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The economic competitiveness of 2G-bioethanol technology should improve through the improvement of the sugar release and the valorization of by-products, especially lignin. Thus, an integrated scheme with corncob was developed to produce ethanol using low dosages of cellulases and value-added products from the semi-simultaneous saccharification and fermentation (SSSF) residue. Enzymatic hydrolysis and SSSF of acid pretreated corncob (< 20 mesh and > 20 mesh) were carried out under cellulase dosages of 5, 10, and 15 FPU/g in the absence and presence of polyethylene glycol 1500 (PEG 1500). The SSSF residue was used to obtain lignosulfonate via sulfomethylation reaction and phenolic acids via alkaline hydrolysis using 4% (w/v) sodium hydroxide and 0–5% (v/v) hydrogen peroxide. Pretreated corncob < 20 mesh allowed the reduction of cellulase dosage to 5 FPU/g without compromising sugar release. The addition of PEG 1500 boosted sugar release, reaching 56.73 g/L glucose under 20% (w/v) solids. The maximum ethanol production of 31.64 g/L was obtained using 5 FPU/g cellulases, 2% (w/w) PEG 1500, and 20% (w/v) solids (gradual addition). FTIR confirmed the preparation of lignosulfonate from SSSF residue, and the surfactant showed good stabilization performance in oil/water systems (emulsification index≈30%). High yields of p-coumaric acid (8045.3 mg/100 g) and ferulic acid (1429.4 mg/100 g) were obtained in alkaline hydrolysis with 5% (v/v) hydrogen peroxide. Based on these findings, corncob is versatile and can create a biorefinery with high economic potential. [ABSTRACT FROM AUTHOR]

Stone-fruit liqueurs contain high contents of the carcinogen ethyl carbamate (EC). In this study, we investigated the effect of plum fruit extract and single antioxidants present in plum fruit extracts on the reduction in the EC content during the macerating process in a plum liqueur model system and authentic plum liqueur. 30% ethanol model plum liqueur treated with 0.2% plum extract showed the lowest EC content with 55% reduction rate after the macerating process compared to the content in the control. Interestingly, neither 0.1% ascorbic acid nor 0.1% p-coumaric acid lowered the EC contents in the model liqueur, while they decreased the EC contents in authentic plum liqueur. This was possibly attributed to the synergistic effect of the plum fruit phenolics with the ascorbic acid and p-coumaric acid antioxidants. Thus, plum extracts can be applied to plum liqueurs to reduce the rate of EC formation. [ABSTRACT FROM AUTHOR]

P‐coumaric acid (p‐CA), a pant metabolite with antioxidant and anti‐inflammatory activity, is extensively utilized in biomedicine, food, and cosmetics industry. In this study, a synthetic pathway (PAL) for p‐CA was designed, integrating three enzymes (AtPAL2, AtC4H, AtATR2) into a higher l‐phenylalanine‐producing strain Escherichia coli PHE05. However, the lower soluble expression and activity of AtC4H in the PAL pathway was a bottleneck for increasing p‐CA titers. To overcome this limitation, the soluble expression of AtC4H was enhanced through N‐terminal modifications. And an optimal mutant, AtC4HL373T/G211H, which exhibited a 4.3‐fold higher kcat/Km value compared to the wild type, was developed. In addition, metabolic engineering strategies were employed to increase the intracellular NADPH pool. Overexpression of ppnk in engineered E. coli PHCA20 led to a 13.9‐folds, 1.3‐folds, and 29.1% in NADPH content, the NADPH/NADP+ ratio and p‐CA titer, respectively. These optimizations significantly enhance p‐CA production, in a 5‐L fermenter using fed‐batch fermentation, the p‐CA titer, yield and productivity of engineered strain E. coli PHCA20 were 3.09 g/L, 20.01 mg/g glucose, and 49.05 mg/L/h, respectively. The results presented here provide a novel way to efficiently produce the plant metabolites using an industrial strain. [ABSTRACT FROM AUTHOR]

Genetic logic gates can be employed in metabolic engineering and synthetic biology to regulate gene expression based on diverse inputs. Design of tunable genetic logic gates with versatile dynamic performance is essential for expanding the usability of these toolsets. Here, using the p-coumaric acid biosensor system as a proof-of-concept, we initially investigated the parameters influencing the buffer (BUF) genetic logic gates. Subsequently, integrating binding sequences from the p-coumaric acid biosensor system and tetR or lacI regulation systems into a constitutive promoter yielded AND genetic logic gates. Additionally, characterized antisense RNAs (asRNAs) or single guide RNAs (sgRNAs) with various repression efficiencies were combined with BUF gates to construct a suite of p-coumaric acid-triggered NOT genetic logic gates. Finally, the designed BUF and NOT gates were combined to construct bifunctional genetic circuits that were subjected to orthogonality evaluation. The genetic logic gates established in this study can serve as valuable tools in future applications of metabolic engineering and synthetic biology.

Potassium bromate (KBrO3) is a common dietary additive, pharmaceutical ingredient, and significant by‐product of water disinfection. p‐coumaric acid (PCA) is a naturally occurring nutritional polyphenolic molecule with anti‐inflammatory and antioxidant activities. The goal of the current investigation was to examine the protective effects of p‐coumaric acid against the liver damage caused by KBrO3. The five groups of animals‐control, KBrO3 (100 mg/kg bw), treatment with KBrO3 along with Silymarin (100 mg/kg bw), KBrO3, followed by PCA (100 mg/bw, and 200 mg/kg bw) were randomly assigned to the animals. Mice were slaughtered, and blood and liver tissues were taken for assessment of the serum biochemical analysis for markers of liver function (alanine transaminase, aspartate transaminase, alkaline phosphatase, albumin, and protein), lipid markers and antioxidant markers (TBARS), glutathione peroxidase [GSH‐Px], glutathione (GSH), and markers of hepatic oxidative stress (CAT), (SOD), as well as histological H&E stain, immunohistochemical stain iNOS, and COX‐2 as markers of inflammatory cytokines. PCA protects against acute liver failure by preventing the augmentation of blood biochemical markers and lipid profiles. In mice liver tissues, KBrO3 increases lipid indicators and depletes antioxidants, leading to an increase in JNK, ERK, and p38 phosphorylation. Additionally, PCA inhibited the production of pro‐inflammatory cytokines and reduced the histological alterations in KBrO3‐induced hepatotoxicity. Notably, PCA effectively mitigated KBrO3‐induced hepatic damage by obstructing the TNF‐α/NF‐kB‐mediated inflammatory process signaling system. Additionally, in KBrO3‐induced mice, PCA increased the intensities of hepatic glutathione (GSH), SOD, GSH‐Px, catalase, and GSH activities. Collectively, we demonstrate the molecular evidence that PCA eliminated cellular inflammatory conditions, mitochondrial oxidative stress, and the TNF‐α/NF‐κB signaling process, thereby preventing KBrO3‐induced hepatocyte damage. Significant statement: Based on our study's biochemical and histological results, we have definitively proven that p‐coumaric acid (PCA) shields the liver in the experimental model against oxidative damage caused by potassium bromate (KBrO3). PCA also prevents oxidative stress. Additionally, in KBrO3‐induced mice, PCA increased the intensities of hepatic glutathione, superoxide dismutase, glutathione peroxidase, catalase, and glutathione reductase activities. Notably, PCA effectively mitigated KBrO3‐induced hepatic damage by obstructing the TNF‐α/NF‐kB‐initiated inflammatory response signaling pathway. Collectively, we provide molecular evidence that PCA reduced cellular inflammation, mitochondrial oxidative stress, and the TNF‐α/NF‐κB signaling cascade to prevent KBrO3‐induced hepatocyte damage. In a nutshell, the results of this investigation suggest that PCA therapy may be helpful in reducing oxidative stress in liver damage brought on by KBrO3. [ABSTRACT FROM AUTHOR]

Copyright of Farabi Medical Journal is the property of Farabi Medical Journal 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.)

Probiotics are defined as “live microorganisms that provide health benefits to the host when administered in adequate amounts.” Probiotics have beneficial effects on human health, including antibacterial activity against intestinal pathogens, regulation of blood cholesterol levels, reduction of colitis and inflammation incidence, regulation of the immune system, and prevention of colon cancer. In addition to probiotic bacteria, some phenolic compounds found in foods we consume (both food and beverages) have positive effects on human health. p-coumaric acid (p-CA) is one of the most abundant phenolic compounds in nature and human diet. The interactions between these two different food components (phenolics and probiotics), resulting in more beneficial combinations called synbiotics, are not well understood in terms of how they will affect the gut microbiota by promoting the probiotic properties and growth of probiotic bacteria. Thus, this study aimed to investigate synbiotic relationship between p-CA and Lactobacillus acidophilus LA-5 (LA-5), Lacticaseibacillus rhamnosus GG (LGG). Probiotic bacteria were grown in the presence of p-CA at different concentrations, and the effects of p-CA on probiotic properties, as well as its in vitro effects on AChE and BChE activities, were investigated. Additionally, Surface analysis was conducted using FTIR. The results showed that treatment with p-CA at different concentrations did not exhibit any inhibitory effect on the growth kinetics of LA-5 and LGG probiotic bacteria. Additionally, both probiotic bacteria demonstrated high levels of antibacterial properties. It showed that it increased the auto-aggregation of both probiotics. While p-CA increased co-aggregation of LA-5 and LGG against Escherichia coli, it decreased co-aggregation against Staphylococcus aureus. Probiotics grown with p-CA were more resistant to pepsin. While p-CA increased the resistance of LA-5 to bile salt, it decreased the resistance of LGG. The combinations of bacteria and p-CA efficiently suppressed AChE and BChE with inhibition (%) 11.04–68.43 and 13.20-65.72, respectively. Furthermore, surface analysis was conducted using FTIR to investigate the interaction of p-coumaric acid with LA-5 and LGG, and changes in cell components on the bacterial surface were analyzed. The results, recorded in range of 4000 –600 cm-1 with resolution of 4 cm-1, demonstrated that p-CA significantly affected only the phosphate/CH ratio for both bacteria. These results indicate the addition of p-CA to the probiotic growth may enhance the probiotic properties of bacteria. [ABSTRACT FROM AUTHOR]

Summary This study focused on the fabrication of zein‐based coatings functionalised by two phenolic acids, caffeic acid (CA) and p‐coumaric acid (pCA), using electrospinning. The electrospun fibres were fabricated with three different concentrations (5%, 10% and 20% w/w) of CA and pCA individually. The average fibre diameter (AFD) increased due to the addition of phenolic acids. Thermogravimetric analysis (TGA) revealed that degradation temperatures of the zein electrospun fibres were not significantly affected (P > 0.05) after the incorporation of CA and pCA. Meanwhile, interactions between zein and the phenolic acids were indicated by surface characterisation. CA‐loaded zein electrospun fibres exhibited increasing antioxidant activity with increasing CA concentration. Both phenolic acid‐loaded zein electrospun fibres displayed favourable antibacterial activities against S. aureus and E. coli foodborne pathogens. Overall, zein electrospun fibres with 20% w/w CA demonstrated the most desirable properties for potential active food packaging application. [ABSTRACT FROM AUTHOR]

Caffeic acid (CA) is a phenolic acid compound widely used in pharmaceutical and food applications. However, the efficient synthesis of CA is usually limited by the resources of individual microbial platforms. Here, a cross-kingdom microbial consortium was developed to synthesize CA from sugarcane bagasse hydrolysate using Escherichia coli and Candida glycerinogenes as chassis. In the upstream E. coli module, shikimate accumulation was improved by intensifying the shikimate synthesis pathway and blocking shikimate metabolism to provide precursors for the downstream CA synthesis module. In the downstream C. glycerinogenes module, conversion of p-coumaric acid to CA was improved by increasing the supply of the cytoplasmic cofactor FAD(H2). Further, overexpression of ABC transporter-related genes promoted efflux of CA and enhanced strain resistance to CA, significantly increasing CA titer from 103.8 mg/L to 346.5 mg/L. Subsequently, optimization of the inoculation ratio of strains SA-Ec4 and CACg27 in this cross-kingdom microbial consortium resulted in an increase in CA titer to 871.9 mg/L, which was 151.6% higher compared to the monoculture strain CA-Cg27. Ultimately, 2311.6 and 1943.2 mg/L of CA were obtained by optimization of the co-culture system in a 5 L bioreactor using mixed sugar and sugarcane bagasse hydrolysate, respectively, with 17.2-fold and 14.6-fold enhancement compared to the starting strain. The cross-kingdom microbial consortium developed in this study provides a reference for the production of other aromatic compounds from inexpensive raw materials. [ABSTRACT FROM AUTHOR]

Copyright of Acta Agriculturae Zhejiangensis is the property of Acta Agriculturae Zhejiangensis 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.)

IntroductionApplying biochar (BC) to reduce toxic substance accumulation in soil, either through direct adsorption or modulation of the microbial community, has received considerable attention. However, a knowledge gap exists regarding how BC regulates microbial community structure and functions to mitigate toxic substance accumulation.MethodsWe previously identified p-coumaric acid (p-CA) as a representative autotoxin in tobacco rhizosphere soil. On this basis, this study simulated a soil environment with p-CA accumulation to investigate the impacts of BC on p-CA, soil physicochemical properties, and microbial community structure and function.ResultsThe results showed that p-CA could be directly adsorbed onto BC, which followed the pseudo-second-order kinetic model (R2 = 0.996). A pot experiment revealed that BC significantly reduced soil p-CA, altered soil microbial composition, and enhanced bacterial community diversity. A weighted correlation network analysis showed a close association between taxon 1 in the microbial network and p-CA, suggesting a pivotal role for this taxon in reducing p-CA, with Devosia and Nocardioides identified as potential key contributors to this process. The prediction of possible keystone taxa functions showed that BC increased the relative abundances of aromatic compound degraders. Mantel tests indicated that soil organic matter exerted the greatest influence on keystone taxa functions and hub genera.DiscussionThese findings suggest that BC may either directly chemisorb p-CA or indirectly facilitate p-CA degradation by regulating the functioning of keystone taxa. The results of this study provide a novel perspective for further investigation of the mechanisms through which BC reduces the accumulation of toxic substances in soil.

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.

There is a balance between DM yield and feed value when choosing types of grasses on a farm depending on the acreages of farmland and types of ruminants to be fed. Therefore, optimisation of the harvest strategy for grass silage is important for profitable dairy farming. Tall fescue has high DM yield and can replace traditional grasses, such as timothy, in Northern Europe in a changing climate as it has been shown to be more drought tolerant. As differences in climate responses previously have been related to differences in cell wall structure between grass species and, consequently, in digestibility, it is highly relevant to compare these species at similar maturity stages and to investigate if a very early harvest date will diminish potential differences between the species. This study evaluated the effects of harvest date and forage species on the concentration of hydroxycinnamic acids in silages and its relationship to feed efficiency of dairy cows. Tall fescue and timothy were harvested at very early date on May 25 or at early date on May 31 in the spring growth cycle. Forty lactating dairy cows were used in a block design. Cows received 1 of 4 treatments: (1) tall fescue harvested at very early date, (2) timothy harvested at very early date, (3) tall fescue harvested at early date, and (4) timothy harvested at early date. Diets were formulated to have the same forage-to-concentrate ratio (49:51 on DM basis). Tall fescue silages showed greater concentrations of DM, ash, and CP than timothy silages. Grasses harvested at early date showed greater concentrations of NDF, ADL, and cell wall than grasses harvested at very early date. Tall fescue silages showed greater concentration of p-coumaric acid and lower in vitro organic matter digestibility (IVOMD) compared to timothy silages. Milk production and composition were not affected by treatments but cows fed tall fescue-based diets showed lower milk protein yield and greater milk urea nitrogen than when timothy-based diets were fed. Furthermore, cows receiving timothy-based diets showed greater feed efficiency compared to cows receiving tall fescue-based diets. Thus, the lower concentration of p-coumaric acid and the higher IVOMD was associated with greater feed efficiency of cows fed timothy-based diets compared to tall fescue-based diets.

With rapid advances in the development of metabolic pathways and synthetic biology toolkits, a persisting challenge in microbial bioproduction is how to optimally rewire metabolic fluxes and accelerate the concomitant high-throughput phenotype screening. Here we developed a biosensor-assisted titratable CRISPRi high-throughput (BATCH) screening approach that combines a titratable mismatch CRISPR interference and a biosensor mediated screening for high-production phenotypes in Escherichia coli. We first developed a programmable mismatch CRISPRi that could afford multiple levels of interference efficacy with a one-pot sgRNA pool (a total of 16 variants for each target gene) harboring two consecutive random mismatches in the seed region of sgRNA spacers. The mismatch CRISPRi was demonstrated to enable almost a full range of gene knockdown when targeting different positions on genes. As a proof-of-principle demonstration of the BATCH screening system, we designed doubly mismatched sgRNA pools targeting 20 relevant genes in E. coli and optimized a PadR-based p-coumaric acid biosensor with broad dynamic range for the eGFP fluorescence guided high-production screening. Using sgRNA variants for the combinatorial knockdown of pfkA and ptsI, the p-coumaric acid titer was increased by 40.6% to o 1308.6 mg/l from glycerol in shake flasks. To further demonstrate the general applicability of the BATCH screening system, we recruited a HpdR-based butyrate biosensor that facilitated the screening of E. coli strains achieving 19.0% and 25.2% increase of butyrate titer in shake flasks with sgRNA variants targeting sucA and ldhA, respectively. This work reported the establishment of a plug-and-play approach that enables multilevel modulation of metabolic fluxes and high-throughput screening of high-production phenotypes.

Abstract Background Phenylpropanoids are a large group of plant secondary metabolites with various biological functions, derived from aromatic amino acids. Cyanobacteria are promising host organisms for sustainable production of plant phenylpropanoids. We have previously engineered Synechocystis sp. PCC 6803 to produce trans-cinnamic acid (tCA) and p-coumaric acid (pCou), the first intermediates of phenylpropanoid pathway, by overexpression of phenylalanine- and tyrosine ammonia lyases. In this study, we aimed to enhance the production of the target compounds tCA and pCou in Synechocystis. Results We eliminated the 4-hydroxyphenylpyruvate dioxygenase (HPPD) activity, which is a competing pathway consuming tyrosine and, possibly, phenylalanine for tocopherol synthesis. Moreover, several genes of the terminal steps of the shikimate pathway were overexpressed alone or in operons, such as aromatic transaminases, feedback insensitive cyclohexadienyl dehydrogenase (TyrC) from Zymomonas mobilis and the chorismate mutase (CM) domain of the fused chorismate mutase/prephenate dehydratase enzyme from Escherichia coli. The obtained engineered strains demonstrated nearly 1.5 times enhanced tCA and pCou production when HPPD was knocked out compared to the parental production strains, accumulating 138 ± 3.5 mg L−1 of tCA and 72.3 ± 10.3 mg L−1 of pCou after seven days of photoautotrophic growth. However, there was no further improvement when any of the pathway genes were overexpressed. Finally, we used previously obtained AtPRM8 and TsPRM8 Synechocystis strains with deregulated shikimate pathway as a background for the overexpression of synthetic constructs with ppd knockout. Conclusions HPPD elimination enhances the tCA and pCou productivity to a similar extent. The use of PRM8 based strains as a background for overexpression of synthetic constructs, however, did not promote tCA and pCou titers, which indicates a tight regulation of the terminal steps of phenylalanine and tyrosine synthesis. This work contributes to establishing cyanobacteria as hosts for phenylpropanoid production.

Recently, we identified the biosynthetic gene cluster of avenalumic acid (ava cluster) and revealed its entire biosynthetic pathway, resulting in the discovery of a diazotization-dependent deamination pathway. Genome database analysis revealed the presence of more than 100 ava cluster-related biosynthetic gene clusters (BGCs) in actinomycetes; however, their functions remained unclear. In this study, we focused on an ava cluster-related BGC in Kutzneria albida (cma cluster), and revealed that it is responsible for p-coumaric acid biosynthesis by heterologous expression of the cma cluster and in vitro enzyme assays using recombinant Cma proteins. The ATP-dependent diazotase CmaA6 catalyzed the diazotization of both 3-aminocoumaric acid and 3-aminoavenalumic acid using nitrous acid in vitro. In addition, the high efficiency of the CmaA6 reaction enabled us to perform a kinetic analysis of AvaA7, which confirmed that AvaA7 catalyzes the denitrification of 3-diazoavenalumic acid in avenalumic acid biosynthesis. This study deepened our understanding of the highly reducing type II polyketide synthase system as well as the diazotization-dependent deamination pathway for the production of avenalumic acid or p-coumaric acid.

In this study, we determine the chemical composition, bioactive compounds profile, antioxidant capacity and antidiabetic potential of two cactus fruits. Pilosocereus gounellei had the highest contents of ash (6.84%), lipid (7.79%), maltose (1.02 mg g−1), soluble fiber (10.85%) and minerals such as Mg. Thirteen volatile compounds (alcohols, terpenes, aldehydes and esters) were found in the fruits. Although higher amounts of quinic acid and quercetrin were found in Cereus Jamacaru, Pilosocereus gounellei had a higher content of p-coumaric acid and rutin. Regarding the functional potential, Cereus Jamacaru had the highest content of total phenolics (65.17 GAE g−1), total flavonoids (26.06 mg EC g−1), antioxidant capacity (28.67; 49.86; 158.79 µM TE g−1 for DPPH, ABTS and ORAC, respectively) and highest inhibition for α-amylase (84.84 ± 0.41%) and protein glycation. In view of their nutritional and bioactive characteristics, these species have great potential to be used in preparations with functional claims.

Endogenous metabolic pathways in microbial cells are usually precisely controlled by sophisticated regulation networks. However, the lack of such regulations when introducing heterologous pathways in microbial hosts often causes unbalanced enzyme expression and carbon flux distribution, hindering the construction of highly efficient microbial biosynthesis systems. Here, using naringenin as the target compound, we developed an Autonomous Cascaded Artificial Dynamic (AutoCAD) regulation system to automatically coordinate the pathway expression and redirect carbon fluxes for enhanced naringenin production. The AutoCAD regulation system, consisting of both intermediate-based feedforward and product-based feedback control genetic circuits, resulted in a 16.5-fold increase in naringenin titer compared with the static control. Fed-batch fermentation using the strain with AutoCAD regulation further enhanced the naringenin titer to 277.2 mg/L. The AutoCAD regulation system, with intermediate-based feedforward control and product-triggered feedback control, provides a new paradigm of developing complicated cascade dynamic control to engineer heterologous pathways.

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. [ABSTRACT FROM AUTHOR]

Ferulic acid (FA) and p-coumaric acid (PCA) are abundantly present in commonly consumed food and beverages. Being polyphenolic compounds, they have been explored for their antioxidant and anti-inflammatory properties. Based on our previous study, we selected these two compounds to further investigate their potential in lipopolysaccharide (LPS)-induced sickness behavior and the ensuing neuroinflammation by specifically focusing on the NLRP3 inflammasome pathway. Male Swiss albino mice were divided into nine groups (n = 6) consisting of Normal Control, LPS, fluoxetine (FLX), FA40, FA160, FA640, PCA40, PCA160, and PCA640 respectively. Each group received respective FA or PCA treatment except Normal Control and LPS, which received the vehicle, carboxymethylcellulose 0.25% w/v. All groups were challenged with LPS 1.5 mg/kg, intraperitoneally except the Normal Control group, which received saline. Behavioral assessments were performed between 1–2 h, and the whole brains were collected at 3 h post-LPS administration. LPS-induced sickness behavior was characterized by significantly reduced spontaneous activity and high immobility time. The expression of NLRP3, ASC, caspase-1 and IL-1β was significantly increased, along with the levels of brain IL-1β suggesting the assembly and activation of NLRP3 inflammasome pathway. Furthermore, the major cytokines involved in sickness behavior, IL-6 and TNF-α were also significantly elevated with the accompanied lipid peroxidation. The results of this study emphasize that within the employed dose ranges of both FA and PCA, both the compounds were effective at blocking the activation of the NLRP3 inflammasome pathway and thereby reducing the release of IL-1β and the sickness behavior symptoms. There was a prominent effect on cytokine levels and lipid peroxidation as well. [ABSTRACT FROM AUTHOR]

Novel p-coumaric acid microemulsion systems were developed to circumvent its absorption and bioavailability challenges. Simplex-lattice mixture design and machine learning methods were employed for optimization. Two optimized formulations were characterized using in vitro re-dispersibility and cytotoxicity on various tumor cell lines (MCF-7, CaCO2, and HepG2). The in vivo bioavailability profiles of the drug loaded in the two microemulsion systems and in the suspension form were compared. The optimized microemulsions composed of Labrafil M1944 CS (5.67%)/Tween 80 (38.71%)/Labrasol (38.71%)/water (16.92%) and Capryol 90 (0.50%)/Transcutol P (26.67%)/Tween 80 (26.67%)/Labrasol (26.67%)/water (19.50%), respectively. They revealed uniform and stable p-coumaric acid-loaded microemulsion systems with a droplet size diameter of about 10 nm. The loaded microemulsion formulations enhanced the drug re-dispersibility in contrast to the drug suspension which exhibited 5 min lag time. The loaded formulae were significantly more cytotoxic on all cell lines by 11.98–16.56 folds on MCF-7 and CaCo2 cells and 47.82–98.79 folds on HepG2 cells higher than the pure drug. The optimized microemulsions were 1.5–1.8 times more bioavailable than the drug suspension. The developed p-coumaric acid microemulsion systems could be considered a successful remedy for diverse types of cancer. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases cause a large number of deaths throughout the world. No research was conducted earlier on p‐coumaric acid's effect on tachycardia, inflammation, ion pump dysfunction, and electrolyte imbalance. Hence, we appraised the above‐said parameters in isoproterenol‐induced myocardial infarcted rats. This investigation included 24 male albino Wistar rats in 4 groups. Normal control Group 1, p‐coumaric acid (8 mg/kg body weight) alone treated Group 2, Isoproterenol (100 mg/kg body weight) induced myocardial infarcted Group 3, p‐coumaric acid (8 mg/kg body weight) pretreated isoproterenol (100 mg/kg body weight) induced Group 4. After 1 day of the last dose of isoproterenol injection (day 10), rats were killed and blood and heart were taken and inflammatory markers, lipid peroxidation, nonenzymatic antioxidants, ion pumps, and electrolytes were measured. The heart rate, serum cardiac troponin‐T, serum/plasma inflammatory markers, and heart proinflammatory cytokines were raised in isoproterenol‐induced rats. Isoproterenol also enhanced plasma lipid peroxidation, lessened plasma nonenzymatic antioxidants, and altered heart ion pumps and serum and heart electrolytes. In this study, p‐coumaric acid pretreatment orally for 7 days to isoproterenol‐induced myocardial infarcted rats prevented changes in the above‐cited parameters. p‐Coumaric acid's anti‐tachycardial, anti‐inflammatory, anti‐ion pump dysfunction and anti‐electrolyte imbalance properties are the mechanisms for these cardioprotective effects. [ABSTRACT FROM AUTHOR]

Phenolic acids are derivatives of benzoic and cinnamic acids, which possess important biological activities at certain concentrations. Trans-cinnamic acid (t-CA) and its derivatives, such as p-coumaric acid (p-CA) and ferulic acid (FA) have been shown to have antibacterial activity against various Gram-positive and -negative bacteria. However, there is limited information available concerning the antibacterial mode of action of these phenolic acids. In this study, we aimed to ascertain metabolic alterations associated with exposure to t-CA, p-CA, and FA in Escherichia coli BW25113 using a nuclear magnetic resonance (NMR)-based metabolomics approach. The results showed that t-CA, p-CA, and FA treatments led to significant changes (p < 0.05) in the concentration of 42, 55, and 74% of the identified metabolites in E. coli, respectively. Partial least-squares discriminant analysis (PLS-DA) revealed a clear separation between control and phenolic acid groups with regard to metabolic response. Moreover, it was found that FA and p-CA treatment groups were clustered closely together but separated from the t-CA treatment group. Arginine, putrescine, cadaverine, galactose, and sucrose had the greatest impact on group differentiation. Quantitative pathway analysis demonstrated that arginine and proline, pyrimidine, glutathione, and galactose metabolisms, as well as aminoacyl-tRNA and arginine biosyntheses, were markedly affected by all phenolic acids. Finally, the H2O2 content of E. coli cells was significantly increased in response to t-CA and p-CA whereas all phenolic acids caused a dramatic increase in the number of apurinic/apyrimidinic sites. Overall, this study suggests that the metabolic response of E. coli cells to t-CA is relatively different from that to p-CA and FA. However, all phenolic acids had a certain impact on oxidative/antioxidant status, genomic stability, arginine-related pathways, and nucleic acid metabolism. [ABSTRACT FROM AUTHOR]

Ferulic acid (FA) and p-coumaric acid (p-CA) are hydroxycinnamic acid inhibitors that are mainly produced during the pretreatment of lignocellulose. To date, the inhibitory mechanism of hydroxycinnamic acid compounds on Saccharomyces cerevisiae has not been fully elucidated. In this study, liquid chromatography-mass spectrometry (LC–MS) and scanning electron microscopy (SEM) were used to investigate the changes in S. cerevisiae cells treated with FA and p-CA. In this experiment, the control group was denoted as group CK, the FA-treated group was denoted as group F, and the p-CA-treated group was denoted as group P. One hundred different metabolites in group F and group CK and 92 different metabolites in group P and group CK were selected and introduced to metaboanalyst, respectively. A total of 38 metabolic pathways were enriched in S. cerevisiae under FA stress, and 27 metabolic pathways were enriched in S. cerevisiae under p-CA stress as identified through Kyoto Encyclopaedia of Genes and Genomes (KEGG) analysis. The differential metabolites involved included S-adenosine methionine, L-arginine, and cysteine, which were significantly downregulated, and acetyl-CoA, L-glutamic acid, and L-threonine, which were significantly upregulated. Analysis of differential metabolic pathways showed that the differentially expressed metabolites were mainly related to amino acid metabolism, nucleotide metabolism, fatty acid degradation, and the tricarboxylic acid cycle (TCA). Under the stress of FA and p-CA, the metabolism of some amino acids was blocked, which disturbed the redox balance in the cells and destroyed the synthesis of most proteins, which was the main reason for the inhibition of yeast cell growth. This study provided a strong scientific reference to improve the durability of S. cerevisiae against hydroxycinnamic acid inhibitors. Key points: • Morphological changes of S. cerevisiae cells under inhibitors stress were observed. • Changes of the metabolites in S. cerevisiae cells were explored by metabolomics. • One of the inhibitory effects on yeast is due to changes in the metabolic network. [ABSTRACT FROM AUTHOR]

Cancer is considered most detrimental due to high mortality worldwide. Among them, skin cancers play a major part by affecting one in three cancer patients globally. About 2–3 million cancer cases were reported to be non-melanoma and melanoma skin cancers, respectively. Although chemotherapeutic drugs act on cancer cells but results in long-lasting morbidities which affects one's quality of life and also works only in the initial stage of the cancer. Hence, an idea of traditional medicine to cure the disease efficiently with less side effects was pursued by the researchers. We have assessed the combination effect of p-coumaric acid and naringin in exerting anticancer activity using A431 (epidermoid carcinoma) cells. The MTT analysis of the combination on A431 cells showed the least IC50 concentration of 41 µg/ml which is effective than the standard drug imiquimod with IC50 concentration of 52 µg/ml. Further, flow cytometric analysis was carried out to identify the molecular mechanism behind the anticancer effects of the combination. The results revealed that the combination arrested the A431 cell cycle at S phase, induced apoptosis as indicated by more early and late apoptotic cells when compared with the control, and further altered reactive oxygen species (ROS) and mitochondrial membrane potential in A431 cells. Hence, the results suggest the potential anticancer effects of p-coumaric acid and naringin combination against the skin cancer (A431) cell line. The observed effects may be additive or synergistic effects in inducing ROS generation and apoptosis, and reducing the viability of A431 cells. [ABSTRACT FROM AUTHOR]

ABSTRACT: Rice husk (RH) is an abundant agro-industrial residue in Uruguay, being the disposal of it an environmental problem because of the pollution it generates. This work had as objective the obtention of phenolic compounds from RH by alkaline hydrolysis and their separation by means of aqueous two-phase systems (ATPS). An experimental design was implemented for the alkaline delignification process, studying the influence of temperature, solid/liquid (S/L) ratio and NaOH concentration on the hydrolysis yield (HY), total phenolic content (TPC), the antioxidant capacity (FRAP and TEAC) and the ferulic and p-coumaric acids content of the hydrolysates. The optimal conditions were 120 °C, S/L ratio 1/30 g/mL and 2 N NaOH. Subsequently, ATPS based on choline chloride and different surfactants, Tween 20 (Tw20) and Tween 80 (Tw80), were used to separate the phenolic compounds from the hydrolysate. The influence of the tie-line length (TLL), volume ratio (VR) and temperature were studied. Ferulic acid and p-coumaric acid migrated to the surfactant rich-phase in all cases. Systems containing Tw80 turned out to have better separation yields (SY), greater than 90%, for both phenolic acids. SY was not affected by use of different TLL and temperatures, although it was affected by changes on VR.

Background: Gray mold, caused by Botrytis cinerea, is one of the major fungal diseases in agriculture. Biological methods are preferred over chemical fungicides to control gray mold since they are less toxic to the environment and could induce the resistance to pathogens in plants. In this work, we try to understand if ginseng defense to B. cinerea could be induced by fungal hypovirulent strain △BcSpd1. BcSpd1 encodes Zn(II)2Cys6 transcription factor which regulates fungal pathogenicity and we recently reported △BcSpd1 mutants reduced fungal virulence. Methods: We performed transcriptomic analysis of the host to investigate the induced defense response of ginseng treated by B. cinerea △BcSpd1. The metabolites in ginseng flavonoids pathway were determined by UPLC-ESI-MS/MS and the antifungal activates were then performed. Results: We found that △BcSpd1 enhanced the ginseng defense response when applied to healthy ginseng leaves and further changed the metabolism of flavonoids. Compared with untreated plants, the application of △BcSpd1 on ginseng leaves significantly increased the accumulation of p-coumaric acid and myricetin, which could inhibit the fungal growth. Conclusion: B. cinerea △BcSpd1 could effectively induce the medicinal plant defense and is referred to as the biological control agent in ginseng disease management.

Abstract Background Phenylpropanoids such as p-coumaric acid represent important precursors for the synthesis of a broad range of plant secondary metabolites including stilbenoids, flavonoids, and lignans, which are of pharmacological interest due to their health-promoting properties. Although extraction from plant material or chemical synthesis is possible, microbial synthesis of p-coumaric acid from glucose has the advantage of being less expensive and more resource efficient. In this study, Corynebacterium glutamicum was engineered for the production of the plant polyphenol precursor p-coumaric acid from glucose. Results Heterologous expression of the tyrosine ammonia-lyase encoding gene from Flavobacterium johnsoniae enabled the conversion of endogenously provided tyrosine to p-coumaric acid. Product consumption was avoided by abolishing essential reactions of the phenylpropanoid degradation pathway. Accumulation of anthranilate as a major byproduct was eliminated by reducing the activity of anthranilate synthase through targeted mutagenesis to avoid tryptophan auxotrophy. Subsequently, the carbon flux into the shikimate pathway was increased, phenylalanine biosynthesis was reduced, and phosphoenolpyruvate availability was improved to boost p-coumaric acid accumulation. A maximum titer of 661 mg/L p-coumaric acid (4 mM) in defined mineral medium was reached. Finally, the production strain was utilized in co-cultivations with a C. glutamicum strain previously engineered for the conversion of p-coumaric acid into the polyphenol resveratrol. These co-cultivations enabled the synthesis of 31.2 mg/L (0.14 mM) resveratrol from glucose without any p-coumaric acid supplementation. Conclusions The utilization of a heterologous tyrosine ammonia-lyase in combination with optimization of the shikimate pathway enabled the efficient production of p-coumaric acid with C. glutamicum. Reducing the carbon flux into the phenylalanine and tryptophan branches was the key to success along with the introduction of feedback-resistant enzyme variants.

p-coumaric acid (p-CA) is a phenolic acid abundantly present in several foods, and lisinopril is a widely employed angiotensin-converting enzyme inhibitor for the treatment of hypertension and endothelial dysfunction. This study was convened to determine the combined antioxidative effect of p-CA and/ lisinopril — in vitro and in vivo. Stock solutions of p-CA (50 mM) and lisinopril (50 mM) were separately prepared. Subsequently, preparation of different combinations of samples (50% p-CA: 50% lisinopril; 75% p-CA: 25% lisinopril; 25% p-CA: 75% lisinopril, 100% p-coumaric acid and 100% lisinopril) was carried out for the determination of in vitro antioxidant properties as typified by DPPH, ABTS, and hydroxyl radical scavenging abilities, Fe2+ chelating ability, reducing property, and inhibition of Fe2+-induced lipid peroxidation. Furthermore, p-coumaric acid (50 and 100 mg/kg) and/or lisinopril (10 mg/kg) were administered orally (p.o.) to rats daily for 14 days. Then, the liver was excised, blood was collected, and the plasma was subsequently prepared. The antioxidant status was assessed by determining catalase, superoxide dismutase, glutathione peroxidase, and glutathione-S-transferase activities as well as the levels of reduced glutathione, total thiol, and lipid peroxidation in rat liver. Combination of p-coumaric acid and lisinopril influenced the antioxidant capacity of lisinopril in vitro, improved antioxidant defense status when compared to control in vivo, and significantly decreased lipid peroxidation in vitro and in vivo. Results from this study indicate that the combination approach of p-CA and lisinopril could represent crucial alternative therapy in the management of free radical mediated damage. [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. [ABSTRACT FROM AUTHOR]

Background: Phenylpropanoids such as p-coumaric acid represent important precursors for the synthesis of a broad range of plant secondary metabolites including stilbenoids, flavonoids, and lignans, which are of pharmacological interest due to their health-promoting properties. Although extraction from plant material or chemical synthesis is possible, microbial synthesis of p-coumaric acid from glucose has the advantage of being less expensive and more resource efficient. In this study, Corynebacterium glutamicum was engineered for the production of the plant polyphenol precursor p-coumaric acid from glucose. Results: Heterologous expression of the tyrosine ammonia-lyase encoding gene from Flavobacterium johnsoniae enabled the conversion of endogenously provided tyrosine to p-coumaric acid. Product consumption was avoided by abolishing essential reactions of the phenylpropanoid degradation pathway. Accumulation of anthranilate as a major byproduct was eliminated by reducing the activity of anthranilate synthase through targeted mutagenesis to avoid tryptophan auxotrophy. Subsequently, the carbon flux into the shikimate pathway was increased, phenylalanine biosynthesis was reduced, and phosphoenolpyruvate availability was improved to boost p-coumaric acid accumulation. A maximum titer of 661 mg/L p-coumaric acid (4 mM) in defined mineral medium was reached. Finally, the production strain was utilized in co-cultivations with a C. glutamicum strain previously engineered for the conversion of p-coumaric acid into the polyphenol resveratrol. These co-cultivations enabled the synthesis of 31.2 mg/L (0.14 mM) resveratrol from glucose without any p-coumaric acid supplementation. Conclusions: The utilization of a heterologous tyrosine ammonia-lyase in combination with optimization of the shikimate pathway enabled the efficient production of p-coumaric acid with C. glutamicum. Reducing the carbon flux into the phenylalanine and tryptophan branches was the key to success along with the introduction of feedback-resistant enzyme variants. [ABSTRACT FROM AUTHOR]

In the present study, we investigated the effect of the p‐Coumaric acid (PCA), a phenolic acid, on potassium bromate (KBrO3) induced oxidative damage, Ras/Raf/MEK signaling, and apoptosis in HepG2 cells. Our findings showed that PCA‐treated cells prevented cytotoxicity compared with KBrO3‐treated cells. Furthermore, KBrO3‐induced oxidative stress and lipid peroxidation was attenuated by PCA and it also increased the antioxidant levels such as SOD, CAT, and GPX. Additionally, PCA inhibited the KBrO3‐induced DNA damage in HepG2 cells. Moreover, PCA treatment suppressed the activation of Ras/Raf/MEK signaling and increased the expression of PRDX‐1. In addition, PCA prevented the KBrO3‐induced apoptosis cascade by altering the expression of proapoptotic, Bax, caspase‐3, and antiapoptotic, Bcl‐2 proteins. The present study proves that PCA inhibited the KBrO3‐induced oxidative stress, DNA damage, and apoptotic signaling cascade in HepG2 cells. Significance statement: We suggest that p‐Coumaric acid (PCA) inhibits KBrO3‐induced toxic cellular and molecular events in HepG2 cells. From this study, it is clear that PCA showed its predominant effect against KBrO3‐induced cytotoxicity, oxidative stress, lipid peroxidation, and DNA impairment by restoring the antioxidant levels and averting ROS generation in HepG2 cells. In addition, PCA reduces the level of DNA damage caused by the activation of MAPK signaling pathways, specifically the Ras/Raf/MEK signaling cascade, in cells treated with KBrO3. Moreover, PCA has the ability to block apoptosis through the increase of antiapoptotic indicators and decrease of proapoptotic molecules. [ABSTRACT FROM AUTHOR]

Background: Apple cider vinegar (ACV) is most commonly used in sweet and sour Chinese cuisine. This study aimed to overcome the side effects of raw ACV, by increasing the concentration of p-Coumaric acid (p-CA), a polyphenolic component of ACV. The combination (diluted ACV with p-CA) has also been compared with individual raw ACV and p-CA to confirm if the overall dosage of the ACV can be reduced to avoid side effects and if the combination therapy had any better effect than the individual component itself. Objective: To evaluate and compare antioxidant, antimicrobial, and wound healing effects of ACV and p-CA combination with individual components ACV and p-CA. Methods: The antimicrobial properties of the samples were assessed by determining the Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) using the broth microdilution method, and zone of inhibition (ZOI) and an ex ovo study was also done to evaluate the antimicrobial effect of the samples in live embryo. For the evaluation of the test samples excision wound was created in Swiss male albino mice weighing 25–30 g of either sex to estimate parameters like wound contraction rate, WBC and platelet count, SOD and GSH levels. Histopathological analysis of the skin was also done. Result: In DPPH and ABTS antioxidant assays, the combined sample (ACV + p-CA) had lower IC50. The combination therapy also showed the best antimicrobial potential against P. aeruginosa and B. subtilis. In this context, ex-ovo antimicrobial study results showed that diluted ACV + p-CA treated live embryo samples had the least bacterial growth after 48 h, in comparison with non-treatment group as well as individually ACV and p-CA treated samples. In vivo study depicted that the highest dose of the combination test sample had the best wound contraction rate and antioxidant marker enzymes elevation compared to diseased control proving the potency to restore the wound healing progression. Conclusion: ACV and p-CA combination can be used with daily intake as this combination can prevent microbial contamination and oxidative stress additionally can repair wounds more safely than raw ACV.

One of the most abundant phenolic acids in honey is p-coumaric acid (pCA), which can be used to identify natural honey from synthetic honey. In this research, a simple, sensitive, and fast method using a modified electrode was developed to determine pCA in honey samples. A carbon paste electrode modified with NiZnFe2O4 nanospinels (NiZnFe2O4/CPE) was used to measure pCA in aqueous samples using Differential Pulse Voltammetry (DPV). NiZnFe2O4 nanospinels were synthesized by the sol-gel method and were characterized by different methods. pCA oxidation peak currents from DPV showed linearity in the range of 1.60–250 μM with a detection limit of 0.48 μM. Repeatability and reproducibility of the developed method and electrode showed a relative standard deviation lower than 0.95%. The developed method based on NiZnFe2O4/CPE kept performance after over 16 days. Satisfactory result for selectivity in the presence of some interference species is an advantage of the developed method. Finally, NiZnFe2O4/CPE was successfully used for the determination of pCA in two honey samples. The pCA values were calculated from the standard addition method and they were 3.41 × 10-5 and 1.70 × 10-5 M, respectively. These results were confirmed by high performance liquid chromatography (HPLC) with UV detector.

We previously reported that p-coumaric acid (PCA) ameliorated high-fat and high-sucrose (HFHS) diet-induced hepatic fibrosis in C57BL/6 mice, but the impact of PCA on HFHS-mediated muscle atrophy are not fully elucidated yet. To investigate this, we randomly divided C57BL/6 mice into three groups: low-fat diet (LF), HFHS diet (60 % kcal fat, 20 % sucrose drinking water), or HFHS + PCA (50 mg/kg BW) for 13 wk. PCA treatment (1) restored muscle fiber size by upregulating myosin heavy chain, (2) reduced lipid accumulation/lipogenesis in skeletal muscle with AMPK activation, and (3) mitigated sarcopenic features by regulating MuRF1/MAFbx, ER stress markers, and TLR/NFkB. PCA (4) improved HFHS-induced mitochondrial dysfunction, evident in enhancing oxidative phosphorylation in skeletal muscle. Palmitate (0.75 mM)-induced inhibition of myotube function and inflammation was prevented by PCA enhancing mitochondrial oxidative phosphorylation in C2C12 myotubes. These findings revealed that PCA effectively mitigates HFHS-mediated skeletal muscle atrophy by targeting muscular inflammation and mitochondrial function.

Dynamic regulation has been proved efficient in controlling gene expression at transcriptional, translational, and post-translational level. However, the dynamic regulation at gene replication level has been rarely explored so far. In this study, we established dynamic regulation at gene copy level through engineering controllable plasmid replication to dynamically control the gene expression. Prototypic genetic circuits with different control logic were applied to enable diversified dynamic behaviors of gene copy. To explore the applicability of this strategy, the dynamic gene copy control was employed in regulating the biosynthesis of p-coumaric acid, which resulted in an up to 78% increase in p-coumaric acid titer to 1.69 g/L in shake flasks. These results indicated the great potential of applying dynamic gene copy control for engineering biosynthesis of valuable compounds in metabolic engineering.

p-Coumaric acid (p-CA) is a phenolic compound that plays a crucial role in mediating multiple signaling pathways. It serves as a defense strategy against plant wounding and is also presumed to play a role in plant development and lignin biosynthesis. This study aimed to investigate the physiological and ionomic effect of p-CA on chia seedlings under salt stress. To this end, chia seedlings were supplemented with Nitrosol® containing 100 μM of p-CA, 100 of mM NaCI, and their combined (100 mM NaCI + 100 μM p-CA) solutions in 2-day intervals for a period of 14 days along with a control containing Nitrosol® only. The treatment of chia seedlings with 100 mM of NaCI decreased their growth parameters and the content of the majority of the essential macro-elements (K, P, Ca, and Mg), except for that of sodium (Na). The simultaneous application of p-CA and a salt stress treatment (p-CA + NaCI) alleviated the effect of salt stress on chia seedlings’ shoots, and this was indicated by the increase in chia biomass. Furthermore, this combined treatment significantly enhanced the levels of the essential microelements Mg and Ca. In summary, this brief report is built on the foundational work of our previous study, which demonstrated that p-CA promotes growth in chia seedlings via activation of O2−. In this brief report, we further show that p-CA not only promotes growth but also mitigates the effects of salt stress on chia seedlings. This mitigation effect may result from the presence of Mg and Ca, which are vital nutrients involved in regulating metabolic pathways, enzyme activity, and amino acid synthesis.

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.

In order to explore the biological functions of active ingredients in dried ginger, high performance liquid chromatography (HPLC) and mass spectrometry (MS) with selective reaction monitoring/multi-reaction monitoring (SRM/MRM) were used for qualitative and quantitative analysis of active ingredients in dried ginger. The antioxidant and uric acid-lowering activities of dried ginger extract and its active components were determined. The results showed that the most abundant phenylpropanoid components in dried ginger extract were phenylalanine, ferulic acid and p-coumaric acid. All these compounds had significant antioxidant capacity in terms of 1,1-diphenyl-2-picrylhydrazyl (DPPH) and hydroxyl radical scavenging capacity and ferric ion reducing power, and the decreasing order of the antioxidant capacity was ferulic acid > dried ginger extract > p-coumaric acid. In vitro xanthine oxidase inhibition assay showed that all the three drugs had strong uric acid lowering activity, the effect of p-coumaric acid being more pronounced than that of ferulic acid and dried ginger extract. Molecular docking revealed that ferulic acid and p-coumaric acid inhibited xanthine oxidase by the formation of hydrogen bonds, van der Waals force and π-π stacking with amino acid residues in the enzyme. In this study, ferulic acid, p-coumaric acid and ginger extract have good antioxidant capacity and xanthine oxidase inhibitory activity in vitro, and therefore have the potential to be developed into new uric acid-lowering products.

Alzheimer's disease (AD) is a progressive neurodegenerative disease for which there is a lack of effective therapeutic drugs. There is great potential for natural products to be used in the development of anti-AD drugs. P-coumaric acid (PCA), a small molecule phenolic acid widely distributed in the plant kingdom, has pharmacological effects such as neuroprotection, but its anti-AD mechanism has not been fully elucidated. In the current study, we investigated the mechanism of PCA intervention in the Aβ25–35-induced AD model using gut microbiomics and serum metabolomics combined with in vitro and in vivo pharmacological experiments. PCA was found to ameliorate cognitive dysfunction and neuronal cell damage in Aβ25–35-injected mice as measured by behavioral, pathological and biochemical indicators. 16S rDNA sequencing and serum metabolomics showed that PCA reduced the abundance of pro-inflammatory-associated microbiota (morganella, holdemanella, fusicatenibacter and serratia) in the gut, which were closely associated with metabolites of the glucose metabolism, arachidonic acid metabolism, tyrosine metabolism and phospholipid metabolism pathways in serum. Next, in vivo and in vitro pharmacological investigations revealed that PCA regulated Aβ25–35-induced disruption of glucose metabolism through activation of PI3K/AKT/Glut1 signaling. Additionally, PCA ameliorated Aβ25–35-induced neuroinflammation by inhibiting nuclear translocation of NF-κB and by modulating upstream MAPK signaling. In conclusion, PCA ameliorated cognitive deficits in Aβ25–35-induced AD mice by regulating glucose metabolism and neuroinflammation, and the mechanism is related not only to restoring homeostasis of gut microbiota and serum metabolites, but also to PI3K/AKT/Glut1 and MAPK/NF-κB signaling.

Cyanobacteria are promising as a biotechnological platform for production of various industrially relevant compounds, including aromatic amino acids and their derivatives, phenylpropanoids. In this study, we have generated phenylalanine resistant mutant strains (PRMs) of the unicellular cyanobacterium Synechocystis sp. PCC 6803, by laboratory evolution under the selective pressure of phenylalanine, which inhibits the growth of wild type Synechocystis. The new strains of Synechocystis were tested for their ability to secrete phenylalanine in the growth medium during cultivation in shake flasks as well as in a high-density cultivation (HDC) system. All PRM strains secreted phenylalanine into the culture medium, with one of the mutants, PRM8, demonstrating the highest specific production of 24.9 ± 7 mg L−1·OD 750 −1 or 610 ± 196 mg L−1 phenylalanine after four days of growth in HDC. We further overexpressed phenylalanine ammonia lyase (PAL) and tyrosine ammonia lyase (TAL) in the mutant strains in order to determine the potential of PRMs for production of trans -cinnamic acid (t CA) and para -coumaric acid (p Cou), the first intermediates of the plant phenylpropanoid pathway. Productivities of these compounds were found to be lower in the PRMs compared to respective control strains, except for PRM8 under HDC conditions. The PRM8 background strain in combination with PAL or TAL expression demonstrated a specific production of 52.7 ± 15 mg L−1·OD 750 −1 t CA and 47.1 ± 7 mg L−1·OD 750 −1 p Cou, respectively, with a volumetric titer reaching above 1 g L−1 for both products after four days of HDC cultivation. The genomes of PRMs were sequenced in order to identify which mutations caused the phenotype. Interestingly, all of the PRMs contained at least one mutation in their ccmA gene, which encodes DAHP synthase, the first enzyme of the pathway for aromatic amino acids biosynthesis. Altogether, we demonstrate that the combination of laboratory-evolved mutants and targeted metabolic engineering can be a powerful tool in cyanobacterial strain development. • Phenylalanine-resistant strains of Synechocystis generated by laboratory evolution. • Evolved resistant strains secrete phenylalanine. • An evolved strain was engineered to produce >1 g/L of cinnamic or coumaric acid. • Whole genome sequencing was applied to evolved strains. • Phenylalanine resistant strains have acquired mutations in DAHP synthase. [ABSTRACT FROM AUTHOR]

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Sulfite is a common preservative in wine, but the spoilage yeast Brettanomyces bruxellensis can produce volatile phenols even with the recommended sulfite dose. The purpose of this study was to examine how wine components, p-coumaric acid (a precursor of volatile phenols), and micronutrients influence culturability, viability, and volatile phenols production by B. bruxellensis under sulfite stress. In red wine, a high sulfite dose (potassium metabisulfite, 100 mg L−1) led to an immediate death phase followed by growth recovery after two weeks. However, 4-ethylphenol (4-EP) was continuously produced by dead or nonculturable cells. Nonetheless, an event of growth recovery could not be observed in the case of the model wine. However, when the model wine was supplemented with minerals and vitamins, both growth recovery and 4-EP production were noticed, suggesting that the minerals and vitamins played an important role in maintaining the viability of cells under the sulfite stress. The yeast could also utilize the p-coumaric acid (p-CA) as an energy source, showing a specific growth rate of 0.0142 h−1 with 1 mM of p-CA in model wine. Furthermore, the sulfite-stressed cells exhibited ATP production by means of proton efflux while utilizing the p-CA. This work highlights the novel finding that the conversion of p-CA into 4-EP provides sufficient energy for the cell to remain metabolically active under the sulfite stress. [ABSTRACT FROM AUTHOR]

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]