Apigenin Derivatives Research Articles

Yield, mineral and polyphenolic composition of two seed-propagated globe artichoke cultivars

Globe artichoke (Cynara cardunculus var. scolymus L. Fiori) is a traditional component of the Mediterranean diet, it is considered a rich source of phenolic compounds. Globe artichoke production is traditionally based on vegetatively propagated varietal types. As for pathologic and economic disadvantages of the former multiplication method, Italian artichoke breeding programs have produced some potential seed propagated hybrids. An experiment was conducted to assess the yield, mineral and polyphenolic profiles of two potential seed-propagated F1 hybrid 'Istar' and 'Romolo'. The artichoke yield recorded on 'Romolo' was significantly higher by 33% in comparison to 'Istar'. The N and K concentrations were significantly lower by 25.5% and higher by 10.1%, respectively, in 'Romolo' in comparison to 'Istar'. Among the macronutrients studied, K was the mineral with the higher concentration, with a mean of 24.9 g kg-1 dw. In addition, the Na concentration and Na/K ratio observed in both cultivars were low. Amongst the caffeoylquinic acids, 5-O-caffeoylquinic acid and 1,5-diO-caffeoylquinic acid were the main compounds. The remaining caffeoylquinic acids (i.e., 1- and 3-O-caffeoylquinic acids, 3,4-, 3,5- and 4,5-di-O-caffeoylquinic acids) were minor compounds in the analyzed samples. Regarding the cultivar effect, the 5-O-caffeoylquinic acid, apigenin 7-O-glucoronide, total caffeoylquinic acids, total apigenin derivatives, were significantly higher in 'Romolo' by 23.1, 180.0, 20.5, and 149.5%, respectively, in comparison to 'Istar', suggesting that specific cultivar should be selected to obtain the desired profile of bioactive compounds. Overall, the seed-propagated cultivars can represent a suitable alternative to the vegetative propagated ones, thus opening new perspectives for the artichoke production.

Phenolic composition profiling of different edible parts and by-products of date palm (Phoenix dactylifera L.) by using HPLC-DAD-ESI/MSn

Fruits and vegetables are an important source of dietary antioxidants and epidemiological studies show that their regular intake in the diet may decrease the risk of several chronic diseases. Phoenix dactylifera L. (date palm or dates) is an important crop, widely used in the Arabian region and in other parts of the world as a food and also in folk medicine, due to its health-promoting properties. Antioxidant phytochemicals present in plant foods are partly responsible for such health benefits. The antioxidants present in dates are mainly phenolics, like flavonoids and phenolic acids. The fruits of dates have been widely studied with regard to their phenolic composition. However, few studies are available in the bibliography regarding other, non-edible parts of the date palm tree. In this context, in the present work the phenolic components of different parts of P. dactylifera (cv. Medjool or Mejhool) - namely, fruit pulp and skin, fronds (leaves), clusters, and pollen - have been investigated using HPLC-DAD-ESI/MSn in the negative ionization mode. The overall analysis of the phenolic compounds revealed that there was a qualitative similarity among the different dates parts analyzed. The method used provided tentative identification of 52 compounds: mainly flavonoid glycosides of quercetin, luteolin, apigenin, chrysoeriol, kaempferol, isorhamnetin, 3-methyl-isorhamnetin, sulfates, and malonyl derivatives. In the present work, more than 30 phenolic derivatives are described for the first time in dates. To the best of our knowledge, kaempferol glycosides and malonyl derivatives have not been described previously in P. dactylifera. The results highlight the importance of P. dactylifera L. as a promising source of functional ingredients and boost its potential use in the food and nutraceutical industries. The MS data, MSn fragmentation pattern, and UV information obtained have been of great help in the interpretation of the compounds detected and in their structural identification.

Mycorrhizal Fungi Collected from the Rhizospheres around Different Olive Cultivars Vary in Their Ability to Improve Growth and Polyphenol Levels in Leeks

<p>Mycorrhizal fungus spores and propagules were collected from the soils in the vicinity of roots of five different olive cultivars. These mycorrhizal fungus communities were amplified in trap cultures and then their effect on the growth and polyphenol levels of leek plants was determined. All mycorrhizal fungus communities increased plant growth in leeks when compared to controls. In addition, communities from the roots of Frantoio and Manzanillo significantly increased plant growth, in terms of plant height and dry weights, as compared to plants that were given mycorrhizal fungus collected from cultivar Mission. Plants inoculated with mycorrhizal fungus from Frantoio also had an increase in 14 polyphenols compared to uninoculated plants. A majority of polyphenol peaks were also higher in leek plants inoculated with mycorrhizal fungi from Frantoio roots when compared to plants inoculated with mycorrhizal fungi from other olive cultivars. The affected polyphenols were identified by mass spectrometry and were mostly found to be derivatives (e.g., pentose, hexose, malonyl, feruyl, and coumaroyl) of quercetin, kaempferol, and apigenin; four remained unidentified. Molecular fingerprinting of mycorrhizal fungus communities from different olive cultivars indicated that fungi of the family Gigasporaceae were a major component of inocula obtained from Frantoio and Manzanillo roots, which were better performers in terms of plant growth and polyphenol content. Mycorrhizal fungi from cv Mission roots were relatively poor performers and were dominated by the mycorrhizae of the family Glomeraceae, specicifally the genus <em>Rhizophagus</em>.</p>

Ulex europaeus: from noxious weed to source of valuable isoflavones and flavanones

The screening and quantification of the main phenolic compounds in leaves and flowers of Ulex europaeus (gorse) was carried out by high-performance liquid chromatography with electrospray ionization mass spectrometric detection (HPLC-ESI–MSn) after ultrasound-assisted extraction with methanol. About 98% of compounds corresponded to flavonoids, distributed as flavonols, flavones, isoflavones and flavanones. Flavonols were mainly quercetin glucosides; most of the found flavones were apigenin derivatives and the isoflavone group was dominated by glycitin. The flavanone group was composed mainly of liquiritigenin derivatives, substances usually found in liquorice (Glycyrrhiza ssp) and associated with high pharmacological relevance; in Ulex they represent about 25% of total polyphenols content. Phenolic acids and saponins were also detected, as minor components. In vitro antioxidant activity (nitric oxide, superoxide assays, ABTS and DPPH assays) of leaves and flowers, and their inhibitory effects towards digestive enzymes related to carbohydrate metabolism (α-glucosidase and α-amylase) were also studied.

Microbial metabolism of prenylated apigenin derivatives by Mucor hiemalis

6-Prenylapigenin (1) and 8-prenylapegenin (2) were semi-synthesized from apigenin by nuclear prenylation. Morusin (3) was isolated from the root bark of Morus alba L. The microbial transformation studies of these three bioactive prenylated apigenin derivatives were performed using eighteen cell cultures in order to select microorganisms capable of transforming them. It was identified that Mucor hiemalis (KCTC 26779) showed the ability to metabolize the parent compounds (1–3) into three new (4–6) and one known (7) glucosylated derivatives with high efficiency. Their structures were established as 6-prenylapigenin 7-O-β-d-glucopyranoside (4), 8-prenylapigenin 7-O-β-d-glucopyranoside (5), morusin 5-O-β-d-glucopyranoside (6), and morusin 4′-O-β-d-glucopyranoside (7) by the spectroscopic methods.

Antioxidant Properties and Flavonoid Profile in Leaves of Calabrian Lavandula multifida L., an Autochthon Plant of Mediterranean Southern Regions.

Lavandula multifida is a rare short-lived plant characteristic of Mediterranean basin able to survive in hot and arid climatic conditions on poorly evolved limestone soils. In this work, we characterize the enzymatic antioxidant system and phenolic composition, as well as the antioxidant properties of L. multifida fresh leaves. Enzymatic patterns show high level of peroxidases, ascorbate peroxidase, and dehydroascorbate reductase activities, when compared with L. angustifolia. The same trend is evident in total carotenoids, ascorbic acid, and reduced glutathione, and in the total antioxidant capacity assay. Moreover, RP-DAD-HPLC analyses of EtOH extract, obtained from fresh leaves, reveal main components, carvacrol, vitexin, and 7- or 8-glucoside derivatives of hypolaetin, scutellarein, luteolin, isoscutellarein, apigenin, and chrysoeriol. The analysis of this autochthon plant depicted a series of strategies adopted by L. multifida to survive in its stressful natural habitat and richness in health-promoting compounds that can be a resource for the preservation of this variety in dangerous of extinction.

Inhibitory effect of flavonoids on human glutaminyl cyclase

Glutaminyl cyclase (QC) plays an important role in the pathogenesis of Alzheimer’s disease (AD) and can be a potential target for the development of novel anti-AD agents. However, the study of QC inhibitors are still less. Here, phenol-4′ (R1-), C5-OH (R2-) and C7-OH (R3-) modified apigenin derivatives were synthesized as a new class of human QC (hQC) inhibitors. The efficacy investigation of these compounds was performed by spectrophotometric assessment and the structure–activity relationship (SAR) was evaluated. Molecular docking was also carried out to analyze the binding mode of the synthesized flavonoid to the active site of hQC.

Anthocyanins and flavonols are responsible for purple color of Lablab purpureus (L.) sweet pods

Lablab pods, as dietary vegetable, have high nutritional values similar to most of edible legumes. Moreover, our studies confirmed that purple lablab pods contain the natural pigments of anthocyanins and flavonols. Compared to green pods, five kinds of anthocyanins (malvidin, delphinidin and petunidin derivatives) were found in purple pods by HPLC-ESI-MS/MS and the major contents were delphinidin derivatives. Besides, nine kinds of polyphenol derivatives (quercetin, myricetin, kaempferol and apigenin derivatives) were detected by UPLC-ESI-MS/MS and the major components were quercetin and myricetin derivatives. In order to discover their molecular mechanism, expression patterns of biosynthesis and regulatory gens of anthocyanins and flavonols were investigated. Experimental results showed that LpPAL, LpF3H, LpF3′H, LpDFR, LpANS and LpPAP1 expressions were significantly induced in purple pods compared to green ones. Meanwhile, transcripts of LpFLS were more abundant in purple pods than green or yellow ones, suggestind that co-pigments of anthocyanins and flavonols are accumulated in purple pods. Under continuously dark condition, no anthocyanin accumulation was detected in purple pods and transcripts of LpCHS, LpANS, LpFLS and LpPAP1 were remarkably repressed, indicating that anthocyanins and flavonols biosynthesis in purple pods was regulated in light-dependent manner. These results indicate that co-pigments of anthocyanins and flavonols contribute to purple pigmentations of pods.

Phenolic Compounds in Chilean Mistletoe (Quintral, Tristerix tetrandus) Analyzed by UHPLC-Q/Orbitrap/MS/MS and Its Antioxidant Properties.

Mass spectrometry has become a method of choice to characterize bioactive compounds in biological samples because of its sensitivity and selectivity. Hybrid ultra-HPLC hyphenated with Orbitrap mass analyzer is an innovative state of the art technology that allows fast and accurate metabolomic analyses. In this work the metabolites of a Chilean mistletoe endemic to the VIII region of Chile were investigated for the first time using UHPLC mass analysis (UHPLC-PDA-HESI-Orbitrap MSn). The anthocyanins, together with the non-pigmented phenolics were fingerprinted and correlated with the antioxidant capacities measured by the bleaching of the DPPH radical, the ferric reducing antioxidant power (FRAP), the superoxide anion scavenging activity assay (SA), and total content of phenolics, flavonoids and anthocyanins measured by spectroscopic methods. Six anthocyanins were identified, and among them, the 3-O-glycosides of delphinidin and cyanidin were the major ones. In addition, several phenolic acids (including feruloylquinic acid, feruloyl glucose, chlorogenic acid) and several flavonols (luteolin, quercetin, apigenin, isorhamnetin and glycoside derivatives) were also identified. The mistletoe leaves showed the highest antioxidant activity as measured by the DPPH radical bleaching, ferric reducing antioxidant power and superoxide anion scavenging activity tests (13.38 ± 0.47 µg/mL, 125.32 ± 5.96 µmolTE/g DW and 84.06 ± 4.59 at 100 µg/mL, respectively).

Antioxidant potential of two Apiaceae plant extracts: A comparative study focused on the phenolic composition

The present study aimed to characterize the extracts prepared from Pimpinella anisum L. (anise) and Coriandrum sativum L. (coriander) (Apiaceae plants) seeds in terms of phenolic composition, and to correlate the obtained profiles with the antioxidant activity. Anise gave the highest abundance in phenolic compounds (42.09±0.11mg/g extract), mainly flavonoids (28.08±0.17mg/g extract) and phenolic acids (14.01±0.06mg/g extract), and also the highest antioxidant potential, measured by the ability to inhibit lipid peroxidation and β-carotene bleaching, the reducing power and the free radical scavenging activity. Apigenin and luteolin derivatives, as also caffeoylquinic acid derivatives seem to be directly related with the higher in vitro antioxidant potential of the anise extract. In contrast, the lower antioxidant potential of coriander seems to be due to its lower abundance in phenolic compounds (2.24±0.01mg/g extract). Further studies are necessary to evaluate the in vivo antioxidant potential of the tested extracts, but the in vitro experiments already performed highlight them as potential health promoters.

Two new flavonoids from Selaginella uncinata

Two new flavonoids, uncinataflavones A (1) and B (2), along with one known compound 6-(5-carboxyl-2-methoxyphenyl)-apigenin (3), were isolated from Selaginella uncinata (Desv.) Spring. All these compounds belong to apigenin derivatives with aryl substituents at C-6 position. The structures of new compounds were elucidated on the basis of comprehensive spectroscopic analyses (UV, IR, 1D, and 2D NMR as well as HR-ESI-MS).

Involvenflavones A–F, six new flavonoids with 3′-aryl substituent from Selaginella involven

Six new flavonoids, involvenflavones A–F (1–6), were isolated from Selaginella involven. Their structures were elucidated based on UV, IR, 1D and 2D NMR as well as HR-ESI-MS techniques. All compounds belong to apigenin derivatives with 3′-aryl substituent. This is the first report of the apigenin derivatives with 3′-aryl substituent from nature resources. These compounds also exhibited a potent effect against the injury of human umbilical vein endothelial cell (HUVECs) induced by high concentrations of glucose in vitro.

Microbial metabolism of prenylated apigenin derivatives

Microbial metabolism of prenylated apigenin derivatives

Phenolic composition of “bud extracts” of Ribes nigrum L., Rosa canina L. and Tilia tomentosa M.

Liquid preparations such as tinctures and “bud extracts” are typical products widely used in European countries but which have been poorly studied to date. Our research was focused on obtaining a phytochemical characterization of secondary metabolites of black currant, dog rose and silver linden bud extracts and evaluating the changes of selected chemical markers over time. 16 different preparations have been analyzed by the use of HPLC-DAD-MS. Several flavonols were identified in black currant samples including quercetin derivatives (6.7–30.4mg/L). Also hydroxycinnamic acids, mainly p-coumaric acid derivatives (4.1–38.9mg/L) were identified. Flavonols such as glycosides of quercetin and kaempferol, hydroxycinnamic acids, and ellagitannins were detected in dog rose samples, with gallotannins being the main components (up to 1.7g/L). The Tilia tomentosa extracts contained flavonols (quercetin, kaempferol, apigenin derivatives) as principal components with the exception of a single commercial extract with hydroxycinnamic acids as the most abundant metabolites. In this study, without applying accelerated ageing protocols, the stability over time of these liquid preparations was evaluated for up to 10 months and demonstrated negligible variations.

Antidiabetic Effects of Aqueous Infusions of Artemisia herba-alba and Ajuga iva in Alloxan-Induced Diabetic Rats.

The aqueous infusions of the aerial parts of Artemisia herba-alba Asso and Ajuga iva Schreber, prepared in accordance with the traditional procedure used in the local folk medicine, have been analysed for their composition and content of phytochemical constituents and examined for their antidiabetic effectiveness in alloxan-induced diabetic rats. Oral administration of A.herba-alba and A.iva infusions was studied in normal and alloxan-induced diabetic rats, which were randomly divided into nine groups, each group consisting of six animals. The drug preparations (100, 200, and 300 mg/kg b. w.) of each plant were given orally to the rats of each group twice daily for 15 days. Compositional analysis of the aqueous infusions revealed the presence of several polyphenols as main components. A.herba-alba infusion was characterised by mono- and di-cinnamoylquinic acids, with 5-caffeoylquinic (chlorogenic) acid being the main compound, followed by 3,5-dicaffeoylquinic acid. Vicenin-2 (apigenin 6,8-di-C-glucoside) appeared to be the most abundant among flavonoids. On the other hand, A.iva showed the exclusive presence of flavonoids, with the flavanone naringin present in relatively high levels together with several apigenin (flavone) derivatives. Oral administration of 300 mg/kg b. w. of the aqueous infusions of A.herba-alba and A.iva exhibited a significant reduction in blood glucose content, showing a much more efficient antidiabetic activity compared to glibenclamide, the oral hypoglycaemic agent used as a positive control in this study. These results suggest that A.herba-alba and A.iva possess significant antidiabetic activity, as they were able to improve the biochemical damage in alloxan-induced diabetes in rats.

Discovery of xanthine oxidase inhibitors and/or α-glucosidase inhibitors by carboxyalkyl derivatization based on the flavonoid of apigenin

Three series of apigenin derivatives have been prepared by coupling the carboxyl alkyl group to 4'-, 5- or 7-hydroxyl groups of apigenin respectively. Preliminary biological evaluation in vitro revealed that xanthine oxidase inhibitory activity was improved by modifications at 4'-position and decreased by similar modifications at 5-, 7-positions while α-glucosidase inhibitory activity was maintained by modifications at 5-, 7-positions but lost by modifications at 4'-position. Administration (ip) of 7e markedly lowered serum uric acid levels in potassium oxonate induced hyperuricemic mouse model and administration (p.o.) of 11d or 11e effectively suppressed the elevation of serum glucose in the oral sucrose tolerance test in mice, while apigenin were not significantly effective in both tests.

A combined strategy of mass fragmentation, post-column cobalt complexation and shift in ultraviolet absorption spectra to determine the uridine 5′-diphospho-glucuronosyltransferase metabolism profiling of flavones after oral administration of a flavone mixture in rats

The use of dietary flavones is becoming increasingly popular for their prevention of cancers, cardiovascular diseases, and other diseases. Despite many pharmacokinetic studies on flavone mixtures, the position(s) of glucuronidation sites on the flavone skeleton in vivo remain(s) uncertain because of the lack of a convenient method to differentiate the isomers in biological samples. Accordingly, this study aimed to develop a new strategy to identify the position of the mono-O-glucuronide of flavones in vivo and to simultaneously determine the parent agent and its major metabolites responsible for complex pharmacokinetic characteristics. The novel strategy involves accurate mass measurements of flavone glucuronides, their [Co(II) (flavone glucuronide-H) (4,7-diphenyl-1,10-phenanthroline)2]+ complexes generated via the post-column addition of CoBr2 and 4,7-diphenyl-1,10-phenanthroline, and their mass spectrometric fragmentation by UPLC–DAD–Q-TOF and the comparison of retention times with biosynthesized standards of different isomers that were identified by analyzing the shift in UV spectra compared with the spectra of their respective aglycones. We successfully generated a metabolite profiling of flavones in rat plasma after oral administration of a flavone mixture from Dracocephalum moldavica L., which was used here as the model to demonstrate the strategy. Twelve flavone glucuronides, which were glucuronidated derivatives of acacetin, apigenin, luteolin, diosmetin, chrysoeriol and cirsimaritin, were detected and identified. Glucuronidation of the flavone skeleton at the 3′-/7-position was more prevalent, however, luteolin 4′-glucuronide levels exceeded luteolin 7-glucuronide levels. Based on the UDP-glucuronosyltransferase (UGT) metabolism profiling of flavones in rat plasma, six main compounds (tilianin, acacetin 7-glucuronide, apigenin 7-glucuronide, luteolin 3′-glucuronide, acacetin, and apigenin) were selected as pharmacokinetic markers. Pharmacokinetic results indicated that their maximal concentrations in blood were obtained within 0.4h, except for the concentration of luteolin 3′-glucronide (approximately 9h). Rat exposure was practically non-linear under the studied dosages (200 to 400mg/kg).

Leaf polyphenol profile and SSR-based fingerprinting of new segregant Cynara cardunculus genotypes.

The dietary value of many plant polyphenols lies in the protection given against degenerative pathologies. Their in planta role is associated with the host's defense response against biotic and abiotic stress. The polyphenol content of a given plant tissue is strongly influenced by the growing environment, but is also genetically determined. Plants belonging to the Cynara cardunculus species (globe artichoke and the cultivated and wild cardoon) accumulate substantial quantities of polyphenols mainly mono and di-caffeoylquinic acid (CQA) in their foliage. Transgressive segregation for CQA content in an F1 population bred from a cross between a globe artichoke and a cultivated cardoon led to the selection of eight segregants which accumulated more CQA in their leaves than did those of either of their parental genotypes. The selections were grown over two seasons to assess their polyphenol profile (CQAs, apigenin and luteolin derivatives and narirutin), and were also fingerprinted using a set of 217 microsatellite markers. The growing environment exerted a strong effect on polyphenol content, but two of the selections were able to accumulate up to an order of magnitude more CQA than either parent in both growing seasons. Since the species is readily vegetatively propagable, such genotypes can be straightforwardly exploited as a source of pharmaceutically valuable compounds, while their SSR-based fingerprinting will allow the genetic identity of clonally propagated material to be easily verified.

Effect of soaking and fermentation on content of phenolic compounds of soybean (Glycine max cv. Merit) and mung beans (Vigna radiata [L] Wilczek)

Mung beans (Vigna radiata [L] Wilczek) purchased from a Spanish company as “green soybeans”, showed a different phenolic composition than yellow soybeans (Glycine max cv. Merit). Isoflavones were predominant in yellow soybeans, whereas they were completely absent in the green seeds on which flavanones were predominant. In order to enhance their health benefits, both types of bean were subjected to technological processes, such as soaking and fermentation. Soaking increased malonyl glucoside isoflavone extraction in yellow beans and produced an increase in apigenin derivatives in the green beans. Lactobacillus plantarum CECT 748 T fermentation produced an increase in the bioactivity of both beans since a conversion of glycosylated isoflavones into bioactive aglycones and an increase of the bioactive vitexin was observed in yellow and green beans, respectively. In spite of potential consumer confusion, since soybean and “green soybean” are different legumes, the health benefits of both beans were enhanced by lactic fermentation.

Chemical Composition and Seasonality of Aromatic Mediterranean Plant Species by NMR-Based Metabolomics.

An NMR-based metabolomic approach has been applied to analyse seven aromatic Mediterranean plant species used in traditional cuisine. Based on the ethnobotanical use of these plants, the approach has been employed in order to study the metabolic changes during different seasons. Primary and secondary metabolites have been detected and quantified. Flavonoids (apigenin, quercetin, and kaempferol derivatives) and phenylpropanoid derivatives (e.g., chlorogenic and rosmarinic acid) are the main identified polyphenols. The richness in these metabolites could explain the biological properties ascribed to these plant species.