Cover
Title Page
Contributors
Preface
Chapter 1: The Physical Chemistry of Polyphenols
1. 1.1 Introduction
2. 1.2 Molecular complexation of polyphenols
3. 1.3 Polyphenols as electron donors
4. 1.4 Polyphenols as ligands for metal ions
5. 1.5 Conclusions
6. References
Chapter 2: Polyphenols in Bryophytes
1. 2.1 Introduction
2. 2.2 Distribution of cyclic and acyclic bis‐bibenzyls in Marchantiophyta (liverworts)
3. 2.3 Biosynthesis of bis‐bibenzyls
4. 2.4 The structures of bis‐bibenzyls and their total synthesis
5. 2.5 Biological activity of bis‐bibenzyls
6. 2.6 Conclusions
7. Acknowledgments
8. References
Chapter 3: Oxidation Mechanism of Polyphenols and Chemistry of Black Tea
1. 3.1 Introduction
2. 3.2 Catechin oxidation and production of theaflavins
3. 3.3 Theasinensins
4. 3.4 Coupled oxidation mechanism
5. 3.5 Bicyclo[3.2.1]octane intermediates
6. 3.6 Structures of catechin oxidation products
7. 3.7 Oligomeric oxidation products
8. 3.8 Conclusions
9. Acknowledgments
10. References
Chapter 4: A Proteomic‐Based Quantitative Analysis of the Relationship Between Monolignol Biosynthetic Protein Abundance and Lignin Content Using Transgenic Populus trichocarpa
1. 4.1 Introduction
2. 4.2 Results
3. 4.3 Discussion
4. 4.4 Materials and methods
5. References
Chapter 5: Monolignol Biosynthesis and Regulation in Grasses
1. 5.1 Introduction
2. 5.2 Unique cell walls in grasses
3. 5.3 Lignin deposition in grasses
4. 5.4 Monolignol biosynthesis in grasses
5. 5.5 Regulation of monolignol biosynthesis in grasses
6. 5.6 Remarks
7. Acknowledgments
8. References
Chapter 6: Creation of Flower Color Mutants Using Ion Beams and a Comprehensive Analysis of Anthocyanin Composition and Genetic Background
1. 6.1 Introduction
2. 6.2 Induction of flower color mutants by ion beams
3. 6.3 Mutagenic effects and the molecular nature of the mutations
4. 6.4 Comprehensive analyses of flower color, pigments, and associated genes in fragrant cyclamen
5. 6.5 Mutagenesis and screening
6. 6.6 Genetic background and the obtained mutants
7. 6.7 Carnations with peculiar glittering colors
8. 6.8 Conclusions
9. Acknowledgments
10. References
Chapter 7: Flavonols Regulate Plant Growth and Development through Regulation of Auxin Transport and Cellular Redox Status
1. 7.1 Introduction
2. 7.2 The flavonoids and their biosynthetic pathway
3. 7.3 Flavonoids affect root elongation and gravitropism through alteration of auxin transport
4. 7.4 Mechanisms by which flavonols regulate IAA transport
5. 7.5 Lateral root formation
6. 7.6 Cotyledon, trichome, and root hair development
7. 7.7 Inflorescence architecture
8. 7.8 Fertility and pollen development
9. 7.9 Flavonols modulate ROS signaling in guard cells to regulate stomatal aperture
10. 7.10 Transcriptional machinery that controls synthesis of flavonoids
11. 7.11 Hormonal controls of flavonoid synthesis
12. 7.12 Flavonoid synthesis is regulated by light
13. 7.13 Conclusions
14. Acknowledgments
15. References
Chapter 8: Structure of Polyacylated Anthocyanins and Their UV Protective Effect
1. 8.1 Introduction
2. 8.2 Occurrence and structure of polyacylated anthocyanins in blue flowers
3. 8.3 Molecular associations of polyacylated anthocyanins in blue flower petals
4. 8.4 UV protection of polyacylated anthocyanins from solar radiation
5. 8.5 Conclusions
6. References
Chapter 9: The Involvement of Anthocyanin‐Rich Foods in Retinal Damage
1. 9.1 Introduction
2. 9.2 Anthocyanin‐rich foods for eye health
3. 9.3 Experimental models to mimic eye diseases and the effect of anthocyanin‐rich foods
4. 9.4 Conclusions
5. References
Chapter 10: Prevention and Treatment of Diabetes Using Polyphenols via Activation of AMP‐Activated Protein Kinase and Stimulation of Glucagon‐like Peptide‐1 Secretion
1. 10.1 Introduction
2. 10.2 Activation of AMPK and metabolic change
3. 10.3 GLP‐1 action and diabetes prevention/suppression
4. 10.4 Future issues and prospects
5. References
Chapter 11: Beneficial Vascular Responses to Proanthocyanidins
1. 11.1 Introduction
2. 11.2 Appraisal of test materials
3. 11.3 Endothelial dysfunction
4. 11.4 In vitro test systems
5. 11.5 Vasorelaxant mechanisms
6. 11.6 Bioavailability and metabolic transformation: the missing link in the evidence to action in the body
7. 11.7 Conclusions
8. References
Chapter 12: Polyphenols for Brain and Cognitive Health
1. 12.1 Introduction
2. 12.2 Studies of total polyphenols and cognition
3. 12.3 Pine bark
4. 12.4 Discussion and conclusions
5. References
Chapter 13: Curcumin and Cancer Metastasis
1. 13.1 Introduction
2. 13.2 Effects of curcumin on intra‐hepatic metastasis of liver cancer
3. 13.3 Effects of curcumin on lymp node metastasis of lung cancer
4. 13.4 Effects of curcumin on tumor angiogenesis
5. 13.5 Conclusions
6. References
Chapter 14: Phytochemical and Pharmacological Overview of Cistanche Species
1. 14.1 Introduction
2. 14.2 Chemical constituents of Cistanche species
3. 14.3 Bioactivities of the extracts and pure compounds from Cistanche species
4. 14.4 Conclusions
5. References
Index
End User License Agreement

List of Tables

Chapter 02
1. Table 2.1 Bis‐bibenzyls found in the Marchantiophyta (liverworts) (Asakawa & Ludwiczuk, 2012).
2. Table 2.2 Biologically active bis‐bibenzyls from liverworts (Asakawa, 1982, 1995, 2008a; Asakawa et al., 2013a, 2013b).
Chapter 04
1. Table 4.1 Core proteins of monolignol biosynthesis in Populus trichocarpa.
2. Table 4.2 Parameter estimates from segmented regression models predicting lignin content of Populus trichocarpa from protein abundance.
Chapter 06
1. Table 6.1 Frequency of flower mutants induced by gamma rays and carbon ions in the chrysanthemum cultivar “Taihei” (Pink flowers).
2. Table 6.2 Frequency of flower mutants induced by carbon ions, EMS, gamma rays, and X‐rays in the carnation cultivar “Vital” (cherry pink flowers).
Chapter 07
1. Table 7.1 Summary of transcription factors that have been demonstrated to control levels of transcripts of genes encoding pathway enzymes of flavonoid biosynthesis and the organism and tissue in which this regulation has been observed.
Chapter 11
1. Table 11.1 Data on the chemical composition of procyanidin samples.
2. Table 11.2 Overview of important inhibitors and their targets.
3. Table 11.3 Vasorelaxant mechanisms studied in procyanidin‐containing plant products.
Chapter 12
1. Table 12.1 Controlled trials of the cognitive effects of polyphenols/polyphenol rich products.
Chapter 14
1. Table 14.1 Chemical types and their distribution in Cistanche species.
2. Table 14.2 PhGs from Cistanche species (1–70).
3. Table 14.3 Benzyl glycosides from Cistanche species (71–76).
4. Table 14.4 Structures of iridoid aglycones (77−87).
5. Table 14.5 Structures of iridoid glycosides (88−102).
6. Table 14.6 Structures of monoterpenoids (103−109).
7. Table 14.7 Structures of ditetrahydrofuran lignans from Cistanche species (110–117).
8. Table 14.8 The structural properties of polysaccharides from C. deserticola.
9. Table 14.9 Other type compounds from Cistanche species.

List of Illustrations

Chapter 01
1. Fig. 1.1 A simplified view of polyphenol bioavailability.
2. Fig. 1.2 Health effects expressed by polyphenols.
3. Fig. 1.3 Pathways of inflammation and oxidative stress in cells. Kinases, proinflammatory transcription factors, and pro‐oxidant enzymes are possible target proteins for polyphenols and their metabolites.
4. Fig. 1.4 Snapshots of the location of quercetin (a) and quercetin 3‐O‐β‐D‐glucuronide (b) in a 1,2‐dioleoyl‐sn‐glycero‐3‐phosphatidylcholine lipid bilayer. Spheres represent the phosphatidyl groups.
5. Fig. 1.5 Schematic description of (a) PCET involving five electrons and (b) HAT.
6. Fig. 1.6 Various geometries of noncovalent ArOH‐‐‐ROO^• arrangements. (a) transoid H‐bonding, (b) cisoid H‐bonding, (c) π–π stacking, and (d) XH–π stacking complexes.
7. Fig. 1.7 Schematic potential energy surfaces with respect to the reaction coordinate (a) corresponding to the electron transfer and (b) defining the internal reorganization energies.
8. Fig. 1.8 Activation of heme iron (metmyoglobin) by lipid hydroperoxides and the role of phenolic antioxidants.
9. Fig. 1.9 Polyphenols and transition metal ions. Acidic conditions: iron binding and subsequent electron transfer. Neutral conditions: binding and autoxidation.
10. Fig. 1.10 Spin density distribution: (a) [Fe^III(Cat¹⁻)(H₂O)₅]⁺² and (b) [Fe^III(Cat²⁻)(H₂O)₄]⁺¹.
11. Fig. 1.11 Electronic structure of the Fe^III–Catecholate complex in its high spin (sextet) state, showing the two possible electronic configurations.
12. Fig. 1.12 Proposed mechanism for the Fe^III‐induced oxidation of catechol (L = H₂O).
Chapter 02
1. Fig. 2.1 Marchantia polymorpha.
2. Fig. 2.2 Marchantia paleacea var. diptera.
3. Fig. 2.3 Pellia epiphylla.
4. Fig. 2.4 Structures of bis‐bibenzyls (1–24, 27) found in the Marchantiophyta (liverworts).
5. Fig. 2.5 Structures of bis‐bibenzyls (25, 26–43) found in the Marchantiophyta (liverworts).
6. Fig. 2.6 Structures of bis‐bibenzyls (44–67a) found in the Marchantiophyta (liverworts).
7. Fig. 2.7 Structures of bis‐bibenzyls (68–77) and their dimers (78–81) found in the Marchantiophyta (liverworts).
8. Fig. 2.8 Structures of bis‐bibenzyls (82–85) found in the Marchantiophyta (liverworts).
9. Fig. 2.9 Structures of acyclic bis‐bibenzyl dimers (82, 85), bis‐bibenzyls (83, 84), and acyclic bis‐bibenzyls (86, 87) found in the Marchantiophyta (liverworts).
10. Fig. 2.10 Biosynthetic pathways for marchantin A (14) (Friederich et al., 1999a, 1999b).
11. Fig. 2.11 Stereochemistry of isoplagiochins C (46) and D (47).
Chapter 03
1. Fig. 3.1 Reversed‐phase high‐performance liquid chromatography (HPLC) profiles of major tea products (maximum absorbance): (a) green tea (Japan), (b) postfermented tea produced under aerobic conditions (Hunan, China), (c) oolong tea (Fujian, China), and (d) black tea (Assam, India). Caf, caffeine; Cat, catechin; Fl, unidentified flavonol glycoside; GA, gallic acid; GC, gallocatechin; GCg, gallocatechin‐3‐O‐gallate; TB, theobromine; TCA, theacitrin A; ThG, theogallin; epigallocatechin (1), epicatechin (2), epigallocatechin‐3‐O‐gallate (3), epicatechin‐3‐O‐gallate (4), theaflavin (5), theaflavin‐3‐O‐gallate (6), theaflavin‐3′‐O‐gallate (7), theaflavin‐3,3′‐di‐O‐gallate (8), theasinensin A (9), theasinensin B (10), and theasinensin C (11). HPLC conditions: Cosmosil 5C₁₈‐AR II (Nacalai Tesque, Japan) column (4.6 × 250 mm i.d.) with gradient elution from 4 to 30% (39 min) and from 30 to 75% (15 minutes) of CH₃CN in 50‐mM H₃PO₄, flow rate, 0.8 ml/minute; column temperature, 35°C; detection, JASCO photodiode array detector MD‐910.
2. Fig. 3.2 Structures of major black tea polyphenols 1–14. The names of structures were the same as described in Fig. 3.1.
3. Fig. 3.3 Production of theaflavin and oxidation of proanthocyanidins.
4. Fig. 3.4 Reversed‐phase HPLC profiles of crushed fresh tea leaves (maximum absorbance): (a) 60% ethanol (EtOH) extract of crushed tea leaves, (b) 60% EtOH extract of crushed tea leaves after treatment with o‐phenylenediamine–acetic acid/EtOH, and (c) 60% EtOH extract of crushed tea leaves after heating at 80°C. HPLC conditions were the same as described in Fig. 3.1.
5. Fig. 3.5 Structures of dehydrotheasinensin A (15) and phenazine derivatives.
6. Fig. 3.6 Oxidation of 1 with radical initiator. AMVN: 2,2′‐azobis(2,4‐dimethyl‐valeronitrile).
7. Fig. 3.7 Degradation of dehydrotheasinensin A (15) on heating: (a) before heating and (b) after heating of aqueous solution of 15 at 90°C for 30 minutes. HPLC column: Develosil C30‐UG‐5 (250 × 4.6 mm, Nomura Chemical) with gradient elution 4–30% (39 minutes) and 30–75% (15 minutes) of CH₃CN in 50‐mM H₃PO₄; flow rate, 0.8 ml/minute; column temperature, 35°C; detection, JASCO photodiode array detector MD‐910.
8. Fig. 3.8 Structures of oxidation products of 15.
9. Fig. 3.9 Production and oxidation of theaflavin by coupled oxidation of 1 and 2.
10. Fig. 3.10 Production of black tea polyphenols from bicyclo[3.2.1]octane intermediates. EGC, epigallocatechin.
11. Fig. 3.11 Minor oxidation products obtained by in vitro enzymatic oxidation of tea catechins.
12. Fig. 3.12 Oxidation products of epicatechin and epicatechin‐3‐O‐gallate.
13. Fig. 3.13 Reversed‐phase HPLC profiles of black tea fractions. Aqueous acetone extract of black tea was successively partitioned with ethyl acetate (AcOEt) and n‐butanol (n‐BuOH) (yields from black tea: AcOEt layer, 9%; n‐BuOH layer, 17%; aqueous layer, 21%). The n‐BuOH fraction was further fractionated by Sephadex LH‐20 column chromatography into five fractions (yields from n‐BuOH layer: Fr. 1 (caffeine), 43%; Fr. 2 (gallic acid and flavonol glycoside), 8.7%; Fr. 3, 8.7%; Fr. 4, 21%; Fr. 5, 16.4%). HPLC conditions were the same as described in Fig. 3.1.
14. Fig. 3.14 ¹³C Nuclear magnetic resonance spectra of oligomeric polyphenols and 3 (in DMSO‐d₆). (a) Spectrum of oligomeric polyphenol fraction obtained from Assam black tea by size‐exclusion column chromatography (Yanagida et al., 2003; Tanaka et al., 2009). (b) Spectrum of 3. A, A‐ring; B, B‐ring; C, C‐ring; G, galloyl group.
Chapter 04
1. Fig. 4.1 The monolignol biosynthetic pathway in Populus trichocarpa. The pathway consists of 20 enzymes (phenylalanine ammonia‐lyases, PtrPAL1‐5; cinnamic acid 4‐hydroxylases, PtrC4H1 and 2; cinnamic acid 3‐hydroxylase, PtrC3H3; hydroxycinnamoyl‐CoA shikimate hydroxycinnamoyl transferases, PtrHCT1 and 6; 4‐coumaric acid:CoA ligases, Ptr4CL3 and 5; caffeoyl‐CoA O‐methyltransferases, PtrCCoAOMT1‐3; cinnamoyl‐CoA reductase, PtrCCR2; coniferaldehyde 5‐hydroxylases, PtrCAld5H1 and 2; 5‐hydroxyconiferaldehyde O‐methyltransferase, PtrAldOMT2; cinnamyl alcohol dehydrogenase, PtrCAD1) and 24 metabolites (bold numbers) that convert phenylalanine to the monolignols. The cofactors are reduced nicotinamide adenine dinucleotide phosphate (NADPH), oxidized nicotinamide adenine dinucleotide phosphate (NADP+), coenzyme A (CoA), adenosine triphosphate (ATP), adenosine monophosphate (AMP), pyrophosphate (PPi), S‐adenosyl methionine (SAM), and S‐adenosyl homocysteine (SAH).
2. Fig. 4.2 Monolignol biosynthetic protein abundance in wild‐type and transgenic Populus trichocarpa. The LC–MS/MS‐based absolute protein abundance of (a) PtrPAL1, (b) PtrPAL2, (c) PtrPAL3, (d) PtrPAL4/5, (e) PtrC4H1, (f) PtrC3H3, (g) PtrCCR2, and (h) PtrCAD1 in stem differentiating xylem of the 92 wild‐type and transgenic P. trichocarpa trees (6 months old). The x‐axis specifies the target gene(s) for downregulation in each transgenic sample. Error bars represent one standard error of biological replicates.
3. Fig. 4.3 Lignin content of wild‐type and transgenic Populus trichocarpa. (a) The absolute lignin content of wild‐type and transgenic P. trichocarpa as weight percentage of the extractive‐free wood, determined by the Klason method. (b) The standardized lignin content for wild‐type (dark gray) and transgenic (light gray) P. trichocarpa, standardized based on the lignin content of corresponding wild‐type samples of the same batch. Frequency values indicate the number of trees.
4. Fig. 4.4 The scatter plots show the relationship between the protein abundance and lignin content for monolignol biosynthetic protein families (a) PtrPAL, (b) PtrC4H, (c) PtrC3H, (d) Ptr4CL, (e) PtrHCT, (f) PtrCCoAOMT, (g) PtrCCR, (h) PtrCAD, (i) PtrCAld5H, and (j) PtrAldOMT. (k) The solid circles represent data from the transgenic trees. The triangles represent transgenic trees exhibiting dwarfed phenotype. The squares represent data from wild‐type. The solid lines represent segmented regression models. Protein abundance (nM) was derived from concentration (μg/g of total protein) using the conversion factor of 0.74 ml/g (water content of SDX tissue) (Shuford et al., 2012).
Chapter 05
1. Fig. 5.1 The monolignol biosynthesis pathway in grasses.
2. Fig. 5.2 Regulation of monolignol biosynthesis in grasses. Genes in boxes are regulators of monolignol biosynthesis. Dashed lines indicate that gene functions have not been verified in grasses.
Chapter 06
1. Fig. 6.1 Cyclamen cultivars, wild species, and flower color mutants shown beside the anthocyanin biosynthesis pathway. Flowers are grouped according to their major anthocyanins. (a) Cyclamen persicum cultivar “Strauss (St).” (b–d) Deeper color mutants “ion246” (b) and “ion3” (c) obtained from fragrant cyclamen cultivar “Uruwashi‐no‐kaori (UR)” (d). (e) C. persicum cultivar “Golden Boy (GB).” (f) A pale yellow‐flowered mutant obtained from a hybrid (GB × Cyclamen purpurascens) “GBCP.” (g) C. persicum cultivar “Pure White (Pw).” (h) A white‐flowered mutant obtained from fragrant cyclamen cultivar “Koko‐no‐kaori (KO).” (i–k) Red–purple‐flowered mutants “KMrp” (i), “KMmv3” (j), and “KMmv35” (k) obtained from fragrant cyclamen cultivar “kaori‐no‐mai (KM).” (l) A hybrid “GBCP” derived from GB × C. purpurascens. (m and n) Fragrant cyclamen cultivars KM (m) and KO (n). (o) Scented wild species C. purpurascens. Fragrant cyclamen cultivars were created by a cross between C. persicum cultivars and C. purpurascens. Flower color mutants were obtained from mutagenized populations of fragrant cyclamen cultivars irradiated with ion beams. ANS, anthocyanidin synthase; AOMT, anthocyanin O‐methyltransferase; Ch2G, chalcone 2′‐glucoside; CHI, chalcone isomerase; Cy3,5dG, cyanidin 3,5‐diglucoside; DFR, dihydroflavonol 4‐reductase; Dp3,5dG, delphinidin 3,5‐diglucoside; F3H, flavanone 3‐hydroxylase; F3′H, flavonoid 3′‐hydroxylase; F3′5′H, flavonoid 3′5′‐hydroxylase; FLS, flavonol synthase; 2′GT, chalcone 2′‐glucosyltransferase; 3GT, anthocyanidin 3‐glucosyltransferase; 5GT, anthocyanin 5‐glucosyltransferase; Mv3G, malvidin 3‐glucoside; Mv3,5dG, malvidin 3,5‐diglucoside; Pn3Nh, peonidin 3‐neohesperidoside; Pn3,5dG, peonidin 3,5‐diglucoside.
2. Fig. 6.2 Carnation with peculiar colors that contain nonacylated anthocyanins. (a) Flowers and transverse sections of petal epidermis of carnation cultivar “Beam Cherry (left)” and “Nazareno (right).” (b) The experimental strain “07MC4” and the mutant “07GRP” with peculiar colors obtained by inactivation of AMalT activity with carbon ion irradiation. The genotype for AMalT locus is shown in parenthesis. AMalT and a bar represent the active and inactive AMalT locus, respectively. The major anthocyanins are shown beside each flower. (c) Flowers of all four types of acylated and nonacylated‐type anthocyanin in carnation. The major anthocyanins are shown beside each flower. AMalT, anthocyanin malyltransferase; Cy3,5cMdG, cyanidin 3,5‐cyclic malyl diglucoside; Cy3,5dG, cyanidin 3,5‐diglucoside; Cy3G, cyanidin 3‐glucoside; Cy3MG, cyanidin 3‐malyl glucoside; Pg3,5cMdG, pelargonidin 3,5‐cyclic malyl diglucoside; Pg3,5dG, pelargonidin 3,5‐diglucoside; Pg3G, pelargonidin 3‐glucoside; Pg3MG, pelargonidin 3‐malyl glucoside.
Chapter 07
1. Fig. 7.1 The flavonol biosynthetic pathway is illustrated, showing enzymatic steps and indicating Arabidopsis transport testa (tt) and tomato anthocyanin mutant names. Bolded sections of the pathway are specific to tomato and petunia. CHI, chalcone isomerase; CHS, chalcone synthase; F3H, flavanone 3‐hydroxylase; F3′H, flavonoid 3′‐hydroxylase; F3′5′H, flavonoid 3′,5′‐hydroxylase; FLS, flavonol synthase; DFR, dihydroflavonol reductase; OMT1, flavone 3′‐O‐methyltransferase 1. Tomato mutants are anthocyaninless (a), anthocyanin reduced (are), and anthocyanin without (aw).
2. Fig. 7.2 A model illustrates how flavonoids may function during root gravitropism. In vertically oriented seedlings, tt4 is deficient in flavonols (yellow) and has elevated PIN2 gene products (green) and shootward auxin transport (black arrows). When roots are reoriented by 90°, flavonol levels increase in the root epidermis, especially in the elongation zone, which may block auxin movement out of the region where differential gravitropic growth occurs. This may concentrate the auxin in the distal elongation zone where root gravitropic bending occurs, enhancing the asymmetric distribution enhancing the rate of gravitropic curvature. In tt4, there is both enhanced auxin movement into and out of this region, reducing the asymmetric distribution of auxin.
3. Fig. 7.3 Lateral root numbers are reduced in the tomato are mutant. (a) Image showing 6‐day‐old seedlings of wild‐type (VF36) and are displaying differences in lateral rooting and hypocotyl pigmentation. (b) Numbers of emerged lateral roots, unemerged lateral root primordia, and combined totals of emerged and primordial roots. Average and SE are presented. Asterisk indicates difference between genotypes with p ≤ 0.05 (n = 15). (c) Lateral root numbers are reported for untransformed VF36, are, and three F3H overexpression lines in each background genotype. Asterisk indicates differences from VF36, and number symbols indicate differences from are, with p ≤ 0.05 (n = 16). Black bars indicate lines in the are background.
4. Fig. 7.4 Flavonol accumulation is absent in tt4 leading to increased ROS and more rapid stomatal closure. Flavonols are visualized by diphenylboric acid 2‐aminoethyl ester (DPBA) (yellow), and ROS is visualized by 2′,7′dihydrodichloro‐fluorescein diacetate (DCF) (green), with chlorophyll in blue. Ethylene overproduction in eto1 leads to enhanced flavonol accumulation and less ROS. Bar = 15 µm. Guard cells of wild‐type and tt4‐2 were examined by light microscopy immediately before treatment with ABA and 45 minutes after treatment with 20 μM ABA. Bar = 15 µm. Watkins et al. (2014). © The fluorescent image is reprinted with permission from American Society of Plant Biologists (www.plantphysiol.org).
5. Fig. 7.5 A model of controls of flavonol synthesis and their function. This figure illustrates the positive effects of ethylene, auxin, sucrose, and light on flavonol synthesis. The action of flavonols in regulating root growth and other developmental processes are summarized with those shown to be mediated through effects on auxin transport and on levels of reactive oxygen species (ROS) indicated.
Chapter 08
1. Fig. 8.1 Structure of anthocyanin forms, Flavylium ion‐quinonoidal base‐pseudobase‐(Z)‐chalcone‐(E)‐chalcone formed at various pH values.
2. Fig. 8.2 The structures of polyacylated anthocyanins reviewed in this chapter: Phacelianin (1), demalonylphacelianin (2), tecophilin (3), heavenly blue anthocyanin (4a), gentiodelphin (5a), cis‐gentiodelphin (5b), alatanin C (6), malonylshisonin (7a), and cis‐malonylshisonin (7b).
3. Fig. 8.3 Long‐range NOEs in the NMR spectrum of phacelianin (1) and Vis‐UV spectra and CD spectra of petal of Phacelia campanularia.
4. Fig. 8.4 Long‐range NOEs of tecophilin (3), Vis‐UV spectra and CD spectra of petal of Tecophilaea cyanocrocus and proposed 3‐D structure of 3.
5. Fig. 8.5 The optimized 3‐D structure of gentiodelphin (5a) obtained by calculation using NMR data and the comparison of the stability of 5a and deacylated pigments.
6. Fig. 8.6 Structure of UVB irradiation products of HBA, and their ¹H NMR spectra (500 MHz) in the low field region recorded in 5% TFAd‐CD₃OD (500 MHZ).
7. Fig. 8.7 Prevention of DNA lesions induced by broad UV‐B with HBA solution screen (5 mM). ▪: Control; ◽: pH 7.5; ◦: 0.5% TFA aq. ▵: 0.5% TFA‐MeOH. Upper: CPDs; lower: 6‐4PPs.
Chapter 09
1. Fig. 9.1 Image showing posterior eye diseases and their common causes. (a) Image of eye structure and each posterior eye disease. (b) Mapping common causes of posterior eye diseases.
2. Fig. 9.2 Anthocyanin‐rich foods used in our experiments.
3. Fig. 9.3 Effect of bilberry extract (BBE) on N‐methyl‐D‐aspartate receptor (NMDA)‐induced retinal damage in mice. Hematoxylin and eosin staining of sections (thickness 5 µm) obtained from mice 7 days after intravitreal injection of NMDA. (a) Representative photographs show nontreated control retina, NMDA‐injected vehicle‐treated retina, retina treated with NMDA injection plus BBE at 10 µg/eye, and retina treated with NMDA injection plus BBE at 100 µg/eye. Horizontal bar represents 25 µm. Vertical bar and arrows indicate inner plexiform layer (IPL) and retinal ganglion cells (RGC), respectively. (b and c) Cell numbers in RGC and thickness of IPL. Data are shown as mean ± SEM (n = 6–11). C, control; V, vehicle; ^##p < 0.01 versus control; ^*p < 0.05 versus vehicle. These results were cited in Matsunaga et al. (2009).
4. Fig. 9.4 Purple rice extract (PRE) inhibited tube formation induced by vascular endothelial growth factor (VEGF) A. (a) Representative photographs of tube formation. Scale bar = 1 mm. Human umbilical vein endothelial cells (HUVECs) were cocultured with human fibroblasts, as described in the section on methods, and incubated for 11 days with or without the indicated concentrations of PRE, with the concomitant addition of VEGF‐A (10 ng/ml). Tube formation was observed in five randomly chosen fields, and tube area (b), length (c), joints (d), and paths (e) were measured using an Angiogenesis Image Analyzer. Data are shown as mean ± SEM (n = 3). C, control; V, vehicle; ^##p < 0.01 versus control (Student’s t‐test); **p < 0.01 versus vehicle (Dunnett’s multiple‐comparison test). These results were cited in Tanaka et al. (2012).
5. Fig. 9.5 Bilberry extract (BBE) inhibited neovascular tufts on oxygen‐induced retinopathy in mice. Retinal flat mounts were examined by FITC–dextran angiography. Representative photographs of retina from saline‐treated eye (a) and BBE‐treated eye (b). Scale bar = 100 µm. (c) Areas of neovascular tufts in saline‐ and BBE‐treated eyes. Each column and bar represent mean ± SEM (n = 9). *p < 0.05 versus saline (paired t‐test). These results were cited in Matsunaga et al. (2010a).
6. Fig. 9.6 Effects of maqui berry extract (MBE) on visible‐light‐induced 661W cell damage. (a) Representative microscopy at 24 hours after light exposure. (b) Representative fluorescence microscopy of Hoechst 33342 (blue color, cell nuclear stained) and propidium iodide (PI; red color, dead cell stained) fluorescence staining at 24 hours after light exposure. Each scale bar represents 250 µm. These results were cited in Tanaka et al. (2013).
7. Fig. 9.7 Effects of purple rice extract (PRE) on retinal damage induced by exposure to light in mice. Hematoxylin and eosin staining of sections (thickness 5 lm) obtained from mice 5 days after light exposure. (a) Representative photographs show nontreated control retina, light‐exposed vehicle‐treated retina, light‐exposed retina treated with PRE at 10 µg/eye. (b) Measurement of the thickness in the outer nuclear layer (ONL) 5 days after light exposure. Data are shown as mean ± SEM (n = 5 or 6). ^#p < 0.05 and ^##p < 0.01 versus control. *p < 0.05 and **p < 0.01 versus vehicle. The scale bar represents 25 µm. These results were cited in Tanaka et al. (2011).
Chapter 10
1. Fig. 10.1 Activation of AMPK leads to various metabolic changes. AMPKK, AMPK kinase.
2. Fig. 10.2 Proposed mechanism for amelioration of hyperglycemia and insulin sensitivity by dietary bilberry extract, BBE. ACC, acetyl‐CoA carboxylase; ACO, acyl‐CoA oxidase; CPT1A, carnitine palmitoyltransferase‐1A; G6Pase, glucose‐6‐phosphatase; PEPCK, phosphoenolpyruvate carboxykinase.
3. Fig. 10.3 Chemical structures of cyanidin 3‐glucoside (C3G) and procyanidins (PCs) contained in dietary black soybean seed coat (BE).
4. Fig. 10.4 Proposed mechanism for amelioration of hyperglycemia and insulin sensitivity by dietary black soybean seed coat (BE) in mice.
5. Fig. 10.5 Overview of actions of GLP‐1 and GIP.
6. Fig. 10.6 Relationship between dietary factors (nutrients, nonnutrients) and incretin action.
7. Fig. 10.7 Stimulation of GLP‐1 secretion by curcuminoids (25 μM) (a), and the dose response of curcumin (1–50 μM) on GLP‐1 secretion (b) in GLUTag cells. Glutamine (10 mM) was used as a positive control. Values are means ± SEM, n = 3. Values without a common letter significantly differ at P < 0.05.
8. Fig. 10.8 Structure–activity relationship between curcumin derivatives and stimulation of GLP‐1 secretion (GLUTag cells).
9. Fig. 10.9 Proposed mechanism for stimulation of GLP‐1 secretion by curcumin.
10. Fig. 10.10 Proposed mechanism for amelioration of hyperglycemia by dietary sweet potato leaves, Suioh, in vivo.
11. Fig. 10.11 GLP‐1 secretion in the medium of GLUTag cells treated with various anthocyanins (a) and/or varying concentrations of D3R (b). (a) The final concentration of anthocyanins and sugars are 100 μM. Values are expressed as the means ± SEM, n = 3–9. Values without a common letter differ significantly at P < 0.05 (Kato et al., 2015). Mal3R, malvidin 3‐rutinoside.
12. Fig. 10.12 (a) The effect of CaMKII inhibitor (KN‐93, 10 μM) on D3R (100 μM)‐induced GLP‐1 secretion. (b and c) Immunoblot analysis of the phosphorylated CaMKII, total CaMKII, and β‐actin protein treated with D3R duration (b) and dose (c) in GLUTag cells. Values are expressed as the means ± SEM, n = 3. Values without a common letter significantly differ at P < 0.05.
13. Fig. 10.13 Proposed mechanism for stimulation of GLP‐1 secretion by D3R in GLUTag cells. ER, endoplasmic reticulum.
Chapter 11
1. Fig. 11.1 Global fatalities and cardiovascular diseases.
2. Fig. 11.2 Representative structures of 2,3‐cis‐ (left) and 2,3‐trans‐procyanidins (right).
3. Fig. 11.3 Simplified illustration of the regulation of vascular tone.
4. Fig. 11.4 Schematic illustration of the endothelium‐dependent NO‐signaling pathway and its role in the response to procyanidins. Endothelial production of NO is triggered via a redox‐sensitive activation of the phosphaditylinositol‐3‐kinase (PI3K)/Akt pathway promoting eNOS catalysis, that is, conversion of L‐arginine to L‐citrulline and NO. Stimulation of the NO‐sensitive soluble guanosyl cyclase (sGC) generates cyclic guanosyl monophosphate (cGMP) from guanosine triphosphate (GTP). Relaxation of the smooth muscle cell is due to cyclic GMP‐dependent protein kinases. PIP2, phosphatidylinositol biphosphate; PIP3, phosphatidylinositol triphosphate; ROS, reactive oxygen species.
5. Fig. 11.5 Schematic illustration of the endothelium‐dependent hyperpolarization factor (EDHF)‐mediated relaxation and modulation of intracellular Ca²⁺ concentrations ([Ca²⁺]_i): current view on responses to procyanidins. Ca²⁺ release from intracellular stores and Ca²⁺ influx from extracellular sources via store‐operated calcium channels (SOCCs) upon store depletion stimulate the opening of endothelial Ca²⁺‐dependent K⁺ channels (K_Ca). Activation of K_Ca hyperpolarizes the endothelial cell and the effluxing K⁺ can spread the effect to the smooth muscle. Increased endothelial [Ca²⁺]_i may enhance eNOS activation. A decrease of cytosolic Ca²⁺ concentration in the smooth muscle cell involves cGMP‐dependent protein kinases (NO signaling), closure of Ca²⁺ channels, and refilling of intracellular stores (SERCA).
Chapter 13
1. Fig. 13.1 Diagram of the pathogenesis of metastasis.
2. Fig. 13.2 Chemical structure of curcumin and its biological properties.
3. Fig. 13.3 Effect of curcumin on intrahepatic metastasis in vivo.
4. Fig. 13.4 Effect of curcumin on the invasion of CBO140C12 cells.
5. Fig. 13.5 Effect of curcumin on the expression of integrin α and β subunits on cell surface of tumor cells.
6. Fig. 13.6 Effect of curcumin on the formation of actin stress fiber on fibronectin‐coated substrate.
7. Fig. 13.7 Tumor growth and lymph node metastasis on day 15 after orthotopic implantation of LLC or LLC‐MLN cells.
8. Fig. 13.8 Effect of curcumin on the growth of the inoculated tumor and mediastinal lymph node metastasis after the orthotopic implantation of LLC cells.
9. Fig. 13.9 Life‐prolonging effect of curcumin, CDDP, and combination treatment.
10. Fig. 13.10 Dual reporter assay for evaluation of anti‐AP‐1 activity of LLC cells treated with curcumin.
11. Fig. 13.11 Effect of curcumin on the mRNAs expression levels of u‐PA and u‐PAR.
12. Fig. 13.12 Effect of curcumin on the tube‐like formation lymphatic endothelial TR‐LE cells.* p < 0.05; ** p < 0.01.
13. Fig. 13.13 Inhibition of IkB kinase is independent of antilymphangiogenic effect of curcumin.
14. Fig. 13.14 Inhibitory effect of curcumin on Akt pathway of lymphatic endothelial cells.
15. Fig. 13.15 Inhibitory effect of curcumin on MMP‐2 activity of lymphatic endothelial cells.
Chapter 14
1. Fig. 14.1 Structures of other lignans (118–125).
2. Fig. 14.2 Structures of other type compounds (139–182).

Contributors

Yoshinori Asakawa, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro‐cho, Tokushima, Japan.

Vincent L. Chiang, Forest Biotechnology Group, Department of Forestry and Environmental Resources, North Carolina State University, Raleigh, NC, USA.

Ling Chuang, Forest Biotechnology Group, Department of Forestry and Environmental Resources, North Carolina State University, Raleigh, NC, USA.

Katherine H. M. Cox, Centre for Human Psychopharmacology, School of health Sciences, Swinburne University, Melbourne, Victoria, Australia.

Olivier Dangles, UMR 408 INRA, Sécurité et Qualité des Produits d’Origine Végétale, University of Avignon, Avignon Cedex 9, France.

Joel J. Ducoste, Civil, Construction and Environmental Engineering, North Carolina State University, Raleigh, NC, USA.

Claire Dufour, UMR 408 INRA, Sécurité et Qualité des Produits d’Origine Végétale, Centre de Recherche PACA, University of Avignon, Avignon Cedex 9, France.

Sheena R. Gayomba, Department of Biology and Center for Molecular Signaling, Wake Forest University, Winston‐Salem, NC, USA.

Hideaki Hara, Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan.

Yoshihiro Hase, Ion Beam Mutagenesis Research Group, Quantum Beam Science Directorate, Japan Atomic Energy Agency, Takasaki, Gunma, Japan.

Fikret Isik, NCSU Cooperative Tree Improvement Program, Department of Forestry and Environmental Resources, North Carolina State University, Raleigh, NC, USA.

Yong Jiang, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China.

Herbert Kolodziej, Institute of Pharmacy, Pharmaceutical Biology, Freie Universität Berlin, Berlin, Germany.

Tadao Kondo, Graduate School of Information Science, Nagoya University, Chikusa, Nagoya, Japan.

Laigeng Li, National Key Laboratory of Plant Molecular Genetics and CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai, China.

Quanzi Li, State Key Laboratory of Tree Genetics and Breeding, Chinese Academy of Forestry, Beijing, China.

Jie Liu, Forest Biotechnology Group, Department of Forestry and Environmental Resources, North Carolina State University, Raleigh, NC, USA.

Philip L. Loziuk, W.M. Keck Fourier Transform Mass Spectrometry Laboratory, Department of Chemistry, North Carolina State University, Raleigh, NC, USA.

Hai‐Ning Lv, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China.

Yosuke Matsuo, Department of Natural Product Chemistry, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.

Gloria K. Muday, Department of Biology and Center for Molecular Signaling, Wake Forest University, Winston‐Salem, NC, USA.

David C. Muddiman, W.M. Keck Fourier Transform Mass Spectrometry Laboratory, Department of Chemistry, North Carolina State University, Raleigh, NC, USA.

Punith P. Naik, Civil, Construction and Environmental Engineering, North Carolina State University, Raleigh, NC, USA.

Kenjirou Ogawa, Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan.

Kin‐ichi Oyama, Research Center for Materials Science, Nagoya University, Chikusa, Nagoya, Japan.

Ikuo Saiki, Division of Pathogenic Biochemistry, Institute of Natural Medicine (INM), University of Toyama, Toyama, Japan.

Andrew Scholey, Centre for Human Psychopharmacology, School of health Sciences, Swinburne University, Melbourne, Victoria, Australia.

Ronald R. Sederoff, Forest Biotechnology Group, Department of Forestry and Environmental Resources, North Carolina State University, Raleigh, NC, USA.

Rui Shi, Forest Biotechnology Group, Department of Forestry and Environmental Resources, North Carolina State University, Raleigh, NC, USA.

Yue‐Lin Song, Modern Research Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China.

Takashi Tanaka, Department of Natural Product Chemistry, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.

Claire Tonnelé, Chimie des Matériaux Nouveaux, University of Mons, Mons, Belgium.

Patrick Trouillas, UMR 850 INSERM, Faculté de Pharmacie, University of Limoges, Limoges Cedex, France.

Takanori Tsuda, College of Bioscience and Biotechnology, Chubu University, Kasugai, Aichi, Japan.

Peng‐Fei Tu, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China.

Sermsawat Tunlaya‐Anukit, Forest Biotechnology Group, Department of Forestry and Environmental Resources, North Carolina State University, Raleigh, NC, USA.

Jack P. Wang, Forest Biotechnology Group, Department of Forestry and Environmental Resources, North Carolina State University, Raleigh, NC, USA.

Justin M. Watkins, Department of Biology and Center for Molecular Signaling, Wake Forest University, Winston‐Salem, NC, USA.

Cranos M. Williams, Electrical and Computer Engineering, North Carolina State University, Raleigh, NC, USA.

Peng Xu, National Key Laboratory of Plant Molecular Genetics and Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai, China.

Chenmin Yang, Forest Biotechnology Group, Department of Forestry and Environmental Resources, North Carolina State University, Raleigh, NC, USA.

Ting‐Feng Yeh, Forestry and Resource Conservation, National Taiwan University, Taipei, Taiwan.

Kumi Yoshida, Natural Product and Bioorganic Chemistry, Graduate School of Information Science, Nagoya University, Chikusa, Nagoya, Japan.

Ke‐Wu Zeng, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China.

Recent Advances in Polyphenol Research

Volume 5 Editors:

Series Editor‐in‐Chief:

Series Editorial Board:

Recent Advances in Polyphenol Research

Dedication

Contributors