ABSTRACT
Pterostilbene (PTS), a methylated analog of resveratrol (RSV), has recently attracted much attention due to its enhanced bioavailability compared to RSV. However, little is known about the radical-scavenging mechanism of PTS. In this study, we investigated the effect of Mg(ClO4)2 on the scavenging reaction of galvinoxyl radical (GOâ¢) by PTS in acetonitrile (MeCN). GO⢠was used as a model for reactive oxygen radicals. The second-order rate constant (kH) for the GOâ¢-scavenging reaction by PTS was more than threefold larger than that by RSV, although thermodynamic parameters, such as the relative O-H bond dissociation energies of the phenolic OH groups, ionization potentials, and HOMO energies calculated by the density functional theory are about the same between PTS and RSV. The oxidation peak potential of PTS determined by the cyclic voltammetry in MeCN (0.10 M Bu4NClO4) was also virtually the same as that of RSV. On the other hand, no effect of Mg (ClO4)2 on the kH values was observed for PTS, in contrast to the case for RSV. A kinetic isotope effect of 3.4 was observed when PTS was replaced by a deuterated PTS. These results suggest that a one-step hydrogen-atom transfer from PTS to GO⢠may be the rate-determining step in MeCN.
ABSTRACT
The biotransformations of capsaicin and dihydrocapsaicin were investigated using cultured plant cells of Phytolacca americana as biocatalysts. Four products, ie 15-hydroxycapsaicin, dihydrocapsaicin, 15-hydroxydihydrocapsaicin, and capsaicin 4-ß-glucoside, were isolated from the suspension cultures of P. americana treated with capsaicin for 3 days, showing that capsaicin was regioselectively hydroxylated, reduced, and glucosylated by cultured P. americana cells. On the other hand, dihydrocapsaicin was regioselectively dehydrogenated, hydroxylated, reduced, and glucosylated to give four products, ie capsaicin, 15-hydroxycapsaicin, 15-hydroxydihydrocapsaicin, and capsaicin 4-ß-glucoside, by cultured P. americana cells. In this paper, it is reported, for the first time, that dihydrocapsaicin is converted into 15-hydroxydihydrocapsaicin by plant cultured cells.
Subject(s)
Capsaicin/chemistry , Capsaicin/metabolism , Phytolacca americana/metabolism , Biotransformation , Hydrogenation , Hydroxylation , Phytolacca americana/cytology , Phytolacca americana/growth & development , StereoisomerismABSTRACT
The relationship between radical-scavenging rate constants (k) in an aprotic medium and thermodynamic parameters calculated by density functional theory (DFT) was investigated for 7 flavonols, which are myricetin (Myr), quercetin (Que), morin (Mor), kaempferol (Kae), 2'-methylquercetin (2'-MeQue), 5'-methylquercetin (5'-MeQue), and 2',5'-dimethylquercetin (Me2Que). The k values were determined for the reaction between the flavonols and galvinoxyl radical used as a reactivity model of reactive oxygen species in deaerated acetonitrile at 298 K. The energy difference values (D HT, HT: hydrogen transfer) between the flavonols and the corresponding radicals, which equal to the relative O-H bond dissociation energies of the OH groups in the flavonols and ionisation potentials (IP) were calculated by DFT at the B3LYP/6-31++G(d) level with C-PCM solvation model parameterised for acetonitrile. Among the 7 flavonols used in this study, calculated IP values of 4 flavonols exhibited a linear correlation with log k, suggesting that the radical-scavenging reaction of these flavonols may proceed via an electron transfer as the rate determining step.
Subject(s)
Flavonols/chemistry , Free Radical Scavengers/chemistry , Antioxidants/chemistry , Benzhydryl Compounds/chemistry , Density Functional Theory , Kinetics , Reactive Oxygen Species/chemistry , Structure-Activity Relationship , ThermodynamicsABSTRACT
Oxyresveratrol and gnetol are naturally occurring stilbene compounds, which have diverse pharmacological activities. The water-insolubility of these compounds limits their further pharmacological exploitation. The glycosylation of bioactive compounds can enhance their water-solubility, physicochemical stability, intestinal absorption, and biological half-life, and improve their bio- and pharmacological properties. Plant cell cultures are ideal systems for propagating rare plants and for studying the biosynthesis of secondary metabolites. Furthermore, the biotransformation of various organic compounds has been investigated as a target in the biotechnological application of plant cell culture systems. Cultured plant cells can glycosylate not only endogenous metabolic intermediates but also xenobiotics. In plants, glycosylation reaction acts for decreasing the toxicity of xenobiotics. There have been a few studies of glycosylation of exogenously administrated stilbene compounds at their 3- and 4'-positions by cultured plant cells of Ipomoea batatas and Strophanthus gratus so far. However, little attention has been paid to the glycosylation of 2'-hydroxy group of stilbene compounds by cultured plant cells. In this work, it is described that oxyresveratrol (3,5,2',4'-tetrahydroxystilbene) was transformed to 3-, 2'-, and 4'-ß-glucosides of oxyresveratrol by biotransformation with cultured Phytolacca americana cells. On the other hand, gnetol (3,5,2',6'-tetrahydroxystilbene) was converted into 2'-ß-glucoside of gnetol by cultured P. americana cells. Oxyresveratrol 2'-ß-glucoside and gnetol 2'-ß-glucoside are two new compounds. This paper reports, for the first time, the glycosylation of stilbene compounds at their 2'-position by cultured plant cells.
Subject(s)
Phytolacca americana/metabolism , Plant Cells/metabolism , Plant Extracts/chemistry , Stilbenes/chemistry , Cells, Cultured , Glycosylation , Magnetic Resonance Spectroscopy , Xenobiotics/metabolismABSTRACT
Daidzein is a common isoflavone, having multiple biological effects such as anti-inflammation, anti-allergy, and anti-aging. α-Tocopherol is the tocopherol isoform with the highest vitamin E activity including anti-allergic activity and anti-cancer activity. Hesperetin is a flavone, which shows potent anti-inflammatory effects. These compounds have shortcomings, i.e., water-insolubility and poor absorption after oral administration. The glycosylation of bioactive compounds can enhance their water-solubility, physicochemical stability, intestinal absorption, and biological half-life, and improve their bio- and pharmacological properties. They were transformed by cultured Nicotiana tabacum cells to 7-ß-glucoside and 7-ß-gentiobioside of daidzein, and 3'- and 7-ß-glucosides, 3',7-ß-diglucoside, and 7-ß-gentiobioside of hesperetin. Daidzein and α-tocopherol were glycosylated by galactosylation with ß-glucosidase to give 4'- and 7-ß-galactosides of daidzein, which were new compounds, and α-tocopherol 6-ß-galactoside. These nine glycosides showed higher anti-allergic activity, i.e., inhibitory activity toward histamine release from rat peritoneal mast cells, than their respective aglycones. In addition, these glycosides showed higher tyrosinase inhibitory activity than the corresponding aglycones. Glycosylation of daidzein, α-tocopherol, and hesperetin greatly improved their biological activities.
Subject(s)
Anti-Allergic Agents/chemical synthesis , Cosmetics/chemical synthesis , Glycosides/chemical synthesis , Hesperidin/chemical synthesis , Isoflavones/chemical synthesis , alpha-Tocopherol/chemical synthesis , Animals , Anti-Allergic Agents/metabolism , Biocatalysis , Cell Culture Techniques , Cosmetics/metabolism , Functional Food/analysis , Glycosides/metabolism , Glycosylation , Hesperidin/metabolism , Humans , Isoflavones/metabolism , Male , Mast Cells/cytology , Mast Cells/drug effects , Mast Cells/metabolism , Monophenol Monooxygenase/antagonists & inhibitors , Monophenol Monooxygenase/metabolism , Plant Cells/metabolism , Primary Cell Culture , Rats , Rats, Wistar , Solubility , Nicotiana/cytology , Nicotiana/metabolism , alpha-Tocopherol/metabolismABSTRACT
The stilbene compound resveratrol was glycosylated to give its 4'-O-ß-D-glucoside as the major product in addition to its 3-O-ß-D-glucoside by a plant glucosyltransferase from Phytolacca americana expressed in recombinant Escherichia coli. This enzyme transformed pterostilbene to its 4'-O-ß-D-glucoside, and converted pinostilbene to its 4'-O-ß-D-glucoside as a major product and its 3-O-ß-D-glucoside as a minor product. An analysis of antioxidant capacity showed that the above stilbene glycosides had lower oxygen radical absorbance capacity (ORAC) values than those of the corresponding stilbene aglycones. The 3-O-ß-D-glucoside of resveratrol showed the highest ORAC value among the stilbene glycosides tested, and pinostilbene had the highest value among the stilbene compounds. The tyrosinase inhibitory activities of the stilbene aglycones were improved by glycosylation; the stilbene glycosides had higher activities than the stilbene aglycones. Resveratrol 3-O-ß-D-glucoside had the highest tyrosinase inhibitory activity among the stilbene compounds tested.
Subject(s)
Glycosides/chemical synthesis , Glycosides/pharmacology , Monophenol Monooxygenase/antagonists & inhibitors , Oxygen Radical Absorbance Capacity , Stilbenes/chemistry , Agaricales/enzymology , Biocatalysis , Chemistry Techniques, Synthetic , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Glucosyltransferases/metabolism , Glycosides/chemistry , Glycosylation , ResveratrolABSTRACT
The glycosylation of pterostilbene by cultured plant cells of Phytolacca americana gave pterostilbene 4'-O-ß-D-glucoside. Both pterostilbene and its 4'-0-ß-D- glucoside induced type XVII collagen expression in the EpiDermFT EFT-400 human skin cell model. Pterostilbene 4'-O-ß-D-glucoside strongly induced type XVII collagen expression rather than pterostilbene.
Subject(s)
Collagen Type XII/biosynthesis , Phytolacca americana/chemistry , Stilbenes/pharmacology , Cells, Cultured , Chromatography, High Pressure Liquid , Glucosides/pharmacology , Hair Follicle/drug effects , Hair Follicle/metabolism , Humans , Skin/cytology , Skin/drug effects , Skin/metabolismABSTRACT
The glycosylation and methylation of quercetin by cultured plant cells of Phytolacca americana gave quercetin 3-Ο-ß-D-glucoside and isorharnnetin 3-Ο-ß-D- glucoside. Myricetin was glycosylated and methylated to syringetin 3-Ο-ß-D-glucoside by cultured P. americana cells.
Subject(s)
Flavonoids/metabolism , Phytolacca americana/metabolism , Quercetin/metabolism , Biotransformation , Cells, Cultured , Flavonoids/chemistry , Glycosylation , Methylation , Molecular Structure , Quercetin/chemistryABSTRACT
Incubation of cultured cells of Strophanthus gratus with trans-resveratrol gave its 4'-O-ß-D-glucoside as the major product in addition to its 3-O-ß-D-glucoside under white and red light-emitting diodes (LEDs). Use of blue LEDs as light sources for biotransformation of trans-resveratrol much improved the yield of its ß-D-glycosides and changed the composition of products, that is, 3-O-ß-D-glucoside was the major product and 4'-O-ß-D-glucoside was the minor one.
Subject(s)
Light , Stilbenes/metabolism , Strophanthus/cytology , Strophanthus/metabolism , Biotransformation , Cells, Cultured , Glycosylation , Resveratrol , Stereoisomerism , Stilbenes/chemistryABSTRACT
Hydroxylation and glycosylation of cinnamic acid, p-coumaric acid, caffeic acid, and ferulic acid were investigated using cultured plant cells of Phytolacca americana as biocatalysts. Regioselective hydroxylation at the 4-position of cinnamic acid and 3-position of p-coumaric acid was observed. Although cinnamic acid was transformed to mono-glucoside products, di-glycosylation occurred in the case of the biotransformation of p-coumaric acid, caffeic acid, and ferulic acid.
Subject(s)
Cinnamates/chemistry , Coumaric Acids/chemistry , Phytolacca americana/cytology , Phytolacca americana/metabolism , Biotransformation , Cells, Cultured , Glycosylation , Hydroxylation , Molecular Structure , PropionatesABSTRACT
Chemo-enzymatic synthesis of the ester-linked monosaccharide conjugate of docetaxel, 7-glycolyldocetaxel 2"-O-ß-D-galactopyranoside, was achieved by using lactase as a biocatalyst. The water-solubility and, EE and LE values for the liposome of 7-glycolyldocetaxel 2"-O-ß-D-galactopyranoside were much higher than those of docetaxel. The immunoliposome containing 7-glycolyldocetaxel 2"-O-ß-D-galactopyranoside showed effective suppression of tumor growth.
Subject(s)
Docetaxel/analogs & derivatives , Glycosides/chemistry , Liposomes/chemistry , Trastuzumab/pharmacology , Docetaxel/chemistry , Drug Delivery Systems , Molecular Structure , Trastuzumab/chemistryABSTRACT
The biotransformation of chrysin was investigated using cultured plant cells of Eucalyptus perriniana as biocatalysts. Chrysin was glucosylated to chrysin 7- 0-ß-D-glucoside and chrysin 7-ß-p-gentiobioside.
Subject(s)
Eucalyptus/cytology , Eucalyptus/metabolism , Flavonoids/chemistry , Cells, Cultured , Glycosylation , Time FactorsABSTRACT
The optical resolution of racemic compounds by stereoselective glucosylation was investigated using plant glucosyltransferase from Phytolacca americana expressed in recombinant Escherichia coli. The glucosyltransferase glucosylated chemoselectively the phenolic hydroxyl group of phenol compounds. The (R)-stereoselective glucosylation of (RS)-denopamine by glucosyltransferase occurred to give (R)-denopamine ß-D-glucoside.
Subject(s)
Escherichia coli/metabolism , Ethanolamines/chemistry , Glucosyltransferases/metabolism , Phytolacca americana/enzymology , Gene Expression Regulation, Enzymologic , Gene Expression Regulation, Plant , Glucosyltransferases/chemistry , Molecular Structure , Phytolacca americana/metabolism , Plant Proteins/genetics , Plant Proteins/metabolismABSTRACT
To enhance their water solubility and pharmacological activities, the stilbenes resveratrol, pterostilbene, and piceatannol were glycosylated to their monoglucosides (ß-glucosides) and diglycosides (ß-maltosides) by cultured cells and cyclodextrin glucanotransferase (CGTase). Cultured cells of Phytolacca americana and glucosyltransferase (PaGT) were capable of glucosylation of resveratrol to its 3- and 4'-ß-glucosides. Pterostilbene was slightly transformed into its 4'-ß-glucoside by P. americana cells. Piceatannol was readily converted into piceatannol 4'-ß-glucoside, with the highest yield among the three substrates. The 3- and 4'-ß-glucosides of resveratrol were subjected to further glycosylation by CGTase to give 3- and 4'-ß-maltoside derivatives. The inhibitory action of resveratrol and pterostilbene toward histamine release induced with compound 48/80 from rat peritoneal mast cells was improved by ß-glucosylation and/or ß-maltosylation (i.e., the inhibitory activity for histamine release of the 3- and 4'-ß-glucosides of resveratrol, the 3- and 4'-ß-maltosides of resveratrol, and the 4'-ß-glucoside of pterostilbene was higher than that of the corresponding aglycones, resveratrol and pterostilbene, respectively). In addition, the phosphodiesterase (PDE) inhibitory activity of resveratrol and pterostilbene was enhanced by ß-glucosylation and/or ß-maltosylation (i.e., the PDE inhibitory activities of the 3- and 4'-ß-glucosides of resveratrol, the 4'-ß-maltoside of resveratrol, and the 4'-ß-glucoside of pterostilbene were higher than those of the corresponding aglycones, resveratrol and pterostilbene, respectively).
Subject(s)
Glycosides/pharmacology , Stilbenes/pharmacology , Animals , Anti-Allergic Agents/chemistry , Anti-Allergic Agents/metabolism , Anti-Allergic Agents/pharmacology , Cells, Cultured , Drug Evaluation, Preclinical , Free Radical Scavengers/chemistry , Free Radical Scavengers/metabolism , Free Radical Scavengers/pharmacology , Glycosides/biosynthesis , Glycosides/chemistry , Glycosylation , Inhibitory Concentration 50 , Phosphodiesterase Inhibitors/chemistry , Phosphodiesterase Inhibitors/metabolism , Phosphodiesterase Inhibitors/pharmacology , Phytolacca americana/cytology , Phytolacca americana/metabolism , Plant Extracts/biosynthesis , Plant Extracts/chemistry , Plant Extracts/pharmacology , Rats , Resveratrol , Solubility , Stilbenes/chemistry , Stilbenes/metabolismABSTRACT
Regioselective glycosylation of 3-, 5-, 6-, and 7-hydroxyflavones was investigated using cultured plant cells of Eucalyptus perriniana and Phytolacca americana as biocatalysts. 3- and 7-Hydroxyflavones were practically glycosylated into the corresponding ß-D-glucosides by E. perriniana and P. americana.
Subject(s)
Eucalyptus/chemistry , Flavones/chemistry , Phytolacca americana/chemistry , Plant Extracts/chemistry , Cells, Cultured , Eucalyptus/growth & development , Flavones/isolation & purification , Glycosylation , Phytolacca americana/growth & development , Plant Extracts/isolation & purification , StereoisomerismABSTRACT
Resveratrol was converted by glucosyltransferase from Phytolacca americana into its 3- and 4'-O-ß-D-glucosides. On the other hand, further glycosylation of resveratrol 4'-O-ß-D-glucoside by cyclodextrin glucanotransferase gave the 4'-O-ß-maltoside, 4'-O-ß-maltotrioside, 4'-O-ß-maltotetraoside, and 4'-O-ß- maltopentaoside of resveratrol. The six resveratrol glycosides synthesized here showed higher phosphodiesterase inhibitory activity than resveratrol.
Subject(s)
Glucosyltransferases/chemistry , Glycosides/chemistry , Neuroprotective Agents/chemistry , Phytolacca americana/enzymology , Plant Proteins/chemistry , Stilbenes/chemistry , Biocatalysis , Glycosides/pharmacology , Neuroprotective Agents/pharmacology , Resveratrol , Stilbenes/pharmacologyABSTRACT
Glycosylation of (+)-ε-viniferin was investigated using glucosyltransferase from Phytolacca americana (PaGT3) as a biocatalyst. (+)-ε-Viniferin was converted by PaGT3 into its 4b- and 13b-ß-D-glucosides, the inhibitory activities on histamine release from rat peritoneal mast cells of which were higher than that of (+)-ε-viniferin.
Subject(s)
Benzofurans/pharmacology , Glucosyltransferases/chemistry , Glycosides/pharmacology , Mast Cells/immunology , Phytolacca americana/enzymology , Plant Proteins/chemistry , Stilbenes/pharmacology , Animals , Benzofurans/chemical synthesis , Biocatalysis , Cells, Cultured , Glucosyltransferases/genetics , Glucosyltransferases/metabolism , Glycosides/chemical synthesis , Histamine/immunology , Histamine Release/drug effects , Male , Mast Cells/drug effects , Phytolacca americana/genetics , Plant Proteins/genetics , Plant Proteins/metabolism , Rats , Rats, Wistar , Stilbenes/chemical synthesisABSTRACT
Resveratrol was glucosylated to its 3- and 4'-ß-glucosides by cultured cells of Phytolacca americana. On the other hand, cultured P. americana cells glucosylated pterostilbene to its 4'-ß-glucoside. P. americana cells converted piceatannol into its 4'-ß-glucoside. The 3- and 4'-ß-glucosides of resveratrol were further glucosylated to 3- and 4'-ß-maltosides of resveratrol, 4'-ß-maltoside of which is a new compound, by cyclodextrin glucanotransferase. Resveratrol 3-ß-glucoside and 3-ß-maltoside showed low 2,2-diphenyl-1-picrylhydrazyl free-radical-scavenging activity, whereas other glucosides had no radical-scavenging activity. Piceatannol 4'-ß-glucoside showed the strongest inhibitory activity among the stilbene glycosides towards histamine release from rat peritoneal mast cells. Pterostilbene 4'-ß-glucoside showed high phosphodiesterase inhibitory activity.
Subject(s)
Glycosides/chemistry , Stilbenes/chemical synthesis , Stilbenes/pharmacology , Animals , Anti-Allergic Agents/chemical synthesis , Anti-Allergic Agents/chemistry , Anti-Allergic Agents/pharmacology , Biphenyl Compounds , Cell Line , Chemistry Techniques, Synthetic , Free Radical Scavengers/chemical synthesis , Free Radical Scavengers/chemistry , Free Radical Scavengers/pharmacology , Histamine Release/drug effects , Male , Neuroprotective Agents/chemical synthesis , Neuroprotective Agents/chemistry , Neuroprotective Agents/pharmacology , Phosphodiesterase Inhibitors/chemical synthesis , Phosphodiesterase Inhibitors/chemistry , Phosphodiesterase Inhibitors/pharmacology , Picrates , Rats , Resveratrol , Stilbenes/chemistryABSTRACT
Quercetin was glucosylated by cultured plant cells of lpomoea batatas to its 3- and 7-O-beta-D-glucosides, and 3,7-O-beta-D-diglucoside. On the other hand, further glycosylation of quercetin 3-O-beta-D-glucoside by cyclodextrin glucanotransferase gave the 3-O-beta-maltoside, 3-O-beta-maltotrioside, and 3-O-[beta-maltotetraosides of quercetin.
Subject(s)
Glucosyltransferases/metabolism , Ipomoea/metabolism , Quercetin/metabolism , Cells, Cultured , Glycosylation , Ipomoea/cytologyABSTRACT
Biotransformation of artepillin C was investigated using cultured plant cells as biocatalysts. Artepillin C was converted into its 4- and 9-beta-D-glucosides, and 4,9-beta-D-diglucoside by cultured cells of Phytolacca americana. In contrast, cultured lpomoea batatas cells glucosylated artepillin C to only its 4- and 9-beta-D-glucosides.