2.3.2 Soil Conditions . . . . . . . . . . . . . 2.3.3 Community . . . . . . . . . . . . . . . 2.3.4 Habitat of High-quality Danshen . 2.4 Geographic Variation and Quality . . . . . 2.4.1 Geographic Variation . . . . . . . . . 2.4.2 Genuineness . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . Biological Characters of Danshen . . . . . . . Zongsuo Liang, Wenting Liu, Xuefeng Feng and Guanghong Cui 3.1 Morphology and Development. . . . . . . 3.1.1 Morphological Characteristics . . 3.1.2 Growth and Development. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xv xvi Contents 3.2 Anatomical Morphological Characteristics of Danshen 3.2.1 Morphological Characteristics of Leaves. . . . . 3.2.2 Morphological Characteristics of Stems . . . . . 3.2.3 Morphological and Structural Characteristics of Roots. . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2.4 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . 3.3 The Reproductive Biological Characters of Danshen . 3.3.1 Phenological Periods of the Flowering of Danshen. . . . . . . . . . . . . . . . . . . . . . . . . 3.3.2 The Exterior Appearances of Flowers and Dynamic Flowering Process of Danshen . 3.3.3 Morphological Characteristics of Danshen Pollen Grains . . . . . . . . . . . . . . . . . . . . . . . 3.3.4 Vitality of Danshen’s Pollen Grains . . . . . . . . 3.3.5 Effects of Pollination Time (Table 3.8) and Pollination Mode on Seed Setting Rate . . 3.3.6 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . 3.4 Study on Danshen’s Pollen [10, 11] . . . . . . . . . . . . . 3.4.1 Morphological Characteristics of Pollen in Genus Salvia. . . . . . . . . . . . . . . . . . . . . . 3.4.2 Morphological Characteristics of Pollen of Different Salvia Groups . . . . . . . . . . . . . . 3.4.3 Morphological Characteristics of Pollen of Species and Cultivated Varieties . . . . . . . . 3.5 Cytological Study on Danshen Plants [13] . . . . . . . . 3.6 Embryologic Study on Danshen. . . . . . . . . . . . . . . . 3.6.1 Development of Macrospores and Female Gametophytes [13] . . . . . . . . . . . . . . . . . . . 3.6.2 Development of Microspores and Male Gametophytes [16] . . . . . . . . . . . . . . . . . . . 3.7 Molecular Biological Study on Danshen . . . . . . . . . . 3.7.1 Isozyme Analysis of Danshen . . . . . . . . . . . . 3.7.2 Studies on the Molecular Identification of Danshen. . . . . . . . . . . . . . . . . . . . . . . . . 3.7.3 Construction of Danshen cDNA Chips and Study on Functional Genomics . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 A Study on the Cultivation of Danshen . . . . . . . . . . Zongsuo Liang and Wenting Liu 4.1 Propagation of Danshen . . . . . . . . . . . . . . . . . . 4.1.1 Propagation by Seeds. . . . . . . . . . . . . . . 4.1.2 Propagation by Rootstalk Division. . . . . . 4.1.3 Propagation by Root Division . . . . . . . . . 4.1.4 Propagation by Cutting . . . . . . . . . . . . . 4.1.5 Propagation by Tissue Culture . . . . . . . . 4.2 A Study on the Biological Characters of Danshen Seeds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ... ... ... 27 27 28 ... ... ... 29 30 31 ... 31 ... 32 ... ... 32 32 ... ... ... 33 33 34 ... 34 ... 35 ... ... ... 35 35 35 ... 35 ... ... ... 40 42 42 ... 43 ... ... 44 47 ...... 49 . . . . . . . . . . . . 49 49 49 49 50 50 ...... 51 . . . . . . . . . . . . . . . . . . . . . . . . Contents xvii 4.2.1 Water Absorption Characters of Danshen Seeds. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.2.2 Influences of Environmental Conditions on Germination of Danshen Seeds . . . . . . . . . . . . 4.2.3 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.3 Influences of Bud Removal on the Yield and Contents of Effective Constituents of Danshen . . . . . . . . . . . . . . . 4.3.1 Exterior Characters of Danshen’s Roots After Treatments . . . . . . . . . . . . . . . . . . . . . . . . 4.3.2 Changes in Yield After Treatments . . . . . . . . . . . 4.3.3 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.4 Summer Dormancy of Danshen . . . . . . . . . . . . . . . . . . . 4.4.1 Growth Characteristics of New Seedlings Growing on Basal Parts of Stems . . . . . . . . . . . . 4.4.2 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.5 Influences of Planting Density on Yield and Contents of Active Constituents of Danshen . . . . . . . . . . . . . . . . . 4.5.1 Influence of Transplanting Density on Survival Rate . . . . . . . . . . . . . . . . . . . . . . . . 4.5.2 Influence of Different Densities on Tanshinol and Tanshinone IIA Contents . . . . . . . . . . . . . . . 4.5.3 A Comparison of the Yields of Danshen Under Different Densities (In Terms of Fresh Weight) . . . . . . . . . . . . . . . . . . . . . . . . 4.5.4 Summary and Discussion . . . . . . . . . . . . . . . . . . 4.6 The Effects of Microelements on the Growth of Danshen and the Accumulation of Effective Constituents . . . . . . . . 4.6.1 Relationship Between Microelements and Tanshinol . . . . . . . . . . . . . . . . . . . . . . . . . . 4.6.2 Relationship Between Microelements and Tanshinone IIA . . . . . . . . . . . . . . . . . . . . . . 4.6.3 Dynamic Growth and Development of Roots Treated with Microelements . . . . . . . . . . . . . . . . 4.6.4 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 Danshen’s In Vitro Culture . . . . . . . . . . . . . . . . . . . Deyou Qiu and Jingyuan Song 5.1 Micropropagation of Danshen . . . . . . . . . . . . . . . 5.2 Cell Culture of Danshen . . . . . . . . . . . . . . . . . . . 5.3 Tissue and Organ Culture of Danshen . . . . . . . . . 5.3.1 Culture of Danshen Adventitious Roots . . . 5.3.2 Culture of Hairy Roots and Crown Gall Tissues of Danshen . . . . . . . . . . . . . . . . . 5.3.3 Culture of Crown Gall Tissues of Danshen. References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51 52 53 54 55 55 56 56 57 59 60 61 61 62 63 64 64 65 66 67 68 ..... 69 . . . . . . . . 69 72 74 74 ..... ..... ..... 75 80 87 . . . . . . . . . . . . xviii 6 7 8 Contents Genetics and Breeding of Danshen . . . . . . . . . . . . . Deyou Qiu and Jingyuan Song 6.1 The Germplasm Resources and Breeding Studies of Danshen . . . . . . . . . . . . . . . . . . . . . . . . . . . 6.2 Mutation Breeding of Danshen . . . . . . . . . . . . . 6.3 Molecular Breeding of Danshen. . . . . . . . . . . . . 6.3.1 Molecular Marker-Assisted Breeding of Danshen. . . . . . . . . . . . . . . . . . . . . . 6.3.2 Studies on the Breeding of Danshen by Genetic Engineering . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ...... 89 ...... ...... ...... 89 90 91 ...... 91 ...... ...... 92 95 Water Soluble Components of Danshen. . . . . . . . . . . . . Lianniang Li 7.1 Literature Review . . . . . . . . . . . . . . . . . . . . . . . . . 7.2 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.3 Chemical Structures of Phenolic Acids . . . . . . . . . . . 7.4 Extraction and Isolation of Phenolic Acids . . . . . . . . 7.4.1 Extraction of Phenolic Acids . . . . . . . . . . . . 7.4.2 Isolation of Phenolic Acids. . . . . . . . . . . . . . 7.4.3 Examples of Phenolic Acid Isolation . . . . . . . 7.5 Spectral Properties of Phenolic Acids . . . . . . . . . . . . 7.5.1 Ultraviolet Spectra. . . . . . . . . . . . . . . . . . . . 7.5.2 Mass Spectrometry . . . . . . . . . . . . . . . . . . . 7.5.3 Nuclear Magnetic Resonance Spectra. . . . . . . 7.6 Physical and Chemical Properties of Phenolic Acids. . 7.6.1 General Properties . . . . . . . . . . . . . . . . . . . . 7.6.2 Stability . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.6.3 Chemical Transformation . . . . . . . . . . . . . . . 7.7 Biosynthetic Pathways of Phenolic Acids . . . . . . . . . 7.8 Synthesis of Phenolic Acids . . . . . . . . . . . . . . . . . . 7.8.1 Synthesis of Danshensu [22]. . . . . . . . . . . . . 7.8.2 Synthesis of Salvianolic Acid F [23] . . . . . . . 7.8.3 Synthesis of Heptamethyl Lithospermate [24] . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Liposoluble Chemical Constituents in Danshen . . . . . . Houwei Luo 8.1 Introduction and Classification. . . . . . . . . . . . . . . . 8.1.1 Early Records of Chemical Study on Tanshinone . . . . . . . . . . . . . . . . . . . . . 8.1.2 Nomenclature and Classification of Liposoluble Constituents in Danshen . . . . 8.2 Extraction and Isolation of Liposoluble Compounds . 8.2.1 Extraction Method. . . . . . . . . . . . . . . . . . . 8.2.2 Separation Methods . . . . . . . . . . . . . . . . . . 8.2.3 Operating Procedure and Examples of Preparative Isolation . . . . . . . . . . . . . . . ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97 98 98 99 99 101 102 103 103 103 103 107 107 109 109 110 110 110 112 116 117 .... 119 .... 119 .... 119 . . . . . . . . 121 128 129 130 .... 139 . . . . . . . . . . . . . . . . . . . . . . . . . 97 . . . . Contents xix 8.2.4 Determining Column Chromatographic Conditions Based on Preseparation on TLC . . . . . 8.2.5 Two Forms of Preparative Columns: Comparison Between Dry Column Chromatography and Gradient Elution . . . . . . . . . . . . . . . . . . . . . 8.2.6 Examples of Gradient Elution . . . . . . . . . . . . . . . 8.3 Spectrum Characteristic of Tanshinone Compounds . . . . . 8.3.1 Ultraviolet Spectrum . . . . . . . . . . . . . . . . . . . . . 8.3.2 Infrared (IR) Absorption Spectrum . . . . . . . . . . . 8.3.3 Nuclear Magnetic Resonance (NMR) Spectrum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8.3.4 Mass Spectrometry . . . . . . . . . . . . . . . . . . . . . . 8.4 The Physicochemical Properties of Tanshinones. . . . . . . . 8.4.1 The Redox Potential of Tanshinones . . . . . . . . . . 8.4.2 The Chemical Stability of Tanshinones and the Influence of Solvents on Their Structures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8.4.3 The Effects of Rings and Conjugation Systems on the Activity of Quinones . . . . . . . . . . 8.5 The Biosynthetic Pathway of Tanshinone and Its Artifacts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8.5.1 The Biosynthesis of Cryptotanshinone . . . . . . . . . 8.6 Chemical Synthesis of Tanshinones . . . . . . . . . . . . . . . . 8.6.1 Total Synthesis of Tanshinone IIA. . . . . . . . . . . . 8.6.2 Diene Addition of 3-methoxyl-benzofuran-4, 7-diketone . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8.6.3 Total Synthesis of Miltionone . . . . . . . . . . . . . . . 8.6.4 Structural Modification of Tanshinone IIA . . . . . . 8.6.5 Structural Modification of Tanshinone I . . . . . . . . 8.7 Triterpenoids of Danshen . . . . . . . . . . . . . . . . . . . . . . . 8.7.1 Isolation and Identification of Przewanoic Acid A and B [87] . . . . . . . . . . . . . . . . . . . . . . 8.7.2 Isolation and Identification of Trijuganoic and Euscaphic Acids [88]. . . . . . . . . . . . . . . . . . 8.7.3 Isolation and Identification of Triterpene Acid from S. Paramiltiorrhiza . . . . . . . . . . . . . . 8.8 The Challenges and Opportunities for the Study of Tanshinones in this Century . . . . . . . . . . . . . . . . . . . 8.8.1 The Chemical Study of Tanshinone Aims at Finding New Targets . . . . . . . . . . . . . . . . . . . 8.8.2 The Biological Activities and the Physicochemical Properties of Compounds . . . . . . . . . . . . . . . . . . 8.8.3 Chemical–biological Research of Tanshinone. . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 205 206 Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 209 142 143 144 145 145 148 151 166 173 173 177 177 185 185 190 190 190 192 194 195 198 198 200 202 204 204 204 About the Chief Editor Dr. Xijun Yan was born in 1953 in Zhenyuan, Gansu province. Dr. Yan is a chief pharmacist, and enjoys the Special Expert’s Allowance from the State Council of China. At present, he is a President of Tianjin Tasly Group; serves as a member of traditional Chinese medicine (TCM) Standardization Technical Committee; the deputy director of Science Popularization Committee of Chinese Pharmaceutical Association; a member of Expert Committee of The National Pharmaceutical Industry Policy Research Project of Chinese Pharmaceutical Association; the vice president of Tianjin Pharmaceutical Association. Dr. Yan is the first person to propose the concept of “modern TMC drugs” and the new mode of TCM R&D, and has engaged for a considerable length of time in research and industrial development of modern Chinese medicine. Dr. Yan has actively undertaken key national projects on the research and development of important new drugs, supervised or participated in 38 projects in the National Key Science and Technology Projects in the 9th and 10th “Five Year Plans”; National Level Promotion Program of Scientific and Technological Achievements; National High-tech Industrialization Demonstration Project, etc. Dr. Yan has 69 patents and more than 50 publications, including The Standards of Diagnosis, Efficacy, and Medication in TCM’s Heart Disorder (one of the editors-in-chief); How TCM Drugs Enter the EC Market (associate editorin-chief); The Ideas and Methods of Modernization of TCM Research (one of the editors-in-chief); The Reflection and Practice of the Modernization of TCM Preparations; On the Trends of Modern TCM Industry, etc. Dr. Yan has been awarded honorary titles like National Model Worker; National Outstanding Scientific and Technological Worker; National Outstanding Pharmaceutical Entrepreneur; National Health Industry and Enterprise Advanced Individual; National Model Worker in Chinese Medicine System. Dr. Yan has received numerous awards, including the Third National Prize for Scientific Advancement, the Second Prize for Scientific Advancement by the People’s Liberation Army, and the First Prize for Scientific Advancement by Tianjin Municipal Government. xxi Introduction by Chief Editor After the hard efforts of an entire decade, by nearly 100 experts from home and abroad, the Dan Shen (Salvia miltiorrhiza) in Medicine is finally going to the press. Danshen (Salvia miltiorrhiza) has a time-honored history of research, development, and application in China’s traditional medicine, and is held in very high esteem by the medical community. We hope that the five-volume series now made available to the readership will make a worthwhile contribution to its research and application. Salvia Carries the Dream of Internationalization of Traditional Chinese Medicine In 1996, China began to formulate and implement a strategy for the modernization of traditional Chinese medicine (TCM). However, the question of how in practice to systematically develop traditional medicine passed on from generation to generation over several millennia, remained a real and persistent challenge to the academic and industrial dimensions of TCM. In 1998, a discussion among several TCM experts from home and abroad gave us the idea of compiling the Dan Shen (Salvia miltiorrhiza) in Medicine. The experts discussed not only the present state and the future prospects of modernizing Chinese medicine itself, but also the growth of the Chinese medicine industry, and the issues in developing big brand modern TCM drugs. The discussion was especially centered on the utilization of Danshen, and the topics ranged from its collection and processing in ancient times to the widespread application of various Danshen preparation, from its effective components to its pharmaceutical action, from its cultivation and plantation to its modern industry chain, from its compound prescriptions and to modern Compound Danshen Dripping Pill (Dantonic™), from its R&D to the rapid growth of a modern TCM enterprise—the Tasly Group. Is it possible that a unique industrial technology and economy grow out from a single TCM drug and a series of research activities focused on the drug? Is it possible that the unique industrial technology and economy stimulate new lines of thinking and novel approaches to the modernization and internationalization of TCM? Is it possible the unique industrial technology and economy push forward the systematic project of TCM research and development? These and several other questions roused profound interest xxiii xxiv Introduction by Chief Editor among experts in deepening the research on Danshen, and the compilation of the Dan Shen (Salvia miltiorrhiza) in Medicine was originated from this initial driving force. For thousands of years, TCM has made enormous contribution to the health and multiplication of the Chinese people. But why is it so hard for TCM to be accepted and acknowledged in the international community? Why do some people still have doubts about the scientific nature of TCM? To be able to continually promote the modernization and internationalization of TCM, these questions must have affirmative answers. In order to introduce Chinese medicine to the rest of the world, and let the international community understand, accept, and use TCM, we must resort to modern technology to re-develop TCM again. We also have to give TCM a fresh interpretation, using the standardized scientific and digitized languages. It is indeed necessary to select a certain Chinese medicine for an exploratory trial, and this Chinese medicine must meet a number of requirements. First, it should have both a long history of inheritance and deep accumulation of clinical knowledge; second, it has been systemically studied with modern means of science and technology, and its effective substances and the mechanism of action have been elucidated, relatively speaking; third, it has made a comparatively great contribution to human health, especially in terms of satisfactory effects in the treatment of serious diseases; fourth, its industrialization has been successful, having representative name brand products; fifth, it has sufficient resources to ensure the sustainable industrialization; and sixth, it should be conducive to a progressive growth of Chinese medical research. We believe that Danshen meets all these requirements, and it could showcase a wealth of innovative achievements and profound knowledge, and become a model in promoting the modernization and internationalization of TCM. Hundreds of Scientists Involved in the Work It is with this underlying ambition in mind that we started data collection, collation, and compilation of the this book. Nearly 100 experts from home and abroad have participated in this huge project. The expert team includes both world renowned senior scientists and young scholars with outstanding achievements. Some of them are from prestigious research institutions and universities, others from industrial regulatory bodies, and still others from the frontline of industrial development. Their expertise covers multiple research areas, including medicinal botany, phytochemistry, pharmaceutical analytics, pharmacology, toxicology, medical preparation, medicine reviewing, TCM, and integrative medicine. We have been particularly fortunate in that our research and compilation work has received strong support and guidance from the academicians Yongyan Wang and Boli Zhang, as well as from several relevant leaders and experts. Each writer adhered to the mission of “being responsible for both past and future generations” and followed stringent scientific spirit and serious academic attitude, searching extensively, and studying strenuously and carefully. They referenced nearly 50,000 pieces of literature, including books, research articles, trial reports,