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Metabolic engineering is a promising approach for the synthesis of valuable compounds. Transcriptional factor-based biosensors are efficient tools to regulate the metabolic pathway dynamically. Here, we engineered the p-coumaric acid responsive regulator PadR from Bacillus subtilis. We found that yveF and yveG, two previously uncharacterized components in the sensor system, showed positive impacts on the regulation of PadR-PpadC sensor system, mostly on assisting the release of the repression by PadR. By site directed PadR engineering, we obtained two mutants, K64A and H38A, which exhibited increased dynamic range and superior sensitivity. To increase the promoter strength of the sensor system and investigate whether the PadR binding boxes can function in a plug-and-play manner, a series of hybrid promoters were constructed. Four of them, P1, P2, P7, and P9, showed increased strength compared to PpadC and can be regulated by PadR and p-coumaric acid. The PadR variants and hybrid promoters obtained in this paper would expand the applicability of this sensor system in future metabolic engineering research.

Pseudomonas putida KT2440 is a promising bacterial chassis for the conversion of lignin-derived aromatic compound mixtures to biofuels and bioproducts. Despite the inherent robustness of this strain, further improvements to aromatic catabolism and toxicity tolerance of P. putida will be required to achieve industrial relevance. Here, tolerance adaptive laboratory evolution (TALE) was employed with increasing concentrations of the hydroxycinnamic acids p-coumaric acid (pCA) and ferulic acid (FA) individually and in combination (pCA ​+ ​FA). The TALE experiments led to evolved P. putida strains with increased tolerance to the targeted acids as compared to wild type. Specifically, a 37 ​h decrease in lag phase in 20 ​g/L pCA and a 2.4-fold increase in growth rate in 30 ​g/L FA was observed. Whole genome sequencing of intermediate and endpoint evolved P. putida populations revealed several expected and non-intuitive genetic targets underlying these aromatic catabolic and toxicity tolerance enhancements. PP_3350 and ttgB were among the most frequently mutated genes, and the beneficial contributions of these mutations were verified via gene knockouts. Deletion of PP_3350, encoding a hypothetical protein, recapitulated improved toxicity tolerance to high concentrations of pCA, but not an improved growth rate in high concentrations of FA. Deletion of ttgB, part of the TtgABC efflux pump, severely inhibited growth in pCA ​+ ​FA TALE-derived strains but did not affect growth in pCA ​+ ​FA in a wild type background, suggesting epistatic interactions. Genes involved in flagellar movement and transcriptional regulation were often mutated in the TALE experiments on multiple substrates, reinforcing ideas of a minimal and deregulated cell as optimal for domesticated growth. Overall, this work demonstrates increased tolerance towards and growth rate at the expense of hydroxycinnamic acids and presents new targets for improving P. putida for microbial lignin valorization.

Growing concern over antimicrobial resistance in chronic wound patients necessitates the exploration of alternative treatments from natural sources. This study suggests that honey’s phenolic compounds may offer antimicrobial benefits, warranting further investigation for therapeutic development. The main aim of this study was to investigate the antimicrobial activity of phenolic compounds and to determine the effects of their sub-inhibitory concentrations against Escherichia coli (E. coli). 3-phenyllactic acid (PLA), p-coumaric acid (PCA), and phloretin were tested against the bacterial strain of E. coli ATCC 25922. Comparison of the antimicrobial activity of honey constituents in vitro was performed using a broth culture assay. Measurement of the inhibitory properties of constituents in vitro was conducted using disc and well diffusion assays. The effects of sub-inhibitory concentrations of PCA on the susceptibility of E. coli ATCC 25922 to penicillin–streptomycin were tested. The results demonstrated that PLA was the most efficient antimicrobial agent, followed by PCA, whereas phloretin, at lower (2 mg/mL) concentrations, led to an increase in the growth of E. coli. Various modifications of the agar diffusion assay did not reveal the antibacterial properties of the studied phytochemicals. The enhancing effect of a sub-inhibitory concentration of PCA in cooperation with penicillin–streptomycin was shown. These findings might be helpful for the further investigation and development of new antimicrobial agents for the treatment of skin infections and wounds.

This paper presents the results of a study of the effects of the lanthanide ions Ce3+, Pr3+, Nd3+ and Sm3+ on the electronic structure and antioxidant and biological (antimicrobial and cytotoxic) properties of p-coumaric acid (p-CAH2). Structural studies were conducted via spectroscopic methods (FTIR, ATR, UV). Thermal degradation studies of the complexes were performed. The results are presented in the form of TG, DTG and DSC curves. Antioxidant properties were determined via activity tests against DPPH, ABTS and OH radicals. The reducing ability was tested via CUPRAC assays. Minimum inhibitory concentrations (MICs) of the ligand and lanthanide complexes were determined on E. coli, B. subtilis and C. albicans microorganisms. The antimicrobial activity was also determined using the MTT assay. The results were presented as the relative cell viability of C. albicans, P. aeruginosa, E. coli and S. aureus compared to controls and expressed as percentages. In the obtained complexes in the solid phase, lanthanide ions coordinate three ligands in a bidentate chelating coordination mode through the carboxyl group of the acid. Spectroscopic analysis showed that lanthanide ions increase the aromaticity of the pi electron system of the ligand. Thermal analysis showed that the complexes are hydrated and have a higher thermal stability than the ligand. The products of thermal decomposition of the complexes are lanthanide oxides. In the aqueous phase, the metal combines with the ligand in a 1:1 molar ratio. Antioxidant activity tests showed that the complexes have a similar ability to remove free radicals. ABTS and DPPH tests showed that the complexes have twice the ability to neutralise radicals than the ligand, and a much higher ability to remove the hydroxyl radical. The abilities of the complexes and the free ligand to reduce Cu2+ ions in the CUPRAC test are at a similar level. Lanthanide complexes of p-coumaric acid are characterised by a higher antimicrobial capacity than the free ligand against Escherichia coli bacteria, Bacillus subtilis and Candida albicans fungi.

The infection of soil-borne diseases has the potential to modify root exudation and the rhizosphere microbiome. However, the extent to which these modifications occur in various monocropping histories remains inadequately explored. This study sampled healthy and diseased American ginseng (Panax quinquefolius L.) plants under 1–4 years of monocropping and analyzed the phenolic acids composition by HPLC, microbiome structure by high-throughput sequencing technique, and the abundance of pathogens by quantitative PCR. First, the fungal pathogens of Fusarium solani and Ilyonectria destructans in the rhizosphere soil were more abundant in the diseased plants than the healthy plants. The healthy American ginseng plants exudated more phenolic acid, especially p-coumaric acid, compared to the diseased plants after 1–2 years of monocropping, while this difference gradually diminished with the increase in monocropping years. The pathogen abundance was influenced by the exudation of phenolic acids, e.g., total phenolic acids (r = −0.455), p-coumaric acid (r = −0.465), and salicylic acid (r = −0.417), and the further in vitro test confirmed that increased concentration of p-coumaric acid inhibited the mycelial growth of the isolated pathogens for root rot. The healthy plants had a higher diversity of rhizosphere bacterial and fungal microbiome than the diseased plants only after a long period of monocropping. Our study has revealed that the cropping history of American ginseng has altered the effect of pathogens infection on rhizosphere microbiota and root exudation. [ABSTRACT FROM AUTHOR]

Honey bees (Apis mellifera L.; Hymenoptera, Apidae) are the most efficient pollinators in agroecosystems, responsible for the successful production of fruits, nuts, and vegetables, but they continue to face debilitating challenges. One of the major factors leading to these challenges could be linked to poor nutrition that results in weakening the colony, increasing susceptibility to pests and pathogens, and reducing the ability of bees to adapt to other abiotic stresses. Extensively used for commercial pollination, honey bee colonies regularly face exposure to limited diversity in their pollen diet as they are placed in flowering monocrops. Lack of access to diverse plant species compromises the availability of plant secondary compounds (phytochemicals), which, in small amounts, provide significant benefits to honey bee health. We analyzed the beneficial phytochemical content of honey and stored pollen (bee bread) samples from colonies in large apiaries through the active bee season. Samples were evaluated for 4 beneficial phytochemicals (caffeine, kaempferol, gallic acid, and p-coumaric acid), which have previously been shown to improve honey bee health. Our results, as relevant to the apiary locations in the study, indicated that p-coumaric acid is uniformly available throughout the season. Caffeine is completely absent, and gallic acid and kaempferol are not regularly available. Our results suggest the need to explore the potential to deliver beneficial phytochemicals as nutritional supplements to improve bee health. It may be vital for the pollination industry to consider such targeted dietary supplementation as beekeepers strive to meet the increasing demand for crop pollination services. [ABSTRACT FROM AUTHOR]

The aim of the research was to evaluate the influence of the ripening stage on the accumulation of polyphenols and antioxidant activity in fruits of Solanum species. The experiment included two factors: I—four different Solanum species (S. melanocerasum, S. nigrum, S. villosum, and S. retroflexum) and II—three ripening stages. High-performance liquid chromatography (HPLC) was used to analyze the individual phenolic compounds (flavonoids and phenolic acids), and the spectrophotometric method was applied to determine antioxidant activity. The results revealed that the accumulation of polyphenols and antioxidant activity in fruits of Solanum species depends on the stage of ripening and species. All studied Solanum species fruits had the highest content of total phenolic acid at ripening stage III and the greatest antioxidant activity at ripening stage I. Fully ripe fruits of S. melanocerasum contained significantly more total flavonoids, whereas S. nigrum contained significantly more total phenolic acids than other investigated Solanum species fruits. The significantly highest antioxidant activity was found in S. melanocerasum fruits at ripening stage I. [ABSTRACT FROM AUTHOR]

SUMMARY: Lignins and their antimicrobial‐related polymers cooperatively enhance plant resistance to pathogens. Several isoforms of 4‐coumarate‐coenzyme A ligases (4CLs) have been identified as indispensable enzymes involved in lignin and flavonoid biosynthetic pathways. However, their roles in plant–pathogen interaction are still poorly understood. This study uncovers the role of Gh4CL3 in cotton resistance to the vascular pathogen Verticillium dahliae. The cotton 4CL3‐CRISPR/Cas9 mutant (CR4cl) exhibited high susceptibility to V. dahliae. This susceptibility was most probably due to the reduction in the total lignin content and the biosynthesis of several phenolic metabolites, e.g., rutin, catechin, scopoletin glucoside, and chlorogenic acid, along with jasmonic acid (JA) attenuation. These changes were coupled with a significant reduction in 4CL activity toward p‐coumaric acid substrate, and it is likely that recombinant Gh4CL3 could specifically catalyze p‐coumaric acid to form p‐coumaroyl‐coenzyme A. Thus, overexpression of Gh4CL3 (OE4CL) showed increasing 4CL activity that augmented phenolic precursors, cinnamic, p‐coumaric, and sinapic acids, channeling into lignin and flavonoid biosyntheses and enhanced resistance to V. dahliae. Besides, Gh4CL3 overexpression activated JA signaling that instantly stimulated lignin deposition and metabolic flux in response to pathogen, which all established an efficient plant defense response system, and inhibited V. dahliae mycelium growth. Our results propose that Gh4CL3 acts as a positive regulator for cotton resistance against V. dahliae by promoting JA signaling‐mediated enhanced cell wall rigidity and metabolic flux. Significance Statement: This study uncovers the biological function of Gh4CL3 in cotton that helped to improve plant resistance against Verticillium dahliae. We believe that this study provides an important addition toward understanding the complex host–pathogen interaction. [ABSTRACT FROM AUTHOR]

It is well established that p-Hydroxycinnamic acids (HCAs), including ferulic, caffeic, sinapic, and p-coumaric acids, possess a characteristic phenylpropanoid C6-C3 backbone and account for about one-third of the phenolic compounds in our diet. HCAs are typically associated with various plant cell wall components, including mono-, di-, and polysaccharides, sterols, polyamines, glycoproteins, and lignins. Interestingly, enzymes produced by intestinal microbes liberate HCAs from these associations. HCAs are completely absorbed in their free form upon ingestion and undergo specific reactions upon absorption in the small intestine or liver. The gut epithelium, composed of intestinal epithelial cells (IECs), acts as a physical barrier against harmful bacteria and a site for regulated interactions between bacteria and the gut lumen. Thus, maintaining the integrity of the epithelial barrier is essential for establishing a physiochemical environment conducive to homeostasis. This review summarizes the protective effects of HCAs on the intestinal barrier, achieved through four mechanisms: preserving tight junction proteins (TJPs), modulating pro-inflammatory cytokines, exerting antioxidant activity, and regulating the intestinal microbiota. [ABSTRACT FROM AUTHOR]

Increasing air pollution is associated with serious human health problems. P‐coumaric acid (PC) is a herbal phenolic compound that exhibits beneficial pharmacological potentials. Here, the protective effect of PC on liver injury induced by air pollution was examined. Thirty‐two adult male Wistar rats (200‐250 g) were divided randomly into four groups (n = 8). The groups were; Control (rats received DMSO and then exposed to clean air), PC (rats received PC and then exposed to clean air), DMSO + Dust (rats received DMSO and then exposed to dust), and PC + Dust (the animals received PC and then exposed to dust). The clean air, DMSO, PC, and dust were administrated 3 days a week for 6 consecutive weeks. The rats were anesthetized and their blood samples and liver sections were taken to conduct molecular, biomedical, and histopathological tests. Dust exposure increased the liver enzymes, bilirubin, triglyceride, cholesterol, and the production of liver malondialdehyde, and decreased in liver total anti‐oxidant capacity and serum high‐density lipoprotein. It also increased the mRNA expression of inflammatory‐related cytokines, decreased the mRNA expression of SIRT‐1, decreased the expression levels of miR‐20b5p, and MEG3 while increased the expression levels of miR‐34a, and HOTAIR. Dust exposure also increased the liver content of three cytokines TNF‐α, NF‐κB, HMGB‐1, and ATG‐7 proteins. PC enhanced liver function against adverse effects of dust through recovering almost all the studied variables. Exposure to dust damaged the liver through induction of oxidative stress, inflammation, and autophagy. PC protected the liver against dust‐induced cytotoxicity. [ABSTRACT FROM AUTHOR]

Copyright of Shipin Kexue/ Food Science is the property of Food Science Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Mammalian erythrocyte is an ideal cell model to study free radical-induced injury since it is enucleated and has a short life span. Various factors can lead to the generation of reactive oxygen species (ROS) in erythrocytes. Evidence indicates that many physiological and pathological conditions develop due to ROS. Erythrocytes when exposed to free radical initiators (FRI) such as H2O2 and azobis (2-amidinopropane) dihydrochloride (AAPH) can result in oxidative stress (OS). Several antioxidants have been employed in various OS conditions to prevent cell damage. However, the alterations due to FRI and antioxidants in erythrocytes are still unclear. Therefore, an in vitro study was conducted using blood samples from male Wistar rats to investigate the influence of FRI and antioxidants such as caffeic acid and p-coumaric acid on erythrocytes. The samples were divided into controls (without FRI; n = 8) and experimentals (with FRI and antioxidants; n = 8). Erythrocyte suspension were assessed for hemoglobin (Hb) and hemolysis, and the hemolysates were analyzed for the following OS markers: SOD, Catalase, TBARS, SH, and AOPP. There were variations in certain OS markers in the experimental groups with respect to controls. Hb significantly decreased in CH group and AOPP significantly increased in CCA, CCO, CCOA, and CCAH groups. SOD and catalase elevated in CCAH and CCOH groups, respectively. TBARS, SH, and hemolysis were maintained in all the groups. The endogenous antioxidant system could scavenge the ROS and protect the erythrocytes from oxidative damage. Azo compounds (AAPH) generate more free radicals when compared to H2O2. OS was minimal in experimental groups as exogenous antioxidants augmented the endogenous antioxidants, however, p-coumaric acid was more efficient than caffeic acid. Hence, these antioxidants can be further employed in similar OS situations. [ABSTRACT FROM AUTHOR]

Objective(s): Studies show that chronic injuries like air pollution or acute damage such as hepatic ischemia-reperfusion (IR) cause various cellular pathologies such as oxidative stress, apoptosis, autophagy, and inflammation in hepatocytes. p-Coumaric acid (p-CA) is known as an antioxidant with many therapeutic impacts on inflammatory-related pathologies. In this experiment, we aimed to assess the hepatoprotective effects of p-CA on liver damage induced by dust and IR injury in adult male rats. Materials and Methods: Forty-eight adult male Wistar rats were divided into 6 groups; Control (CTRL); sham; DMSO+Dust+Laparotomy (LPT); DMSO+Dust+Ischemia-reperfusion (IR); p-CA+Dust+LPT; and p-CA+Dust+IR. Clean air, DMSO, p-CA, and dust were administrated 3 days a week for 6 consecutive weeks. Animals were sacrificed, the blood samples were aspirated and the liver sections were prepared for biochemical and histopathological assessments. Results: Significantly (P

Seerat Mehdi,1 Fiaz-ud-Din Ahmad,1 Arslan Hussain Lodhi,1 Umair Khurshid,2 Ahmed Awais Khalid,1 Sheikh Safeena Sidiq,1 Liaqat Hussain,3 Mirza Shaharyar Baig1 1Department of Pharmacology, Faculty of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, Pakistan; 2Department of Pharmaceutical Chemistry, Faculty of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, Pakistan; 3Department of Pharmacology, Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Faisalabad, PakistanCorrespondence: Fiaz-ud-Din Ahmad, Department of Pharmacology, Faculty of Pharmacy, The Islamia University of Bahawalpur, Khawaja Fareed Campus, Railway Road, Bahawalpur, 63100, Pakistan, Tel +92-320-8402376, Email fiaz.ahmad@iub.edu.pkAim: Liver regulates metabolism of biomolecules and injury of liver causes distortion of metabolic functions. This injury may be oxidative or inflammatory induced by numerous factors including alcohol, pathogens and xenobiotics. This scientific study was planned to investigate the anti-inflammatory and anti-oxidant potential of p-coumaric acid (p-CA) on Lipopolysaccharide/D-Galactosamine (LPS/D-GalN) induced liver injury.Methods: DPPH analysis, reducing power assay and HPLC analysis were performed during in-vitro studies of p-CA. Similarly, in-vivo experiments were performed using Wistar Albino rats. Normal control and intoxicated group received (5mL/kg normal saline p.o), standard treatment groups received ascorbic acid (100mg/kg p.o) and silymarin (25mg/kg p.o), while p-CA treatment groups received (100mg/kg p.o) for 28-days. After completion of 28-days, LPS/D-GalN injection (300 mg D-GalN/kg and 10 μg LPS/kg i.p.) was given at 6th, 12th and 24-hours to all groups except normal control group. Animals were sacrificed; serum and liver samples were harvested and subjected to biochemical and histological examinations, respectively.Results: The results revealed that p-CA possess strong antioxidant activity. Increased levels of leukocyte infiltration (TLC), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin (TBIL), lipid panel (eg TG, TC, LDL-C, VLDL-C), whereas decreased HDL-C levels noticed in LPS/D-GalN groups as compared to normal control groups. Pro-Inflammatory markers (eg TNF-α, IL-6, IL-1β) and lipid peroxidation marker, eg malondialdehyde (MDA) increased while superoxide dismutase (SOD) and reduced glutathione (GSH) levels were decreased significantly in groups treated with LPS/D-GalN. ANOVA with Bonferroni post hoc analysis was used for statistical analysis of. H&E staining was done to assess architectural abnormalities among liver cells.Conclusion: In conclusion, p-CA could ameliorate LPS/D-GalN induced hepatic injury via regulation of immune responses, liver function enzymes, lipid profile, oxidative stress and pro-inflammatory markers.Keywords: p-coumaric acid, lipopolysaccharide, D-galactosamine, oxidative stress, inflammation

The phenolic acids, ferulic acid and p-coumaric acid, are components of plant cell walls in grasses, including many of our major food crops. They have important health-promoting properties in grain, and influence the digestibility of biomass for industrial processing and livestock feed. Both phenolic acids are assumed to be critical to cell wall integrity and ferulic acid, at least, is important for cross-linking cell wall components, but the role of p-coumaric acid is unclear. Here we identify alleles of a BAHD p-coumaroyl arabinoxylan transferase, HvAT10, as responsible for the natural variation in cell wallesterified phenolic acids in whole grain within a cultivated two-row spring barley panel. We show that HvAT10 is rendered non-functional by a premature stop codon mutation in half of the genotypes in our mapping panel. This results in a dramatic reduction in grain cell wall-esterifed p-coumaric acid, a moderate rise in ferulic acid, and a clear increase in the ferulic acid to p-coumaric acid ratio. The mutation is virtually absent in wild and landrace germplasm suggesting an important function for grain arabinoxylan p-coumaroylation pre-domestication that is dispensable in modern agriculture. Intriguingly, we detected detrimental impacts of the mutated locus on grain quality traits where it was associated with smaller grain and poorer malting properties. HvAT10 could be a focus for improving grain quality for malting or phenolic acid content in wholegrain foods. [ABSTRACT FROM AUTHOR]

Feruloyl esterases (FAEs) hydrolyze the ester bonds between hydroxycinnamic acids and arabinose residues of plant cell walls and exhibit considerable diversity in terms of substrate specificity. Here, we report the crystal structure of an FAE from Fusarium oxysporum (FoFaeC) at 1.7 Å resolution in complex with p‐coumaric acid, which is the first ligand‐bound structure of a tannase‐like FAE. Our data reveal local conformational changes around the active site upon ligand binding, suggesting alternation between an active and a resting state of the enzyme. A swinging tyrosine residue appears to be gating the substrate binding pocket, while the lid domain of the protein exerts substrate specificity by means of a well‐defined hydrophobic core that encases the phenyl moiety of the substrate. [ABSTRACT FROM AUTHOR]

Decellularized liver‐derived extracellular matrix is a unique combination of a complex milieu of growth factors and proteins that stimulate biochemical, physical, and mechanical cues to the cells. However, the lack of mechanical strength hindering the applicability of extracellular matrix (ECM) is an outstanding challenge. Herein, to deal with this problem, decellularized kelp is introduced as a crosslinking material thereby strengthening the physical structure of ECM for its utilization as a wound‐healing material. Consequently, a significant architectural change is observed in the ECM by forming a solid‐shaped scaffold. Nevertheless, the hindrance of high pH is addressed by incorporating the acidic drug p‐coumaric acid. To evaluate the innate regenerative abilities, the scaffolds are applied to rat excisional wounds. A remarkable wound healing capability is demonstrated by both the EK scaffolds, but a faster regeneration is achieved with only EK‐20@cou. The speculated hypothesis is that the incorporation of p‐coumaric acid can offer many additional bioactive benefits to the scaffold such as remarkable biocompatibility, antioxidant, and anti‐bacterial properties that are deliberately supported by the in vitro results. In silico molecular simulations (MS) validated that p‐Cou released from the EK‐20@Cou scaffold is accountable for the observed extraordinary regenerative behavior as compared to EK‐20(PW). [ABSTRACT FROM AUTHOR]

Introduction and aim. Stored erythrocytes develop lesions involving changes in their structure and function reducing their efficacy. Oxidative Stress (OS) being one of the main causes of storage lesion, can be attenuated by antioxidants as additives in the storage solution. This study aims to evaluate the effect of p-Coumaric acid (CA) on erythrocytes during whole blood storage. Material and methods. Blood collected from Male Wistar rats was stored at 4°C in CPDA-1 solution for 21 days. Blood samples were stored with and without 1mM CA (CA 1) and 10 mM CA (CA 10). The erythrocytes were isolated every week during storage and the biomarkers for OS and antioxidant status were analysed. Results. Superoxide dismutase and catalase elevated on day 14. Conjugate dienes decreased in CA 10 on day 14. Thiobarbituric acid reactive substances increased on day 7 and decreased on day 14 in CA groups. Protein sulfhydryls decreased in controls and CA 1 on day 14 whereas, it was maintained in CA 10. Conclusion. Coumaric acid upregulated the antioxidant enzymes and protected the cells from oxidative damage. Thus, coumaric acid can be employed as a potent additive during storage and opens new avenues of employing it in similar OS situations in erythrocytes. [ABSTRACT FROM AUTHOR]

Copyright of Journal of South-Central Minzu University (Natural Science Edition) is the property of Journal of South-Central Minzu University (Natural Science Edition) Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

This study aimed to investigate the effects of levodopa (L-dopa), p-coumaric acid, and combinations in the neuroblastoma (N1E-115) cell. L-dopa and L-dopa plus p-coumaric acid group caused oxidative stress by increasing 12.5 and 3.7-fold in superoxide dismutase gene, 11.5 and 4.8-fold increase in catalase gene, respectively. In L-dopa and L-dopa plus p-coumaric acid application, p21 gene expression increased 1.3-fold and 3.2-fold, and the cell cycle stopped in the G1 phase in response to stress in the treatment groups. In the application of L-dopa plus p-coumaric acid to N1E-115 cells, the BCL-2 gene, which is an apoptosis inhibitor, was suppressed and the BAX gene increased 13-fold compared to the control. As a result, it was determined that the cytotoxic effect of L-dopa plus p-coumaric acid application was less than the individual application of the substances, and p-coumaric acid had an inhibitory effect on L-dopa-induced stress.

In situ poloxamer-based gels are increasingly being explored as ocular drug delivery carriers to extend the release of active substances, thereby enhancing bioavailability. The objective of this study was to develop thermally stable in situ gels incorporating balsam poplar bud extract, propolis extract, and p-coumaric acid solution and to evaluate the physicochemical parameters of these gelified eye drops. This research assessed the compatibility of poloxamer-based eye drops with active components, their physicochemical properties, stability post-sterilization and during storage, and the release profiles of the active compounds. Fifteen eye drop formulations were prepared and categorized into three groups based on active components. One of the active components was propolis extract. As an alternative to propolis, eye drops containing the plant precursor, balsam poplar bud extract, were developed. The third group’s active component was p-coumaric acid, a dominant phenolic acid in propolis and balsam poplar bud extracts. The study reported phenolic contents of 76.63 CAE mg/g for propolis and 83.25 CAE mg/g for balsam poplar bud aqueous extracts, with balsam poplar bud extracts showing higher SPF values (14.0) compared to propolis (12.7), while p-coumaric acid solution exhibited the highest SPF values (25.5). All eye drops were transparent, with pH values meeting the requirements for ocular drops. Formulations containing 8–10% poloxamer 407 met the criteria for in situ gels. All formulations remained stable for 90 days. Conclusion: The study results indicate that the formulated gels possess suitable physicochemical properties, are resistant to applied autoclaving conditions, and exhibit an extended release of active compounds with an increase in poloxamer content.

Abstract The aromatic compound p-coumaric acid (p-CA) is a secondary metabolite produced by plants. This aromatic acid and derived compounds have positive effects on human health, so there is interest in producing them in biotechnological processes with recombinant Escherichia coli strains. To determine the physiologic response of E. coli W3110 to p-CA, dynamic expression analysis of selected genes fused to a fluorescent protein reporter as well as RNA-seq and RT-qPCR were performed. The observed transcriptional profile revealed the induction of genes involved in functions related to p-CA active export, synthesis of cell wall and membrane components, synthesis of amino acids, detoxification of formaldehyde, phosphate limitation, acid stress, protein folding and degradation. Downregulation of genes encoding proteins involved in energy production, carbohydrate import and metabolism, as well as several outer and plasma membrane proteins was detected. This response is indicative of cell envelope damage causing the leakage of intracellular components including amino acids and phosphate-containing compounds. The cellular functions responding to p-CA that were identified in this study will help in defining targets for production strains improvement.

BackgroundSwitchgrass (Panicum virgatum L.) is a promising bioenergy feedstock because it can be grown on marginal land and produces abundant biomass. Recalcitrance of the lignocellulosic components of the switchgrass cell wall to enzymatic degradation into simple sugars impedes efficient biofuel production. We previously demonstrated that overexpression of OsAT10, a BAHD acyltransferase gene, enhances saccharification efficiency in rice.ResultsHere we show that overexpression of the rice OsAT10 gene in switchgrass decreased the levels of cell wall-bound ferulic acid (FA) in green leaf tissues and to a lesser extent in senesced tissues, and significantly increased levels of cell wall-bound p-coumaric acid (p-CA) in green leaves but decreased its level in senesced tissues of the T0 plants under greenhouse conditions. The engineered switchgrass lines exhibit an approximate 40% increase in saccharification efficiency in green tissues and a 30% increase in senesced tissues.ConclusionOur study demonstrates that overexpression of OsAT10, a rice BAHD acyltransferase gene, enhances saccharification of lignocellulosic biomass in switchgrass.

The phenolic acids, ferulic acid and p-coumaric acid, are components of plant cell walls in grasses, including many of our major food crops. They have important health-promoting properties in grain, and influence the digestibility of biomass for industrial processing and livestock feed. Both phenolic acids are assumed to be critical to cell wall integrity and ferulic acid, at least, is important for cross-linking cell wall components, but the role of p-coumaric acid is unclear. Here we identify alleles of a BAHD p-coumaroyl arabinoxylan transferase, HvAT10, as responsible for the natural variation in cell wall-esterified phenolic acids in whole grain within a cultivated two-row spring barley panel. We show that HvAT10 is rendered non-functional by a premature stop codon mutation in half of the genotypes in our mapping panel. This results in a dramatic reduction in grain cell wall-esterifed p-coumaric acid, a moderate rise in ferulic acid, and a clear increase in the ferulic acid to p-coumaric acid ratio. The mutation is virtually absent in wild and landrace germplasm suggesting an important function for grain arabinoxylan p-coumaroylation pre-domestication that is dispensable in modern agriculture. Intriguingly, we detected detrimental impacts of the mutated locus on grain quality traits where it was associated with smaller grain and poorer malting properties. HvAT10 could be a focus for improving grain quality for malting or phenolic acid content in wholegrain foods.

Agro-industrial by-products are a sustainable source of natural additives that can replace the synthetic ones in the food industry. Grape pomace is an abundant by-product that contains about 70% of the grape's polyphenols. Polyphenols are natural antioxidants with multiple health-promoting properties. They are secondary plant metabolites with a wide range of solubilities. Here, a novel extraction process of these compounds was developed using enzymes that specifically liberates target polyphenols in the appropriate hydroalcoholic mixture. Tannase, cellulase, and pectinase retained 22, 60, and 52% of their activity, respectively, in ethanol 30% v/v. Therefore, extractions were tested in ethanol concentrations between 0 and 30% v/v. Some of these enzymes presented synergistic effects in the extraction of specific polyphenols. Maximum yield of gallic acid was obtained using tannase and pectinase enzymes in ethanol 10% v/v (49.56 ± 0.01 mg L−1 h−1); in the case of p-coumaric acid, by cellulase and pectinase treatment in ethanol 30% v/v (7.72 ± 0.26 mg L−1 h−1), and in the case of trans-resveratrol, by pectinase treatment in ethanol 30% v/v (0.98 ± 0.04 mg L−1 h−1). Also, the effect of enzymes and solvent polarity was analysed for the extraction of malvidin-3-O-glucoside, syringic acid, and quercetin. Previous studies were mainly focused on the maximization of total polyphenols extraction yields, being the polyphenolic profile the consequence but not the driving force of the optimization. In the present study, the basis of a platform for a precise extraction of the desire polyphenols is provided. Key points: • Enzymes can be used up to ethanol 30% v/v. • The specific enzymes' action determines the polyphenolic profile of the extracts. • The yields obtained of target polyphenols are competitive. [ABSTRACT FROM AUTHOR]

Objective(s): Studies show that chronic injuries like air pollution or acute damage such as hepatic ischemia-reperfusion (IR) cause various cellular pathologies such as oxidative stress, apoptosis, autophagy, and inflammation in hepatocytes. p-Coumaric acid (p-CA) is known as an antioxidant with many therapeutic impacts on inflammatory-related pathologies. In this experiment, we aimed to assess the hepatoprotective effects of p-CA on liver damage induced by dust and IR injury in adult male rats. Materials and Methods: Forty-eight adult male Wistar rats were divided into 6 groups; Control (CTRL); sham; DMSO+Dust+Laparotomy (LPT); DMSO+Dust+Ischemia-reperfusion (IR); p-CA+Dust+LPT; and p-CA+Dust+IR. Clean air, DMSO, p-CA, and dust were administrated 3 days a week for 6 consecutive weeks. Animals were sacrificed, the blood samples were aspirated and the liver sections were prepared for biochemical and histopathological assessments. Results: Significantly (P<0.05), the results represented that dust and IR can potentially increase the levels of ALT, AST, direct and total bilirubin, triglyceride, and cholesterol in serum. Also, MDA, TNF-α, NF-κB, HMGB-1, and ATG-7 levels were increased in hepatocytes. Gene expression of Nrf2, HOX-1, IL-6, HOTAIR, and miR-34a showed an incremental trend in the liver tissue. Total antioxidant capacity (TAC) in hepatocytes was decreased following dust exposure and IR induction. Also, miR-20b-5p, MEG3, and SIRT1 in the liver were decreased in dust and dust+IR groups. Conclusion: p-CA alleviated pathological changes caused by dust exposure and IR injury. p-CA protected hepatic injury induced by dust and IR by inhibition of oxidative injury, inflammation, and autophagy. [ABSTRACT FROM AUTHOR]

Ferulic acid (FA) and p-coumaric acid (pCA) in bagasse, wheat straw, corn straw, and corncob were extracted by alkaline hydrolysis and characterized by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). It was found that the FA and most of the pCA in gramineous biomass could be dissociated and released after being treated with 1 M NaOH at 100°C for 4 h. The yields of pCA/FA in bagasse, wheat straw, corn straw, and corncob determined by GC-FID are 39.8/11.5, 13.7/11.0, 28.0/11.0, and 35.1/14.5 mg/g, respectively. The raw materials and the treated solid residues were characterized by gel-state 2D Heteronuclear Single Quantum Coherence Nuclear Magnetic Resonance (2D HSQC NMR). It was found that only a small amount of lignin was detected in the residue after alkali treatment, indicating that the alkali treatment conditions can effectively cleave the FA and pCA. Additionally, the lignin in the alkali solution was recovered and characterized by 2D HSQC NMR. The FA was not able to be detected by NMR, whereas a small amount of pCA remained in the alkali lignin. This study reveals the structural change of residual lignins during the quantitative isolation of FA and pCA, which is essential for the selective isolation of pCA/FA and valorization of residual alkali lignin. [ABSTRACT FROM AUTHOR]

In monocropping systems autotoxins, such as phenolic compounds, could accumulate in soil and affects the soil microbial communities, however, the specific effects on microbial species are unknown. We determined the responses of cucumber rhizosphere Fusarium and Bacillus spp. communities to exogenously applied p-coumaric acid (0.02, 0.05, 0.1, 0.2 μmol/g soil) by polymerase chain reaction denaturing gradient gel electrophoresis (PCR-DGGE) technique. Results showed that all concentrations of p-coumaric acid changed the community structure of Fusarium spp. and p-coumaric acid at 0.2 μmol/g soil decreased the number of bands as indicated by Shannon-Wiener and evenness index of Fusarium spp. community. However, p-coumaric acid did not affect the structure of Bacillus spp. community. These results indicated that the p-coumaric acid showed different effects on Fusarium and Bacillus spp. communities. [ABSTRACT FROM AUTHOR]

The paper examines the use of natural antioxidant and anti-inflammation substances as therapeutic candidates for brain disease. Para-coumaric acid (pCA), a phenolic compound with a variety of medicinal properties, was used against deterioration caused by various diseases. Recently, pCA has gained attention for use against cardiovascular disease but less so for neurodegenerative disease (i.e., Parkinson's disease). Therefore, the present study intended to investigate the effect of pCA against rotenone-induced Parkinson's disease-like pathology in mice. Thirty male institute of cancer research (ICR) mice were randomly divided into three experimental groups: Sham-veh, Rot-veh, and Rot-pCA100. Rotenone (Rot) 2.5 mg/kg was subcutaneously injected every 48 h in the rotenone groups. Alternately, a 100 mg/kg pCA dose was given every 48 h via intragastric gavage to the Rot-pCA100 group for 6 weeks. Motor ability was assessed at the second, fourth, and sixth week before brain collection for biochemical and histological analyses. Results indicated significant motor deficits appeared from the second to sixth week after rotenone injection. Brain analysis detected a significant effect of rotenone in the increase of malondialdehyde and tumor necrosis factor-alpha (TNF-α). This result was observed in accordance with a reduction of tyrosine hydroxylase (TH) and an increase of neuronal degeneration in the substantia nigra par compacta (SNc) and striatum. However, pCA was able to reverse all of the deterioration (i.e., reduced malondialdehyde and TNF-α) rotenone had caused, and it protected against TH and neuronal loss in the SNc and striatum. Therefore, the present study has depicted the neuroprotective effect of pCA against rotenone-induced Parkinson's disease-like pathology in mice. Benefits of pCA include anti-lipid peroxidation and anti-inflammatory effects, inhibition of neurodegeneration, and a nurturing effect on the TH level in the SNc and striatum, leading to mitigation of motor deficits. [ABSTRACT FROM AUTHOR]

In this study, the antibacterial effects of para-coumaric acid (PCA), as an intermediate product in the phenylpropanoid biosynthesis pathway, on the virulence of Aeromonas hydrophila in both in vivo and in vitro conditions were assayed. First, the minimum inhibitory concentration (MIC) of PCA against A. hydrophila was determined. The existence of ascV and aopB virulence genes as essential components of the Type III secretion system (T3SS) of A. hydrophila was determined using RT-PCR analysis. Then, the effect of sub-MIC concentrations of PCA on the expression of ascV and aopB genes of bacteria was investigated using qRT-PCR. In the in vivo phase of the study, 135 juvenile common carp (weighing 30.2 ± 4.53 g) were equally divided into three groups in triplicates. Group 1 was fed with un-supplemented food, whereas groups 2 and 3 were fed with food supplemented with PCA or oxytetracycline (OTC), respectively, for 5 days. Following that, all groups were challenged with A. hydrophila, and mortality rates, the presence of A. hydrophila in surviving fish, and the expression of the ascV and aopB genes in the fish head kidney were assessed. Our results revealed that the expression of ascV and aopB genes was significantly suppressed after exposure to sub-MICs of PCA compared to control in both in vivo and in vitro assays (p < 0.05). Although the PCA-treated group showed higher mortality (= 36.7%) compared to the OTC group following bacterial challenge (= 23.3%), the expression of ascV and aopB genes in isolated bacteria in the PCA group was significantly lower than that in the OTC and control groups (p < 0.05). This is the first report of the in vitro and in vivo effects of PCA on decreasing the virulence properties of A. hydrophila in fish. It can be concluded that PCA has an inhibitory effect on the virulence and pathogenicity of A. hydrophila and may be effective in the control of Aeromonas infections in fish farms. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease and has become a growing public health concern worldwide. Polyphenols may improve high-fat diet (HFD)-related NAFLD. Our previous study found that ferulic acid (FA) and p-coumaric acid (p-CA) were the polyphenols with the highest content in foxtail millet. In this study, we investigated the mechanism underlying the impact of ferulic acid and p-coumaric acid (FA/p-CA) on non-alcoholic fatty liver (NAFLD). The association of FA and p-CA with fatty liver was first analyzed by network pharmacology. Synergistic ameliorating of NAFLD by FA and p-CA was verified in oleic acid (OA) and palmitic acid (PA) (FFA)-treated hepatocytes. Meanwhile, FA/p-CA suppressed final body weight and TG content and improved liver dysfunction in HFD-induced NAFLD mice. Mechanistically, our data indicated that FA and p-CA bind to histone deacetylase 1 (HDAC1) to inhibit its expression. The results showed that peroxisome proliferator activated receptor gamma (PPARG), which is positively related to HDAC1, was inhibited by FA/p-CA, and further suppressed fatty acid binding protein (FABP) and fatty acid translocase (CD36). It suggests that FA/p-CA ameliorate NAFLD by inhibiting free fatty acid uptake via the HDAC1/PPARG axis, which may provide potential dietary supplements and drugs for prevention of NAFLD. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effect of p-coumaric acid (p-CA) on haloperidol-induced catalepsy in Swiss albino male mice. Methods: To induce catalepsy, haloperidol (1 mg/kg i.p.) was administered for 21 consecutive days. p-CA (50, 75, and 100 mg/kg, PO) was administered 30 min before haloperidol injection for 21 consecutive days. For catalepsy, locomotor activity and motor coordination scores were recorded on the 17, 14, and 21 days of drug treatment, while the gait analysis score was recorded on day 21. After behavioral testing, animals were sacrificed, and various biochemical and histopathology tests of the brain were conducted. Dopamine, malondialdehyde, reduced glutathione (GSH), superoxide dismutase (SOD), and catalase activity were examined in the brain. Results: Chronic administration of haloperidol significantly increased catalepsy in mice. It also produced hypolocomotion, motor coordination, and gait disturbance in mice. p-CA significantly inhibited haloperidol-induced catalepsy. Haloperidol significantly increased malondialdehyde levels in the brain. While dopamine levels in the brain dropped along with GSH, SOD, and catalase activity levels, which also had an impact on the histology of the brain. p-CA significantly reduced haloperidol-induced increases in brain oxidative stress, dopamine levels in the brain, and brain histology in mice. Discussion: p-CA significantly reduced haloperidol-induced catalepsy, possibly through reducing oxidative stress and increasing brain dopamine levels. It can be a good candidate drug for extrapyramidal symptoms in Parkinson's disease and adjuvant therapy with antipsychotic drugs. [ABSTRACT FROM AUTHOR]

Abstract Background Aromatic compounds, such as p-coumaric acid (p-CA) and caffeic acid, are secondary metabolites of various plants, and are widely used in diet and industry for their biological activities. In addition to expensive and unsustainable methods of plant extraction and chemical synthesis, the strategy for heterologous synthesis of aromatic compounds in microorganisms has received much attention. As the most abundant renewable resource in the world, lignocellulose is an economical and environmentally friendly alternative to edible, high-cost carbon sources such as glucose. Results In the present study, carboxymethyl-cellulose (CMC) was utilized as the sole carbon source, and a metabolically engineered Saccharomyces cerevisiae strain SK10-3 was co-cultured with other recombinant S. cerevisiae strains to achieve the bioconversion of value-added products from CMC. By optimizing the inoculation ratio, interval time, and carbon source content, the final titer of p-CA in 30 g/L CMC medium was increased to 71.71 mg/L, which was 155.9-fold higher than that achieved in mono-culture. The de novo biosynthesis of caffeic acid in the CMC medium was also achieved through a three-strain co-cultivation. Caffeic acid production was up to 16.91 mg/L after optimizing the inoculation ratio of these strains. Conclusion De novo biosynthesis of p-CA and caffeic acid from lignocellulose through a co-cultivation strategy was achieved for the first time. This study provides favorable support for the biosynthesis of more high value-added products from economical substrates. In addition, the multi-strain co-culture strategy can effectively improve the final titer of the target products, which has high application potential in the field of industrial production.

Abstract Response surface methodology (RSM) was used to optimize the degree of esterification of p-coumaric acid to triolein via lipase-catalyzed acidolysis, and enzyme load, reaction time and mole ratio of substrates were selected as variables in the experimental design. The results showed that the model employed was highly sufficient for determining the effectiveness and interaction of three selected variables, enzyme load, reaction time and the mole ratio of substrates, on the dependent variable, the degree of esterification. Although the optimization point was not found in the selected range of the three variables, the steepest ascent analysis suggested that an increase of these three variables might lead to a stationary point. However, based on the limitations on increasing the range of tested variables, including possible oxidation of synthesized lipids and increased cost, the degree of esterification so yielded in the designed central composite design should be the one closest to the possible ideal optimized degree. The p-coumarates so produced exhibited varying antioxidant performance in the tested muscle food model, which could be explained by their different lipophilicity. Moreover, the potential health benefits of synthesized phenolic lipids have been discussed. Graphical Abstract

This study assessed the i n vitro anthelmintic activity of ethyl acetate extract (Cn-EtOAc) and its bioactive fractions (CnR3 and CnR5) obtained from Chamaecrista nictitans aerial parts against two Haemonchus contortus (Hc) isolates, one resistant (strain Hc IVM-R) and another susceptible (strain Hc IVM-S) to ivermectin. Ferulic acid and p -coumaric acid were identified in the bioactive fractions; therefore, their commercial standards were also assessed. A colocalization analysis between the ferulic acid commercial standard and eggs of the Hc IVM-R strain was performed using confocal laser scanning microscopy and the ImageJ program. The ovicidal effects of the Cn-EtOAc extract, bioactive fractions and commercial compounds were tested through the egg hatching inhibition (EHI) assay on H. contortus isolates Hc IVM-R and Hc IVM-S. The Cn-EtOAc caused 88 % and 92 % EHI at 5000 µg/mL on Hc IVM-R and Hc IVM-S, respectively. Fractions CnR3 and CnR5 displayed the highest ovicidal activity against Hc IVM-S, with effective concentrations (EC 90) of 2134 and 601 µg/mL, respectively. Meanwhile, the commercial standards ferulic acid and p -coumaric acid also resulted in higher effectiveness on the same strain, with EC 90 of 57.5 and 51.1 µg/mL. A colocalization analysis of ferulic acid and eggs of Hc IVM-R revealed that this compound is localized to the cuticle surface of the embryo inside the egg parasite. The results demonstrated that both ferulic and p -coumaric acids interrupt the egg-hatching processes of the two Hc isolates. Both phenolic acids isolated from C. nictitans and commercial standards exhibited the best anthelmintic effect on Hc IVM-S. These findings indicate that the phenolic acids were less effective in egg hatch inhibiting on the Hc IVM-R strain compared to the Hc IVM-S strain. [Display omitted] [ABSTRACT FROM AUTHOR]

• Solubility measurements for three cinnamic acid derivatives in Deep Eutectic Solvents. • Density and viscosity measurements of ChCl:1,2 butanediol (1:4) and ChCl:1,4 butanediol (1:4). • ChCl:1,4 butanediol (1:4) and ChCl:1,2 butanediol (1:4) exhibit the highest solvation capacity. • Dissolution process is endothermic and not spontaneous for all systems studied. • UNIQUAC and NRTL activity coefficient models successfully correlate the experimental solubility data. This work presents experimental solubility measurements for three cinnamic acid derivatives (CADs) namely caffeic acid (CA), p-coumaric acid (p-CA) and ferulic acid (FA) in three Deep Eutectic Solvents (DESs), choline chloride-1,2 butanediol (ChCl:1,2 butanediol (1:4)), choline chloride-1,4 butanediol (ChCl:1,4 butanediol (1:4)) and choline chloride-acetic acid (ChCl:Acetic Acid (1:2)). All measurements were performed in the temperature range of 293.15 to 323.15 K and at atmospheric pressure. Density and viscosity measurements of pure DESs ChCl:1,2 butanediol (1:4) and ChCl:1,4 butanediol (1:4) are also reported. ChCl:1,4 butanediol (1:4) and ChCl:1,2 butanediol (1:4) reveals the highest solvation capacity for CADs among the examined solvents, while p-CA was found to be less soluble than CA and FA in all solvents. Thermodynamic functions of dissolution were also determined using the Van't Hoff equation and the results imply that the process is endothermic for all systems studied. Finally, UNIQUAC and NRTL activity coefficient models were satisfactorily implemented to correlate the experimental solubilities. [ABSTRACT FROM AUTHOR]

The study aimed to develop a novel, transparent and non-toxic coating with antimicrobial, antioxidant, and antifogging properties. The p -coumaric acid-grafted chitosan (CS-PCA) was synthesized via a carbodiimide coupling reaction and then characterized. The CS-PCA coatings were further prepared using the casting method. The CS-PCA coatings obtained exhibited excellent transparency, UV-light barrier ability, and antifogging properties, as confirmed by spectroscopy and antifogging tests. The CS-PCA coatings showed stronger antioxidant capacity and antimicrobial properties against Escherichia coli , Staphylococcus aureus and Botrytis cinerea compared to CS. The multifunctional coatings were further coated on the polyethylene cling film and their effectiveness was confirmed through a strawberry preservation test. The decay of the strawberries was reduced by CS-PCA coated film at room temperature. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • p-Coumaric acid ameliorated post-traumatic spatial cognitive decline in rats. • p-Coumaric acid mitigated TBI-induced hippocampal LTP impairment in rats. • p-Coumaric acid modulated oxidative-antioxidative status in TBI rats. • p-Coumaric acid prevented TBI-induced neuronal loss in rats. This study investigated the efficacy of p-coumaric acid (p-CA), a natural phenolic compound, on traumatic brain injury (TBI)-induced spatial cognitive deficits and the possible involved mechanisms. Rats received p-CA (100 mg/kg, orally) 30 min after diffuse TBI induction. Spatial memory, neuroplasticity, oxidative stress, and histological alterations were evaluated at scheduled time points. TBI reduced spatial memory capacity on days 1, 3, and 7 in the water-maze task, which was associated with suppressed hippocampal long-term potentiation (LTP) at the perforant path-dentate gyrus (PP-DG) synapses. These deficits were accompanied by the inhibition of the activities of antioxidant enzymes and the promotion of lipid peroxidation in the hippocampal and cerebral cortex areas. Moreover, TBI resulted in neuronal loss in the DG. Interestingly, p-CA treatment ameliorated all the above-mentioned TBI outcomes. The findings demonstrate that p-CA alleviates TBI-induced spatial cognitive impairment, possibly by mitigating hippocampal synaptic dysfunction, modulating oxidative-antioxidative status, and preventing neuronal loss. [ABSTRACT FROM AUTHOR]

PHBV films incorporating 3, 6 and 9% ferulic acid (FA) or p-coumaric acid (PCA) were obtained by melt blending and compression moulding. The films’ microstructures and thermal behaviours were analysed as well as their mechanical, optical and barrier properties. The overall and specific migration of the materials in different food simulants was also characterised. FA was homogeneously mixed with the polymer, whereas PCA was mainly dispersed as fine particles in the PHBV matrices due to its higher melting point. These structural features promoted differences in the physical properties of the films depending on the compound concentration. As the concentration of both compounds rose, the barrier capacity of the films to oxygen, and to a lesser extent water vapour, was enhanced. While FA promoted the extensibility of the films, 9% PCA enhanced their brittleness. Both compounds affected the crystallisation pattern of the polymer, promoting smaller crystalline formations and a slight decrease in crystallinity. Although the overall migration of every film formulation was lower than the overall migration limit (OML), the release of active compounds was dependent on the food simulant; almost total release was noted in ethanol containing simulants but was more limited in aqueous systems. Therefore, these films could be used as food contact materials, contributing to extending the food’s shelf life.

The popping expansion is a characteristic that is positively related with the quality of popcorn. A positive correlation between the volume of expansion and the thickness of the pericarp, and between the proportion of the opaque/shiny endosperm and the grain weight and volume, were postulated. However, there are no reports in the literature that address the importance of cell wall components in the popping expansion. Here, we investigate the biochemical composition of the pericarp cell walls of three inbred lines of popcorn with different popping expansion. Inbred lines GP12 (expansion volume >40 mL g−1), P11 (expansion volume 30 mL g−1) and P16 (expansion volume 14 mL g−1) were used for the analysis and quantification of monosaccharides by HPAEC-PAD, and ferulic and p-coumaric acids and lignin by HPLC. Our hypothesis is that the biochemical composition of the pericarp cell walls may be related to greater or lesser popping expansion. Our data suggest that the lignin content and composition contribute to popping expansion. The highest concentration of lignin (129.74 μg mg−1; 12.97%) was detected in the pericarp cell wall of the GP12 inbred line with extremely high popping expansion, and the lowest concentration (113.52 μg mg−1; 11.35%) was observed in the P16 inbred line with low popping expansion. These findings may contribute to indicating the quantitative trait locus for breeding programs and to developing other methods to improve the popping expansion of popcorn.

Abstract Background Phenylpropanoids represent a diverse class of industrially important secondary metabolites, synthesized in plants from phenylalanine and tyrosine. Cyanobacteria have a great potential for sustainable production of phenylpropanoids directly from CO2, due to their photosynthetic lifestyle with a fast growth compared to plants and the ease of generating genetically engineered strains. This study focuses on photosynthetic production of the starting compounds of the phenylpropanoid pathway, trans-cinnamic acid and p-coumaric acid, in the unicellular cyanobacterium Synechocystis sp. PCC 6803 (Synechocystis). Results A selected set of phenylalanine ammonia lyase (PAL) enzymes from different organisms was overexpressed in Synechocystis, and the productivities of the resulting strains compared. To further improve the titer of target compounds, we evaluated the use of stronger expression cassettes for increasing PAL protein levels, as well as knock-out of the laccase gene slr1573, as this was previously reported to prevent degradation of the target compounds in the cell. Finally, to investigate the effect of growth conditions on the production of trans-cinnamic and p-coumaric acids from Synechocystis, cultivation conditions promoting rapid, high density growth were tested. Comparing the different PALs, the highest specific titer was achieved for the strain AtC, expressing PAL from Arabidopsis thaliana. A subsequent increase of protein level did not improve the productivity. Production of target compounds in strains where the slr1573 laccase had been knocked out was found to be lower compared to strains with wild type background, and the Δslr1573 strains exhibited a strong phenotype of slower growth rate and lower pigment content. Application of a high-density cultivation system for the growth of production strains allowed reaching the highest total titers of trans-cinnamic and p-coumaric acids reported so far, at around 0.8 and 0.4 g L−1, respectively, after 4 days. Conclusions Production of trans-cinnamic acid, unlike that of p-coumaric acid, is not limited by the protein level of heterologously expressed PAL in Synechocystis. High density cultivation led to higher titres of both products, while knocking out slr1573 did not have a positive effect on production. This work contributes to capability of exploiting the primary metabolism of cyanobacteria for sustainable production of plant phenylpropanoids.

In this study, two types of mesoporous silica with different pore structures and volumes were synthesized by the soft-templating method. The two types of mesoporous silica, type MCM-41 and MCM-48, were loaded with three polyphenols—caffeic acid, p-coumaric acid and trans-ferulic acid—in the same ratio of mesoporous silica:polyphenol (1:0.4 w/w). The materials obtained were characterized from a morphological and structural point of view through different analysis techniques. Through X-ray diffraction (XRD), the crystallization plane and the ordered structure of the mesoporous silica were observed. The difference between the two types of materials containing MCM-41 and MCM-48 was observed through the different morphologies of the silica particles through scanning electron microscopy (SEM) and also through the Brunauer–Emmet–Teller (BET) analysis, that the surface areas and volumes of pores was different between the two types of mesoporous silica, and, after loading with polyphenols, the values were reduced. The characteristic bands of silica and of polyphenols were easily observed by Fourier-transform infrared spectroscopy (FTIR), and, through thermogravimetric analysis (TGA), the residual mass was determined and the estimated amount of polyphenol in the materials and the efficient loading of mesoporous silica with polyphenols could be determined. The in vitro study was performed in two types of simulated biological fluids with different pH—simulated gastric fluid (SGF) and simulated intestinal fluid (SIF). The obtained materials could be used in various biomedical applications as systems with controlled release of natural polyphenols and the most suitable application could be as food supplements especially when a mixture of such materials is used or when the polyphenols are co-loaded within the mesoporous silica. [ABSTRACT FROM AUTHOR]

In this study, the definition and optimization of a medium for cost-effective heterologous production as well as efficient recovery of the plant secondary metabolite p -coumaric acid (p -CA) was performed. Experimental designs were carried out to this end. First, a Plackett Burman design was used to choose the important factors that affect p -CA production. Then, a central composite face centered design was used to find the optima of the two major parameters, C/N ratio and pH. Finally, a four-component optimized semi-defined (OSD) medium was developed and experimented in both biphasic and control batch fermentations. In comparison to the results of previous biphasic fermentations work using a classic defined medium (a 2X Yeast Nitrogen Base medium without Amino Acids), OSD medium was 10 times less expensive per litre. At pH 4.5, the final p -CA production in OSD medium was approximately 61 % of the p -CA content reached in the classic defined medium. At pH 6.0, the production of p -CA in OSD medium was 55 % of the p -CA reached in the YNB medium. [Display omitted] • High C/N ratio and controlled pH of 6.0 promote p -coumaric acid (p -CA) production. • Extractive biphasic fermentation improved yeast growth compared to control. • Optimized semi-defined (OSD) medium was 10 times cheaper than 2X YNB medium. • OSD medium in biphasic fermentation at pH 4.5 prevented p -CA decarboxylation. [ABSTRACT FROM AUTHOR]

The most important side effect of gentamicin (GM) is nephrotoxicity. p-Coumaric acid (PCA) is a phenolic compound that scavenges free radicals, reduces fibrosis, and tissue damage. This study investigates the protective effect of PCA on tissue damage and kidney function in gentamicin-induced nephrotoxicity (GIN). Thirty-five rats were separated into five groups and each group contained seven animals: control group, ethanol group, GM group, PCA group, and GM + PCA group. At the end of the seven-day treatment, the rats were sacrificed after blood and kidney tissue samples were taken. While serum urea, creatinine, and neutrophil gelatinase-associated lipocalin (NGAL) levels increased significantly in the GM group compared to the control, they showed a significant decrease in the GM + PCA group compared to the GM. Serum tumor necrosis factor-α (TNF-α) and tissue malondialdehyde (MDA) levels were significantly increased in the GM group compared to the control. While the tissue total oxidant status (TOS) and oxidative stress index (OSI) values of the GM group were significantly higher than the control, they showed a significant decrease in the GM + PCA group compared to the GM. In the histopathological examination, significant tubular necrosis and tubulointerstitial inflammation were detected in the proximal tubules in the GM group compared to the control, while a significant decrease was observed in the severity of these findings in the GM + PCA group compared to the GM. This study shows that PCA has biochemical and histopathological ameliorating effects on GIN in the rat model. [ABSTRACT FROM AUTHOR]

Natural supplements are important in diabetes and oxidative stress management. A complexation‐mediated antihyperglycemic and antioxidant synergism between zinc(II) and p‐coumaric acid was investigated. p‐Coumaric acid was complexed with ZnSO4 and characterized by FT‐IR, 1H NMR, and mass spectroscopy. The antioxidant and antihyperglycemic potential of the complex and precursors were evaluated with different experimental models. Molecular docking with target proteins linked to diabetes was performed. A Zn(II)‐bicoumarate.2H2O complex was formed. The in vitro radical scavenging, α‐glucosidase inhibitory, antiglycation, and anti‐lipid peroxidative activities of the complex were several folds stronger than p‐coumaric acid. In Chang liver cells and rat liver tissues, the complex inhibited lipid peroxidation (IC50 = 56.2 and 398 μM) and GSH depletion (IC50 = 33.9 and 38.7 μM), which was significantly stronger (2.3–5.4‐folds) than p‐coumaric acid and comparable to ascorbic acid. Zn(II) and p‐coumaric synergistically modulated (1.7‐ and 2.8‐folds than p‐coumaric acid) glucose uptake in L‐6 myotubes (EC50 = 10.7 μM) and rat muscle tissue (EC50 = 428 μM), which may be linked to the observed complexation‐mediated increase in tissue zinc uptake. Glucose uptake activity was accompanied by increased hexokinase activity, suggesting increased glucose utilization. Docking scores α‐glucosidase, GLUT‐4, and PKB/Akt showed stronger interaction with the complex (−6.31 to −6.41 kcal/mol) compared to p‐coumaric acid (−7.18 to −7.74 kcal/mol), which was influenced by the Zn(II) and bicoumarate moieties of the complex. In vitro, the complex was not hepatotoxic or myotoxic. Zn(II) complexation may be a therapeutic approach for improving the antioxidative and glycemic control potentials of p‐coumaric acid. Practical applications: In functional medicine, natural supplements, plant‐derived phenolics, and nutraceuticals are becoming popular in the management of diseases, including diabetes and oxidative stress. This has been largely attributed to their perceived holistic medicinal profile and the absence of notable toxicity concerns. In the past two decades, considerable attention has been drawn toward zinc mineral as a possible therapeutic supplement for diabetes due to its role in insulin secretion and reported insulin mimetic potentials. p‐Coumaric acid is a known natural antioxidant with reported diabetes‐related pharmacological effects. In this study, we took advantage of these properties and complexed both natural supplements, which resulted in a more potent nutraceutical with improved glycemic control and antioxidant potential. The complexation‐mediated synergistic interaction between zinc and p‐coumaric acid could be an important therapeutic approach in improving the use of these natural supplements or nutraceuticals in managing diabetes and associated oxidative complications. [ABSTRACT FROM AUTHOR]

Purpose: Bladder cancer (BC) is among the most frequent malignancies worldwide. Novel non-invasive markers are needed to diagnose and stage BC with more accuracy than invasive procedures like cystoscopy. To date, no study has identified urine metabolites characteristic of all BC stages. To discover novel urine metabolomic profiles to diagnose and stage non-muscle-invasive (NMIBC) and muscle-invasive (MIBC) patients using mass spectrometry-based metabolomics. Methods: We prospectively recruited 198 BC patients and 98 age- and sex-matched healthy volunteers without evidence of renal or bladder condition confirmed by ultrasound, from whom we collected a first morning urine sample (before surgery in patients). In a discovery stage, an untargeted metabolomic analysis was conducted in urine samples of a selection of 64 BC patients (19 TaG1, 11 TaG3, 20 T1G3, 12 T2G3, 1 T2G2, 1 T3G3) and 20 controls to identify dysregulated metabolites. Next, after exhaustive multivariate analysis, confirmed dysregulated metabolites were validated in an independent cohort of 134 BC patients (19 TaG1, 62 TaG2, 9 TaG3, 15 T1G2, 16 T1G3, 4 T2G2, 9 T2G3) and 78 controls. Results: We validated p-cresol glucuronide as potential diagnostic biomarker for BC patients compared to controls (AUC = 0.79). For NMIBC, p-cresol glucuronide was valuable as staging biomarker (AUC = 0.803). And among NMIBCs, p-coumaric acid may be a potential specific staging biomarker for the TaG1 NMIBC; however, future validation experiments should be conducted once the precise version of the standard is commercially available. Remarkably, for MIBC we validated spermine as potential specific staging biomarker (AUC = 0.882). Conclusion: Ours is the first metabolomics study conducted in urine of a thoroughly characterized cohort comprising all stages of NMIBC, MIBC and healthy controls in which we identified non-invasive diagnostic and staging biomarkers. These may improve BC management, thus reducing the use of current harmful diagnostic techniques. [ABSTRACT FROM AUTHOR]

D-galactose (D-gal) induced senescence in rodents is a widely used model for assessment of molecules affecting brain ageing. Chronic administration of D-gal causes neuroinflammation leading to cognitive deficit and memory impairment which represent Alzheimer's dementia. In present study, we investigated the neuroprotective effects of the natural phenol, p-Coumaric acid (PCA) and its underlying mechanism in the chronic D-gal treated mice. Subcutaneous administration of D-gal (150 mg/kg) to Swiss albino mice for 42 consecutive days resulted in cognitive impairment as observed in Morris water maize (MWM) and Y maze test, which was ameliorated by concurrent treatment with PCA (80 mg/kg, and 100 mg/kg, p.o.). Importantly, PCA treatment attenuated the D-gal induced oxidative stress and significantly inhibited acetylcholinesterase (AChE) activity in mice brain. Furthermore, PCA treatment significantly lowered levels of inflammatory marker nuclear factor kappa B (NFκB) and reduced levels of proapoptotic enzyme caspase3. We also observed that PCA treatment exhibited β-secretase enzyme (BACE1) inhibitory effect. However, our results revealed that PCA treatment failed to decrease the level of advanced glycation end products both in vitro and in vivo. Taken together, current study demonstrated the significant neuroprotective effect of PCA against D-gal induced oxidative stress, neuroinflammation, cognitive impairment and apoptosis. [ABSTRACT FROM AUTHOR]