O-coumaric acid ester, a potential early signaling molecule in Pinus pinea and Pisolithus arhizus symbiosis established in vitro

Three new 5-deoxyflavonoid and dihydroflavonoids 2, 3 and 4 have been isolated from the methanolic extract of Abutioln pakistanicum aerial parts, for which structures were elucidated explicitly by extensive MS- and NMR-experiments. In addition to these, 3,7,4′-trihydroxy-3′-methoxy flavonol (1) is reported for the first time from Abutioln pakistanicum. Compound 2 and 4 are p-coumaric acid esters while compounds 2–4 exhibited α-glucosidase inhibitory activity. Docking studies indicated that the ability of flavonoids 2, 3 and 4 to form multiple hydrogen bonds with catalytically important residues is decisive hence is responsible for the inhibition activity. The docking results signified the observed in-vitro activity quite well which is in accordance with previously obtained conclusion that phenol moiety and hydroxyl group are critical for the inhibition of α-glucosidase enzyme.

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The Impact of Antioxidants from the Diet on Breast Cancer Cells Monitored by Raman Microspectroscopy

Letters in Drug Design & Discovery ◽

10.2174/1570180815666180502120804 ◽

2018 ◽

Vol 16 (2) ◽

pp. 127-137

Author(s):

Paula Sofia Coutinho Medeiros ◽

Ana Lúcia Marques Batista de Carvalho ◽

Cristina Ruano ◽

Juan Carlos Otero ◽

Maria Paula Matos Marques

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Cell Line ◽

Breast Cancer Cells ◽

Triple Negative ◽

Breast Adenocarcinoma ◽

Coumaric Acid ◽

Human Breast ◽

The Impact

Background: The impact of the ubiquitous dietary phenolic compound p-coumaric acid on human breast cancer cells was assessed, through a multidisciplinary approach: Combined biological assays for cytotoxicity evaluation and biochemical profiling by Raman microspectroscopic analysis in cells. </P><P> Methods: Para-coumaric acid was shown to exert in vitro chemoprotective and antitumor activities, depending on the concentration and cell line probed: a significant anti-invasive ability was detected for the triple-negative MDA-MB-231 cells, while a high pro-oxidant effect was found for the estrogen- dependent MCF-7 cells. A striking cell selectivity was obtained, with a more noticeable outcome on the triple-negative MDA-MB-231 cell line. Results: The main impact on the cellular biochemical profile was verified to be on proteins and lipids, thus justifying the compound´s anti-invasive effect and chemoprotective ability. Conclusion: p-Coumaric acid was thus shown to be a promising chemoprotective/chemotherapeutic agent, particularly against the low prognosis triple-negative human breast adenocarcinoma.

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In Vitro Gastrointestinal Digestion Impact on the Bioaccessibility and Antioxidant Capacity of Bioactive Compounds from Tomato Flours Obtained after Conventional and Ohmic Heating Extraction

Foods ◽

10.3390/foods10030554 ◽

2021 ◽

Vol 10 (3) ◽

pp. 554

Author(s):

Marta C. Coelho ◽

Tânia B. Ribeiro ◽

Carla Oliveira ◽

Patricia Batista ◽

Pedro Castro ◽

...

Keyword(s):

Gastrointestinal Tract ◽

Phenolic Compounds ◽

Antioxidant Capacity ◽

Bioactive Compounds ◽

Solid Fraction ◽

Ohmic Heating ◽

Coumaric Acid ◽

Insoluble Dietary Fiber ◽

The Impact

In times of pandemic and when sustainability is in vogue, the use of byproducts, such as fiber-rich tomato byproducts, can be an asset. There are still no studies on the impact of extraction methodologies and the gastrointestinal tract action on bioactive properties. Thus, this study used a solid fraction obtained after the conventional method (SFCONV) and a solid fraction after the ohmic method (SFOH) to analyze the effect of the gastrointestinal tract on bioactive compounds (BC) and bioactivities. Results showed that the SFOH presents higher total fiber than SFCONV samples, 62.47 ± 1.24–59.06 ± 0.67 g/100 g DW, respectively. Both flours present high amounts of resistant protein, representing between 11 and 16% of insoluble dietary fiber. Furthermore, concerning the total and bound phenolic compounds, the related antioxidant activity measured by 2,2′-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS) radical cation decolorization assay presented significantly higher values for SFCONV than SFOH samples (p < 0.05). The main phenolic compounds identified in the two flours were gallic acid, rutin, and p-coumaric acid, and carotenoids were lycopene, phytofluene, and lutein, all known as health promoters. Despite the higher initial values of SFCONV polyphenols and carotenoids, these BCs’ OH flours were more bioaccessible and presented more antioxidant capacity than SFCONV flours, throughout the simulated gastrointestinal tract. These results confirm the potential of ohmic heating to modify the bioaccessibility of tomato BC, enhancing their concentrations and improving their antioxidant capacity.

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Transdermal Delivery Systems for Ibuprofen and Ibuprofen Modified with Amino Acids Alkyl Esters Based on Bacterial Cellulose

International Journal of Molecular Sciences ◽

10.3390/ijms22126252 ◽

2021 ◽

Vol 22 (12) ◽

pp. 6252

Author(s):

Paula Ossowicz-Rupniewska ◽

Rafał Rakoczy ◽

Anna Nowak ◽

Maciej Konopacki ◽

Joanna Klebeko ◽

...

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Bacterial Cellulose ◽

Acid Ester ◽

Active Pharmaceutical Ingredient ◽

Amino Acid Ester ◽

Isopropyl Ester ◽

Isopropyl Esters ◽

Transdermal Application

The potential of bacterial cellulose as a carrier for the transport of ibuprofen (a typical example of non-steroidal anti-inflammatory drugs) through the skin was investigated. Ibuprofen and its amino acid ester salts-loaded BC membranes were prepared through a simple methodology and characterized in terms of structure and morphology. Two salts of amino acid isopropyl esters were used in the research, namely L-valine isopropyl ester ibuprofenate ([ValOiPr][IBU]) and L-leucine isopropyl ester ibuprofenate ([LeuOiPr][IBU]). [LeuOiPr][IBU] is a new compound; therefore, it has been fully characterized and its identity confirmed. For all membranes obtained the surface morphology, tensile mechanical properties, active compound dissolution assays, and permeation and skin accumulation studies of API (active pharmaceutical ingredient) were determined. The obtained membranes were very homogeneous. In vitro diffusion studies with Franz cells were conducted using pig epidermal membranes, and showed that the incorporation of ibuprofen in BC membranes provided lower permeation rates to those obtained with amino acids ester salts of ibuprofen. This release profile together with the ease of application and the simple preparation and assembly of the drug-loaded membranes indicates the enormous potentialities of using BC membranes for transdermal application of ibuprofen in the form of amino acid ester salts.

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p-Coumaric Acid Enhances Hypothalamic Leptin Signaling and Glucose Homeostasis in Mice via Differential Effects on AMPK Activation

International Journal of Molecular Sciences ◽

10.3390/ijms22031431 ◽

2021 ◽

Vol 22 (3) ◽

pp. 1431

Author(s):

Linh V. Nguyen ◽

Khoa D. A. Nguyen ◽

Chi-Thanh Ma ◽

Quoc-Thai Nguyen ◽

Huong T. H. Nguyen ◽

...

Keyword(s):

Glucose Homeostasis ◽

Blood Glucose Control ◽

Whole Body ◽

Ampk Activation ◽

Coumaric Acid ◽

Leptin Signaling ◽

Differential Effects ◽

Leptin Sensitivity ◽

Ampk Activity

AMP-activated protein kinase (AMPK) plays a crucial role in the regulation of energy homeostasis in both peripheral metabolic organs and the central nervous system. Recent studies indicated that p-Coumaric acid (CA), a hydroxycinnamic phenolic acid, potentially activated the peripheral AMPK pathway to exert beneficial effects on glucose metabolism in vitro. However, CA’s actions on central AMPK activity and whole-body glucose homeostasis have not yet been investigated. Here, we reported that CA exhibited different effects on peripheral and central AMPK activation both in vitro and in vivo. Specifically, while CA treatment promoted hepatic AMPK activation, it showed an inhibitory effect on hypothalamic AMPK activity possibly by activating the S6 kinase. Furthermore, CA treatment enhanced hypothalamic leptin sensitivity, resulting in increased proopiomelanocortin (POMC) expression, decreased agouti-related peptide (AgRP) expression, and reduced daily food intake. Overall, CA treatment improved blood glucose control, glucose tolerance, and insulin sensitivity. Together, these results suggested that CA treatment enhanced hypothalamic leptin signaling and whole-body glucose homeostasis, possibly via its differential effects on AMPK activation.

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β-Cyclodextrin Does not Alter the Bioaccessibility and the Uptake by Caco-2 Cells of Olive By-Product Phenolic Compounds

Nutrients ◽

10.3390/nu10111653 ◽

2018 ◽

Vol 10 (11) ◽

pp. 1653 ◽

Cited By ~ 6

Author(s):

Aurélia Malapert ◽

Valérie Tomao ◽

Marielle Margier ◽

Marion Nowicki ◽

Béatrice Gleize ◽

...

Keyword(s):

Phenolic Compounds ◽

In Vitro Digestion ◽

Intestinal Cell ◽

Coumaric Acid ◽

Two Phase ◽

Cell Monolayers ◽

Vegetation Water ◽

And Storage ◽

Olive Mill

Alperujo—a two-phase olive mill waste that is composed of olive vegetation water and solid skin, pulp, and seed fragments - is a highly valuable olive by-product due to its high content in phenolic compounds. In this study, we assessed whether β-cyclodextrin (β-CD), which is used to extract and protect alpejuro phenolic compounds (hydroxytyrosol-O-glucoside, tyrosol, caffeic, and p-coumaric acids) could impact on their bioaccessibility (i.e., the percentage of molecule found in the aqueous phase of the digesta) and uptake by intestinal cells, by using an in vitro digestion model and Caco-2 TC7 cells in culture, respectively. Our results showed that β-CD did not change the bioaccessibility of the selected phenols. Hydroxytyrosol-O-glucoside and caffeic did not cross Caco-2 cell monolayers. Conversely ferulic acid, identified as the main caffeic acid intestinal metabolite, was absorbed through intestinal cell monolayers (~20%). Interestingly, β-CD moderately but significantly improved the local absorption of tyrosol and p-coumaric acid (2.3 + 1.4% and 8.5 ± 4.2%, respectively, p < 0.05), even if their final bioavailability (expressed as bioaccessibility × absorption by Caco-2 cells) was not modified (16.2 ± 0.6% vs. 16.8 ± 0.5% for tyrosol and 32.0 ± 3.2% vs. 37.2 ± 3.2% for p-coumaric acid, from pure alperujo and alperujo complexed with β-CD, respectively). Overall, our results show that β-CD is an interesting extraction and storage agent for phenolic compounds that does not alter their in vitro bioavailability.

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p-Coumaric Acid Protects Human Lens Epithelial Cells against Oxidative Stress-Induced Apoptosis by MAPK Signaling

Oxidative Medicine and Cellular Longevity ◽

10.1155/2018/8549052 ◽

2018 ◽

Vol 2018 ◽

pp. 1-7 ◽

Cited By ~ 13

Author(s):

Jiao Peng ◽

Ting-ting Zheng ◽

Yue Liang ◽

Li-fang Duan ◽

Yao-dong Zhang ◽

...

Keyword(s):

Oxidative Stress ◽

Epithelial Cells ◽

Mapk Signaling ◽

Human Lens ◽

Lens Epithelial Cells ◽

Dependent Manner ◽

Coumaric Acid ◽

Underlying Mechanisms ◽

Induced Apoptosis

To protect against oxidative stress-induced apoptosis in lens epithelial cells is a potential strategy in preventing cataract formation. The present study aimed at studying the protective effect and underlying mechanisms of p-coumaric acid (p-CA) on hydrogen peroxide- (H2O2-) induced apoptosis in human lens epithelial (HLE) cells (SRA 01–04). Cells were pretreated with p-CA at a concentration of 3, 10, and 30 μM before the treatment of H2O2 (275 μM). Results showed that pretreatment with p-CA significantly protected against H2O2-induced cell death in a dose-dependent manner, as well as downregulating the expressions of both cleaved caspase-3 and cleaved caspase-9 in HLE cells. Moreover, p-CA also greatly suppressed H2O2-induced intracellular ROS production and mitochondrial membrane potential loss and elevated the activities of T-SOD, CAT, and GSH-Px of H2O2-treated cells. As well, in vitro study showed that p-CA also suppressed H2O2-induced phosphorylation of p-38, ERK, and JNK in HLE cells. These findings demonstrate that p-CA suppresses H2O2-induced HLE cell apoptosis through modulating MAPK signaling pathways and suggest that p-CA has a potential therapeutic role in the prevention of cataract.

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Antifibrotic properties of caveolin-1 scaffolding domain in vitro and in vivo

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00295.2007 ◽

2008 ◽

Vol 294 (5) ◽

pp. L843-L861 ◽

Cited By ~ 101

Author(s):

Elena Tourkina ◽

Mathieu Richard ◽

Pal Gööz ◽

Michael Bonner ◽

Jaspreet Pannu ◽

...

Keyword(s):

Lung Fibrosis ◽

Smooth Muscle Actin ◽

Lung Fibroblasts ◽

Normal Lung ◽

Signaling Molecule ◽

Caveolin 1 ◽

Tenascin C ◽

Ecm Proteins

Lung fibrosis involves the overexpression of ECM proteins, primarily collagen, by α-smooth muscle actin (ASMA)-positive cells. Caveolin-1 is a master regulator of collagen expression by cultured lung fibroblasts and of lung fibrosis in vivo. A peptide equivalent to the caveolin-1 scaffolding domain (CSD peptide) inhibits collagen and tenascin-C expression by normal lung fibroblasts (NLF) and fibroblasts from the fibrotic lungs of scleroderma patients (SLF). CSD peptide inhibits ASMA expression in SLF but not NLF. Similar inhibition of collagen, tenascin-C, and ASMA expression was also observed when caveolin-1 expression was upregulated using adenovirus. These observations suggest that the low caveolin-1 levels in SLF cause their overexpression of collagen, tenascin-C, and ASMA. In mechanistic studies, MEK, ERK, JNK, and Akt were hyperactivated in SLF, and CSD peptide inhibited their activation and altered their subcellular localization. These studies and experiments using kinase inhibitors suggest many differences between NLF and SLF in signaling cascades. To validate these data, we determined that the alterations in signaling molecule activation observed in SLF also occur in fibrotic lung tissue from scleroderma patients and in mice with bleomycin-induced lung fibrosis. Finally, we demonstrated that systemic administration of CSD peptide to bleomycin-treated mice blocks epithelial cell apoptosis, inflammatory cell infiltration, and changes in tissue morphology as well as signaling molecule activation and collagen, tenascin-C, and ASMA expression associated with lung fibrosis. CSD peptide may be a prototype for novel treatments for human lung fibrosis that act, in part, by inhibiting the expression of ASMA and ECM proteins.

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