Ellagic Acid as Green Corrosion Inhibitor: a Necessary Validation

Corrosion of metals is an unavoidable but controllable process. Among techniques developed to slow down or prevent metal deterioration the addition of small amount of inhibitors directly in the corrosive environment is a quite common strategy. In particular, among organic compounds effectively used as adsorption inhibitors (thanks to N, O and/or S atoms that act as anchoring groups for metal surface) only a few percentage belongs to the so called \u201cgreen inhibitor\u201d class. In this field most of the studies employ plant extracts being rich in phytochemical constituents considered to be potential eco-friendly corrosion inhibitors. However, the often extraordinary complexity of crude extracts makes difficult the rationalization of the inhibition mechanism. So, from a purely academic point of view, the study of pure compounds is often encouraged. Among potential green inhibitors our attention has been focused on ellagic acid (EA) that can be obtained by hydrolysis of ellagitannin contained in peels of pomegranate. Ellagic acid is a polyphenol having four phenolic and two lactone groups that should act like two and one couples of equivalent sites, respectively, due to the C2h molecular symmetry. Up to know the corrosion inhibition properties of EA was only marginally studied in literature, both theoretically and experimentally. However some reported results need to be validated because of discrepancies concerning some fundamental chemical physical features of the target acid, like i) solubility in pure water (9 mg/dm3 versus 1.2 g/dm3) and ii) pKa values for the two acid dissociation processes. For this purposes, using UV-Vis absorption spectroscopy, a mainly-aqueous medium was selected to assure homogeneity of the EA-based solution; after that the corrosion inhibition properties of ellagic acid toward mild steel was studied by weight loss measurements (according to ASTM G1 standard practice) and by electrochemical tests. Preliminary results performed in 1% v/v MeOH/H2O mixture with HCl 0.05 M point to potentially interesting inhibition effect even working with 1.0 1910\u20135 M EA (i.e., 3 mg/dm3)

Bioactive Phenolic Compounds From Agri-Food Wastes : An Update on Green and Sustainable Extraction Methodologies

Phenolic compounds are broadly represented in plant kingdom, and their occurrence in easily accessible low-cost sources like wastes from agri-food processing have led in the last decade to an increase of interest in their recovery and further exploitation. Indeed, most of these compounds are endowed with beneficial properties to human health (e.g., in the prevention of cancer and cardiovascular diseases), that may be largely ascribed to their potent antioxidant and scavenging activity against reactive oxygen species generated in settings of oxidative stress and responsible for the onset of several inflammatory and degenerative diseases. Apart from their use as food supplements or as additives in functional foods, natural phenolic compounds have become increasingly attractive also from a technological point of view, due to their possible exploitation in materials science. Several extraction methodologies have been reported for the recovery of phenolic compounds from agri-food wastes mostly based on the use of organic solvents such as methanol, ethanol, or acetone. However, there is an increasing need for green and sustainable approaches leading to phenolic-rich extracts with low environmental impact. This review addresses the most promising and innovative methodologies for the recovery of functional phenolic compounds from waste materials that have appeared in the recent literature. In particular, extraction procedures based on the use of green technologies (supercritical fluid, microwaves, ultrasounds) as well as of green solvents such as deep eutectic solvents (DES) are surveyed

Green Corrosion Inhibitors from Natural Sources and Biomass Wastes

Over the past decade, green chemistry has been emphasizing the importance of protecting the environment and human health in an economically beneficial manner aiming at avoiding toxins and reducing wastes. The field of metallic materials degradation, generally faced by using toxic compounds, found a fertile research field in green chemistry. In fact, the use of inhibitors is a well-known strategy when metal corrosion needs to be prevented, controlled, or retarded. Green inhibitors are biodegradable, ecologically acceptable and renewable. Their valorization expands possible applications in industrial fields other than \u2018waste to energy\u2019 in the perspective of circular economy. Although lot of experimental work has been done and many research papers have been published, the topic of green inhibitors is still an open issue. The great interest in the field expanded the research, resulting in high numbers of tested molecules. However, the most frequently adopted approaches are conventional and, hence, not suitable to fully characterize the potential efficacy of inhibitors. All the mentioned aspects are the object of the present review and are meant as a constructive criticism to highlight the weak points of the green inhibitors field as to re-evaluate the literature and address the future research in the field that still lacks rationalization

Pectin-Based Formulations for Controlled Release of an Ellagic Acid Salt with High Solubility Profile in Physiological Media

Among bioactive phytochemicals, ellagic acid (EA) is one of the most controversial because its high antioxidant and cancer-preventing effects are strongly inhibited by low gastrointestinal absorption and rapid excretion. Strategies toward an increase of solubility in water and bioavailability, while preserving its structural integrity and warranting its controlled release at the physiological targets, are therefore largely pursued. In this work, EA lysine salt at 1:4 molar ratio (EALYS), exhibiting a more than 400 times increase of water solubility with respect to literature reports, was incorporated at 10% in low methoxylated (LM) and high methoxylated (HM) pectin films. The release of EA in PBS at pH 7.4 from both film preparations was comparable and reached 15% of the loaded compound over 2 h. Under simulated gastric conditions, release of EA from HM and LM pectin films was minimal at gastric pH, whereas higher concentrations-up to 300 μM, corresponding to ca. 50% of the overall content-were obtained in the case of the HM pectin film after 2 h incubation at the slightly alkaline pH of small intestine environment, with the enzyme and bile salt components enhancing the release. EALYS pectin films showed a good prebiotic activity as evaluated by determination of short chain fatty acids (SCFAs) levels following microbial fermentation, with a low but significant increase of the effects produced by the pectins themselves. Overall, these results highlight pectin films loaded with EALYS salt as a promising formulation to improve administration and controlled release of the compound

A novel co-monomer based on Ellagic Acid for free radical polymerization of N-vinyl-2-pyrrolidone

INTRODUCTION Ellagic Acid (EA) is one of the most abundant and relevant antioxidants present in fruits such as berries and in pomegranate [1]; on the other hand, its poor solubility both in water and in organic solvents limits its reactivity and its use as food supplements. The aim of the present work is to modify the structure of the EA in order to use it as co-monomer for radical polymerization of N-vinyl-2-pyrrolidone (NVP) achieving two main goals: protection of antioxidant moiety; different release pathway. MATERIALS AND METHODS EA was reacted with methacryloyl chloride via a hetero-phase reaction in anhydrous CH2Cl2 to obtain a high purity tetra-ester allyl derivate (EAMAC). Polymers were then obtained via bulk photopolymerization of N-vinyl-2-pyrrolidon with different quantities of EAMAC in a square-shaped PTFE mold for 1h. The release assay was performed using hydrolytic and enzymatic conditions. RESULTS AND DISCUSSION EAMAC is the only product obtained since other partially substituted esters (i.e. mono-, bi- and three-esters) are not present: it was obtained with high yield ( 4880%w/w) and was fully characterized via 1H-NMR and MS [ESI-Q-Tof MS= 587.48 m/z (EAMAC + Na+)]. Thermal properties were assessed via DSC obtaining a single melting peak at 263\ub0C: degradation starts immediately after melting. EAMAC was used as a co-monomer for NVP bulk photopolymerization; the reaction was performed avoiding the use of photoinitiator. It was observed that the irradiation with UV of EAMAC starts the reaction of polymerization transferring the radical to the NVP. Cross-linked polymers containing different amount of EAMAC were obtained. The release of EA was assessed both using solutions having different pHs and via enzymatic hydrolytic conditions. CONCLUSIONS The reaction of EA with methacryloyl chloride leads to obtain a single, reactive derivate of EA able to react with vinyl monomers, that is highly soluble in organic solvents. Moreover, EAMAC acts as radical initiator avoiding the use of photoinitiator and it leads to obtain crosslinked water-compatible polymers. EA can be released from the polymer and the kinetic of the release is related to the kinetic of the hydrolysis of the ester bonds existing between EA and methacrylic moieties bonded to polyvinyl pirrolydone (PVP) chains. REFERENCES [1] Verotta, L.; Panzella, L.; Antenucci, S.; Calvenzani, V.; Tomay, F.; Petroni, K.; Caneva, E.; Napolitano, A. Fermented pomegranate wastes as sustainable source of ellagic acid: antioxidant properties, anti-inflammatory action, and controlled release under simulated digestion conditions. Submitted to Food Chemistry, 2017 ACKNOWLEDGEMENT Work supported by Fondazione Cariplo and Regione Lombardia for the project \u2018\u2018BIOPLANT\u2019\u2019

Antioxidant properties of agri-food byproducts and specific boosting effects of hydrolytic treatments

Largely produced agri\u2010food byproducts represent a sustainable and easily available source of phenolic compounds, such as lignins and tannins, endowed with potent antioxidant properties. We report herein the characterization of the antioxidant properties of nine plant\u2010derived byproducts. 2,2\u2010Diphenyl\u20101\u2010picrylhydrazyl (DPPH) and ferric reducing/antioxidant power (FRAP) assays indicated the superior activity of pomegranate peels and seeds, grape pomace and pecan nut shell. An increase in the antioxidant potency was observed for most of the waste materials following a hydrolytic treatment, with the exception of the condensed tannin\u2010rich pecan nut shell and grape pomace. UV\u2010Vis and HPLC investigation of the soluble fractions coupled with the results from IR analysis and chemical degradation approaches on the whole materials allowed to conclude that the improvement of the antioxidant properties was due not only to removal of non\u2010active components (mainly carbohydrates), but also to structural modifications of the phenolic compounds. Parallel experiments run on natural and bioinspired model phenolic polymers suggested that these structural modifications positively impacted on the antioxidant properties of lignins and hydrolyzable tannins, whereas significant degradation of condensed tannin moieties occurred, likely responsible for the lowering of the reducing power observed for grape pomace and pecan nut shell. These results open new perspectives toward the exploitation and manipulation of agri\u2010food byproducts for application as antioxidant additives in functional

Ellagic Acid Recovery by Solid State Fermentation of Pomegranate Wastes by Aspergillus niger and Saccharomyces cerevisiae : a Comparison

Abstract: Fermentation in solid state culture (SSC) has been the focus of increasing interest because of its potential for industrial applications. In previous studies SSC of pomegranate wastes by Aspergillus niger has been extensively developed and optimized for the recovery of ellagic acid (EA), a high value bioactive. In this study we comparatively investigated the SSC of powdered pomegranate husks by A. niger and Saccharomyces cerevisiae and evaluated the recovery yields of EA by an ultrasound and microwave-assisted 7:3 water/ethanol extraction. Surprisingly enough, the yields obtained by S. cerevisiae fermentation (4% w/w) were found 5-fold higher than those of the A. niger fermented material, with a 10-fold increase with respect to the unfermented material. The EA origin was traced by HPLC analysis that showed a significant decrease in the levels of punicalagin isomers and granatin B and formation of punicalin following fermentation. Other extraction conditions that could warrant a complete solubilization of EA were evaluated. Using a 1:100 solid to solvent ratio and DMSO as the solvent, EA was obtained in 4% yields from S. cerevisiae fermented husks at a high purity degree. Hydrolytic treatment of S. cerevisiae fermented pomegranate husks aorded a material freed of the polysaccharides components that gave recovery yields of EA up to 12% w/w

Fractional dynamics pharmacokinetics–pharmacodynamic models

While an increasing number of fractional order integrals and differential equations applications have been reported in the physics, signal processing, engineering and bioengineering literatures, little attention has been paid to this class of models in the pharmacokinetics–pharmacodynamic (PKPD) literature. One of the reasons is computational: while the analytical solution of fractional differential equations is available in special cases, it this turns out that even the simplest PKPD models that can be constructed using fractional calculus do not allow an analytical solution. In this paper, we first introduce new families of PKPD models incorporating fractional order integrals and differential equations, and, second, exemplify and investigate their qualitative behavior. The families represent extensions of frequently used PK link and PD direct and indirect action models, using the tools of fractional calculus. In addition the PD models can be a function of a variable, the active drug, which can smoothly transition from concentration to exposure, to hyper-exposure, according to a fractional integral transformation. To investigate the behavior of the models we propose, we implement numerical algorithms for fractional integration and for the numerical solution of a system of fractional differential equations. For simplicity, in our investigation we concentrate on the pharmacodynamic side of the models, assuming standard (integer order) pharmacokinetics

Cytotoxic activity of Thai medicinal plants against human cholangiocarcinoma, laryngeal and hepatocarcinoma cells in vitro

<p>Abstract</p> <p>Background</p> <p>Cholangiocarcinoma is a serious public health in Thailand with increasing incidence and mortality rates. The present study aimed to investigate cytotoxic activities of crude ethanol extracts of a total of 28 plants and 5 recipes used in Thai folklore medicine against human cholangiocarcinoma (CL-6), human laryngeal (Hep-2), and human hepatocarcinoma (HepG2) cell lines in vitro.</p> <p>Methods</p> <p>Cytotoxic activity of the plant extracts against the cancerous cell lines compared with normal cell line (renal epithelial cell: HRE) were assessed using MTT assay. 5-fluorouracil was used as a positive control. The IC₅₀(concentration that inhibits cell growth by 50%) and the selectivity index (SI) were calculated.</p> <p>Results</p> <p>The extracts from seven plant species (<it>Atractylodes lancea</it>, <it>Kaempferia galangal</it>, <it>Zingiber officinal</it>, <it>Piper chaba</it>, <it>Mesua ferrea</it>, <it>Ligusticum sinense</it>, <it>Mimusops elengi</it>) and one folklore recipe (Pra-Sa-Prao-Yhai) exhibited promising activity against the cholangiocarcinoma CL-6 cell line with survival of less than 50% at the concentration of 50 μg/ml. Among these, the extracts from the five plants and one recipe (<it>Atractylodes lancea</it>, <it>Kaempferia galangal</it>, <it>Zingiber officinal</it>, <it>Piper chaba</it>, <it>Mesua ferrea</it>, and Pra-Sa-Prao-Yhai recipe) showed potent cytotoxic activity with mean IC₅₀values of 24.09, 37.36, 34.26, 40.74, 48.23 and 44.12 μg/ml, respectively. All possessed high activity against Hep-2 cell with mean IC₅₀ranging from 18.93 to 32.40 μg/ml. In contrast, activity against the hepatoma cell HepG2 varied markedly; mean IC₅₀ranged from 9.67 to 115.47 μg/ml. The only promising extract was from <it>Zingiber officinal </it>(IC₅₀= 9.67 μg/ml). The sensitivity of all the four cells to 5-FU also varied according to cell types, particularly with CL-6 cell (IC₅₀= 757 micromolar). The extract from <it>Atractylodes lancea </it>appears to be both the most potent and most selective against cholangiocarcinoma (IC₅₀= 24.09 μg/ml, SI = 8.6).</p> <p>Conclusions</p> <p>The ethanolic extracts from five plants and one folklore recipe showed potent cytotoxic activity against CL-6 cell. Sensitivity to other cancerous cell lines varied according to cell types and the hepatocarcinoma cell line. HepG2 appears to be the most resistant to the tested extracts.</p

Ellagitannins of the fruit rind of pomegranate (Punica granatum) antagonize in vitro the host inflammatory response mechanisms involved in the onset of malaria

<p>Abstract</p> <p>Background</p> <p>The sun-dried rind of the immature fruit of pomegranate (<it>Punica granatum</it>) is presently used as a herbal formulation (OMARIA, Orissa Malaria Research Indigenous Attempt) in Orissa, India, for the therapy and prophylaxis of malaria. The pathogenesis of cerebral malaria, a complication of the infection by <it>Plasmodium falciparum</it>, is an inflammatory cytokine-driven disease associated to an up-regulation and activity of metalloproteinase-9 and to the increase of TNF production. The <it>in vitro </it>anti-plasmodial activity of <it>Punica granatum (Pg) </it>was recently described. The aim of the present study was to explore whether the anti-malarial effect of OMARIA could also be sustained via other mechanisms among those associated to the host immune response.</p> <p>Methods</p> <p>From the methanolic extract of the fruit rind, a fraction enriched in tannins (<it>Pg</it>-FET) was prepared. MMP-9 secretion and expression were evaluated in THP-1 cells stimulated with haemozoin or TNF. The assays were conducted in the presence of the <it>Pg</it>-FET and its chemical constituents ellagic acid and punicalagin. The effect of urolithins, the ellagitannin metabolites formed by human intestinal microflora, was also investigated.</p> <p>Results</p> <p><it>Pg</it>-FET and its constituents inhibited the secretion of MMP-9 induced by haemozoin or TNF. The effect occurred at transcriptional level since MMP-9 mRNA levels were lower in the presence of the tested compounds. Urolithins as well inhibited MMP-9 secretion and expression. <it>Pg</it>-FET and pure compounds also inhibited MMP-9 promoter activity and NF-kB-driven transcription.</p> <p>Conclusions</p> <p>The beneficial effect of the fruit rind of <it>Punica granatum </it>for the treatment of malarial disease may be attributed to the anti-parasitic activity and the inhibition of the pro-inflammatory mechanisms involved in the onset of cerebral malaria.</p