Dan Shen (Salvia miltiorrhiza) in Medicine (eBook)

Editor Xijun Yan is the President of Tianjin Tasly Group and a Member of the TCM Standardization Technical Committee.

Preface to Dan Shen (Salvia miltiorrhiza)in Medicine 5
Preface to Volume 1. Biologyand Chemistry 7
Editing Committee 8
Contents 13
About the Chief Editor 18
Introduction by Chief Editor 19
1 Materia Medica and Plant Resource 27
1.1 Nomenclature 27
1.1.1 Common Name 27
1.1.2 Names in Literature [3] 27
1.1.3 Names in Different Regions [3] 27
1.1.4 Commercial Names [3] 28
1.1.5 Prescription Names [3] 28
1.2 Etymology 28
1.3 Materia Medica Studies 28
1.4 Resource Survey 29
1.4.1 and Danshen [6] 30
1.4.1.1 Danshen () 30
1.4.1.2 Danshen 30
1.4.1.3 Danshen (S. Przewalskii Maxim. 30
1.4.1.4 Danshen (S. Yunnanensis C. 31
1.4.1.5 Sanye ( Danshen (S. 31
1.4.1.6 Danshen (S. Miltiorrhiza Bunge F. Alba C. Y. Wu et H. 31
1.4.1.7 Danshen (S. Miltiorrhiza Bunge var. Charbonnelii (L00E9veill00E9) C. 31
1.4.1.8 Baihua Ganxi Shuwei (White Flower Sage of Western Gansu) (S. Przewalskii Maxim. var. Alba X. L. Huang et H. 31
1.4.1.9 Shaomao Ganxi Shuwei (Less Hair Sage in Western Gansu) (S. Przewalskii var. 32
1.4.1.10 Danshen (S. Paramiltiorrhiza H. W. Li el X. 32
1.4.1.11 Danshen (S. 32
1.4.1.12 Qiaomai Di Shuwei (Buckwheat Field Sage) (S. 32
1.4.1.13 Maoye Qiaomai Di Shuwei (Hairy Leaf Buckwheat Field Sage) (S. Kiaometiensis L00E9v. F. 33
1.4.1.14 Changguan Shuwei (Long Crest Sage) (S. 33
1.4.1.15 Maodihuang Shuwei (Foxglove Sage) (S. 33
1.4.1.16 Huanghua Shuwei (Yellow Flower Sage) (S. 33
1.4.1.17 Chenghuang Shuwei (Orange Yellow Sage) (S. 33
1.4.1.18 Lise Shuwei (Dark Brown Sage) (S. 34
1.4.1.19 Xueshan Shuwei (Snow Mountain Sage) (S. 34
1.4.2 Species Confused with Danshen [6] 34
1.4.2.1 Qiancao (Rubia Cordifolia 34
1.4.2.2 Zhusha Gen (Ardisia 35
1.4.2.3 Shuisu Caosu (Phlomis 35
1.4.2.4 Xiaku Cao (Self-Heal) ( 35
1.4.2.5 Tu Huoxiang (Local Ageratum) ( 35
1.4.2.6 Weilingcai Gen (Potentilla Root) ( 36
1.4.2.7 Huanghua Jiaohao (Incarvillea Lutea Bur. 36
References 36
2 Distribution and Habitat of Danshen 37
2.1 37
2.2 37
2.3 38
2.3.1 Climatic Conditions 38
2.3.1.1 Liaodong& hx2013
2.3.1.2 Shanxi, Liaoning, and Loess Plateau Region 38
2.3.1.3 South of Huaihe River and the Lower-middle Reaches of Yangtze River Region 38
2.3.1.4 Other Regions 38
2.3.2 38
2.3.3 38
2.3.4 of High-quality Danshen 38
2.4 and Quality 39
2.4.1 39
2.4.1.1 39
2.4.1.2 39
2.4.1.3 40
2.4.1.4 41
2.4.2 41
2.4.2.1 Indicators and Data Evaluation 41
2.4.2.2 Correlation Between Geographical Condition and Chemical 42
2.4.2.3 About the of Danshen 43
References 44
3 Biological Characters of Danshen 45
3.1 and 45
3.1.1 45
3.1.1.1 45
3.1.1.2 45
3.1.1.3 46
3.1.1.4 47
3.1.1.5 48
3.1.1.6 Life Span of 49
3.1.2 and 50
3.1.2.1 of 50
3.1.2.2 of and 50
3.1.2.3 Accumulation of Effective in and the of Danshen's 52
3.1.2.4 of 52
3.2 Anatomical of Danshen 53
3.2.1 of 53
3.2.1.1 53
3.2.1.2 54
3.2.2 of 54
3.2.2.1 54
3.2.2.2 54
3.2.2.3 55
3.2.3 Morphological and Structural Characteristics of 55
3.2.4 Conclusion 56
3.3 The Reproductive Biological Characters of Danshen 57
3.3.1 Phenological Periods of the of Danshen 57
3.3.2 The Exterior Appearances of and Dynamic Process of Danshen 58
3.3.3 of Danshen 58
3.3.4 Vitality of Danshen's 58
3.3.5 Effects of Time (Table 3.8) and Mode on Seed Setting Rate 59
3.3.6 Conclusion 59
3.4 Study on Danshen's [10, 11] 60
3.4.1 of in Genus Salvia 60
3.4.2 of of Different Salvia Groups 61
3.4.3 of of Species and Cultivated Varieties 61
3.5 Cytological Study on Danshen Plants [13] 61
3.6 Embryologic Study on Danshen 61
3.6.1 of and [13] 61
3.6.2 of and [16] 66
3.7 Molecular Biological Study on Danshen 68
3.7.1 Analysis of Danshen 68
3.7.2 Studies on the Molecular Identification of Danshen 69
3.7.3 Construction of Danshen and Study on 70
References 73
4 A Study on the Cultivation of Danshen 74
4.1 of Danshen 74
4.1.1 by 74
4.1.2 by 74
4.1.3 by Root Division 74
4.1.4 by 75
4.1.5 by 75
4.2 A Study on the Biological Characters of Danshen 76
4.2.1 Water Absorption Characters of Danshen 76
4.2.2 Influences of s on Germination of Danshen 77
4.2.2.1 Temperature 77
4.2.2.2 Germination Bed 77
4.2.2.3 Seed Quality 78
4.2.2.4 Pretreatments 78
4.2.3 Conclusion 78
4.3 Influences of on the and Contents of Effective of Danshen 79
4.3.1 Exterior Characters of Danshen's After Treatments 80
4.3.2 Changes in After Treatments 80
4.3.2.1 Changes in Contents (See Table 4.11) 80
4.3.2.2 Changes in Tanshinone Content After Different Treatments of Danshen (See Tables 4.13, 4.14) 81
4.3.3 Conclusion 81
4.4 of Danshen 81
4.4.1 Characteristics of New Growing on Basal Parts of 82
4.4.2 Discussion 84
4.5 Influences of on and Contents of Active of Danshen 85
4.5.1 Influence of on Survival Rate 86
4.5.2 Influence of Different Densities on and Contents 86
4.5.3 A Comparison of the s of Danshen Under Different Densities (In Terms of Fresh Weight) 87
4.5.4 Summary and Discussion 88
4.6 The Effects of on the of Danshen and the Accumulation of Effective 89
4.6.1 Relationship Between and 89
4.6.2 Relationship Between and Tanshinone IIA 90
4.6.3 Dynamic and of Treated with 91
4.6.4 Summary 92
References 93
5 Danshen's In Vitro Culture 94
5.1 Micropropagaation of Danshen 94
5.2 of Danshen 97
5.3 Tissue and Organ Culture of Danshen 99
5.3.1 Culture of Danshen 99
5.3.2 Culture of and Tissues of Danshen 100
5.3.2.1 Culture of Danshen 102
5.3.3 Culture of Tissues of Danshen 105
References 112
6 Genetics and Breeding of Danshen 113
6.1 The Resources and Studies of Danshen 113
6.2 Mutation of Danshen 114
6.3 Molecular of Danshen 115
6.3.1 Molecular Marker-Assisted of Danshen 115
6.3.2 Studies on the of Danshen by Genetic Engineering 116
6.3.2.1 Studies on the Mechanism of Biosynthesis of Active of Danshen 116
6.3.2.2 Agrobacteria-Mediated Danshen 116
of Danshen by Agrobacteria 116
6.3.2.3 of Regenerated Plants from 118
References 119
7 Water Soluble Components of Danshen 120
7.1 Literature Review 120
7.2 Introduction 121
7.3 Chemical Structures of 121
7.4 Extraction and Isolation of 122
7.4.1 Extraction of 122
7.4.1.1 Extraction with Water and Precipitation with Ethanol 122
7.4.1.2 Macroporous Resin Chromatography 122
7.4.1.3 Extraction with Ethanol and Dissolution in Water 124
7.4.2 Isolation of 124
7.4.2.1 Silica Gel Dry Column Chromatography 124
7.4.2.2 Flash Chromatography 125
7.4.2.3 Preparative TLC 125
7.4.2.4 Sephadex LH-20 Column Chromatography 125
7.4.2.5 High-pressure Liquid Chromatography 125
7.4.3 Examples of Phenolic Acid Isolation 125
7.4.3.1 Isolation of A, B, C, D, and E 125
7.4.3.2 Isolation of Magnesium Lithospermate B and Ammonium& hx2013
7.4.3.3 Isolation of A-H [9, 10] 126
7.5 of 126
7.5.1 Ultraviolet Spectra 126
7.5.2 Mass Spectrometry 126
7.5.3 Nuclear Magnetic Resonance Spectra 126
7.5.3.1 NMR Spectra of 1H 126
7.5.3.2 NMR Spectra of 13C 129
7.5.3.3 Two-dimensional Nuclear Magnetic Resonance 129
7.6 Physical and Chemical Properties of 130
7.6.1 General Properties 130
7.6.2 Stability 132
7.6.2.1 Effect of pH 132
7.6.2.2 Effect of Temperature 132
7.6.3 Chemical Transformation 132
7.6.3.1 Methylation of 132
7.6.3.2 Hydrolysis of Methylated s 133
7.6.3.3 Transformation of A 133
7.6.3.4 Transformation of B 133
7.7 of 133
7.8 Synthesis of 133
7.8.1 Synthesis of Danshensu [22] 133
7.8.2 Synthesis of F [23] 135
7.8.3 Synthesis of Heptamethyl Lithospermate [24] 139
References 140
8 Liposoluble Chemical Constituents in Danshen 141
8.1 Introduction and Classification 141
8.1.1 Early Records of Chemical Study on 141
8.1.2 Nomenclature and Classification of Liposoluble Constituents in Danshen 143
8.1.2.1 Some Explanations 143
8.1.2.2 Classification of Liposoluble Constituents in Danshen 144
Diterpenoid 144
Tricyclic Diterpene Quinone 146
Royleanone 147
Compounds Related to Biogenesis of 148
Other Compounds 149
8.2 Extraction and Isolation of Liposoluble Compounds 150
8.2.1 Extraction Method 151
8.2.1.1 Selection of Raw Medicinal Material 151
8.2.1.2 Extraction Method Based on Ethanol 152
8.2.1.3 Supercritical Fluid Technique 152
8.2.2 Separation Methods 152
8.2.2.1 Analytical Method 153
Monitoring the Quality of Medicinal Materials 153
Assay of the Active Constituents in Danshen Preparations 153
Studies on Tissue Culture 153
Study on in Vivo Metabolism of 154
8.2.2.2 Preparative Method 155
Systemic Chemical Separation 155
TLC Used to Separate Microconstituents 156
Chemical Study on in China 156
Study on Used for Therapy of Coronary Heart Disease 157
Separation Method Based on Bioactivity 158
8.2.2.3 General Operations for the Isolation of Known Constituents in Danshen 159
Separation According to the Structure of a Known Compound 160
Collection and Detection of Eluent 160
Preisolation with TLC 160
8.2.3 Operating Procedure and Examples of Preparative Isolation 161
8.2.3.1 Physicochemical Detection of Liposoluble Components of Danshen 161
Sec34 161
Liposoluble Constituents Containing Only a Single Double Bond 161
8.2.3.2 Thin-layer Isolation Based on Same Chromophore 162
8.2.3.3 Adsorbents and Developing Solvent 162
8.2.4 Determining Column Chromatographic Conditions Based on Preseparation on TLC 164
8.2.5 Two Forms of Preparative Columns: Comparison Between Dry Column Chromatography and Gradient Elution 165
8.2.5.1 Dry Column Chromatography 165
8.2.5.2 Gradient Elution 166
8.2.6 Examples of Gradient Elution 166
8.2.6.1 Separation of Ferruginol, , and Ro-09-0680 166
8.2.6.2 Isolation of [11] and 166
8.2.6.3 Isolation of A, B, and C 167
8.3 Spectrum Characteristic of Compounds 167
8.3.1 Ultraviolet Spectrum 167
8.3.1.1 of 168
8.3.1.2 Confirmation of New Ring Systems by UV Absorption [35] 170
8.3.1.3 The Limitations of the 170
8.3.2 Infrared (IR) Absorption Spectrum 170
8.3.2.1 Application of on the Identification of 171
8.3.2.2 Structure Identification of 1- and 171
8.3.2.3 Structure Identification of Royleanone-type Compound 171
8.3.2.4 [17] and 1, 2- [23] 172
8.3.2.5 Structural Identification of A and B [15] 172
8.3.3 Nuclear Magnetic Resonance (NMR) Spectrum 173
8.3.3.1 1H- of II 173
8.3.3.2 1H- of IIA (14) 174
8.3.3.3 1H- of Methyl Tanshinonate (6) 174
8.3.3.4 1H-NMR Spectra of I (33), II (34) and (35) [28] 174
8.3.3.5 1H- of I [29] (36) 175
8.3.3.6 1H- of I (37) [21] 175
8.3.3.7 1H of IIB [30] 175
8.3.3.8 1H-NMR Spectra of Danshenxinkun A (39), B (40), C (41) [13] 176
8.3.3.9 1H-NMR Spectra of (46) [11] and Danshenspiroketallactone (42) [53] 176
8.3.3.10 1H-NMR Spectra of (27), I (28) [8], 1-Dehydromiltirone (29) [25] 177
8.3.3.11 1H- of (47) [10] 178
8.3.3.12 1H-NMR Spectra of Anhydride of (48) and Anhydride of (49) 178
8.3.3.13 1H-NMR Spectra of a (10), B (11), C (12) [19] 178
8.3.3.14 1H- of (13) [19] 178
8.3.3.15 1H-NMR Spectra of C (21) and F (22) [20] 179
8.3.3.16 1H-NMR Spectra of Methylene (8) [17] and 1, I (9) [23] 179
8.3.3.17 1H- of Hydroxymethylene (25) [54] 179
8.3.3.18 1H-NMR Spectra of (50) [25], (52) and (53) [55] 180
8.3.3.19 1H-NMR Spectra of A (19) and B (20) 180
8.3.3.20 1H-NMR Spectra of II (16) [24] and I (26) [23] 181
8.3.3.21 1H-NMR Spectra of (17) and 1, 2, 15, (18) 181
8.3.3.22 1H- of Cryptomethyl Tanshinoate (23) 181
8.3.3.23 1H-NMR Spectra of V (62), and VI (63) [36] 182
8.3.3.24 NMR Spectra of Salvionone (59), (61) [35] 182
8.3.3.25 1H-NMR Spectra of I (56), II (57)[38] 183
8.3.3.26 NMR Spectra of Epi-Danshenspiroketallactone (43), (45), (44) 185
8.3.3.27 1H-NMR Spectra of Danshenol-A (55) and Danshenol-B (54) 185
8.3.3.28 of Paramiltioic Acid [56] 188
8.3.4 Mass Spectrometry 188
8.3.4.1 Dehydration After the Loss of Side Chain in Ring A 189
8.3.4.2 Direct Dehydration 192
8.3.4.3 Dehydration After the Loss of CO 192
8.3.4.4 The Dehydration Process of Compounds with a Hydroxyl Ring A 193
8.3.4.5 The Effect of Ring D on the Dehydration Process 193
8.4 The Physicochemical Properties of s 195
8.4.1 The Redox Potential of s 195
8.4.1.1 The Influence of IA on Free Radicals of Lipids 196
8.4.1.2 The Relationship Between the Structure and Antioxidation Activity of s 197
8.4.1.3 Inhibiting the Oxidation of Low-density Lipoprotein by s 198
8.4.2 The Chemical Stability of s and the Influence of Solvents on Their Structures 199
8.4.3 The Effects of Rings and Conjugation Systems on the Activity of Quinones 199
8.4.3.1 Factors Affecting Solubility: A Molecular Structure Perspective 200
The Molecular Field and the Geometry Optimization of s 200
The Hydrophilic/Hydrophobic Ratio 200
Non-bonded Interactions 202
8.4.3.2 A Variety of Chromatographic Techniques can Provide a Hydrophobic Index Value of the Different Structures of s 203
Using Reverse HPLC to Obtain Hydrophobicity Data 204
Using Partition Chromatography to Reflect Oil& hx2013
Chromatography on Thin Film of Polyamide 204
8.4.3.3 Comparison of s 205
8.5 The of and Its Artifacts 207
8.5.1 The Biosynthesis of 207
8.5.1.1 The Products of IA (The Formation of Artifacts) 209
8.5.1.2 The Biogensis of Danshen Lactone and Danshenspiroketallactone 209
8.5.1.3 The Chemical Connection of Secondary Metabolites in Danshen 210
8.5.1.4 The Formation Order of the Secondary Metabolites 211
8.6 212
8.6.1 212
8.6.2 Diene Addition of 3- 212
8.6.2.1 Diene Addition of 3-methyl-4,5-benzofurandione 214
8.6.3 214
8.6.4 Structural Modification of IA 216
8.6.4.1 Synthesis Compound IX 217
8.6.4.2 Synthesis of 4,5,6,7,8, 9-hexahydro-2-(N-pyrrolidinyl)-methyl-3,9-dimethyl-phenanthrene[1, 2b]furan(X a) 217
8.6.5 Structural Modification of 217
8.6.5.1 Synthesis of N-4,5-dihydro-3, 9-dimethyl-4,5-diketonephenanthrene [1,2b] Furan Sodium Glycinate (A8) 218
8.7 Triterpenoids of Danshen 220
8.7.1 Isolation and Identification of Przewanoic Acid A and B [87] 220
8.7.1.1 Przewanoic Acid A (1) 221
8.7.1.2 Przewanoic Acid B (2) 221
8.7.2 Isolation and Identification of Trijuganoic and Euscaphic Acids [88] 222
8.7.3 Isolation and Identification of Triterpene Acid from S. Paramiltiorrhiza 224
8.8 The Challenges and Opportunities for the Study of s in this Century 226
8.8.1 The Chemical Study of Aims at Finding New Targets 226
8.8.2 The Biological Activities and the Physicochemical Properties of Compounds 226
8.8.3 Chemical& hx2013
References 228
Index 231