Search Results (781)

Leaves from California yerba santa (Eriodictyon californicum) have been used historically by indigenous peoples for medicinal purposes. Recent research has ascribed potential pharmaceutical effects to leaf polyphenols, without a consideration of other constituents. Based on prior analyses of polyphenols in leaves sampled in nature, five accessions known to be rich in sterubin and five accessions known to be rich in eriolic acid C were grown from seeds in Ontario, Oregon, and samples of their leaves were harvested and evaluated for their essential oil and polyphenol contents. The major essential oil components in E. californicum were 1,8-cineole (0.6–35.5%), (Z)-β-ocimene (6.8–15.7%), terpinen-4-ol (8.3–16.1%), α-pinene (2.6–13.6%), β-phellandrene (1.9–11.7%), γ-terpinene (4.6–7.9%), ethyl (E)-cinnamate (0.2–8.9%), α-terpineol (1.5–5.2%), p-cymene (2.0–5.3%), and β-pinene (0.6–6.8%). Fifteen polyphenols with a prominence of eriolic acid C, rosmarinic acid, sterubin, homoeriodictyol, 6-methoxynaringenin, hesperetin, and eriodictyol were identified. Essential oils may contribute to the medicinal properties of the leaves of California yerba santa. Results from the ten samples were evaluated for both polyphenols and essential oils; the variations in several essential oils may be correlated to variations in some of the polyphenols. Full article

In this research, PLA biocomposites reinforced with 20 wt% flax fibers modified with 1, 5, 10, and 20% concentrations of trans-cinnamic acid (TC) were prepared. The materials were systematically characterized to evaluate their structural, thermal, viscoelastic, surface, and functional properties. Thermal stability and phase transitions were analyzed using thermogravimetric analysis (TG) and differential scanning calorimetry (DSC), while viscoelastic behavior and molecular relaxation processes were investigated by dynamic mechanical analysis (DMA). To elucidate failure mechanisms and interfacial quality, fracture surface morphology after tensile testing was observed using scanning electron microscopy (SEM). Surface wettability was determined through water contact angle measurements, and antibacterial activity against Escherichia coli and Staphylococcus aureus was evaluated to assess the functional potential of the developed biocomposites. The results demonstrated that moderate fiber modification improved interfacial adhesion and enhanced thermo-mechanical performance. The highest contact angles were observed for 5% and 10% TC concentrations, indicating increased surface hydrophobicity, while strong antibacterial activity (R ≥ 6) was achieved for 10% and 20% TC. The research confirms that trans-cinnamic acid concentration governs multiple structure–property relationships, enabling controlled tuning of mechanical reinforcement and antibacterial functionality. Full article

Background/Objectives: Proso millet (Panicum miliaceum L.), a drought-tolerant cereal vital to semi-arid agriculture, faces severe yield losses from head smut disease caused by the pathogen Sporisorium destruens. Although partial resistance exists, the dynamic molecular mechanisms governing its defense response across developmental stages remain poorly understood. Methods: Here, we performed untargeted metabolomics on leaf samples from Inoculated Asymptomatic (IA) and Inoculated Symptomatic (IS) plants of the partially resistant cultivar ‘Chishu 13’ at four key growth stages following pathogen inoculation, with group classification validated by qPCR. Using weighted metabolite co-expression network analysis (WGCNA) combined with differential metabolite screening, we identified 18 metabolites markedly enriched in the tricarboxylic acid (TCA) cycle, metabolite transport-related processes, and phenylpropanoid biosynthesis pathways. Results: Notably, L-phenylalanine accumulated substantially in IA plants relative to IS plants and correlated closely with biosynthesis of key defensive phenylpropanoids, including cinnamic acid and p-coumaric acid. Our results reveal distinct temporal patterns in metabolic reprogramming that correlate with resistance outcomes in Inoculated Asymptomatic plants: early stages are characterized by differential regulation of energy metabolism, while later stages show enhanced phenylpropanoid biosynthesis. These stage-specific metabolic adaptations are strongly associated with successful defense outcomes. Conclusions: These findings elucidate stage-specific metabolic adaptations that distinguish successful defense in IA plants from susceptibility in IS plants, providing robust biomarkers and stage-targeted strategies for breeding smut-resistant millet varieties. Full article

Corn, paddy, wheat, sorghum, and cassava serve as the primary energy sources in both human and animal diets. This study aimed to evaluate their nutrient release patterns in a simulated gastrointestinal environment and to assess the in vitro biological activity of the metabolites produced during digestion. The results showed that wheat exhibited the highest dry matter degradation in the stomach–jejunum–ileum digestion stage, while wheat and paddy showed the highest crude protein degradation compared with the other starch sources. In addition, wheat had a higher total free sugar concentration than paddy, sorghum, and cassava. Among the individual free sugars, such as D-sorbitol and D-(+)-trehalose, were found to have the highest concentrations in wheat, whereas cassava had the highest D(−)-fructose concentration. Several differential metabolites, including valeric acid, caproic acid, octanoic acid, and azelaic acid were highly released in paddy, whereas glucaric acid, threonic acid, phenylacetic acid, and shikimic acid were highly released in cassava, and 4-hydroxycinnamic acid was highly released in paddy and sorghum. Four unique metabolites were identified during the digestion process of five starch sources. Particularly, isocitric acid and trans-Cinnamic acid were released only from cassava; caffeic acid was released only from sorghum and corn; and pimelic acid was released only from paddy and wheat. Furthermore, cassava was distinct from the other starch sources, displaying a higher abundance of differential metabolites within the glucagon signaling pathway as mapped in KEGG pathway analysis. In summary, compared with other starch sources, wheat provides more dry matter, protein, and sugars for the body. Cassava is unlikely to offer any advantage in glycemic regulation, while paddy and cassava possess stronger biological activity in terms of differential metabolites. Full article

Fusarium ear rot (FER), caused by F. verticillioides, is a devastating disease in maize, leading to substantial yield losses and mycotoxin contamination. Therefore, revealing the molecular mechanisms underlying FER resistance is essential for crop breeding. Here, we performed integrated transcriptomic and metabolomic analyses on two maize inbred lines with contrasting FER resistance: the resistant line ZL30-12 (ZL30) and the susceptible line 92C0468U (92C). Following F. verticillioides inoculation, ZL30 exhibited sustained inhibition of fungal colonization and fumonisin accumulation, whereas 92C showed progressive disease development and elevated fumonisin levels. Both transcriptomic and metabolomic analyses converged on the phenylpropanoid pathway, with DEGs enriched in phenylpropanoid metabolism and DAMs enriched in phenylpropanoid biosynthesis, highlighting its central role in resistance. Further integrative analysis revealed that the lignin biosynthetic process, a key branch of phenylpropanoid metabolism, plays an important role in resistance. Several key DEGs (ZmPAL, ZmHCT, peroxidases, and ZmCOMT) and DAMs (sinapic acid, sinapaldehyde, coniferin, cinnamic acid, and caffeic acid) were differentially regulated between the two lines. Correlation analysis revealed a significant correlation between ZmCOMT expression and sinapic acid accumulation. RT-qPCR validation confirmed the expression patterns of key lignin-associated genes. The elevated activation of lignin biosynthesis in ZL30, via time-dependent induction of key genes (ZmPAL, ZmHCT, and peroxidases), suggests an increase in lignin accumulation, which likely reinforces cell wall integrity and restricts fungal invasion, thereby contributing to FER resistance. Collectively, these findings provide insights into the molecular mechanisms of FER resistance and identify key lignin-associated genes as promising targets for maize breeding. Full article

The present study was designed to evaluate the effects of eighteen different extracts derived from basil (Ocimum basilicum L.) leaves on spontaneous contractions, as well as contractions induced by potassium chloride (KCl) and acetylcholine in the ileum of rats, under in vitro conditions. The extracts were prepared with 96% v/v, 80% v/v, and 60% v/v ethanol, and absolute (100%) v/v, 80% v/v, and 60% v/v methanol, employing extraction techniques that included maceration, digestion, and sonication-assisted methods. Chemical characterization of the extracts revealed the presence of various phenolic acids, including rosmarinic, chlorogenic, caftaric, salvianolic acid B, cinnamic, caffeic, and chicoric acid, as well as flavonoids such as rutin and salvigenin. The evaluated extracts produced significant, concentration-dependent inhibitory effects on rat ileal contractions. Notably, the extract obtained via maceration with 80% methanol exhibited the most pronounced relaxant effects on spontaneous muscle contractions, achieving a maximum reduction of 46.16 ± 2.11%. Furthermore, the extract prepared with the same solvent using sonication-assisted extraction demonstrated superior efficacy in diminishing both the frequency and amplitude of KCl-induced ileal contractions, reducing contraction intensity caused by elevated potassium ion levels to 59.48 ± 3.34% at a maximum concentration of 1.5 mg/mL, thereby indicating its potential as a potent calcium channel blocker. Additionally, the extract prepared with 60% methanol through sonication-assisted extraction resulted in the most substantial reduction of acetylcholine-induced ileal contractions, decreasing contraction intensity to 35.74 ± 1.54% at the maximum concentration of 1.5 mg/mL, which suggests a high level of neurophysiological activity. By comparing extracts with different phytochemical profiles, this study provides additional insight into how variations in phenolic composition may influence different mechanisms of smooth muscle relaxation. This study affirms the significant spasmolytic properties of basil leaf extracts, thereby supporting their potential application in the management of gastrointestinal motility disorders. Full article

The cultivation of asparagus (Asparagus officinalis L.) is plagued by two serious issues: “asparagus decline” and “asparagus replant problem”. The average lifespan of an asparagus plant is 15 to 20 years. However, its productivity decreases after a few years (asparagus decline). Even when these asparagus plants are replaced with new ones, the new plants remain unproductive (asparagus replant problem). The main causes of these problems are a Fusarium infection and asparagus autotoxicity. Several reviews have been conducted on Fusarium. Despite the accumulation of evidence on asparagus autotoxicity in the literature over the past four decades, no review has focused specifically on asparagus autotoxicity. It has been reported that asparagus growth is inhibited by asparagus root residues, leachates, root exudates, and rhizosphere soils. Several phenylpropanoids, including trans-cinnamic acid, p-coumaric acid, caffeic acid, and ferulic acid, have been identified as asparagus autotoxic substances in these root residues, root exudates, rhizosphere soils, growth media, and/or plant tissues. Tryptophan, 3,4-methylenedioxycinnamic acid, and iso-agatharesinol were also identified as asparagus autotoxic substances. These substances may cause autotoxicity by disrupting phytohormone levels, cellular metabolism, impairing membrane function, and by inducing oxidative stress. Although cinnamic, p-coumaric, caffeic, and ferulic acids have been reported to act as antibiotics, these compounds have also been shown to weaken the defense mechanisms of asparagus against pathogen infection, and enhance the Fusarium pathogenicity. The presence of these autotoxic substances, coupled with a Fusarium infection, may create a vicious cycle that worsens “asparagus decline” and “asparagus replant problem”. This is the first review to focus on the asparagus autotoxicity. Full article

Background: Dengue virus (DENV) does not have any effective antiviral therapy. The Cinnamomum verum has cinnamic acid and oleic acid that could inhibit important viral proteins. Aim: To compare their inhibitory capacity with the key DENV proteins through molecular docking, molecular dynamics and in silico ADMET. Methods: Phytochemical profiling of the ethanolic extract of the bark was done by GCMS. AutoDock Vina (version 1.2.0) was used to dock cinnamic acid and oleic acid to key proteins of DENV (NS5, NS3, and envelope) in the presence of ribavirin as the reference. The best complexes were then subjected to 50 ns of molecular dynamics simulation and stability measured by RMSD, RMSF, Rg, SASA, hydrogen bonding and RDF. Validated in silico tools were used to predict the ADMET properties. Results: Analysis of GC–MS revealed cinnamic acid (85.92%) and oleic acid (5.33%). The outcome of docking was that the cinnamic acid had the greatest affinity with NS5 (−5.970 kcal/mol) and the capsid protein (−5.755 kcal/mol), and oleic acid showed the highest affinity with the capsid (−6.150 kcal/mol) and then with NS5 (−5.209 kcal/mol). Both ligands had a relatively weak interaction with NS3. Simulation of the molecular dynamics showed the stability of the top complexes, especially the cinnamic acid–NS5 complex, that retained low RMSD (1.6–1.9 A), stable Rg and SASA profiles, and continued hydrogen bonding during the 50 ns period. The use of cinnamic acid in ADMET projections was more preferable, as it was more soluble, orally bioavailable (0.91), and drug-like (QED 0.65), but oleic acid revealed higher lipophilicity and lower drug-like properties (QED 0.29). Conclusions: Cinnamic acid showed specificity towards the NS5 proteins with the help of stable dynamics and good predicted pharmacokinetics, which are features that make it a promising multi-target anti-DENV scaffold. Oleic acid exhibited poor affinity and poor pharmacokinetic properties. The findings are predictive and must be validated using biochemical, cellular, and toxicological means to prove the antiviral efficacy and safety. Full article

The paper discusses a comprehensive analysis of contemporary approaches to the structural modification of phenolic acids from the benzoic (C₆–C₁) and cinnamic (C₆–C₃) series, which have a wide range of biological activity. The main directions of chemical transformation of phenolic compounds that aim to improve their pharmaco-logical potential, stability, and bioavailability are discussed. The given study also makes an accent on the relationship between the structural features and biological effects of various phenolic acid derivatives, including antioxidant, anti-inflammatory, antimicrobial, and antitumor activity. The purpose of this investigation is to systematize current data on strategies for the structural modification of phenolic acids, to identify key areas of their chemical transformation, and to determine the most promising methods for creating biologically active compounds with improved pharmacological properties. The study was aimed at systematizing the accumulated knowledge and identifying promising areas for further research in the field of structural design of phenolic acid derivatives. Based on the analysis of experimental data and literature sources, key trends in the development of new medicinal compounds using the example of natural phenolic acids were characterized, and prospects for their use in medicine and pharmaceutical chemistry were shown. Full article

Staphylococcus epidermidis (S. epidermidis) poses a significant clinical challenge, particularly in the context of biofilm-associated infections, with increasing antibiotic resistance further complicating infection eradication. In the present study, the effects of cinnamic acid and its derivatives (ferulic acid, p-coumaric acid, and sinapic acid), alone and in combination with the β-lactam antibiotic cloxacillin, on biofilm formation by a single methicillin-resistant S. epidermidis (MRSE) clinical strain were explored. The expression of the biofilm-associated icaADBC operon genes and the icaR repressor gene was assessed using Real-Time PCR as an exploratory analysis under sub-minimal inhibitory concentrations (sub-MICs) of the tested compounds. Furthermore, confocal microscopy was used to qualitatively assess selected structural changes in the biofilm. Their occurrence was demonstrated depending on the fractional inhibitory concentration (FIC) levels used. The results revealed variable and nonlinear patterns of gene expression in response to the tested concentrations. Additionally, compound-dependent differences in anti-biofilm-related responses were observed. Overall, the findings provide insight into the potential influence of cinnamic acid derivatives combined with cloxacillin on biofilm-associated processes in S. epidermidis. Full article

Date palm (Phoenix dactylifera L.) by-products from bioethanol production represent an underutilized resource rich in bioactive molecules. This study aims to their valorization through characterization of polysaccharides and phenolic compounds from the Medjool variety, both before and after yeast fermentation for bioethanol production. Three sequential types of by-products were analyzed—Ext1 (post hot-extraction), Ext2 (post fermentation), and Ext3 (post distillation)—and compared with Dat-Me. High Performance Liquid Chromatograp-Diode Array Detector-Mass Spectrometry (HPLC-DAD-MS) analysis allowed identifying 22 phenolic compounds, primarily cinnamic acid derivatives and glycosylated flavones such as luteolin and chrysoeriol. Fermentation increased total phenolic content from dry weight, while leading to an improved polysaccharide recovery (i.e., from 14.2% to 42.1% dry weight). Two polysaccharide fractions (F1 and F2) were isolated and characterized by ¹H-NMR and Dynamic Light Scattering (DLS). F1 is a pectic polysaccharide, with a galacturonic acid content ranging from 24.2% (Ext3) to 52.2% (Dat-Me), a degree of methylation (DM) between 34.4 and 50.6%, and a degree of acetylation (DA) of 23.6–42.2%. F2 consists of a non-pectic polysaccharide, characterized by a low galacturonic acid content (5.6–6.8%) and a DM of 12.6–47.1%, but it is highly acetylated, with a DA ranging from 90.1 to 93.3%. DLS analysis confirmed fermentation-induced depolymerization, with molecular weights ranging from 6.6 × 10⁴ to 8.5 × 10⁵ KDa for both the fractions. Overall, Medjool date by-products obtained after bioethanol production represent a sustainable source of high-value phenolic antioxidants and polysaccharides with different structures suitable for future applications in food, pharmaceutical, and cosmetic formulations. Full article

This study evaluated the antimicrobial and antioxidant activities and chemical properties of four wild edible macrofungi—Tuber aestivum (Wulfen) Spreng., Terfezia claveryi Chatin, Agaricus arvensis Schaeff. and Bovistella utriformis (Bull.) Demoulin & Rebriev—collected from different regions of Türkiye, with particular emphasis on the role of phenolic compounds. Methanol and hexane extracts were assessed for antimicrobial activity against Gram-positive, Gram-negative, multidrug-resistant (MDR) bacterial strains, and Candida albicans using minimum inhibitory concentration (MIC) assays. Total phenolic content (TPC) was determined, and antioxidant capacities were evaluated using DPPH (2,2-diphenyl-1-picrylhydrazyl), ABTS (2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid)), FRAP (ferric reducing antioxidant power), and CUPRAC (cupric ion reducing antioxidant capacity) assays. The chemical profiles of hexane extracts were characterized by GC–MS analysis, whereas methanol extracts were analyzed by LC–MS/MS. Methanol extracts with high content of phenolic compounds exhibited markedly higher antimicrobial activity than hexane extracts, especially against Gram-positive bacteria. B. utriformis and A. arvensis displayed the highest phenolic contents (29.61 ± 0.6 and 27.14 ± 0.59 mg GAE/g DW, respectively) and antioxidant activities, revealing a strong positive correlation between TPC and antioxidant capacity. LC–MS/MS analysis revealed catechin, cinnamic acid, and caffeic acid as prominent phenolic constituents, highlighting the role of polyphenols in the observed bioactivity. GC–MS profiling predominantly identified fatty acid methyl esters, particularly linoleic and oleic acids, together with minor phenolic derivatives, suggesting a possible synergistic interaction contributing to the overall biological potential. The results highlight phenolic-rich macrofungi as valuable natural sources of antioxidant and antimicrobial agents with potential applications. Full article

Background/Objective: Coffee is the most highly consumed beverage worldwide, and coffee drinkers exhibit decreased mortality and protection from aging-related diseases. This study investigates the role of orphan nuclear receptor 4A1 (NR4A1) in mediating the effects of brewed coffee and the major polyphenolic and polyhydroxy compounds in brewed coffee and also in determining their binding to NR4A1. Methods: The interactions of brewed coffee and several of the major individual compounds in brewed coffee with the ligand-binding domain of NR4A1 were determined using a fluorescent binding assay. For specific compounds, binding was also carried out by surface plasmon resonance, and molecular docking studies were also performed. NR4A1-responsive Rh30 cancer cells were used as models to determine NR4A1-dependent transactivation, cell growth inhibition and inhibition of specific gene products, and in some studies, knockdown of NR4A1 by RNA interference was also determined. Inhibition of lipopolysaccharide-induced IkBα by key polyphenolics was also investigated in RAW264.7 macrophages. Results: Brewed coffee and several polyphenolics, including caffeic acid, ferulic acid, chlorogenic acid, p-coumaric acid, several cinnamic acid derivatives, kahweol, and cafestrol, bound NR4A1 in binding assays, and most Kd values were <10 µM. Brewed coffee and the major polyphenolics inhibited growth of NR4A1-responsive Rh30 cells, and this was attenuated in NR4A1-deficient Rh30 cells. These same compounds also exhibited NR4A1-dependent effects on transactivation and gene product responses in Rh30 and RAW264.7 macrophages and exhibited inverse NR4A1 agonist activity. In contrast, the NR4A1-dependent activity of caffeine and quinic acid was highly variable, suggesting that they are selective NR4A1 ligands. Conclusions: The results of this study demonstrate that brewed coffee and its major polyphenolics and polyhydroxy constituents are NR4A1 ligands and that NR4A1 may play an important role in the health-protective effects of coffee. These results, coupled with recent studies, indicate that NR4A1 and its ligands may play an important role in diet and health. Full article

Heat stress-induced systemic metabolic disorder serves as the core pathological basis of organismal damage. Although mung bean polyphenols (MBPs) had been preliminarily validated in cellular heat-stress models for their intestinal tissue-protective potential, whether they can alleviate heat-stress injury in vivo by remodeling the metabolic crosstalk network between the gut and systemic circulation remains mechanistically unclear. In this study, we innovatively employed an integrated multi-omics approach combining physiological phenotype, gut metabolome, and serum metabolome analyses based on a Balb/c heat stress (41 °C) mouse model, systematically constructing the metabolic phenotype regulatory network of MBPs. The results demonstrated that MBPs not only significantly improved oxidative stress (elevating GSH-Px and T-AOC, reducing MDA), immune-inflammation (down-regulating IL-1β and TNF-α), and stress hormone (lowering cortisol) phenotypes, but also specifically reversed the disturbances in intestinal and serum metabolic profiles induced by heat stress, particularly restoring key pro-inflammatory mediators such as Leukotriene E4 and 5-HETE. Arachidonic acid metabolism, tryptophan metabolism, histidine metabolism, and Fc epsilon RI signaling pathway constituted the core network of heat-stress metabolic disorder and MBP regulation. Furthermore, the study revealed that alterations in hub metabolites—Indolelactic Acid, Trans-Cinnamic Acid, Leukotriene E4, 5-HETE, and N(omega)-Hydroxyarginine—were significantly correlated with phenotypic improvements. This confirms that mung bean polyphenols dynamically dismantle the “pro-inflammatory-oxidative stress” pathological coupling by constructing a novel protective axis centered on the indole metabolism–melatonin–endogenous antioxidant system and successfully established a novel protective axis driven by gut-derived beneficial metabolites that promotes systemic antioxidant function, thereby elucidating the systemic mechanism underlying the alleviation of heat-stress injury at the metabolic network level. Full article

Resistance to apoptosis represents a major limitation of platinum-based chemotherapy in colorectal carcinoma, frequently arising from impaired p53 signaling and inefficient execution of programmed cell death. In this study, we investigated the anticancer activity of Erica spiculifolia extract (ESE) and its ability to synergistically enhance cisplatin cytotoxicity in HT-29 colorectal carcinoma cells. Cell viability was assessed using the MTT assay, followed by formal combination analysis based on the Chou–Talalay methodology. Combination experiments employed a non-constant ratio regimen in which a fixed ESE concentration (45 µg/mL) was combined with serial cisplatin dilutions (45.0–2.8 µg/mL) to define interaction behavior across multiple effect levels. Quantitative analysis revealed a strong superadditive effect, with Combination Index values well below 1 and markedly elevated Dose Reduction Indices for cisplatin, indicating substantial dose-sparing across effect levels. To elucidate the molecular basis of this synergism, apoptosis-related protein expression was profiled using a membrane-based immunoassay. Combined ESE and cisplatin treatment induced full-scale p53 reactivation, including restoration of phosphorylated p53 isoforms associated with DNA damage-dependent apoptotic signaling. Acridine orange/propidium iodide staining confirmed a pronounced increase in early and late apoptotic/necrotic cells following combination treatment. UHPLC-HRMS analysis identified kaempferol 3-O-glucoside (8830.19 ± 11.01 ng/mg dw) and myricitrin (3074 ± 3.12 ng/mg) as predominant flavonols, followed by naringenin 7-O-glucoside (5958.96 ± 9.98 ng/mg), while chlorogenic, cinnamic, quinic, and gallic acids were the main phenolic acids detected. These constituents may contribute to HT-29 cell sensitization to cisplatin. Full article