Flavonoid Chemistry Research Articles

Structural Elucidation of Some Flavonoids Isolated from Litsea costalis and Their Biological Evaluation

Litsea costalis is a well-known medicinal plant in tropical and subtropical areas. Four significant flavonoids were extracted and characterized from the plant leaf extract. One component was discovered for the first time in flavonoid chemistry, flavan-4-ol, (3′, 4′-methylenedioxy-5,7-dimethoxy chroman-4-ol). Three flavonoids were discovered for the first time in this plant. The detected products are (+)-pinostrobin, (+)-onysilin, and (+)-pinocembrin. The fourth component was characterized for the first time in this plant and introduced in flavonoid chemistry. The extracted component antioxidant activity against DPPH indicated an IC50 value of around 30 µg/mL.

Protein Adducts and Protein Oxidation as Molecular Mechanisms of Flavonoid Bioactivity.

There are tens of thousands of scientific papers about flavonoids and their impacts on human health. However, despite the vast amount of energy that has been put toward studying these compounds, a unified molecular mechanism that explains their bioactivity remains elusive. One contributing factor to the absence of a general mechanistic explanation of their bioactivity is the complexity of flavonoid chemistry in aqueous solutions at neutral pH. Flavonoids have acidic protons, are redox active, and frequently auto-oxidize to produce an array of degradation products including electrophilic quinones. Flavonoids are also known to interact with specificity and high affinity with a variety of proteins, and there is evidence that some of these interactions may be covalent. This review summarizes the mechanisms of flavonoid oxidation in aqueous solutions at neutral pH and proposes the formation of protein-flavonoid adducts or flavonoid-induced protein oxidation as putative mechanisms of flavonoid bioactivity in cells. Nucleophilic residues in proteins may be able to form covalent bonds with flavonoid quinones; alternatively, specific amino acid residues such as cysteine, methionine, or tyrosine in proteins could be oxidized by flavonoids. In either case, these protein-flavonoid interactions would likely occur at specific binding sites and the formation of these types of products could effectively explain how flavonoids modify proteins in cells to induce downstream biochemical and cellular changes.

A Unique Acylated Flavonol Glycoside from Prunus persica (L.) var. Florida Prince: A New Solid Lipid Nanoparticle Cosmeceutical Formulation for Skincare.

Polyphenols are known dietary antioxidants. They have recently attracted considerable interest in uses to prevent skin aging and hyperpigmentation resulting from solar UV-irradiation. Prunus persica (L.) leaves are considered by-products and were reported to have a remarkable antioxidant activity due to their high content of polyphenols. This study aimed at the development of a cosmeceutical anti-aging and skin whitening cream preparation using ethanol leaves extract of Prunus persica (L.) (PPEE) loaded in solid lipid nanoparticles (SLNs) to enhance the skin delivery. Chemical investigation of PPEE showed significantly high total phenolic and flavonoids content with notable antioxidant activities (DPPH, ABTS, and β-carotene assays). A unique acylated kaempferol glycoside with a rare structure, kaempferol 3-O-β-4C1-(6″-O-3,4-dihydroxyphenylacetyl glucopyranoside) (KDPAG) was isolated for the first time and its structure fully elucidated. It represents the first example of acylation with 3,4-dihydroxyphenyl acetic acid in flavonoid chemistry. The in-vitro cytotoxicity studies against a human keratinocytes cell line revealed the non-toxicity of PPEE and PPEE-SLNs. Moreover, PPEE, PPEE-SLNs, and KDPAG showed good anti-elastase activity, comparable to that of N-(Methoxysuccinyl)-Ala-Ala-Pro-Val-chloromethyl ketone. Besides, PPEE-SLNs and KDPAG showed significantly (p < 0.001) higher anti-collagenase and anti-tyrosinase activities in comparison to EDTA and kojic acid, respectively. Different PPEE-SLNs cream formulae (2% and 5%) were evaluated for possible anti-wrinkle activity against UV-induced photoaging in a mouse model using a wrinkle scoring method and were shown to offer a highly significant protective effect against UV, as evidenced by tissue biomarkers (SOD) and histopathological studies. Thus, the current study demonstrates that Prunus persica leaf by-products provide an interesting, valuable resource for natural cosmetic ingredients. This provides related data for further studying the potential safe use of PPEE-SLNs in topical anti-aging cosmetic formulations with enhanced skin permeation properties.

Sorghum Root Flavonoid Chemistry, Cultivar, and Frost Stress Effects on Rhizosphere Bacteria and Fungi

Biotic stresses, including fungal infections, result in increased production of flavonoid compounds, including 3-deoxyanthocyanidins (3-DAs), in the leaf tissues of Sorghum bicolor. Our objectives were to determine whether sorghum genotypic variation influenced root flavonoid and 3-DA concentrations and rhizosphere microbial communities and to identify how these relationships were affected by abiotic stress. We evaluated root chemicals and rhizosphere microbiomes of five near-isogenic lines of sorghum before and after a late-season frost. Roots were analyzed for total flavonoids, total phenolics, 3-DA concentrations, and antioxidant activity. Amplicon sequencing of 16S ribosomal RNA genes and internal transcribed spacer regions was performed on rhizosphere soils. Concentrations of luteolinidin (a 3-DA) and total flavonoids differed between several lines before frost; however, these relationships changed after frost. Luteolinidin increased in three lines after frost, whereas total flavonoids decreased in all the lines after frost. Lines that differed in luteolinidin and total flavonoid concentrations before frost were different from those after frost. Rhizosphere community compositions also differed before and after frost but only fungal community compositions differed among sorghum lines. Bacterial community compositions were highly correlated with total flavonoid and luteolinidin concentrations. Furthermore, a greater number of bacterial taxa were correlated with total flavonoids and luteolinidin compared with fungal taxa. Collectively, this study provides evidence that plant genotypic variation influences root flavonoids and rhizosphere community composition and that these relationships are affected by frost. Plant–microbe interactions and secondary metabolite production may be important components to include for selective breeding of sorghum for frost stress tolerance.

DO EQUOL’S C-RING HYDROGENS CONTRIBUTE TO FREE RADICAL SCAVENGING?

Free radical scavenging potency of physiologically active equol molecule, derived by gut microbiota from soy isoflavone daidzein, was investigated by using M06-2X/6-311++G(d,p) level of theory, accompanied with the TST and Eckart tunneling corrections for the estimation of rate constants. Phenolic hydrogens of equol are recognized as much more abstractable than C-ring hydrogens. This finding is opposite to the one very recently suggested, but in accordance with well-known facts related to the flavonoid chemistry and phenolic O−H vs C−H reactivity.

Flavonoid chemistry and neuroprotection

Flavonoid chemistry and neuroprotection

Grape berry flavonoids: a review of their biochemical responses to high and extreme high temperatures

Climate change scenarios predict an increase in average temperatures and in the frequency, intensity, and length of extreme temperature events in many wine regions around the world. In already warm and hot regions, such changes may compromise grape growing and the production of high quality wine as high temperature has been found to affect berry composition critically. Most recent studies focusing on the sole effect of temperature, separated from light and water, on grape berry composition found that high temperature affects a wide range of metabolites, and in particular flavonoids-key compounds for berry and wine quality. A decrease in total anthocyanins is reported in most cases, and appears to be directly associated with high temperature. Changes in anthocyanin composition, and flavonol and proanthocyanidin responses are however less consistent, and reflect the complexity of the underlying biosynthetic pathways and diversity of experimental treatments that have been used in these studies. This review examines the impact of high temperature on the biosynthesis, accumulation, and degradation of flavonoids, and attempts to reconcile the diversity of responses in relation to the latest understanding of flavonoid chemistry and molecular regulation.

Phenolic chemistry of the seagrass Zostera noltei Hornem. Part 1: First evidence of three infraspecific flavonoid chemotypes in three distinctive geographical regions

The flavonoid content of Zostera noltei leaves was investigated over a broad spatial scale using chromatographic and spectroscopic techniques (HPLC-DAD, LC/MS and NMR). Samples were collected at fifteen localities covering Mediterranean Sea and NE Atlantic coast, and representative of three types of coastal ecosystems: mesotidal bays, coastal lagoons, and open-sea. Three geographically distinct flavonoid chemotypes were identified on the basis of their respective major compound. One is characterized by apigenin 7-sulfate (Eastern part of Gulf of Cadiz), one by diosmetin 7-sulfate (French Atlantic coast and Mediterranean Sea), and the third contained similar quantities of the above two compounds (Mauritania and South Portugal). Our results show that metabolomic profiling using a combination of analytical techniques is a tool of choice to characterize chemical phenotype accurately. This work emphasizes for the first time the spatial variability in the flavonoid chemistry of Z. noltei throughout Atlantic and Mediterranean range, and constitutes the first report of chemical races in the Zosteraceae family. This infraspecific chemical differentiation should be considered when dealing with the role of Z. noltei in coastal ecosystems or in the selection of the best population donor for Z. noltei beds restoration. Combined with molecular identification, phenolic fingerprinting might be helpful to elucidate the evolutionary history of Z. noltei.

Enzymatic deglycosylation of flavonoids in deep eutectic solvents-aqueous mixtures: paving the way for sustainable flavonoid chemistry

The low solubility of glycosylated flavonoids represents a hurdle to conduct efficient enzymatic deglycosylations in aqueous media. To overcome this drawback, environmentally-unfriendly dimethylsulfoxide (DMSO) is typically used as co-solvent. Using a specific diglycosidase from Acremonium sp. DSM24697 for the deglycosylation of the rutinosylated flavonoid (hesperidin) as model reaction, this communication explores the use of (non-hazardous and biodegradable) deep eutectic solvents (DESs) as co-solvents in flavonoid biocatalysis. The enzymatic deglycosylation was observed when DES composed of choline chloride and glycerol or ethylene-glycol was used at proportions of up to 40% (DES-Buffer, v/v), displaying a promising framework to combine enhanced flavonoid solubilities and high enzymatic activities. The deglycosylation activity significantly increased when the single DES components – glycerol and ethylene-glycol – were added (e.g. 140% of enzyme activity at glycerol at 40% v/v), whereas deleterious effects were observed when choline chloride was solely added, presumably due to its chaotropic effect. Future research opportunities may be envisaged in the genetic design to evolve more robust biocatalysts, and in tailoring DES to deliver more enzyme-compatible solvents.

Hybridization of Quercus aliena Blume and Q. serrata Murray in Korea

This research was conducted in order to understand the hybridization between Quercus aliena Blume and Q. serrata Murray in Korea which show wide range of morphological variations within species and interspecific variations of diverse overlapping characteristics caused by hybridization. Morphological analysis (principal components analysis; PCA) of 116 individuals representing two species and their intermediates were performed. As a result, two species were clearly distinguished in terms of morphology, and intermediate morpho-types assumed to be hybrids between the two species were mostly located in the middle of each parent species in the plot of the principal components analysis. There was a clear distinction between two species in trichome distribution pattern which is an important diagnostic character in taxonomy of genus Quercus, whereas intermediate morpho-types showed intermediate state between two species’ trichome distributions. Forty-two individuals representing two species and their intermediates were examined for leaf flavonoid constituents. Twenty-three flavonoid compounds were isolated and identified: They were glycosylated derivatives of flavonols, kaempferol, quercetin, isorhamnetin and myricetin. The flavonoid constituents of Q. aliena were five glycosylated derivatives: kaempferol 3-O-galactoside, kaempferol 3-O-glucoside, quercetin 3-O-galactoside, quercetin 3-O-glucoside, and Isorhamnetin 3-O-glucoside. The flavonoid constituents of Q. serrata had 20 diverse flavonol compounds including five flavonoid compounds found in Q. aliena. It was found that there is a clear difference in flavonoid constituents of Q. aliena and Q. serrata. Flavonoid chemistry is very useful in recognizing each species and putative hybrids. The flavonoid constituents of intermediates were a mixture of the two species’ constituents and they generally showed similar characteristics to morpho-types. The hybrids between Q. aliena and Q. serrata showed morphologically and chemically diverse characteristics and it is assumed that there are frequent interspecific hybridization and introgression.

Taxonomy and geographic distribution of Carex lucorum var. austrolucorum (section Acrocystis, Cyperaceae)

Carex lucorum currently comprises two morphologically similar varieties. We revise the taxonomy of C. lucorum, and map the distribution of the taxa. Based on multivariate analyses and analyses of variance of measured characters, allopatry, and previous studies revealing differences in achene micromorphology, chromosome differences, and flavonoid chemistry, we elevate C. lucorum var. austrolucorum to species status as C. austrolucorum. We provide an identification key to C. lucorum and its closest relatives.

A flavonoid survey of Fraxinus (Oleaceae) in eastern Asia, and the overlooked species Fraxinus hopeiensis T. Tang in northern China

From a survey of 14 flavonoids of 19 Asian taxa of Fraxinus, flavonols were present in most taxa of sects. Ornus, Fraxinus, and Sciadanthus, while flavones were only detected in Fraxinus lanuginosa in Japan and Fraxinus hopeiensis in China of sect. Ornus and Fraxinus chiisanensis in Korea (as incertae sedia sensu Wallander). The present data failed to clearly distinguish many taxa within the genus because of the extreme monotony of flavonoid content. However, the dichotomy on a smaller scale was observed in Fraxinus, where this chemical approach was useful in the determination of natural groupings of the overlooked taxon F. hopeiensis in China, F. lanuginosa in Japan, and F. chiisanensis in Korea. The gain of O-flavone appears to be a significant evolutionary step; however, the sporadic occurrence of O-flavone in some species is the result of chemical advancement. The present study demonstrated that flavonoid chemistry may indeed be as variable as the morphological features, with no significant flavonoid differences observed at the species level. However, F. hopeiensis, found in the mountain regions of Hebei in northern China, has petals like Fraxinus sieboldiana and F. lanuginosa and is clearly different from other related taxa, including Fraxinus rhynchophylla and Fraxinus chinensis. This study shows that F. hopeiensis is morphologically, chemically, and geographically distinct and should be treated as a distinct species.

Molecular phylogeny of Nassauvia (Asteraceae, Mutisieae) based on nrDNA ITS sequences

The phylogeny of the genus Nassauvia and closely related genera was reconstructed using sequences from the internal transcribed spacer regions (ITS) of nuclear ribosomal DNA. The genus Triptilion is nested within Nassauvia, making the latter genus paraphyletic. Neither of the two subgenera Nassauvia and Strongyloma is resolved as monophyletic, and none of the sections of subgenus Nassauvia is recovered as monophyletic. The evolution of the compound secondary inflorescences has been complex in Nassauvia, with the highly aggregated forms representing the original condition in the genus. However, the ancestral condition is equivocal in several clades, and there are alternative reconstructions for the gains–losses of the variously aggregated conditions. There has been at least one gain of solitary capitula in Nassauvia. The evolution of flavonoid chemistry has been complex in Nassauvia, and flavonoids are of limited phylogenetic-taxonomic utility in the genus. Gains–losses of flavonols occur only on terminals whereas changes in flavones and C-glycosyl flavones occur at various levels in the tree. Gains–losses of methylation of flavones and flavonols occur only on terminals.

Flavonoid chemistry of Fallopia sect. Reynoutria (Polygonaceae) in Korea

Fifteen populations comprising three taxa and a putative hybrid of Fallopia sect. Reynoutria in Korea were examined for their leaf flavonoid constituents. Nineteen flavonoid compounds were isolated and identified; they were glycosylated derivatives of the flavonols quercetin and kaempferol, and of the flavones apigenin and luteolin. Among them, quercetin 3-O-galactoside and quercetin 3-O-glucoside were major flavonoid constituents, and present in all taxa. The flavonoid data appear to be very useful for taxon delimitation, and all taxa examined are readily distinguished by their flavonoid profiles. In addition, the flavonoid data suggest that the Nonsan population may be of hybrid origin involving F. japonica var. japonica, F. forbesii, and F. sachalinensis. In F. japonica var. japonica, there is no apparent correlation between their levels of polyploidy and flavonoid chemistry, but geographical variation of the flavonoid profiles among some populations was detected.

Flavonoid glycosides of the black locust tree, Robinia pseudoacacia (Leguminosae)

Four flavone glycosides isolated from extracts of the leaves of Robinia pseudoacacia (Leguminosae) were characterised by spectroscopic and chemical methods as the 7- O-β- d-glucuronopyranosyl-(1 → 2)[α- l-rhamnopyranosyl-(1 → 6)]-β- d-glucopyranosides of acacetin (5,7-dihydroxy-4′-methoxyflavone), apigenin (5,7,4′-trihydroxyflavone), diosmetin (5,7,3′-trihydroxy-4′-methoxyflavone) and luteolin (5,7,3′,4′-tetrahydroxyflavone). Assignment of glycosidic 1H and 13C resonances in their NMR spectra was facilitated by 2 J HC correlations detected using the H2BC (heteronuclear two-bond correlation) pulse sequence. Spectroscopic analysis of two known triglycosides, acacetin 7- O-β- d-glucopyranosyl-(1 → 2)[α- l-rhamnopyranosyl-(1 → 6)]-β- d-glucopyranoside (previously unrecorded from this species) and acacetin 7- O-β- d-xylopyranosyl-(1 → 2)[α- l-rhamnopyranosyl-(1 → 6)]-β- d-glucopyranoside (‘acacetin trioside’), enabled inconsistencies in the literature relating to these structures to be resolved. Comparison of the flavonoid chemistry of leaves and flowers of R. pseudoacacia using LC–UV and LC–MS showed that flavone 7- O-glycosides, particularly of acacetin, predominated in the former, whereas the latter comprised mainly flavonol 3,7-di- O-glycosides, including several examples new to this species. Tissue dependent differences in flavonoid chemistry were also evident from the glycosylation patterns of the compounds.

Hebe saxicola (Plantaginaceae)—a new threatened species from western Northland, North Island, New Zealand

A new species, Hebe saxicola, is described from Maungaraho Rock, a prominent rock outcrop near Tokatoka, western Northland, North Island, New Zealand. This species was previously included in H. perbella from which it is distinguished by its ecology, smaller stature, shorter and wider leaves with dull rather than glossy upper leaf surfaces, less colourful flowers that open pale lavender or lilac soon fading to white, shorter corolla tube, broader lanceolate to ovate, subacute corolla lobes, mostly glabrous ovaries, and glabrous capsules. There is also some evidence that the flavonoid chemistry of H. saxicola is distinct from H. perbella. Hebe saxicola is probably most closely allied to H. adamsii, currently known only from Unuwhao Bush, Te Paki, c. 238 km north of Maungaraho Rock. Hebe saxicola is regarded as Threatened “Nationally Critical” using the New Zealand Threat Classification System. as H. saxicola is a segregate of H. perbella, a new circumscription for H. perbella and updated information on ecology, distribution, and conservation is provided.

Flavonoids chemistry of the adonis amurensis complex in eastern Asia

Flavonoids were isolated and identified from flowers and/or leaves of the Adonis amurensis complex. This complex has been a persistent source of taxonomic confusion due to the exclusive use of continuous variation in flower morphology for species definition and recognition. Nineteen flavonoids, including C‐glycosylflavones, O‐glycosylflavones, and flavonol O‐glycosides were characterized. The flavonoids isolated from flowers and leaves of the A. amurensis complex were not the same. The phenogram indicated three major clusters; A. multiflora, A. ramosa‐A. pseudoamurensis, and A. amurensis. A. amurensis was characterized by a higher flavonoid diversity composed of a variety of C‐glycosylflavones, while A. multiflora was generally characterized by a reduced flavonoid profiles. It is probable that evolutionary advancement is reflected in loss of some of C‐glycosylflavone and all of O‐glycosylflavone synthesis, resulting in A. multiflora within this series. The present study has demonstrated that the flavonoid chemistry may indeed be as variable as the morphological features, and no significant flavonoid differences at the species level were observed. It was suggested that parallel and/or radiate modes of evolution could have taken place within this complex.

Systematic aspects of foliar flavonoids in subsect. Carpinus ( Carpinus, Betulaceae)

Foliar flavonoids from nine taxa of subsection Carpinus ( Carpinus, Betulaceae) were examined. A total of 10 compounds were isolated and identified, mainly mono- and di-glycosides of flavones (apigenin and luteolin) and/or flavonols (myricetin, kaempferol and quercetin). By comparing the results of flavonoid chemistry with the morphological characteristics and geographic distribution patterns, subsection Carpinus might be differentiated into two ancestor-based groups, one consisting of Carpinus tientaiensis, Carpinus londoniana, and Carpinus betulus, the other Carpinus viminea var. viminea, C. viminea var. chiukiangensis, Carpinus laxiflora, and Carpinus caroliniana. A major trend in the reduction of the number of compounds from the primitive to the advanced was observed in subsect. Carpinus, and the chemical simplification seems to be related to species differentiation within the subsection. The presence of isoflavones in C. laxiflora and C. caroliniana revealed their advancement chemically, but C. betulus and C. londoniana showed no chemical differentiation. Overall intercontinental divergence of Carpinus was not confirmed by this study. A number of infraspecific taxa in the subsect. Carpinus were chemically identical with their original varieties except the C. viminea complex. This might be because sect. Carpinus is undergoing slower radiation; significant biochemical differentiation among infraspecific taxa seems not to have occurred yet. These flavonoid data reflected intrasectional parallelisms and intersectional radiation in Carpinus.

Composition and distribution of leaf flavonoids in Hebe and Leonohebe (Plantaginaceae) in New Zealand — 2. “Apertae”, “Occlusae”, and “Grandiflorae”

A taxonomic revision of Hebe and Leonohebe in New Zealand has involved studies of plant morphology and flavonoid chemistry. This paper is the second in a series that summarises the composition and taxonomic distribution of leaf flavonoids in the two genera. It outlines the distribution of flavonoids in species of “Apertae”, “Occlusae”, and “Grandiflorae” (informal infrageneric groups of Hebe). Presence/absence data are presented for 85 flavonoids from 377 samples of 42 species (as well as some samples of uncertain taxonomic placement). Flavonoid variation within and between species is illustrated using a series of ordination analyses. Most species in each of “Apertae” and “Grandiflorae” and many in “Occlusae” can be distinguished by their flavonoid profiles, generally through possession of unique combinations of compounds.

Geographic variation in the Hebe albicans complex (Plantaginaceae) — morphology and flavonoid chemistry

Variation in morphology and flavonoid chemistry is appraised in populations of H. albicans, H. recurva, and the tag name entity H. “glaucophylla NW Nelson”, which together comprise the H. albicans complex. Morphological comparisons include a morphometric study of leaf variation. Comparisons in flavonoid chemistry are made with several other species of “Subcarnosae” and small‐leaved “Occlusae”. It is proposed that members of the H. albicans complex be included within a single species, H. albicans, and that no subspecific taxa be recognised. Hebe albicans, as treated here, is a glaucous‐leaved shrub of rocky places in NW Nelson. Its has a decumbent to upright habit, and variable leaf shape. Two chromosome numbers (2n = 40, 80) have been recorded.