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Macrophage infiltration is a hallmark pathological change observed in early stage myocardial ischemia/reperfusion (MI/R) injury and one of the main causes of myocardial damage. Here, we investigated the effects of p-Coumaric acid (p-CA) on macrophage polarization following MI/R injury and its mechanisms. In vitro, p-CA decreases the expression of LPS/IFN-γ-induced M1 macrophage markers (TNF-α, IL-6, iNOS and CCL2) and increases IL-4-induced M2 macrophage markers (IL-10, CD206, Arg1 and Mrc) in mouse bone marrow-derived macrophages (BMDMs). Additionally, p-CA elevated indoleamine 2, 3-dioxygenase (IDO) protein expression levels, M2 macrophage polarization and M2 macrophage markers through IL-4. In contrast, repression of IDO attenuated p-CA functions regulating BMDMs through IL-4. In vivo, IDO expression was downregulated in mouse hearts subjected to MI/R injury. Treatment of p-CA increased IDO expression in the hearts of MI/R mice. Functionally, p-CA decreases M1 macrophage markers, the number of M1 macrophages and inflammation around heart tissue following MI/R injury. Importantly, p-CA reduces cardiomyocyte apoptosis caused by MI/R. Altogether, our study identified that p-CA modulates macrophage polarization by promoting IDO expression and that p-CA attenuates macrophage-mediated inflammation following MI/R by promoting M2 macrophage polarization through IDO.

P-Coumaric acid (p-CA) is a hydroxycinnamic acid, an organic compound that is a hydroxyl derivative of cinnamic acid. P-CA is the most abundant isomer in nature and can be found in a wide variety of edible plants such as fungi, peanuts, navy beans, tomatoes, carrots, basil, and garlic. Recently, the therapeutic properties of p-CA have received a great deal of attention from scientific society. Here, we described the medicinal effects of p-CA on various pathological conditions. This review was performed via evaluating PubMed reported studies from January 2010 to January 2020. Also, reference lists were checked to find additional studies. All intermediation or complementarity of animal models, case-control and cohort studies, in vitro studies, and controlled trials (CTs) on p-CA were acceptable. However plant extract studies without indication of main active substances were excluded due to the considerable diversities and heterogeneities. According to recent evidence regarding the beneficial effects of p-CA, numerous diseases such as nephropathies, cardiovascular diseases, neuroinflammatory diseases, liver diseases, cancers, and some metabolic disorders could potentially be controlled by this natural herb. Interestingly, autophagy is a novel molecular mechanism involved in the crosstalk between classic effects of p-CA and introduces alternative therapeutic pathways for this compound. Much work remains in clarifying the main therapeutic properties among the various p-CA effects; these will be the subject of forthcoming work, resulting in presenting further mechanism of action.

Background p-Coumaric acid (pCA) is an essential bioactive compound for nutraceutical and pharmaceutical purposes; however, high-level pCA biosynthesis via in vivo is challenging due to the complexity of pathways and genetic designs. Hence, to produce pCA in a one-step reaction, it is crucial to establish whole-cell (WC) biocatalyst of recombinant tyrosine ammonia lyase (EC 4.3.1.23) with high activity, stability, and robustness properties. Methods Three different tyrosine ammonia lyase (TAL) genes were cloned and overexpressed under T7 promoter in Escherichia coli BL21(DE3). First, a copy GroELS was integrated in E. coli chromosome using a phage attack approach while rare codons and fusion TrxA-tag were cloned in a plasmid with the best TAL (Rhodotorula toluroides; RtTAL) for pCA production. Further optimization was conducted to the effect of temperature, medium, inducer, and metal ions, as well as biotransformation parameters. Significant findings Optimal pCA biotransformation was first explored using recombinant RtTAL in a low-cost medium with glycerol and lactose. Integrating a single copy of GroELS in E. coli chromosome and inserting the TrxA-tag, p32a-RtTAL/BD::7G, exhibited markedly elevated specific enzymatic activity of 16.14 μM mg−1 min−1 and conversion up to 94.8%. Moreover, RtTAL showed a 50% increase in the presence Mn2+ metal ions, while the whole-cell biocatalyst converted tyrosine to high-level of pCA up to 2.1 g/L by summation of 5-repeated batch reaction.

In recent decades, rates of insulin resistance and hypertension increase dramatically due to many factors. One of them is excessive fructose consumption. P-coumaric acid has potent antioxidant and anti hyperglycemic properties. Aim of the work: In this study, we examined the ability of p-coumaric acid to prevent high fructose induced hypertension and the possible underlying mechanisms. Material and methods: 24 adult male albino rats were divided randomly into 3 groups; control group, fructose group received fructose 60% dissolved in water for 5 weeks and P-coumaric acid + fructose group received P-coumaric acid dissolved in carboxy methyl cellulose 100ml/kg/day orally for 2 weeks then fructose 60% dissolved in water for 5 weeks. For each rat, blood pressure was measured and a blood sample was taken by retro orbital method under ether anesthesia for measurement of plasma level of glucose,triglycerides (TG) and high density lipoprotein (HDL), then triglycerides glucose (TYG) index and atherogenic index were calculated. Results: Fructose group showed significant increases of blood pressure, plasma glucose, TG, TYG index and atherogenic index while showed a significant decrease of plasma HDL when compared to control group (p < 0.01). P-coumaric acid reversed these results. Conclusion: P-coumaric acid protects against hypertension induced by high fructose diet.

Cider apple cultivars typically contain high concentrations of tannins (phenolic compounds) and/or acids. The phenolic content of some cider apples far exceeds that of white wine grapes, yet modern...

This study combined in vitro digestion and INT-407 cells to evaluate the bioaccessibility of anthocyanins in the small intestinal epithelial cells. Black soybean, grape, and purple sweet potato were chosen as they have a different anthocyanin composition. After the aqueous extract was digested under in vitro gastric and intestinal conditions, the digested mixture was incubated in the media of INT-407 for 2 h at 37 °C. Low proportion (

p-Coumaric acid (pCA) is a hydroxycinnamic acid derivative commonly found in many natural products that has been extensively studied for its anticancer activity in multiple cell lines. In this repo...

Phenolic compounds such as vanillic and p‐coumaric acids are pollutants of major concern in the agro‐industrial processing, thereby their effective detection in the industrial environment is essential to reduce exposure. Herein, we present the quenching effect of these compounds on the electrochemiluminescence (ECL) of the Ru(bpy)32+/TPrA (TPrA=tri‐n‐propylamine) system at a disposable screen‐printed carbon electrode. Transient ECL profiles are obtained from multiple video frames following 1.2 V application by a smartphone‐based ECL sensor. A wide range of detection was achieved using the sensor with limit of detection of 0.26 μM and 0.68 μM for vanillic and p‐coumaric acids, respectively. The estimated quenching constants determined that the quenching efficiency of vanillic acid is at least two‐fold that of p‐coumaric acid under the current detection conditions. The present ECL quenching approach provided an effective method to detect phenolic compounds using a low‐cost, portable smartphone‐based ECL sensor.

OBJECTIVE: In this study, it was aimed to evaluate the protective efficacy of the University of Wisconsin (UW) and histidine-tryptophan-ketoglutarate (HTK) preservation solutions enriched with P-coumaric acid and ellagic acid.MATERIAL AND METHODThirty-six Wistar albino male rats were divided into equal 6ng groups: (Group 1) UW; (Group 2) UW + P-coumaric; (Group 3) UW + Elagic; (Group 4) HTK ;. (Group 5) HTK + P-Coumaric; (Group 6) HTK + Elagic. After the liver perfusion was performed, samples were taken from the liver tissue and perfusion fluid at 0, 6 and 12 hours. At the sixth hour, liver biopsies were performed for histopathological and electron microscopic examination.RESULTSIn groups enriched with p-coumaric acid (group 2 and group 5), antioxidant enzyme activities, which were higher than the control groups, were decreased at the 0th hour and the difference disappeared at the 6th and 12th hour. In the groups enriched with Ellagic acid, the highest antioxidant enzyme activity was in group 6, when the groups were evaluated in terms of cytokine activity, which are inflammatory parameters, the group with the highest anti-inflammatory cytokines IL4 and IL10 was found to be in group 6, and in group 3, the results were found with group 6. it was found to be similar. In group 2 and group 5, although the results were lower than the control group, the difference was not significant (P> 0.05). It was observed that the results in group 6, in which the lowest values ​​in terms of inflammatory cytokines TNF-α, IL1 and IL6 were in group 3, were higher than in group 3, but significantly lower than the control group, especially in terms of IL6 values ​​(P, AMAÇ: Bu çalışmada, P-kumarik asit ve ellagik asit ile zenginleştirilmiş Wisconsin Üniversitesi (UW) ve histidin-triptofan-ketoglutarat (HTK) koruma solüsyonlarının koruyucu etkinliğininin değerlendirilmesi amaçlanmıştır.MATERYAL ve METOD: Otuz altı Wistar albino erkek sıçan eşit 6ngruba ayrıldı: (Grup 1) UW; (Grup 2) UW + P-coumaric; (Grup 3) UW+Elagic; (Grup 4) HTK;. (Grup 5) HTK + P-Coumaric; (Grup 6) HTK + Elagic. Karaciğer perfüzyonu yapıldıktan sonra 0, 6 ve 12. saatte karaciğer dokusundan ve perfüzyon sıvısından örnekler alındı. Altıncı saatte histopatolojik ve elektron mikroskopik inceleme için KC biyopsileri yapıldı.BULGULAR: P-coumaric asit ile zenginleştirilmiş gruplarda (grup 2 ve grup5) 0. saatte kontrol gruplarına göre yüksek olan antioksidan enzim aktivitelerinin azaldığı ve 6 ve 12. saatte farkın ortadan kalktığı görüldü. Ellagic asit ile zenginleştirilen gruplarda ise en yüksek en yüksek antioksidan enzim aktivitesinin grup 6’da olduğu, gruplar inflamatuar parametreler olan sitokin aktivitesi açısından değerlendirildiğinde antiinflamatuar sitokinler olan IL4 ve IL10 değerinin en yüksek olduğu grubun grup 6 olduğu, grup 3 de de sonuçların grup 6 ile benzer olduğu görüldü. Grup 2 ve grup 5’de ise sonuçların kontrol grubuna göre düşük olmasına rağmen farkın anlamlı olmadığı tespit edildi (P>0.05). İnflamatuar sitokinler olan TNF- α, IL1 ve IL6 açısından en düşük değerlerin grup 3’de olduğu grup 6 daki sonuçların ise grup 3’e göre yüksek olmakla birlikte özellikle IL6 değerleri açısından kontrol grubuna göre anlamlı oranda düşük olduğu görüldü (P

The cardioprotective potential of p-coumaric acid (pCA) against Doxorubicin (Dox)-mediated cardiotoxicity in normal animals has been previously documented. The present study sought to examine the e...

There is a growing interest in finding safe and natural anti-microbial compounds as a valid alternative to conventional chemical treatments for managing post-harvest fruit diseases. This study investigated the anti-fungal capacity of orange peel polyphenolic extract (OPE) against three relevant post-harvest fungal pathogens, Monilinia fructicola, Botrytis cinerea and Alternaria alternata. OPE extract at 1.5 g/L inhibited (100%) the mycelial growth and conidial germination of the three target fungi. At lower concentration, the effect varied, depending on the dose applied and target fungi. When the anti-fungal activity of the main phenolic compounds in sweet orange peel, namely, the flavonoids (naringin, hesperidin and neohesperidin) and phenolic acids (ferulic and p-coumaric), were evaluated, ferulic acid and p-coumaric acid displayed significantly higher inhibitory capacity in synthetic medium, while the activity of flavonoids was limited. Synergism between compounds was not detected, and the inhibitory activity of OPE may be attributed to an additive effect of phenolic acids. Interestingly, in peach-based medium, ferulic acid remained active against M. fructicola and A. alternata and was more efficient than p-coumaric to control B. cinerea. These results highlight peel orange waste as an excellent source of anti-fungal compounds, suggesting the possibility of using ferulic acid or ferulic acid-rich extracts, either alone or in combination with other post-harvest treatment, as a natural alternative to reduce post-harvest losses and, also, enhance the shelf-life of fruit.

Leptadenia reticulata (Retz.) Wight and Arn is an important medicinal plant of Asclepiadaceae family. In the present study regeneration was attempted using leaf and nodal explants in Murashige and Skoog’s (MS) medium fortified with sucrose (3%) and different cytokinins like 6-benzyladenine (BA), kinetin (Kn) and adenine sulphate (AdSO4) in 5–20 µM concentration range and auxins like indole-3-acetic acid (IAA), 1-naphthaleneacetic acid (NAA), 2,4-dichlorophenoxyacetic acid (2,4-D) in 0.1–1.0 µM concentration range. Through leaf explants total 21.70 ± 2.06 somatic embryos were recorded in 100% cultures in BA (15 µM) with AdSO4 (15 µM). Further these embryos were transferred to static medium augmented with gibberellic acid (GA3, 1 µM) facilitated development of plantlets within 8 weeks. Inoculating nodal explants in BA (10 µM) with AdSO4 (10 µM) formed total 5.10 ± 0.33 shoots (100% response). Callus and shoot cultures derived through leaf and nodal explants respectively were further qualitatively and quantitatively analyzed for their biosynthetic potential. High-performance thin layer chromatography (HPTLC) fingerprints of the samples confirmed that the in vitro shoots showed almost similar banding patterns in comparison with in vivo shoots in terms of number of peaks and band on TLC plate, whereas in callus samples the banding pattern was differed. Further quantification of p-coumaric acid revealed that in in vivo and in vitro shoots it was in LOD (10 µg) range but out of LOQ (100 µg). Whereas it was quantified 78.08 ± 2.20 mg g−1 of dry weight (DW) in 6 weeks old callus cultures obtained from BA (20 µM) + NAA (0.5 µM) fortified medium, which indicate that it can become a chemical marker for L. reticulata. This protocol can be utilized for true-to-type plant regeneration as well as conservation of this threatened medicinal plant. Chemical fingerprint can be utilized for authentication of L. reticulata and callus cultures as an alternative source to wild plants for production of p-coumaric acid. SEs were efficiently developed in L. reticulata. In vitro cultures were able to synthesize metabolites but callus is prominent source for p-coumaric acid. Hence it can be alternative to wild plants.

Objective: To evaluate the effect of p-coumaric acid against adriamycin-induced hepatotoxicity in rats. Methods: The rats were divided into 4 groups. The control group received solvent; the p-coumaric acid group was treated with 100 mg/kg of p-coumaric acid orally for five consecutive days; the adriamycin group was administered with a single dose of adriamycin (15 mg/kg, i.p.), and the p-coumaric acid + adriamycin group was given p-coumaric acid five days before adriamycin administration. Twenty-four hours after the last administration, blood samples were collected for biochemical analysis, and liver tissues were removed for histopathological and immunohistochemistrical studies. Moreover, the levels of tissue lipid peroxidation and enzyme activities of glutathione peroxidase, superoxide dismutase, and catalase in liver tissue were measured. Results: Treatment with p-coumaric acid protected the liver from the toxicity of adriamycin by attenuating the increase in alkaline phosphatase, alanine transaminase, aspartate transaminase, total bilirubin, total cholesterol, triglyceride, and low-density lipoprotein cholesterol and lessening the decrease in high-density lipoprotein cholesterol and albumin. p-Coumaric acid also raised the levels of glutathione peroxidase, superoxide dismutase, and catalase, as well as decreased lipid peroxidation in liver tissue and hepatic IL- 1β expression. Additionally, histopathological study confirmed the protective effect of p-coumaric acid against liver damage. Conclusions: p-Coumaric acid can alleviate adriamycin-induced hepatotoxicity.

p-Coumaric acid is a ubiquitous molecule, widely distributed in the vegetal kingdom and often found in the human diet. A systematic, rational search for new p-coumaric acid derivatives was performed using a computer-assisted protocol based on chemical properties. A total of 156 derivatives were generated by adding functional groups to the initial structure and employing a selection score (SS) developed for that purpose. A reduced subset of 10 p-coumaric acid derivatives was selected, which have the best drug-like behavior and lower toxicity. Reactivity indexes, pKa values, and bond dissociation energies were computed to estimate the antioxidant capability. According to the obtained results, three p-coumaric acid derivatives have been classified as the most promising candidates to act as chemical antioxidants. These derivatives are predicted to be better for that purpose than p-coumaric acid itself, through the electron transfer and/or H transfer mechanisms. In addition, they may act as new scaffolds of non-nitrocatechol inhibitors against COMT for the treatment of Parkinson's disease without the side effects of the known inhibitors. The presented results are expected to encourage additional inquiries on these molecules, using both theoretical and experimental approaches.

Obesity is accompanied by adipose tissue inflammation that subsequently reduces thermogenic potential in brown and beige (brown-like) adipocytes. We previously reported that peanut sprout (PS) inhibited triglyceride accumulation via fatty acid oxidation in adipocytes. However, it is unknown whether PS reverses diet-induced obesity/inflammation and protects against the inflammation-induced inhibition of browning. To investigate this, C57BL/6 male mice, as an in vivo model, were randomly assigned to three different diets and fed for 8 weeks: (i) low-fat diet (LF, 11% kcal from fat), (ii) high-fat diet (HF, 61% kcal from fat), or (iii) HF diet with PS (4% PS in diet, HF + PS). As an in vitro model, lipopolysaccharides (LPS)-induced macrophages and 3T3-L1 adipocytes in the absence (white adipocytes) or presence of dibutyryl-cAMP (Bt-cAMP, beige adipocytes) were used. The supplementation of PS improved HF-diet-mediated body weight gain, dyslipidemia, and hyperglycemia as compared to the HF group. Although there was a marginal impact on visceral hypertrophy, PS reversed the adipocyte inflammation. In parallel, LPS-mediated induction of inflammation was impeded by PS extract (PSE) in macrophages and adipocytes. PSE also protected against LPS-induced suppression of adipocyte browning in Bt-cAMP-treated adipocytes with mitochondrial activation. The phenolic acid analysis showed that among the constituent of PSE, p-coumaric acid (PCA) was identified as a polyphenol that showed a similar effect to PSE. PCA treatment was also able to maintain a higher temperature than the control group upon cold exposure. Taken together, PCA-enriched PS attenuated HF-diet-induced obesity and protected against LPS-induced inflammation and the inhibition of browning via mitochondrial activation.

A tyrosinase inhibitor was separated from camellia pollen with the aid of solvent fraction, macroporous adsorptive resin chromatography, and high‐speed countercurrent chromatography. The inhibitor was identified to be p‐coumaric acid ethyl ester (p‐CAEE) by nuclear magnetic resonance and mass spectrum. Its inhibitory activity (IC50 = 4.89 μg/ml) was about 10‐fold stronger than arbutin (IC50 = 51.54 μg/ml). The p‐CAEE inhibited tyrosinase in a noncompetitive model with the K I and K m of 1.83 μg/ml and 0.52 mM, respectively. Fluorescence spectroscopy analysis showed the p‐CAEE quenched an intrinsic fluorescence tyrosinase. UV‐Vis spectroscopy analysis showed the p‐CAEE did not interact with copper ions of the enzyme. Docking simulation implied the p‐CAEE induced a conformational change in the catalytic region and thus changed binding forces of L‐tyrosine. Our findings suggest that p‐CAEE plays an important role in inhibiting tyrosinase and provides a reference for developing pharmaceutical, cosmetic, and fruit preservation products using pollen., p‐Coumaric acid ethyl ester was first found in camellia pollen. The inhibition is reversible and dose‐dependent. p‐Coumaric acid ethyl ester altered the structure of tyrosinase. p‐Coumaric acid ethyl ester and pollen had potential applications for pharmaceutical, cosmetic, and fruit preservation. p‐Coumaric acid ethyl ester (p‐CAEE) can inhibit the activity of tyrosinase in a noncompetitive manner and can cause the transformation of tyrosinase.

Following biomass fractionation of corn stover using γ-valerolactone (GVL) pretreatment, the resulting lignin stream was subjected to base hydrolysis reactions to achieve the isolation of p-coumari...

Resveratrol is a plant secondary metabolite with multiple health-beneficial properties. Microbial production of resveratrol in model microorganisms requires extensive engineering to reach commercially viable levels. Here, we explored the potential of the non-conventional yeast Yarrowia lipolytica to produce resveratrol and several other shikimate pathway-derived metabolites (p-coumaric acid, cis,cis-muconic acid, and salicylic acid). The Y. lipolytica strain expressing a heterologous pathway produced 52.1 ± 1.2 mg/L resveratrol in a small-scale cultivation. The titer increased to 409.0 ± 1.2 mg/L when the strain was further engineered with feedback-insensitive alleles of the key genes in the shikimate pathway and with five additional copies of the heterologous biosynthetic genes. In controlled fed-batch bioreactor, the strain produced 12.4 ± 0.3 g/L resveratrol, the highest reported titer to date for de novo resveratrol production, with a yield on glucose of 54.4 ± 1.6 mg/g and a productivity of 0.14 ± 0.01 g/L/h. The study showed that Y. lipolytica is an attractive host organism for the production of resveratrol and possibly other shikimate-pathway derived metabolites., Highlights • Oleaginous yeast Y. lipolytica was engineered for production of aromatic compounds. • High resveratrol production required increased activities of Aro4p and Aro7p. • Multiple integration of resveratrol biosynthetic genes improved production. • Fed-batch fermentation enabled de novo production of 12.4 g/L resveratrol.

The natural antioxidants are well known for their antioxidative activity without side effects when compared to antibiotics. Hence, the present study aimed at evaluating p-Coumaric acid as an antioxidant additive on the blood and mRNA levels of antioxidant-related factors in common carp (Cyprinus carpio). Fish fed the basal diet supplemented with p-Coumaric at 0, 0.5, 1, and 1.5 g/kg for 56 days, then the serum, intestine, and liver samples were collected. The growth performance of fish fed with CA showed significantly (P0.05) improved FW, WG, and SGR compared to those of the control one. However, the feed conversion ratio was significantly (P0.05) reduced in fish fed 1 and 1.5 g/kg diet levels. SOD was not significantly differed among the groups fed with varied p-Coumaric acid (P0.05). Serum GPX and TAC were enhanced considerably by p-Coumaric acid regarding the control with the highest being in fish fed 1.5 g/kg diet (P0.05). Serum CAT was more elevated in fish provided p-Coumaric acid at 1 or 1.5 g/kg than the control while fish fed 0.5 g/kg did not display significant changes. MDA level significantly decreased by all p-Coumaric acid groups compared to the control one, and the lowest level was observed in 1.5 g/kg (P0.05). The mRNA level of CAT was significantly upregulated in the liver by p-Coumaric acid at 1 or 1.5 g/kg (P0.05), while the intestine CAT did not influence by p-Coumaric acid (P0.05). The measured SOD in the liver and intestine samples revealed no changes in common carp fed p-Coumaric acid (P0.05). GPX was significantly upregulated in the intestine by p-Coumaric acid at 1 or 1.5 g/kg (P0.05), whereas the liver GPX was upregulated by p-Coumaric acid at 1.5 g/kg. The mRNA level of the GST gene in the intestine of common carp was upregulated by p-Coumaric acid at 1.5 g/kg, whereas the liver displayed upregulated GST in fish fed 1 g/kg diet. The present study approved the application of p-Coumaric acid as a natural antioxidant for friendly, sustainable aquaculture.

Understanding the contribution of stem cell wall components to lodging is important in developing breeding programs aimed at reducing lodging in cereal crops. This study is one of the first to investigate the correlation between the amounts of cell wall-bound ferulic acid, p-coumaric acid, and lignin in the nodes and internodes of cereals (oat, wheat, and barley) and their lodging susceptibility during grain fill. All samples, except two-row barley, were susceptible to lodging and expressed a significantly lower stalk strength. Lignin and phenolic contents between nodes and internodes of all samples were significantly different, with internodes having higher amounts (5.5-7.0 and 10.9-16.2 μg/g p-coumaric acid, and 2.5-3.2 and 3.9-7.1 μg/g ferulic acid in nodes and internodes, respectively). The acid-soluble lignin content was different between nodes and internodes but not between crops. This data set did not correlate with lodging classification, possibly due to sample size and type.

Resistance to therapeutic agents and the highly toxic side effects of synthetic drugs has spurred new research in the treatment of colon cancer, which has high morbidity and mortality ratios. This study aims to clarify the molecular mechanisms of the anticarcinogenic properties of methanol extract of Viburnum opulus L. (EVO)and its main active compound, trans-p -coumaric acid ( p -CA), on human colon cancer cells (DLD-1, HT-29, SW-620, Caco-2) and healthy colon epithelial cells (CCD-18Co). The effects of EVO on controlled cell death (apoptosis) and the cell division cycle were determined by flow cytometry. Alteration in mRNA and protein expressions of switch genes in colorectal carcinoma (APC, MLH1, TP53, SMAD4, KRAS, and BRAF) were determined by qRT-PCR and Western blot, respectively. Our results show that EVO possesses a strong reducing capacity and free-radical scavenging activity. HPLC analyses prove that p -CAis the main compound of EVO. EVO and p -CA inhibit the proliferation of human colon cancer cells DLD-1 and HT-29 in a dose-dependent manner. EVO increases apoptosis of DLD-1 cells and halts the cell cycle in the G2 stage in HT-29 cells. mRNA and protein expressions of p53 and SMAD-4 are upregulated, while BRAFs are downregulated. The results were directly proportional to p -CA. EVO and p -CA up- and downregulate switch genes and protein expressions of DLD-1 cells, which alter the expression of 186 other genes. This is the first study of pharmacological exploration of V.opulus in human colon cancer. Its antiproliferative effects may be due to the presence of p -CA.

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 the present study, biomass and lipid production of the biodiesel promising green microalga Tetradesmus obliquus BPL16 were studied by application of p-coumaric acid as a suggested novel growth regulator found predominantly in phenolics-rich streams. It was used in its pure form along with two phytohormones (jasmonic acid and salicylic acid). Using 100 μM jasmonic acid, 10 μM salicylic acid and 1 mM p-coumaric acid improved biomass production by 85.4%, 54.9% and 34.1%, respectively, over the control. In addition, significant increments in lipid content by 22%, 105.6%, and 145.4%, respectively, over the control were obtained at the aformentioned concentrations. Neutral lipids were significantly improved under elicitor-supplemented conditions. Moreover, fatty acid methyl esters (FAMEs) profile was also vitally influenced with drastic increase in oleic acid (C18:1) proportion by 81.7% and 73.6% over the control at 10 μM of jasmonic acid and 1 mM of p-coumaric acid, respectively. Application of p-coumaric acid resulted in estimated biodiesel energy output of 10.8 MJ kg−1 which represented 141% and 9.4% higher than the control and jasmonic acid, respectively. In conclusion, the present study suggested p-coumaric acid as a novel growth regulator for instant synchronized growth and lipid accumulation in microalgae for enhanced biodiesel production.

International audience; The high fiber content of cereal coproducts used in animal feed reduces the digestibility and nutrient availability. Therefore, the aim of this study was to elucidate the ability of two carbohydrase complexes to degrade the cell wall of wheat, maize, and rice during in vitro digestion. One complex was rich in cell-wall-degrading enzymes (NSPase 1), and the other was similar but additionally enriched with xylanases and arabinofuranosidases (NSPase 2). Degradation of arabinoxylan, the main cereal cell wall polysaccharide, was followed directly by gas-liquid chromatography (GLC) and indirectly through phenolic acid liberation as quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The effect was additionally visualized using a unique multispectral autofluorescence approach. Wheat fractions, in particular aleurone, were susceptible to degradation as judged from the redistribution of arabinoxylan (25% reduction in insoluble arabinoxylan), whereas the highest relative liberation of ferulic acid was observed in rice bran (6%). All cereal fractions, except for maize, had a higher release of ferulic acid with NSPase 2 than NSPase 1 (38% in rice and wheat bran, 30% in wheat whole grain, and 28% in wheat aleurone). Thus, the carbohydrase complexes were able to degrade important cell wall components during in vitro digestion but apparently through different mechanisms in wheat, maize, and rice.

Cinnamic acids and their derivatives are found in abundance in fruits, vegetables, and other food products of plant origin. The trans-cinnamic and p-coumaric acids in particular have been a subject...

Introduction: Many physiological, biochemical and toxicological reactions are occurred in liver. Therefore, healthy function of this organ is vital for the whole body. In spite of having potent endogenous antioxidant system, lots of reactions in liver make it more susceptible to stressors. It is established that improving the potency of liver antioxidants can increase its ability to resist against different kinds of oxidative stressors. Therefore, this study designed to determine whether p-coumaric alleviate ischemia-reperfusion-induced hepatic injury (IRI) in rats. Methods: Thirty-two rats were randomly assigned in sham, p-coumaric acid (PC), ischemia-reperfusion (IR) and p-coumaric acid pretreated IR (PC+IR) groups (n=8 in each group). Animals in sham group underwent laparotomy but not IR injury; rats in PC group did not experience any surgical procedures; IR and PC+IR groups underwent hepatic IR injury. P-coumaric acid at 100mg/kg were given for 7 consecutive days to PC and PC+IR groups. The last dose of p-coumaric acid was injected just before surgery on 7th days of experiment. The levels of malondialdehyde, TAC, ALT and AST were determined. A molecular evaluation to quantify the gene expression of SOD and GPx was done in liver homogenate. Results: P-coumaric mitigated the hepatic injuries induced by IR and improved TAC, ALT, AST, SOD and GPx. This pretreatment was also decreased MDA level. Conclusion: The current outcomes showed that PC via improving the endogenous level of antioxidants in liver tissues and inhibiting IR-induced inflammation maintain the liver structure and function of liver against IR.

Background Atopic dermatitis (AD) is associated with chronic skin inflammatory reactions. p-coumaric acid (pCA) is an active ingredient of Panax ginseng Meyer (Araliaceae). Methods Here, we estimated an anti-AD effect of pCA on activated mast cells, activated splenocytes, and a mouse model of AD. Cytokines levels were measured by ELISA and protein activation was analyzed by Western blotting. 2,4-dinitrofluorobenzene (DNFB) was used to induce AD-like skin lesions. Results The treatment with pCA suppressed the productions and mRNA expressions of thymic stromal lymphopoietin (TSLP), TNF-ɑ, IL-6, and IL-1β in HMC-1 cells. pCA downregulated the expressions of RIP2 and caspase-1, phosphorylated-(p)p38/pJNK/pERK, and pIKKβ/pIkBɑ/NF-κB in HMC-1 cells. pCA also decreased the productions of TSLP, TNF-ɑ, IL-6, IL-4, and IFN-γ in the supernatant of stimulated splenic cells. Comparing to DNFB-sensitized control group, pCA-treated group alleviated pathological changes of AD-like lesions. pCA decreased the proteins and mRNA expressions levels of TSLP, IL-6, and IL-4 in the skin lesions. Caspase-1 activation was also downregulated by pCA treatment in the AD-like lesions. The serum levels of histamine, IgE, TSLP, TNF-ɑ, IL-6, and IL-4 were suppressed following treatment with pCA. Conclusion This study suggests that pCA has the potential to improve AD by suppressing TSLP as well as inflammatory cytokines via blocking of caspase-1/NF-κB signal cascade.

This study was preformed to establish a simple and reliable HPLC/UV analytical method to determine p-coumaric acid contents for the standardization of water extracts of Allium hookeri and Curcuma longa complex as functional health food ingredients. The quantitative HPLC method was optimized using a reversed-phase C18 column at 35°C with methanol and H2O (30:70, v/v) as the gradient mobile phase at a flow rate of 1.0 mL/min and along with detection wavelength of UV 300 nm. This HPLC/UV analytical method exhibited good specificity and high linearity in the tested range of 1.0–10.0 mg/mL with excellent coefficient of determination (R2) of 1.0. The limit of detection and limit of quantification were 0.08 and 0.24 μg/mL, respectively. In addition, the relative standard deviation values from the intra and inter-day precision measurements were 0.4 and 0.1%, respectively. These results indicate that the established HPLC/UV analytical method is simple, specific, precise, accurate, and reproducible and so could be employed in the quantitative analysis of p-coumaric acid as a functional compound in Allium hookeri Thwaites and Curcuma longa complex.

Objective: To explore the probable in vitro, in situ and in vivo mechanisms of gallic acid (GA) and p-coumaric acid (PCA) as anti-hyperglycemic agents.Animals and methods: Male albino rats were allocated into four groups, group1 was used as normal control. Group 2 was established as a diabetic control and group3 and 4 were treated with an oral dose of GA and PCA, respectively.Results: GA and PCA revealed a significant decrease in the activity of α-amylase, a noticeable rise in glucose induced-insulin secretion and glucose-uptake in peripheral glucose-uptake in vitro, increase also liver glycogen and serum insulin levels in vivo. Further, GA and PCA exhibited a significant reduction in intestinal glucose absorption in situ compared to blank.Conclusion: The antihyperglycemic activities of GA and PCA can be mediated through delaying intestinal glucose absorption, enhancing β-cell activity and promoting glucose uptake by peripheral tissue via enhancing insulin sensitivity.

Sorghum is important as a cereal crop, and also as livestock feed and a renewable energy crop because it produces a large amount of biomass. In grass plants like sorghum, hydroxycinnamates such as ferulic acids (FA) and p-coumaric acids (pCA) are characteristically ester-linked to the cell wall, and are believed to affect cell wall digestibility. Genetic manipulation of the esterification of FA and pCA to the cell wall appears to be one of the solutions to increase the digestibility of the cell wall so as to utilize sorghum biomass effectively. In this study, we measured esterified FA and pCA in each stage of internode elongation and determined the accumulation pattern of each hydroxycinnamate. The results revealed that FA were mainly accumulated during the cell elongation stage, and that pCA accumulation was increased after the cell elongation stage. Furthermore, 6 of the 12 sorghum BAHD acyltransferase genes were significantly expressed in the elongating internodes, suggesting that these genes might be involved in the feruloylation and/or p-coumaroylation of the cell wall in sorghum internodes.

p-Coumaric acid (p-CA) is a bioactive natural product and an important industrial material for pharmaceuticals and nutraceuticals. It can be synthesized from deamination of l-tyrosine by tyrosine ammonia lyase (TAL). In this work, we discovered two aromatic amino acid lyase genes, Sas-tal and Sts-tal, from Saccharothrix sp. NRRL B-16348 and Streptomyces sp. NRRL F-4489, respectively, and expressed them in Escherichia coli BL21(DE3). The two enzymes were functionally characterized as TAL. The optimum reaction temperature for Sas-TAL and Sts-TAL is 55 °C and 50 °C, respectively; while, the optimum pH for both TALs is 11. Sas-TAL had a kcat/Km value of 6.2 μM−1 min−1, while Sts-TAL had a much higher efficiency with a kcat/Km value of 78.3 μM−1 min−1. Both Sts-TAL and Sas-TAL can also take l-phenylalanine as the substrate to yield trans-cinnamic acid, and Sas-TAL showed much higher phenylalanine ammonia lyase activity than Sts-TAL. Using E. coli/Sts-TAL as a whole-cell biocatalyst, the productivity of p-CA reached 2.88 ± 0.12 g (L h)−1, which represents the highest efficiency for microbial production of p-CA. Therefore, this work not only reports the identification of two new TALs from actinomycetes, but also provides an efficient way to produce the industrially valuable material p-CA.

The hydroxycinnamic acids p‐coumaric acid (pCA) and ferulic acid (FA) add diversity to the portfolio of products produced by using grass‐fed lignocellulosic biorefineries. The level of lignin‐bound pCA in Zea mays was modified by the alteration of p‐coumaroyl‐CoA monolignol transferase expression. The biomass was processed in a lab‐scale alkaline‐pretreatment biorefinery process and the data were used for a baseline technoeconomic analysis to determine where to direct future research efforts to couple plant design to biomass utilization processes. It is concluded that future plant engineering efforts should focus on strategies that ramp up accumulation of one type of hydroxycinnamate (pCA or FA) predominantly and suppress that of the other. Technoeconomic analysis indicates that target extraction titers of one hydroxycinnamic acid need to be >50 g kg−1 biomass, at least five times higher than observed titers for the impure pCA/FA product mixture from wild‐type maize. The technical challenge for process engineers is to develop a viable process that requires more than 80 % reduction of the isolation costs., Stream on: A competitive lignocellulosic biorefinery will need to produce multiple product streams that include liquid fuel, solid fuel, and commodity chemicals. In this study, some key parameters are identified for the extraction of the valuable commodity chemicals p‐coumaric acid and ferulic acid from one of the waste streams in an alkaline‐pretreatment‐based biorefinery.

The protective effect and mechanism of action of p-coumaric acid for alleviating palmitic acid (PA)-induced hepatocyte injury were investigated using a PA-induced human hepatoma cell (HepG2)-based hepatocellular injury model and MTT cell viability determinations. Additionally, reduced glutathione content and catalase activity were detected using commercial kits, while intracellular lipid accumulation and total triglyceride content were measured using Oil Red O staining and a triglyceride quantification kit, respectively. Meanwhile, levels of proteins (fatty acid synthase, sterol regulatory element-binding protein-1, stearoyl-CoA desaturase-1) and proliferator-activated receptor-α mRNA were determined using western blotting and real-time quantitative polymerase chain reaction, respectively. After p-coumaric acid targets were identified using network pharmacological analysis, cyclooxygenase-2 (COX-2) expression was assessed via western blotting, while prostaglandin E2 accumulation was measured via an enzyme-linked immunosorbent assay. Notably, PA-treated hepatocytes exhibited increased viability (87.3 ± 2.2% vs 65.5 ± 2.5% for untreated cells), with reduced intracellular lipid accumulation reflecting promotion of lipolysis and fatty acid β-oxidation; this protective effect may depend on inhibition of both PA-induced HepG2 cell COX-2 expression and PGE2 accumulation.