Nitrogen-doped carbon dots derived from ellagic acid and L-tyrosine for photothermal anticancer and anti-inflammation.

Photothermal therapy (PTT) of tumor would ineluctably cause oxidative stress and related inflammation in adjacent normal tissues, leading to a discounted therapeutic outcome. To address this issue, herein an innovative therapeutic strategy that integrates photothermal anticancer and normal cell protection is developed. A new type of nitrogen-doped carbon dot (ET-CD) has been synthesized in one step by hydrothermal method using ellagic acid and L-tyrosine as reaction precursors. The as-prepared ET-CD exhibits high photothermal conversion efficiency and good photothermal stability. After intravenous injection, ET-CD can accumulate at the tumor site and the hyperthermia generated under near infrared laser irradiation effectively ablates tumor tissues, thereby significantly inhibiting tumor growth. Importantly, owing to the inherited antioxidant activity from ellagic acid, ET-CD can remove reactive oxygen and nitrogen species produced in the body and reduce the levels of inflammatory factors induced by oxidative stress, so as to alleviate the damage caused by heat-induced inflammation to normal cells and tissues while photothermal anticancer. These attractive features of ET-CD may open the exploration of innovative therapeutic strategies to promote the clinical application of PTT.

Recovery of Ellagic Acid from Pomegranate Peels with the Aid of Ultrasound-Assisted Alkaline Hydrolysis.

The pomegranate processing industry generates worldwide enormous amounts of by-products, such as pomegranate peels (PPs), which constitute a rich source of phenolic compounds. In this view, PPs could be exploited as a sustainable source of ellagic acid, which is a compound that possesses various biological actions. The present study aimed at the liberation of ellagic acid from its bound forms via ultrasound-assisted alkaline hydrolysis, which was optimized using response surface methodology. The effects of duration of sonication, solvent:solid ratio, and NaOH concentration on total phenol content (TPC), antioxidant activity, and punicalagin and ellagic acid content were investigated. Using the optimum hydrolysis conditions (i.e., 32 min, 1:48 v/w, 1.5 mol/L NaOH), the experimental responses were found to be TCP: 4230 ± 190 mg GAE/100 g dry PPs; AABTS: 32,398 ± 1817 µmol Trolox/100 g dry PPs; ACUPRAC: 29,816 ± 1955 µmol Trolox/100 g dry PPs; 59 ± 3 mg punicalagin/100 g dry PPs; and 1457 ± 71 mg ellagic acid/100 g dry PPs. LC-QTOF-MS and GC-MS analysis of the obtained PP extract revealed the presence of various phenolic compounds (e.g., ellagic acid), organic acids (e.g., citric acid), sugars (e.g., fructose) and amino acids (e.g., glycine). The proposed methodology could be of use for food, pharmaceutical, and cosmetics applications, thus reinforcing local economies.

Synthesis of Boronate Affinity-Based Oriented Dummy Template-Imprinted Magnetic Nanomaterials for Rapid and Efficient Solid-Phase Extraction of Ellagic Acid from Food.

Ellagic acid (EA) is a natural polyphenol and possesses excellent in vivo bioactivity and antioxidant behaviors, which play an important role in the treatment of oxidative stress-related diseases, such as cancer. Additionally, EA is also known as a skin-whitening ingredient. The content of EA would determine its efficacy. Therefore, the accurate analysis of EA content can provide more information for the scientific consumption of EA-rich foods and cosmetics. Nevertheless, the analysis of EA in these samples is challenging due to the low concentration level and the presence of interfering components with high abundance. Molecularly imprinted polymers are highly efficient pretreatment materials in achieving specific recognition of target molecules. However, the traditional template molecule (EA) could not be absolutely removed. Hence, template leakage continues to occur during the sample preparation process, leading to a lack of accuracy in the quantification of EA in actual samples, particularly for trace analytes. In addition, another drawback of EA as an imprinting template is that EA possesses poor solubility and a high price. Gallic acid (GA), called dummy templates, was employed for the synthesis of MIPs as a solution to these challenges. The approach used in this study was boronate affinity-based oriented surface imprinting. The prepared dummy-imprinted nanoparticles exhibited several significant advantages, such as good specificity, high binding affinity ((4.89 ± 0.46) × 10-5 M), high binding capacity (6.56 ± 0.35 mg/g), fast kinetics (6 min), and low binding pH (pH 5.0) toward EA. The reproducibility of the dummy-imprinted nanoparticles was satisfactory. The dummy-imprinted nanoparticles could still be reused even after six adsorption-desorption cycles. In addition, the recoveries of the proposed method for EA at three spiked levels of analysis in strawberry and pineapple were 91.0-106.8% and 93.8-104.0%, respectively, which indicated the successful application to real samples.

Hyaluronic Acid/Ellagic Acid as Materials for Potential Medical Application.

The aim of this work was to develop and characterize a thin films composed of hyaluronic acid/ellagic acid for potential medical application. Its principal novelty, distinct from the prior literature in terms of hyaluronic acid films supplemented with phenolic acids, resides in the predominant incorporation of ellagic acid-a distinguished compound-as the primary constituent of the films. Herein, ellagic acid was dissolved in two different solvents, i.e., acetic acid (AcOH) or sodium hydroxide (NaOH), and the surface properties of the resultant films were assessed using atomic force microscopy and contact angle measurements. Additionally, various physicochemical parameters were evaluated including moisture content, antioxidant activity, and release of ellagic acid in phosphate buffered saline. Furthermore, the evaluation of films' biocompatibility was conducted using human epidermal keratinocytes, dermal fibroblasts, and human amelanotic melanoma cells (A375 and G361), and the antimicrobial activity was elucidated accordingly against Staphylococcus aureus ATCC 6538 and Pseudomonas aeruginosa ATCC 15442. Our results showed that the films exhibited prominent antibacterial properties particularly against Staphylococcus aureus, with the 80HA/20EA/AcOH film indicating the strong biocidal activity against this strain leading to a significant reduction in viable cells. Comparatively, the 50HA/50EA/AcOH film also displayed biocidal activity against Staphylococcus aureus. This experimental approach could be a promising technique for future applications in regenerative dermatology or novel strategies in terms of bioengineering.

Green and shape-tunable synthesis of ellagic acid crystalline particles by tannic acid for neuroprotection against oxidative stress.

Oxidative stress (OS) plays an important role in the emergence and prevention of neurodegenerative diseases, such as Alzheimer's disease (AD). Excess reactive oxygen species (ROS) accumulated in a neuronal cell can lead to OS, producing cell injury and death. Seeking nanoantioxidants against AD-related oxidative stress has attracted a lot of attention, especially those potential antioxidant agents derived from natural polyphenols. However, the transformation of abundant plant polyphenols to antioxidative biomaterials against OS is still challenging. In this work, we report a new method to transform amorphous tannic acid (TA) into tailorable shaped ellagic acid (EA) crystalline particles without using an organic solvent. EA crystalline particles were generated from TA, which underwent a chemical transformation, in situ metal phenolic coordination and acid-induced assembly process, and the size and shape could be controlled by varying the amount of acid. As-prepared EA crystalline particles showed excellent stability in water and lysosomal mimicking fluid and possess unique fluorescence properties and a strong response in mass spectrometry, which is beneficial for their imaging analysis in cells and tissues. More importantly, EA particles have shown significant H2O2-related ROS scavenging ability, a high cellular uptake capacity, an excellent neuroprotective effect in PC12 cells, a high drug loading capacity and BBB permeability to enter the brain. Our study suggested that the EA crystalline particles show great potential for OS-mediated AD treatment.

Enhancing the Bioavailability of the Ellagitannin, Geraniin: Formulation, Characterization, and in vivo Evaluation.

Geraniin (GE), an ellagitannin (ET) renowned for its promising health advantages, faces challenges in its practical applications due to its limited bioavailability. This innovative and novel formulation of GE and soy-phosphatidylcholine (GE-PL) complex has the potential to increase oral bioavailability, exhibiting high entrapment efficiency of 100.2 ± 0.8 %, and complexation efficiency of 94.6 ± 1.1 %. The small particle size (1.04 ± 0.11 µm), low polydispersity index (0.26 ± 0.02), and adequate zeta potential (-26.1 ± 0.12 mV), indicate its uniformity and stability. Moreover, the formulation also demonstrates improved lipophilicity, reduced aqueous and buffer solubilities, and better partition coefficient. It has been validated by various analytical techniques, including Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and X-ray diffraction (XRD) studies. Oral bioavailability and pharmacokinetics of free GE and GE-PL complex investigated in rabbits demonstrated enhanced plasma concentration of ellagic acid (EA) compared to free GE. Significantly, GE, whether in its free form or as part of the GE-PL complex, was not found in the circulatory system. However, EA levels were observed at 0.5 h after administration, displaying two distinct peaks at 2 ± 0.03 h (T1max) and 24 ± 0.06 h (T2max). These peaks corresponded to peak plasma concentrations (C1max and C2max) of 588.82 ng/mL and 711.13 ng/mL respectively, signifying substantial 11-fold and 5-fold enhancements when compared to free GE. Additionally, it showed an increased area under the curve (AUC), the elimination half-life (t1/2, el) and the elimination rate constant (Kel). The formulation of the GE-PL complex prolonged the presence of EA in the bloodstream and improved its absorption, ultimately leading to a higher oral bioavailability. In summary, the study highlights the significance of the GE-PL complex in overcoming the bioavailability limitations of GE, paving the way for enhanced therapeutic outcomes and potential applications in drug delivery and healthcare.

Ultra-High-Performance Liquid Chromatography-Electrospray Ionization-High-Resolution Mass Spectrometry for Distinguishing the Origin of Ellagic Acid Extracts: Pomegranate Peels or Gallnuts.

Ellagic acid, known for its various biological activities, is widely used. Ellagic acid from pomegranate peels is safe for consumption, while that from gallnuts is only suitable for external use. However, there is currently no effective method to confirm the source of ellagic acid. Therefore, this study establishes an analysis method using ultra-high-performance liquid chromatography-electrospray ionization-high-resolution mass spectrometry (UHPLC-ESI-HR-MS) to identify the components of crude ellagic acid extracts from pomegranate peels and gallnuts. The analysis revealed that there was a mix of components in the crude extracts, such as ellagic acid, palmitic acid, oleic acid, stearic acid, and 9(10)-EpODE. Furthermore, it could be observed that ellagic acid extracted from gallnuts contained toxic substances such as anacardic acid and ginkgolic acid (15:1). These components could be used to effectively distinguish the origin of ellagic acid from pomegranate peels or gallnuts. Additionally, a rapid quantitative analysis method using UHPLC-ESI-MS with multiple reaction monitoring (MRM) mode was developed for the quality control of ellagic acid products, by quantifying anacardic acid and ginkgolic acid (15:1). It was found that one of three ellagic acid health care products contained ginkgolic acid (C15:1) and anacardic acid at more than 1 ppm.

Sono-assembly of ellagic acid into nanostructures significantly enhances aqueous solubility and bioavailability.

INTRODUCTION: Ellagic acid (EA), commonly found in foods, offers significant health benefits in combating chronic diseases. However, its therapeutic potential is hindered by its extremely poor solubility and bioavailability. METHOD: In this study, EA nanoparticles (EA NPs) were produced using a sono-assembly method, without additional agents. RESULTS: EA NPs exhibited stick-like nanoparticle structures with an average size of 147.3 ± 0.73 nm. EA NPs likely adopt a tunnel-type solvate structure, with 4 water participating in disruption of intramolecular hydrogen bonds in EA and establishment of intermolecular hydrogen bonds between EAs. Importantly, EA NPs exhibited remarkable enhancements in water solubility, with 120.7-fold increase in water, and 97.8-fold increase in pH 6.8 buffer. Moreover, ex vivo intestinal permeability studies demonstrated significant improvements (P < 0.5). These findings were further supported by in vivo pharmacokinetic studies, where EA NPs significantly enhanced the relative bioavailability of EA by 4.69 times.

Intracellular Ellagic Acid Derived from Goat Urine DMSO Fraction (GUDF) Predicted as an Inhibitor of c-Raf Kinase.

BACKGROUND: Dietary chemicals and their gut-metabolized products are explored for their anti-proliferative and pro-cell death effects. Dietary and metabolized chemicals are different from ruminants such as goats over humans. METHODS: Loss of cell viability and induction of death due to goat urine DMSO fraction (GUDF) derived chemicals were assessed by routine in vitro assays upon MCF-7 breast cancer cells. Intracellular metabolite profiling of MCF-7 cells treated with goat urine DMSO fraction (GUDF) was performed using an in-house designed vertical tube gel electrophoresis (VTGE) assisted methodology, followed by LC-HRMS. Next, identified intracellular dietary chemicals such as ellagic acid were evaluated for their inhibitory effects against transducers of the c-Raf signaling pathway employing molecular docking and molecular dynamics (MD) simulation. RESULTS: GUDF treatment upon MCF-7 cells displayed significant loss of cell viability and induction of cell death. A set of dietary and metabolized chemicals in the intracellular compartment of MCF-7 cells, such as ellagic acid, 2-hydroxymyristic acid, artelinic acid, 10-amino-decanoic acid, nervonic acid, 2,4-dimethyl-2-eicosenoic acid, 2,3,4'- Trihydroxy,4-Methoxybenzophenone and 9-amino-nonanoic acid were identified. Among intracellular dietary chemicals, ellagic acid displayed a strong inhibitory affinity (-8.7 kcal/mol) against c-Raf kinase. The inhibitory potential of ellagic acid was found to be significantly comparable with a known c-Raf kinase inhibitor sorafenib with overlapping inhibitory site residues (ARG450, GLU425, TRP423, VA403). CONCLUSION: Intracellular dietary-derived chemicals such as ellagic acid are suggested for the induction of cell death in MCF-7 cells. Ellagic acid is predicted as an inhibitor of c-Raf kinase and could be explored as an anti-cancer drug.

Evaluation of the acute toxicity of ellagic acid and gallic acid incorporated in Poloxamer407® gel, in Zophobas morio larvae.

Gallic acid (GA) has antioxidant, anti-inflammatory and antimicrobial properties, while ellagic acid (EA) demonstrates anticancer, antiviral and photoprotective activity. In this study, the combination of these substances incorporated into a poloxamer gel was tested to verify the individual effect of the substances, in addition to taking advantage of a probable complementary effect, aiming to provide additional therapeutic benefits. As a result of the incorporation, formulations containing GA, EA and GA + EA were obtained, which were evaluated for the effects of the Freeze-thaw cycle on pH, which revealed a significant decrease (p < 0.05) in most samples, including the vehicle (without drug) and the gel containing both drugs. No sample showed variation outside the normal pH range for the skin, with values ranging from 4.8 to 6.0. Regarding conductivity, the GA, EA and GA + EA formulations showed a reduction (p < 0.05) after the freeze-thaw cycle. The drug content in the formulations ranged from 95.86% to 101.35% initially to 91.30% to 101.51% after the freeze-thaw cycle. Regarding the drug release, the results revealed the following cumulative percentages: GA-3% - 92.58% after 1.5 h; AE-3% - 51.60% after 6 h; GA + EA (1.5% = 1.5%) - 99.91% after 2 h; GA + EA- (1.5% = 1.5%) released 57.06%, after 6 h. Regarding toxicity, it was observed that the group treated with GA showed a lower survival rate of the larvae (40%) at the dose 3000 mg/Kg in the formulation. Following the same trend, in the acute lethal concentration (ALC50) test performed using Zophobas morio larvae, an ALC50 of 2191.51 mg/Kg was observed for GA at 48 h. Melanin analysis showed a decrease in concentrations of 30 mg/Kg in the GA group, 3 mg/Kg of EA and 3, 300, 3000 mg/Kg of GA + EA, of the pure drugs. In the groups with the drugs incorporated into the gel, there was a significant decrease (P < 0.05) in melanin in the vehicle (gel), at concentrations of 300 and 3000 mg/Kg of GA and EA. On the other hand, in the combination of GA + EA, a reduction was observed at concentrations of 3 and 30 mg/Kg when compared to the control group. Thus, the gel showed good quality as a pharmaceutical formulation for topical use and low toxicity, making it promising for use in skin therapies.

Ellagic Acid from Hull Blackberries: Extraction, Purification, and Potential Anticancer Activity.

Ellagic acid (EA) is present at relatively high concentrations in many berries and has many beneficial health effects, including anticancer properties. To improve the development and utilization of blackberry fruit nutrients, we divided Hull blackberry fruits into five growth periods according to color and determined the EA content in the fruits in each period. The EA content in the green fruit stage was the highest at 5.67 mg/g FW. Single-factor tests and response surface methodology were used to optimize the extraction process, while macroporous resin adsorption and alkali dissolution, acid precipitation, and solvent recrystallization were used for purification. The highest purity of the final EA powder was 90%. The anticancer assessment results determined by MTT assay showed that EA inhibited HeLa cells with an IC50 of 35 µg/mL, and the apoptosis rate of the cells increased in a dose-dependent manner, with the highest rate of about 67%. We evaluated the changes in the mRNA levels of genes related to the EA-mediated inhibition of cancer cell growth and initially verified the PI3K/PTEN/AKT/mTOR pathway as the pathway by which EA inhibits HeLa cell growth. We hope to provide a theoretical basis for the deep exploration and utilization of this functional food.

Multi-target bioactive compound screening from the infructescence of Platycarya strobilacea Sieb. et Zucc. by affinity chromatography using immobilized ß2 -adrenoceptor and muscarinic-3 acetylcholine receptor as the stationary phase.

As a main source for the recognition and identification of lead compounds, traditional Chinese medicine plays a pivotal role in preventing diseases for years. However, screening bioactive compounds from traditional Chinese medicine remains challenging because of the complexity of the systems and the occurrence of the synergic effect of the compounds. The infructescence of Platycarya strobilacea Sieb. et Zucc is prescribed for allergic rhinitis treatment with unknown bioactive compounds and unclear mechanisms. Herein, we immobilized the ß2 -adrenoceptor and muscarine-3 acetylcholine receptor onto the silica gel surface to prepare the stationary phase in a covalent bond through one step. The feasibility of the columns was investigated by the chromatographic method. Ellagic acid and catechin were identified as the bioactive compounds targeting the receptors. The binding constants of ellagic acid were calculated to be (1.56 ± 0.23)×107  M-1 for muscarine-3 acetylcholine receptor and (2.93 ± 0.15)×107  M-1 for ß2 -adrenoceptor by frontal analysis. While catechin can bind with muscarine-3 acetylcholine receptor with an affinity of (3.21 ± 0.05)×105  M-1 . Hydrogen bonds and van der Waals' force were the main driving forces for the two compounds with the receptors. The established method provides an alternative for multi-target bioactive compound screening in complex matrices.

Ellagic acid from pomegranate peel: Consecutive countercurrent chromatographic separation and antioxidant effect.

Ellagic acid is one of the most representative natural antioxidants, and is rich in pomegranate peel. In this study, a consecutive countercurrent chromatographic (CCC) separation method was established to improve the preparative efficiency of ellagic acid from pomegranate peel. By optimizing the solvent system, sample size and flow rate, 280 mg of ellagic acid was obtained from 5 g of crude sample from pomegranate peel by CCC after six consecutive injections. Moreover, the values of EC50 for ellagic acid in scavenging ABTS·+ and DPPH· were 4.59 ± 0.07 and 10.54 ± 0.07 µg/ml, respectively, indicating a strong antioxidant activity. This study not only established a high-throughput method for the preparation of ellagic acid, but also provided a successful example for the development of and research on other natural antioxidants.

Chemical Characterization and Multidirectional Biological Effects of Different Solvent Extracts of Arum elongatum: in Vitro and in Silico Approaches.

Arum elongatum (Araceae) is widely used traditionally for the treatment of abdominal pain, arterial hypertension, diabetes mellitus, rheumatism and hemorrhoids. This study investigated the antioxidant properties, individual phenolic compounds, total phenolic and total flavonoid contents (HPLC/MS analysis), reducing power and metal chelating effects of four extracts obtained from A. elongatum (ethyl acetate (EA), methanol (MeOH), methanol/water (MeOH/water) and infusion). The inhibitory activity of the extracts were also determined against acetylcholinesterase, butyrylcholinesterase, tyrosinase, amylase and glucosidase enzymes. The MeOH/water extracts contained the highest amount of phenolic contents (28.85 mg GAE/g) while the highest total flavonoid content was obtained with MeOH extract (36.77 mg RE/g). MeOH/water demonstrated highest antioxidant activity against DPPH⋅ radical at 38.90 mg Trolox equivalent per gram. The infusion extract was the most active against ABTS+ ⋅ (133.08 mg TE/g). MeOH/water extract showed the highest reducing abilities with the CUPRAC value of 102.22 mg TE/g and the FRAP value of 68.50 mg TE/g. A strong metal chelating effect was observed with MeOH/water extract (35.72 mg EDTAE/g). The PBD values of the extracts ranged from 1.01 to 2.17 mmol TE/g. EA extract displayed the highest inhibitory activity against AChE (2.32 mg GALAE/g), BChE (3.80 mg GALAE/g), α-amylase (0.56 mmol ACAE/g) and α-glucosidase (9.16 mmol ACAE/g) enzymes. Infusion extract was the most active against tyrosinase enzyme with a value of 83.33 mg KAE/g. A total of 28 compounds were identified from the different extracts. The compounds present in the highest concentration were chlorogenic acids, 4-hydroxybenzoic acid, caffeic acid, p-coumaric acid, ferulic acid, isoquercitrin, delphindin 3,5-diglucoside, kaempferol-3-glucoside and hyperoside. The biological activities of A. elongatum extracts could be due to the presence of compounds such as gallic acid, chlorogenic acids, ellagic acid, epicatechin, catechin, kaempferol, 4-hydroxybenzoic acid, caffeic acid, p-coumaric acid, ferulic acid, quercetin, isoquercitrin, and hyperoside. Extracts of A. elongatum showed promising biological activities which warrants further investigations in an endeavor to develop biopharmaceuticals.

Ellagic Acid and Its Metabolites as Potent and Selective Allosteric Inhibitors of Liver Pyruvate Kinase.

Liver pyruvate kinase (PKL) has recently emerged as a new target for non-alcoholic fatty liver disease (NAFLD), and inhibitors of this enzyme could represent a new therapeutic option. However, this breakthrough is complicated by selectivity issues since pyruvate kinase exists in four different isoforms. In this work, we report that ellagic acid (EA) and its derivatives, present in numerous fruits and vegetables, can inhibit PKL potently and selectively. Several polyphenolic analogues of EA were synthesized and tested to identify the chemical features responsible for the desired activity. Molecular modelling studies suggested that this inhibition is related to the stabilization of the PKL inactive state. This unique inhibition mechanism could potentially herald the development of new therapeutics for NAFLD.

Characterizations of food-derived ellagic acid-Undaria pinnatifida polysaccharides solid dispersion and its benefits on solubility, dispersity and biotransformation of ellagic acid.

The current study was aimed to enhance the solubility, dispersibility and biotransformation efficacy of ellagic acid (EA) by preparing food-derived ellagic acid-Undaria pinnatifida polysaccharides solid dispersion (EA/UPP SD). The results demonstrated that the solubility of EA/UPP SD was improved from 0.014 mg/mL to 0.383 mg/mL, and the enhancement was related to converting to a more amorphous state and restraining its self-aggregation during the mechanochemical process. The structure of EA/UPP SDs was mostly maintained by hydrogen bonds and hydrophobic interactions between EA and UPP. Moreover, the result of in vitro anaerobic incubations showed the biotransformation process was improved with EA/UPP SD addition to substrate due to the advance of microbial accessibility in EA dispersion. Altogether, these results indicated that the EA/UPP SDs expanded the application of EA by increasing the solubility and dispersity, and provided a theoretical basis for bioconversion efficiency enhancement.

Ellagic Acid and Its Anti-Aging Effects on Central Nervous System.

Aging is an unavoidable biological process that leads to the decline of human function and the reduction in people's quality of life. Demand for anti-aging medicines has become very urgent. Many studies have shown that ellagic acid (EA), a phenolic compound widely distributed in dicotyledonous plants, has powerful anti-inflammation and antioxidant properties. Moreover, it has been demonstrated that EA can enhance neuronal viability, reduce neuronal defects, and alleviate damage in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and cerebral ischemia. This paper reviews the biochemical functions and neuroprotective effects of EA, showing the clinical value of its application.

Effects of drying methods and solvent extraction on quantification of major bioactive compounds in pomegranate peel waste using HPLC.

Bioactive compound characterization is an essential step for utilizing pomegranate peel waste as food and nutraceuticals ingredients. In the present investigation, the effects of different drying methods (freeze, tray-oven, and sun) and extraction solvents such as methanol, ethanol, water, acetone, and hexane were investigated on the extraction and recovery of major bioactive compounds (ellagic acid, gallic acid, quercetin, and punicalagin) of pomegranate peel for two pomegranate varieties (i.e., Bhagwa and Ganesh) using high-performance liquid chromatography (HPLC). The results indicated that the freeze dried pomegranate peel powder of both pomegranate varities potential to extraction higher amount of bioactive compounds with methanol as extraction solvent as compared to other drying methods and solvents. Freeze-dried peel powder of Bhagwa pomegranate showed a higher amount of gallic acid (32.2 mg/g), ellagic acid (13.6 mg/g), punicalagin (15.2 mg/g), and quercetin (2.5 mg/g) with methanol solvent as compared to the other extract of Bhagwa and Ganesh varieties. The basis on the results of the current study, it can be concluded that the freeze-drying method of drying pomegranate peel powder and methanol as an extraction solvent are effective to recover higher amounts of bioactive compounds that can be utilized in food and pharmaceutical sectors at commercial scale.

In silico and in vitro studies on the inhibition of laccase activity by Ellagic acid: Implications in drug designing for the treatment of Cryptococcal infections.

In recent years, the increased frequency of drug-resistant strains of Cryptococcus neoformans has depleted our antifungal armory. In the present study, we investigated the inhibitory potential of ellagic acid (EA) against C. neoformans laccase through in silico and in vitro studies. For the first time, a homology modelling was established to model laccase and modelled protein served as a receptor for docking EA. Thermodynamic stability of the docked complex was ascertained by molecular dynamics simulation (MD). The analysis of root mean square deviation and fluctuation of alpha carbons of protein justifies the stability of the bound EA in the binding pocket of laccase. Frontier molecular orbitals of the EA was studied by density functional theory-based optimization by using the Lee-Yang-Parr correlation functional (B3LYP) approach. Negative values of the highest occupied/unoccupied molecular orbitals (HOMO/LUMO) indicated that laccase with EA forms a stable complex. Interestingly, EA inhibited laccase activity both in vitro and in yeast cells of C. neoformans. Moreover, EA treatment remarkably inhibited the proliferation of C. neoformans inside macrophages. The findings of the present study unveil the molecular basis of the interactions of laccase with EA, which may prove to be beneficial for designing laccase inhibitors as potential anti-cryptococcal agents.

The bioactivity and applications of pomegranate peel extract: A review.

Pomegranate peel (PP) is a by-product in the processing of pomegranate products, which is usually discarded as a waste. However, a large number of researches have shown that pomegranate peel extract (PPE) is rich in a variety of phenolic substances, among which ellagic acid (EA), as one of the main active components, has significant biological activities, such as anti-oxidation, anti-tumor, anti-inflammatory, neuroprotection, anti-viral, and anti-bacterial. We analyzed the mechanism of EA's biological activity, and discussed its application in the food industry, for instance, food preservation, food additives, and functional foods. Combined with the research status of PPE, we discussed the limitations and development potential of PPE, in order to provide theoretical reference and scientific basis for the development and utilization of pomegranate by-products. PRACTICAL APPLICATIONS: Pomegranate peel (PP), the inedible part of the fruit, is usually treated as waste. In recent years, researchers have been committed to exploring various bioactive ingredients in PP and exploring its potential benefits to human health, which has far-reaching significance. In this paper, the chemical constituents of polyphenols in PP were reviewed, mainly focusing on the biological activity and mechanism of ellagic acid (EA). We reviewed the applications and invention patents of pomegranate peel extract (PPE) in food field, including food preservation, food additive, and functional foods, providing reference for the recycling and reuse of PP.