Search Results (61)

Objectives: This study investigated the effects of 2-week ingestion of hemp fiber (high and low doses) versus placebo bars on gut permeability and plasma metabolite shifts during recovery from 2.25 h intensive cycling. Hemp hull powder is a rich source of two bioactive compounds, N-trans-caffeoyl tyramine (NCT) and N-trans-feruloyl tyramine (NFT), with potential gut health benefits. Methods: The study participants included 23 male and female cyclists. A three-arm randomized, placebo-controlled, double-blind, crossover design was used with two 2-week supplementation periods and 2-week washout periods. Supplement bars provided 20, 5, or 0 g/d of hemp hull powder. Participants engaged in an intensive 2.25 h cycling bout at the end of each of the three supplementation periods. Five blood samples were collected before and after supplementation (overnight fasted state), and at 0 h-, 1.5 h-, and 3 h-post-exercise. Five-hour urine samples were collected pre-supplementation and post-2.25 h cycling after ingesting a sugar solution containing 5 g of lactulose, 100 mg of ¹³C mannitol, and 1.9 g of mannitol in 450 mL of water. An increase in the post-exercise lactulose/¹³C mannitol ratio (L:¹³CM) was used as the primary indicator of altered gut permeability. Other outcome measures included muscle damage biomarkers (serum creatine kinase, myoglobin), serum cortisol, complete blood cell counts, and shifts in plasma metabolites using untargeted metabolomics. Results: No trial differences were found for L:¹³CM, cortisol, blood cell counts, and muscle damage biomarkers. Orthogonal partial least-squares discriminant analysis (OPLSDA) showed distinct trial differences when comparing high- and low-dose hemp fiber compared to placebo supplementation (R2Y = 0.987 and 0.995, respectively). Variable Importance in Projection (VIP) scores identified several relevant metabolites, including 3-hydroxy-4-methoxybenzoic acid (VIP = 1.9), serotonin (VIP = 1.5), 5-hydroxytryptophan (VIP = 1.4), and 4-methoxycinnamic acid (VIP = 1.4). Mummichog analysis showed significant effects of hemp fiber intake on multiple metabolic pathways, including alpha-linolenic acid, porphyrin, sphingolipid, arginine and proline, tryptophan, and primary bile acid metabolism. Conclusions: Hemp fiber intake during a 2-week supplementation period did not have a significant effect on post-exercise gut permeability in cyclists (2.25 h cycling bout) using urine sugar data. On the contrary, untargeted metabolomics showed that the combination of consuming nutrient-rich hemp fiber bars and exercising for 135 min increased levels of beneficial metabolites, including those derived from the gut in healthy cyclists. Full article

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by recurrent episodes and an inability to achieve a complete cure. The spermidine derivative (di-p-coumaroyl-caffeoyl spermidine, SPDD), as a key alkaloid, exhibits unique health benefits. However, it has not yet been reported whether SPDD can improve dextran sulfate sodium (DSS)-induced colitis in mice. Herein, we investigated the effects and mechanisms of SPDD on DSS-induced colitis in mice. SPDD was successfully purified from rose bee pollen and was found to have a protective effect on colitis, evidenced by reduced disease activity index (DAI) scores and colonic inflammation, increased colonic length and upregulated the expression of tight junction proteins (TJs) in the model (p < 0.05). Importantly, the IL-17 signaling pathway showed significant enrichment by RNA sequencing (RNA-seq) technology with SPDD treatment, which resulted in the downregulation of MAPK4 expression (p < 0.05). Furthermore, SPDD weakened the interaction between MAPK4 and AKT, resulting in a decrease in the phosphorylation level of AKT, thereby reducing the expression of IL-6, IL-1β, iNOS, and COX-2, and alleviating colitis (p < 0.05). In addition, SPDD treatment also ameliorated TNF-α-induced inflammation in Caco-2 cells. Overall, our study demonstrated that SPDD reversed colonic inflammation in colitis mice through the MAPK4/AKT pathway and might be a promising candidate for UC intervention. Full article

As a part of our ongoing search for bioactive constituents of Artemisia capillaris, we isolated 4-O-caffeoyl-2-C-methyl-d-threonic acid (PPT-14). This is a rare caffeic acid ester derivative that is reported here for the first time in the Artemisia species, which is the third occurrence in any plant species worldwide. In this study, we evaluated the anti-diabetic potential of PPT-14 using in vitro and in silico approaches. PPT-14 demonstrated significant inhibitory activity against two crucial enzymes linked to diabetes progression and complications: protein tyrosine phosphatase 1B (PTP1B) and aldose reductase (AR). These had IC₅₀ values of 64.92 and 19.50 µM, respectively. Additionally, PPT-14 exhibited free radical scavenging activity with 2,2-diphenyl-2-picrylhydrazyl (IC₅₀ 14.46 µM). Molecular docking and 200 ns molecular dynamics simulations confirmed that there were stable binding interactions with the key residues of PTP1B and AR, highlighting strong affinity and dynamic stability. Pharmacokinetic analyses revealed favorable water solubility, adherence to Lipinski’s Rule of Five, and minimal interactions with cytochrome P450 enzymes, indicating the drug-like potential of PPT-14. Toxicity studies confirmed its safety profile, showing no genotoxicity, hepatotoxicity, or significant toxicity risks, with an acceptable oral LD₅₀ value of 2.984 mol/kg. These findings suggest that PPT-14 could be a promising multitarget lead compound for ameliorating diabetes and its associated complications. Full article

The Italian Carciofo di Paestum (C. scolymus) PGI, an artichoke variety from the Campania region, was investigated for its potential to reuse by-products for food supplements. EtOH:H₂O 50:50 and 75:25 extracts of its leaves were analyzed for phenolic and flavonoid content and antioxidant activity (TEAC: 1.90 and 1.81 mM of Trolox; DPPH IC₅₀: 106.31 µg/mL and 128.21 µg/mL; FRAP: 1.68 and 1.58 mM FeSO₄/g extract). To further investigate the antioxidant potential, the ability of the two extracts to scavenge reactive species was assessed in Caco-2 cell cultures, showing a dose-dependent antioxidant capacity. To highlight metabolites responsible for the activity, LC-ESI/HRMSMS analysis was achieved, revealing 28 compounds (sesquiterpenes, megastigmanes, quinic acid and hydroxycinnamic acid derivatives, flavonoids, lignans, triterpenoid saponins, and polar fatty acids), of which structures were determined using 1D- and 2D-NMR analysis. In addition, quantitative determination of caffeoyl, dicaffeoyl, and quinic acid derivatives (CQAs) was performed through LC-ESI/QTrap/MS/MS, highlighting that the most abundant compound was 5-caffeoylquinic acid (6), with values of 9.310 and 7.603 mg/g extract in EtOH:H₂O (75:25) and EtOH:H₂O (50:50), respectively. The analysis showed that extracts were rich in bioactive compounds, suggesting their potential for development into antioxidant-based food supplements that may protect cells from oxidative stress and support overall wellness. Full article

Rhododendron simsii Planchon is an important ornamental species in the northern hemisphere. Flower color is an important objective of Rhododendron breeding programs. However, information on anthocyanin synthesis in R. simsii is limited. In this research, the regulatory mechanism of anthocyanin biosynthesis in R. simsii was performed through the integrated analysis of metabolome and RNA-seq. A total of 805 and 513 metabolites were screened by positive and negative ionization modes, respectively, In total, 79 flavonoids contained seven anthocyanidins, 42 flavanones, 10 flavans, 13 flavones, and seven flavonols. Methylated and glycosylated derivatives took up the most. Differentially accumulated metabolites were mainly involved in “flavone and flavonol biosynthesis”, “cyanoamino acid metabolism”, “pyrimidine metabolism”, and “phenylalanine metabolism” pathways. For flavonoid biosynthesis, different expression of shikimate O-hydroxycinnamoyltransferase, caffeoyl-CoA O-methyltransferase, flavonoid 3′-monooxygenase, flavonol synthase, dihydroflavonol 4-reductase/flavanone 4-reductase, F3′5′H, chalcone synthase, leucoanthocyanidin reductase, and 5-O-(4-coumaroyl)-D-quinate 3′-monooxygenase genes ultimately led to different accumulations of quercetin, myricetin, cyanidin, and eriodictyol. In flavone and flavonol biosynthesis pathway, differential expression of F3′5′H, flavonoid 3′-monooxygenase and flavonol-3-O-glucoside/galactoside glucosyltransferase genes led to the differential accumulation of quercetin, isovitexin, and laricitrin. This research will provide a biochemical basis for further modification of flower color and genetic breeding in R. simsii and related Rhododendron species. Full article

Sweet potatoes (Ipomoea batatas) are highly profitable, contribute to food security, and their leaves rich in phytonutrients. This study examined the optimal leaf harvesting stage by harvesting newly formed leaves (leaves 1 to 5) to achieve the highest concentration of carotenoids, phenolic compounds, antioxidant properties and mineral content. Leaves of five purple-fleshed sweet potato genotypes ‘2019-11-2’ and ‘2019-1-1’, ‘Purple-purple’, and from the USA ‘08-21P’ and ‘16-283P’ were harvested based on tuber life cycle [vegetative 8 weeks after planting (VS-8WAP), tuber initiation (TIS-12WAP), and tuber maturation phases (TMS-16WAP)]. At the 8WAP stage, leaves of genotype ‘2019-11-2’ had the highest concentrations of cyanidin-caffeoyl-sophoroside-glucoside (17.64 mg/kg), cyanidin-caffeoyl-feruloyl-sophoroside-glucoside (41.51 mg/kg), peonidin-caffeoyl-hydroxybenzoyl-sophoriside-glucoside (45.25 mg/kg), and peonidin caffeoyl-feruloyl-sophoriside-glucoside (24.47 mg/kg), as well as antioxidant scavenging activity. In contrast, ‘Purple-purple’ harvested at TIS-12WAP showed the highest concentration of caffeoylquinic acid derivatives. Zeaxanthin, lutein, all trans-β-carotene, and cis-β-carotene are the most abundant carotenoids in genotype ‘08-21P’ at VS-8WAP. As a result, local genotypes ‘2019-11-2’ harvested at 8WAP and ‘Purple-purple’ harvested at 12WAP are potential sources of anthocyanins and caffeoylquinic acid derivatives. Conversely, USA’s genotype ‘08-21P’ at the VS-8WAP stage is an excellent source of carotenoids. The leaves of USA’s ‘08-21P’ genotype and the local ‘2019-11-2’ genotype at TMS-16WAP exhibited the highest content of Fe and Mn, respectively. The study identified the optimal leaf stage for consumption of leaves and for use as a functional ingredient. Full article

Clovamide (N-caffeoyl-L-3,4-dihydroxyphenylalanine, N-caffeoyldopamine, N-caffeoyl-L-DOPA) is a derivative of caffeic acid, belonging to phenolamides (hydroxycinnamic acid amides). Despite a growing interest in the biological activity of natural polyphenolic substances, studies on the properties of clovamide and related compounds, their significance as bioactive components of the diet, as well as their effects on human health are a relatively new research trend. On the other hand, in vitro and in vivo evidence indicates the considerable potential of these substances in the context of maintaining human health or using them as pharmacophores. The name “clovamide” directly derives from red clover (Trifolium pratense L.), being the first identified source of this compound. In the human diet, clovamides are mainly present in chocolate and other cocoa-containing products. Furthermore, their occurrence in some medicinal plants has also been confirmed. The literature reports deal with the antioxidant, anti-inflammatory, neuroprotective, antiplatelet/antithrombotic and anticancer properties of clovamide-type compounds. This narrative review summarizes the available data on the biological activity of clovamides and their potential health-supporting properties, including prospects for the use of these compounds for therapeutic purposes. Full article

In recent years, caffeic acid and its derivatives have received increasing attention due to their obvious physiological activities and wide distribution in nature. In this paper, to clarify the status of research on plant-derived caffeic acid and its derivatives, nuclear magnetic resonance spectroscopy data and possible biosynthetic pathways of these compounds were collected from scientific databases (SciFinder, PubMed and China Knowledge). According to different types of substituents, 17 caffeic acid and its derivatives can be divided into the following classes: caffeoyl ester derivatives, caffeyltartaric acid, caffeic acid amide derivatives, caffeoyl shikimic acid, caffeoyl quinic acid, caffeoyl danshens and caffeoyl glycoside. Generalization of their ¹³C-NMR and ¹H-NMR data revealed that acylation with caffeic acid to form esters involves acylation shifts, which increase the chemical shift values of the corresponding carbons and decrease the chemical shift values of the corresponding carbons of caffeoyl. Once the hydroxyl group is ester, the hydrogen signal connected to the same carbon shifts to the low field (1.1~1.6). The biosynthetic pathways were summarized, and it was found that caffeic acid and its derivatives are first synthesized in plants through the shikimic acid pathway, in which phenylalanine is deaminated to cinnamic acid and then transformed into caffeic acid and its derivatives. The purpose of this review is to provide a reference for further research on the rapid structural identification and biofabrication of caffeic acid and its derivatives. Full article

Grape seeds represent a rich source of phenolic compounds that exhibit various health benefits. Therefore, grape seed powders can be a potential functional ingredient in the formulation of different nutritionally valuable food products. The aim of this study was the UHPLC Orbitrap MS4 characterization of phenolic compounds and their derivatives in indigenous (Smederevka, Tamjanika, and Prokupac) and international (Italien Riesling, Muscat Hamburg, Merlot, and Cabernet Sauvignon) grape seed powders. Phenolic compounds were extracted from grape seed powders with 80% methanol containing 0.1% HCl and analyzed by UHPLC Orbitrap MS. The identification of phenolic compounds was conducted based on their monoisotopic mass, MS fragmentation (MS4, MS3, MS2), available standards and literature data. Using standards, gallic, protocatechinic, p-hydroxybenzoic, and vanillic acids were identified in the seed extracts of all analyzed grape varieties. On the other hand, gentisic acid was not detected in the seed extracts of the Smederevka and Merlot varieties. Other phenolic acids and their derivatives, such as ellagic acid (300 m/z), gallic acid hexoside (331 m/z), dihydroxybenzoic acid hexoside (315 m/z), caffeoyl tartaric acid (311 m/z), and coumaroyl tartaric acid (295 m/z), were identified in all analyzed seed extracts based on exact mass and MS2 fragmentation. Commonly present flavan-3-ols (catechin, epicatechin, and catechin gallate) and different B-type procyanidins (B-type procyanidin dimer, trimer, and gallate isomers) were also identified in all analyzed samples. To the best of our knowledge, the procyanidin profiles of the indigenous variety Tamjanika (eight compounds) were analyzed for the first time. Flavonol aglycones (taxifolin and quercetin) and glycosides (quercetin, isorhamnetin, and kaempferol glycosides) were also identified, but their presence in the seeds was selective and closely dependent on grape varieties. In sum, grape seed powders of indigenous and international varieties contain different classes of phenolic compounds, primarily flavan-3-ols, procyanidins, and phenolic acids, which increase and favor their future application in the food industry. Full article

Ramie (Boehmeria nivea [L.] Gaud.), a nutritious animal feed, is rich in protein and produces a variety of secondary metabolites that increase its palatability and functional composition. Ethylene (ETH) is an important plant hormone that regulates the growth and development of various crops. In this study, we investigated the impact of ETH sprays on the growth and metabolism of forage ramie. We explored the mechanism of ETH regulation on the growth and secondary metabolites of forage ramie using transcriptomic and metabolomic analyses. Spraying ramie with ETH elevated the contents of flavonoids and chlorogenic acid and decreased the lignin content in the leaves and stems. A total of 1076 differentially expressed genes (DEGs) and 51 differentially expressed metabolites (DEMs) were identified in the leaves, and 344 DEGs and 55 DEMs were identified in the stems. The DEGs that affect phenylpropanoid metabolism, including BGLU41, LCT, PER63, PER42, PER12, PER10, POD, BAHD1, SHT, and At4g26220 were significantly upregulated in the leaves. Ethylene sprays downregulated tyrosine and chlorogenic acid (3-O-caffeoylquinic acid) in the leaves, but lignin biosynthesis HCT genes, including ACT, BAHD1, and SHT, were up- and downregulated. These changes in expression may ultimately reduce lignin biosynthesis. In addition, the upregulation of caffeoyl CoA-O-methyltransferase (CCoAOMT) may have increased the abundance of its flavonoids. Ethylene significantly downregulated metabolites, affecting phenylpropanoid metabolism in the stems. The differential 4CL and HCT metabolites were downregulated, namely, phenylalanine and tyrosine. Additionally, ETH upregulated 2-hydroxycinnamic acid and the cinnamyl hydroxyl derivatives (caffeic acid and p-coumaric acid). Cinnamic acid is a crucial intermediate in the shikimic acid pathway, which serves as a precursor for the biosynthesis of flavonoids and lignin. The ETH-decreased gene expression and metabolite alteration reduced the lignin levels in the stem. Moreover, the HCT downregulation may explain the inhibited lignin biosynthesis to promote flavonoid biosynthesis. In conclusion, external ETH application can effectively reduce lignin contents and increase the secondary metabolites of ramie without affecting its growth and development. These results provide candidate genes for improving ramie and offer theoretical and practical guidance for cultivating ramie for forage. Full article

Sweet potato vine tips are abundant in chlorogenic acid (CGA). In this study, CGA was extracted from vegetable and conventional sweet potato vine tips using ethanol, followed by subsequent purification of the extract through a series of sequential steps. Over 4 g of the purified product was obtained from 100 g of sweet potato vine tip powder, producing more than 85% of purified CGA. The LC-MS analysis of all samples indicated that 4-CQA was the predominant isomer in both sweet potato cultivars. Significant variations of p-coumaroyl quinic acids, feruloyl quinic acids, dicaffeoyl quinic acids, and tricaffeoyl quinic acid were identified, whereas the mono-caffeoyl quinic acids did not vary when the two sweet potato varieties were compared. Compared to conventional sweet potatoes, vegetable sweet potatoes exhibit a high negative correlation between 4-CQA and 5-pCoQA, while showing a high positive correlation between 3,5-CQA and 3-pCoQA. A series of principal component analyses (PCA) using CGA isomers enables a clear differentiation between vine tips derived from vegetable and conventional sweet potatoes. The model of linear discriminant analysis, based on the characteristic CGA, achieved a 100% accuracy rate in distinguishing between vegetable and conventional sweet potatoes. The high purity of sweet potato CGA (SCGA) exhibited potent anti-breast cancer activity. The results demonstrated that SCGA significantly suppressed the clonogenicity of MB231 and MCF7 cells, and impeded the migratory, invasive, and lung metastatic potential of MB231 cells. Full article

Dark chocolate dragée confectionary was made with BRS Clara raisins pre-treated with extra virgin olive oil (EVOO). The evaluation of the changes in the phenolic composition (flavonols, hydrocinnamic acid derivatives (HCADs), stilbenes and flavan-3-ol monomers, dimers, and proanthocyanidins (PAs)) resulting from the covering process showed that the chocolate coating was responsible for an increase in the concentrations of flavan-3-ols and PAs when compared to just the raisins. For the flavonols and HCADs, a reduction in the total concentration of compounds was observed when comparing the dragées to the raisins. Furthermore, there was a strong influence of chocolate in the qualitative profile with the emergence of new compounds (quercetin-3-pentoside, kampfterol-3-rutinoside, p-coumaric acid, and caffeoyl-aspartate). The combination of these ingredients (raisins and chocolate) resulted in a dark chocolate coated raisin (DC) with good sensory acceptance and a more complex phenolic composition that may positively contribute to its functional quality. Full article

Helichrysum italicum has piqued the interest of many researchers in recent years, mostly for its essential oil, but increasingly for its polyphenolic content as well. In the current study, we examine the polyphenolic composition of H. italicum grown in Bulgaria. The polyphenolic complex was fractionated with solvents of various polarities, including hexane, chloroform, ethyl acetate, and butanol, in order to assess the biological impact of the components. HPLC-PDA and UHPLC-MS/MS were used to examine all fractions. The green coffee fingerprint profile was employed as a “surrogate standard” in the polyphenolic components detection approach. From the UHPLC-MS/MS analysis, we identified 60 components of the polyphenolic complex such as quercetin 3-O-glucuronide, quercetin acetyl-glycoside, isorhamnetin acetyl-glycoside, isorhamnetin caffeoyl-glycoside, quercetin caffeoyl-malonyl-glycoside, isorhamnetin coumaroyl-glycoside, coumaroyl-caffeoylquinic acid, and diCQA-acetyl-derivative were first reported in the composition of H. italicum. The biological activity of the fractions was evaluated in vitro and in silico, which included the fight against oxidative stress (hydrogen peroxide scavenging activity (HPSA), hydroxyl radical scavenging activity (HRSA), metal-chelating activity (MChA)) and nitrosative (nitric oxide scavenging activity) (NOSA)), in vitro anti-inflammatory, and anti-arthritic activity. Results are presented as IC₅₀ ± SD μg/mL. The analysis showed that the EtOAc fraction was characterized by highest HPSA (57.12 ± 1.14 μg/mL), HRSA (92.23 ± 1.10 μg/mL), MChA (5.60 ± 0.17 μg/mL), and NOSA (89.81 ± 2.09 μg/mL), while the hexane and chloroform fractions showed significantly higher in vitro anti-inflammatory activity (30.48 ± 2.33 μg/mL, 62.50 ± 1.69 μg/mL) compared to the standard ibuprofen. All three fractions showed potential anti-arthritic activity (102.93 ± 8.62 μg/mL, 108.92 ± 4.42 μg/mL, 84.19 ± 3.89 μg/mL). Full article

Rapeseed’s (Brassica napus L.) colorful petals have important ornamental values. However, the mechanisms of regulating petals coloration in rapeseed are still unknown. In our study, we investigated the key differential coloring substances in nine rapeseed cultivars with different petal colors, and 543 metabolites were detected and characterized through UPLC-HESI-MS/MS. Among them, the kinds and contents of flavonols, flavones, and anthocyanidins were the main contributors to petals’ coloration. Tamarixetin-, quercetin-, butin-, naringenin- and luteolin-derivates were the main pigment bases in white and yellow petals. Peonidin-3,5-O-diglucoside, peonidin-3-O-(6″-O-caffeoyl)glucoside, and quercetin-derivatives were the main coloring substances in pink petals. Acylated cyanidin derivatives might lead to a series of different purple petal colors. Glycosylated anthocyanins were responsible for the coloration of rapeseed red petals, and peonidin-3-O-glucoside and kaempferol-derivatives were mainly detected from the red petals. These results provide comprehensive insights into the difference in flavonoid metabolites in rapeseed petals with different colors and supply theoretical supports for the breeding of novel colorful rapeseed cultivars. Full article

The members of the genus Hypericum have great potential to develop functional uses in nutraceutical and pharmaceutical applications. With this in mind, we aimed to determine the chemical profiling and biological properties of different extracts (ethyl acetate, methanol and water) from two Hypericum species (H. montbretii and H. origanifolium). We combined two approaches (LC-DAD-MS and LC-NMR) to identify and quantify chemical compounds of the extracts. Antioxidant properties (free radical quenching, reducing power and metal chelating) and enzyme inhibitory effects (cholinesterase, tyrosinase, amylase and glucosidase) were determined as biological properties. The tested extracts were rich in caffeic acid derivatives and flavonoids, and among them, 3-caffeoyl quinic acid and myricetin-3-O-rhamnoside were found to be the main compounds. The total phenolic and flavonoid levels were determined to be 50.97–134.99 mg GAE/g and 9.87–82.63 mg RE/g, respectively. With the exception of metal chelating, the methanol and water extracts showed stronger antioxidant properties than the ethyl acetate extracts. However, different results were obtained for each enzyme inhibition assay, and in general, the ethyl acetate extracts present more enzyme-inhibiting properties than the water or methanol extracts. Results from chemical and biological analyses were combined using multivariate analysis, which allowed establishing relationships between composition and observed effects of the Hypericum extracts based on the extraction solvents. To gain more insights between chemical compounds and enzyme-inhibiting effects, we performed molecular docking analysis. We observed favorable interactions between certain compounds and the tested enzymes during our analysis, confirming the data obtained from the multivariate approach. In conclusion, the obtained results may shed light on the road from natural sources to functional applications, and the tested Hypericum species may be considered potential raw materials, with promising chemical constituents and biological activities. Full article