Search Results (17)

Background/Objectives: Products from various parts of Crataegus species are traditionally applied as a cardiotonic. In Europe and the USA, mainly Crataegus monogyna Jacq. (Lindm.) and Crataegus laevigata (Poir.) DC (synonym Crataegus oxyacantha L.) are used, but worldwide, other Crataegus species are also used. Phytotherapeutic preparations with a standardised content of flavonoids and/or oligomeric procyanidins are commercially available. The products are generally considered as safe and are at most associated with minor and atypical adverse reactions. The aim of this study was to critically assess the information about the safety of Crataegus-containing products in humans. Methods: A scoping review of the literature about adverse reactions associated with Crataegus-containing products was performed. Next, individual case safety reports (ICSRs) were assessed, which were included in VigiBase (the World Health Organisation’s global database of adverse event reports for medicines and vaccines) and in the database of the Netherlands Pharmacovigilance Centre Lareb. The findings are discussed in relation to the literature. Results: The scoping review yielded 23 clinical studies with single-herb and 14 with multi-herb preparations, from which only a few minor gastrointestinal and cardiac events had been reported. A total of 1527 reports from VigiBase, from 1970 to 2023, were analysed, as well as 13 reports from Lareb. The most frequently reported adverse reactions belonged to the system organ classes ‘gastrointestinal disorders’, ‘skin and subcutaneous tissue disorders’, ‘general disorders and administration site conditions’, ‘cardiac disorders’ or ‘nervous system disorders’. In 277 reports of VigiBase, a single-herb product was the only suspect for causing the adverse reaction(s). Of these, 12.6% were graded as serious. Conclusions: The results of our study provide deeper insight in the adverse reaction profile of Crataegus-containing products and should contribute to their safe application in the treatment of less severe forms of cardiac failure. Full article

The herbivore Cameraria ohridella (kingdom Animalia) and the pathogen Erysiphe flexuosa (kingdom Fungi) are considered pests and biotic stressors of Aesculus hippocastanum (chestnut trees). The impact of both pests on the accumulation of secondary metabolites in chestnut leaves was investigated. Specifically, the interactive effect of both pests on metabolite accumulation and their potential role in enhancing the resistance of chestnut trees to biological stress was the focus of this study. Aesculus hippocastanum leaves with varying degrees of Cameraria ohridella infestation and Erysiphe flexuosa infection were used in this research. Leaf samples were collected during the plant vegetative growth phase and evaluated for pest infection and secondary metabolite content. Eight main polyphenols were identified in the leaves: (1) neochlorogenic acid, (2) (−)-epicatechin, (3) procyanidin trimer A-type, (4) procyanidin tetramer A-type, (5) quercetin-3-O-arabinoside, (6) quercetin-3-O-rhamnoside, (7) kaempferol-3-O-arabinoside, and (8) kaempferol-3-O-rhamnoside. It was found that the accumulation of metabolites, primarily those derived from epicatechin and quercetin, during the initial vegetation phase (up to 11.05 or 09.05), strongly depended on the later degree of pest infection. The differences observed in the metabolite dynamics in the chestnut leaves, depending on the extent of infection, indicate the development of a metabolic response mechanism in chestnut trees to biological stress. Full article

High-quality dark chocolates (70% cocoa content) can have shades from light to dark brown color. This work aimed at revealing compounds that discriminate black and brown chocolates. From 37 fine chocolate samples from years 2019 and 2020 provided by Valrhona,8 dark black samples and 8 light brown samples were selected. A non-targeted metabolomics study was performed based on ultra-high performance liquid chromatography—high resolution mass spectrometry/mass spectrometry experiments, univariate, multivariate, and feature-based molecular networking analyses. Twenty-seven overaccumulated discriminating compounds were found for black chocolates. Among them, glycosylated flavanols including monomers and glycosylated A-type procyanidin dimers and trimers were highly representative. Fifty overaccumulated discriminating compounds were found for brown chocolates. Most of them were B-type procyanidins (from trimers to nonamers). These phenolic compounds may be partially related to the chocolate colors as precursors of colored compounds. This study increases the knowledge on the chemical diversity of dark chocolates by providing new information about the phenolic profiles of black and brown chocolates. Full article

Proanthocyanidins (PACs) have been proven to possess a wide range of biological activities, but complex structures limit their study of structure–function relationships. Therefore, an efficient and general method using hydrophilic interaction high-performance liquid chromatography coupled with high-resolution quadrupole time-of-flight tandem mass spectrometry (HILIC-QTOF-MS) was established to analyze PACs from different plant materials. This method was successfully applied to characterize PACs from Chinese bayberry (Myrica rubra Sieb. et Zucc.) leaves (BLPs), sorghum testa (STPs) and grape seeds (GSPs). BLPs with the degree of polymerization (DP) from 1 to 8 were separated. BLPs are mainly B-type prodelphinidins and A-type BLPs were first found in this study. STPs and GSPs belonging to procyanidins showed DP from 3 to 11 and 2 to 12, respectively. A-type linkages were found for every DP of STPs and GSPs, which were first found. These results showed that HILIC-QTOF-MS can be successfully applied for analyzing PACs from different plant materials, which is necessary for the prediction of their potential health benefits. Full article

Agroforestry by-products have gained rising attention in recent years as they represent inexpensive and abundant raw materials that are a source of added-value chemicals, e.g., for food and pharmaceutical applications, as well as for bioenergy generation. Pinus pinaster Ait. bark extracts are consumed worldwide for their cardiovascular benefits, whilst the health potential of Pinus pinea L. bark has not yet been deeply exploited. Therefore, this study highlights the chemical characterisation of Portuguese P. pinaster Ait. and P. pinea L. bark polar extracts, via ultra-high performance liquid chromatography-diode array detection-tandem mass spectrometry (UHPLC-DAD-MSⁿ) analysis, and their antioxidant and antibacterial activities. Quinic acid, an A-type procyanidin dimer isomer, protocatechuic acid, and quercetin were identified for the first time as P. pinea L. bark components. Moreover, this bark demonstrated a higher total content of identified polar compounds than P. pinaster Ait. bark, with quinic acid being the most abundant compound identified. Regarding antioxidant activity, the pine bark polar extracts exhibited strong reducing power and 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2-azinobis-(3-ethyl-benzothiazoline-6-sulfonic acid (ABTS) radical scavenging effects compared to natural antioxidants. Moreover, the bactericidal actions of pine bark extracts were shown against Staphylococcus aureus and Escherichia coli at a 3.13–25 mg mL⁻¹ range. Globally, these promising insights can boost the sustainable exploitation of P. pinea L. bark, as already occurs with P. pinaster Ait. bark, for the food and biomedical fields. Full article

The number of people worldwide suffering from Alzheimer’s disease (AD) and type 2 diabetes (T2D) is on the rise. Amyloid polypeptides are thought to be associated with the onset of both diseases. Amyloid-β (Aβ) that aggregates in the brain and human islet amyloid polypeptide (hIAPP) that aggregates in the pancreas are considered cytotoxic and the cause of the development of AD and T2D, respectively. Thus, inhibiting amyloid polypeptide aggregation and disaggregation existing amyloid aggregates are promising approaches in the therapy and prevention against both diseases. Therefore, in this research, we evaluated the Aβ/hIAPP anti-aggregation and disaggregation activities of A-type procyanidins 1–7 and their substructures 8 and 9, by conducting structure–activity relationship studies and identified the active site. The thioflavin-T (Th-T) assay, which quantifies the degree of aggregation of amyloid polypeptides based on fluorescence intensity, and transmission electron microscopy (TEM), employed to directly observe amyloid polypeptides, were used to evaluate the activity. The results showed that catechol-containing compounds 1–6 exhibited Aβ/hIAPP anti-aggregation and disaggregation activities, while compound 7, without catechol, showed no activity. This suggests that the presence of catechol is important for both activities. Daily intake of foods containing A-type procyanidins may be effective in the prevention and treatment of both diseases. Full article

Endothelial dysfunction in obesity plays a key role in the development of cardiovascular diseases, and it is characterized by increased vascular tonus and oxidative stress. Thus, this study aimed to investigate the vasodilatory and antioxidant activities of Mandevilla moricandiana ethyl acetate fraction and subfractions. Vascular effects were investigated on aorta isolated from control and monosodium glutamate (MSG) induced-obese Wistar rats, and antioxidant activity was assessed by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and oxygen radical absorbance capacity (ORAC) methods. The ethyl acetate fraction (MMEAF) induced a concentration-dependent vasodilation on aortic rings through the NO pathway, with the involvement of histamine H1 and estrogen ERα receptors and showed potent antioxidant activity. In aorta of MSG obese rats, maximal relaxation to acetylcholine was increased in the presence of MMEAF (3 µg/mL), indicating that MMEAF ameliorated obesity-induced endothelial dysfunction. Quercetin and kaempferol aglycones and their correspondent glycosides, as well as caffeoylquinic acid derivatives, A-type procyanidin trimer, ursolic and oleanolic triterpenoid acids were identified in subfractions from MMEAF and seem to be the metabolites responsible for the vascular and antioxidant activities of this fraction. Full article

Flavan-3-ols, procyanidins and their monomers are major flavonoids present in peanuts that show a wide range of biological properties and health benefits, based on their potent antioxidant activity. Procyanidin oligomers, especially A-type, are reportedly abundant in peanut skin; however, their localization in the raw peanut testa remains poorly understood. Therefore, we performed matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) to investigate the localization of flavan-3-ols in peanut testa. 1,5-Diaminonaphthalene was coated onto the peanut section by matrix vapor deposition/recrystallization, and MALDI-MSI measurements were performed in the negative-ion mode. Peaks matching the m/z values of flavan-3-ol [M − H]⁻ ions were observed in the mass spectrum extracted from the outer epidermis of the peanut testa, using the region of interest function. Catechin and/or epicatechin, five A-type, and one B-type procyanidins were assigned by the fragment ions generated by retro-Diels-Alder, heterocyclic ring fission, and quinone methide reactions detected in MALDI-tandem MS spectra. These flavan-3-ols were localized in the outer epidermis of the peanut testa. This information will contribute to improving the extraction and purification efficiencies of flavan-3-ols from peanut testa. As flavan-3-ols display anti-microbial activity, it is speculated that flavan-3-ols present in the outer epidermis of peanut testa act to prevent pathogen infection. Full article

Extracts from the roots of Paullinia pinnata L. are used in West Africa as traditional remedies for a variety of diseases including infestations with soil-transmitted helminths. Based on the results of an ethnopharmacological survey in Ghana, an aqueous acetone (70%) extract was investigated for its anthelmintic and phytochemical properties. Partitioning of the crude extract followed by several fractionation steps of the ethyl acetate phase using Sephadex^® LH-20, fast centrifugal partition chromatography, RP-18-MPLC and HPLC led to isolation of six oligomeric A-type procyanidins (1 to 6). To determine the anthelmintic activity, the crude extract, fractions and isolated compounds were tested in vitro against the model organism Caenorhabditis elegans. A significantly better activity was observed for the trimeric A-type procyanidin (1) compared to a B-type trimer. However, this effect could not be generalized for the tetrameric procyanidins, for which the type of the interflavan-linkage (4→6 vs. 4→8) had the greatest impact on the bioactivity. Besides the procyanidins, three novel compounds, isofraxidin-7-O-α-l-rhamnopyranosyl-(1″→6′)-β-d-glucopyranoside (17), 4-methoxycatechol-2-O-(5′′-O-vanilloyl-β-apiofuranosyl)-(1′′→2′)-β-glucopyranoside (18) and a 6-(3-methoxy-4-hydroxyphenyl)-hexane-2,4-diol-2-O-hexoside (19) were isolated together with further ten known compounds (7 to 16), mainly coumarins and coumarinolignans. Except for 3-β-d-glucopyranosyloxy-4-methyl-2(5H)-furanone (15), none of the isolated compounds has previously been described for P. pinnata. The anthelmintic activity was attributed to the presence of procyanidins, but not to any of the other compound classes. In summary, the findings rationalize the traditional use of P. pinnata root extracts as anthelmintic remedies. Full article

Yeast are able to modulate many sensory parameters of wines during red must fermentation. The effect on color and on the formation of derived pigments during fermentation has been studied thoroughly since the 90s. Yeast can increase grape anthocyanin’s color by acidification by hyperchromic effect (increase of flavylium molecules). Recent studies with non-Saccharomyces species, as Lachancea thermotolerans, described the intense effect of some strains on anthocyanin’s color, and subsequent, stability, by strongly reducing wine’s pH during fermentation. Moreover, selected yeast strains of Saccharomyces have been shown to release metabolites such as pyruvic acid or acetaldehyde that promote the formation of vitisin A and B pyranoanthocyanins during must fermentation. Schizosaccharomyces pombe, because of its specific metabolism, can produce higher concentrations of pyruvate, which enhances the formation of vitisin A-type derivatives. The hydroxycinnamate decarboxylase activity that some Saccharomyces strains express during fermentation also promotes the formation of vinylphenolic derivatives. Some non-Saccharomyces species, such as S. pombe or P. guilliermondii can also improve the production of these derivatives compared to selected strains of Saccharomyces cerevisiae. Lastly, some yeasts are also able to modulate the formations of polymeric pigments between grape anthocyanins and flavonoids, such as catechins and procyanidins. Full article

Tectaria coadunata, an ethnomedicinal fern used in Nepal to treat a large number of diseases, has been poorly studied with regard to its phytochemical composition and possible bioactivity. This study was performed with the aim of supporting traditional medicine as a new source of bioactive constituents. Phytochemical compositions of methanol extracts were determined by nuclear magnetic resonance (NMR), liquid chromatography–diode array detector–mass spectrophotometry (LC-DAD-MS), and liquid chromatography–fluorescence–mass spectrometry. Quali-quantitative data revealed large amount of procyanidins, mainly of the A-type, as well as eriodictyol-7-O-glucuronide and luteolin-7-O-glucoronide as main constituents. The antioxidant, cytotoxic, and inhibitory activity of five enzymes that are implicated in human diseases was evaluated for the extract and fractions. High free-radical scavenging activity in 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) assays and inhibitory activities against cholinesterases and tyrosinase were observed. Furthermore, a moderate cytotoxic effect was observed on the 2008 and BxPC3 cell lines. Overall results showed potential usefulness of this fern as a source of phytochemicals for pharmaceutical uses. Full article

Previous studies showed that a series of purified condensed tannins (CTs) from warm-season perennial legumes exhibited high variability in their modulation of methane production during in vitro rumen digestion. The molecular weight differences between these CTs did not provide correlation with either the in vitro CH₄ production or the ability to precipitate bovine serum albumin. In an effort to delineate other structure-activity relationships from these methane abatement experiments, the structures of purified CTs from these legumes were assessed with a combination of methanolysis, quantitative thiolysis, ¹H-¹³C HSQC NMR spectroscopy and ultrahigh-resolution MALDI-TOF MS. The composition of these CTs is very diverse: procyanidin/prodelphinidin (PC/PD) ratios ranged from 98/2 to 2/98; cis/trans ratios ranged from 98/2 to 34/66; mean degrees of polymerization ranged from 6 to 39; and % galloylation ranged from 0 to 75%. No strong correlation was observed between methane production and the protein precipitation capabilities of the CT towards three different proteins (BSA, lysozyme, and alfalfa leaf protein) at ruminal pH. However, a strong non-linear correlation was observed for the inhibition of methane production versus the antioxidant activity in plant sample containing typical PC- and PD-type CTs. The modulation of methane production could not be correlated to the CT structure (PC/PD or cis/trans ratios and extent of galloylation). The most active plant in methane abatement was Acacia angustissima, which contained CT, presenting an unusual challenge as it was resistant to standard thiolytic degradation conditions and exhibited an atypical set of cross-peak signals in the 2D NMR. The MALDI analysis supported a 5-deoxy flavan-3-ol-based structure for the CT from this plant. Full article

Extraction with organic solvents is a traditional method to isolate bioactive compounds, which is energy-wasting and time-consuming. Therefore, enzyme and ultrasound treatments were combined to assist the extraction of oligomeric procyanidins from litchi pericarp (LPOPC), as an innovative approach to replace conventional extraction methods. Under optimum conditions (enzyme concentration 0.12 mg/mL, ultrasonic power 300 W, ultrasonic time 80 min, and liquid/solid ratio 10 mL/g), the yield of LPOPC could be improved up to 13.5%. HPLC analysis indicated that the oligomeric procyanidins (OPC) content of LPOPC from proposed extraction was up to 89.6%, mainly including (−)-epicatechin, procyanidin A1, A2, and A-type procyanidin trimer. Moreover, LPOPC powder was added in baked food to inhibit the lipid peroxidation. It was found that 0.2% (w/w) of LPOPC could maintain the quality of cookies in the first 7 days, by decreasing the peroxide values. The procyanidin dimers and trimers in LPOPC played more important roles as antioxidants compared to monomers during storage. The results also showed that the combined extraction process can be considered as a useful and efficient method for the extraction of functional components from other plant sources. Full article

The phenolic composition of skin and flesh from Malus domestica apples (Anna cultivar) and Prunus domestica plums (satsuma cultivar) commercial cultivars in Costa Rica, was studied using Ultra Performance Liquid Chromatography coupled with High Resolution Mass Spectrometry (UPLC-DAD-ESI-MS) on enriched-phenolic extracts, with particular emphasis in proanthocyanidin and flavonoids characterization. A total of 52 compounds were identified, including 21 proanthocyanidins ([(+)-catechin and (−)-epicatechin]) flavan-3-ols monomers, five procyanidin B-type dimers and two procyanidin A-type dimers, five procyanidin B-type trimers and two procyanidin A-type trimers, as well as one procyanidin B-type tetramer, two procyanidin B-type pentamers, and two flavan-3-ol gallates); 15 flavonoids (kaempferol, quercetin and naringenin derivatives); nine phenolic acids (protochatechuic, caffeoylquinic, and hydroxycinnamic acid derivatives); five hydroxychalcones (phloretin and 3-hydroxyphloretin derivatives); and two isoprenoid glycosides (vomifoliol derivatives). These findings constitute the first report of such a high number and diversity of compounds in skins of one single plum cultivar and of the presence of proanthocyanidin pentamers in apple skins. Also, it is the first time that such a large number of glycosylated flavonoids and proanthocyanidins are reported in skins and flesh of a single plum cultivar. In addition, total phenolic content (TPC) was measured with high values observed for all samples, especially for fruits skins with a TPC of 619.6 and 640.3 mg gallic acid equivalents/g extract respectively for apple and plum. Antioxidant potential using 2,2-diphenyl-1-picrylhidrazyl (DPPH) and oxygen radical absorbance capacity (ORAC) methods were evaluated, with results showing also high values for all samples, especially again for fruit skins with IC₅₀ of 4.54 and 5.19 µg/mL (DPPH) and 16.8 and 14.6 mmol TE/g (ORAC) respectively for apple and plum, indicating the potential value of these extracts. Significant negative correlation was found for both apple and plum samples between TPC and DPPH antioxidant values, especially for plum fruits (R = −0.981, p < 0.05) as well as significant positive correlation between TPC and ORAC, also especially for plum fruits (R = 0.993, p < 0.05) and between both, DPPH and ORAC antioxidant methods (R = 0.994, p < 0.05). Full article

Dry leaf extracts of eastern teaberry (Gaultheria procumbens L.) were evaluated as a source of bioactive phytocompounds through systematic activity testing and phytochemical profiling. The antioxidant efficiency was tested using five complementary in vitro models (DPPH; FRAP; linoleic acid (LA) peroxidation assay; O₂^•− and H₂O₂ scavenging tests) in parallel with standard antioxidants. The 75% methanol extract and its diethyl ether, ethyl acetate (EAF), n-butanol and water fractions exhibited the dose-dependent responses in all assays, with the highest capacities found for EAF (DPPH EC₅₀ = 2.9 μg/mL; FRAP = 12.8 mmol Fe²⁺/g; IC₅₀ for LA-peroxidation = 123.9 μg/mL; O₂^•− SC₅₀ = 3.9 μg/mL; H₂O₂ SC₅₀ = 7.2 μg/mL). The EAF had also the highest anti-inflammatory activity in the inhibition tests of lipoxygenase and hyaluronidase (60.14% and 21.83% effects, respectively, at the concentration of 100 μg/mL). Activity parameters of the extracts correlated strongly with the levels of total phenolics (72.4–270.7 mg GAE/g), procyanidins, and phenolic acids, whereas for flavonoids only moderate effects were observed. Comprehensive UHPLC-PDA-ESI-MS³ and HPLC-PDA studies led to the identification of 35 polyphenols with a procyanidin A-type trimer, quercetin 3-O-glucuronide, isomers of caffeoylquinic acids, and (‒)-epicatechin being the dominant components. Significant activity levels, high phenolic contents and high extraction yields (39.4%–42.5% DW for defatted and crude methanol extracts, respectively) indicate the value of eastern teaberry leaves as bioactive products. Full article