Heterogeneity of transport and metabolism of Tormentillae rhizoma constituents across human intestinal epithelium cellular model.

Tormentilla erecta (L.) Raeusch is a widespread plant in Europe and Western Asia. Its rhizomes (Tormentilae rhizoma) are the main ingredient of herbal alcoholic beverages and can be used as a natural preservative in beer production. Apart from its unique taste qualities, therapeutic properties in gastrointestinal tract ailments are attributed to the tincture obtained from Tormentillae rhizoma. The presented research aimed to determine the mutual relationship between the components of Tormentillae tincture, present in popular alcoholic beverages, and intestinal epithelium (Caco-2 cell monolayers). A comprehensive qualitative and quantitative analysis of the tincture was performed, including the determination of condensed and hydrolyzable tannins as well as triterpenoids (UHPLC-DAD-MS/MS). Incubation of the tincture with Caco-2 monolayers has shown that only triterpenes pass through the monolayer, while condensed tannins are mainly bound to the monolayer surface. Ellagic acid derivatives were the only components of the Tormentillae tinctura being metabolized by cell monolayers to the compounds not previously described in the literature, which may be crucial in the treatment of intestinal diseases with inflammatory background.

A validated high-performance liquid chromatography method for detecting geniposide, ellagic acid, piperine, costunolide and dehydrocostus lactone in Liuwei Muxiang capsules.

In this study, a sensitive high-performance liquid chromatography detector was established and validated for the simultaneous determination of geniposide, ellagic acid, piperine, costunolide and dehydrocostuslactone in Liuwei Muxiang Capsules. The analysis was achieved on CHANIN 100-5-C18-H column (5µm, 250 mm×4.6 mm) with the temperature of 30oC. Gradient elution was applied using 0.1% phosphoric acid solution-methanol-acetonitrile (50:50) as mobile phase at the flow rate of 1.0 mL/min. The determination was performed at the wavelength of 225 nm (detecting geniposide), 254 nm (detecting ellagic acid), 343 nm (detecting piperine) and 225 nm (detecting costunolide and dehydrocostuslactone) along with the sample volume of 10µL. The linear ranges of geniposide, ellagic acid, piperine, costunolide and dehydrocostuslactone demonstrated good linear relationships within their respective determination ranges. The average recoveries were 100.04%, 99.86%, 99.79%, 100.17% and 100.41%, respectively. RSD% was 1.3%, 1.2%, 1.2%, 1.2%, 1.5%, respectively. The developed method was proved to be simple, accurate and sensitive, which can provide a quantitative analysis method for the content determination of geniposide, ellagic acid, piperine, costunolide and dehydrocostuslactone in Liuwei Muxiang capsules.

Ellagic acid inhibits dihydrotestosterone-induced ferroptosis and promotes hair regeneration by activating the wnt/ß-catenin signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Androgenic alopecia (AGA) is the most prevalent form of hair loss in clinical practice and affects the physical and psychological well-being of adolescents. Paeonia lactiflora Pallas (PL), which is widely used in traditional Chinese medicine, enhances blood function and promotes hair growth, and ellagic acid (EA), a polyphenol in PL extract, shows strong antioxidant, anti-aging, and anti-inflammatory properties and also plays a role in the treatment of various skin conditions. However, its role and mechanism of action in AGA remain unclear. AIM OF THE STUDY: To determine whether EA can rescue slow hair regeneration by regulating dihydrotestosterone (DHT)-induced ferroptosis in AGA mice and clarify the effect of EA on DHT-induced ferroptosis in dermal papilla cells (DPCs). MATERIALS AND METHODS: Male C57BL/6 mice were used to establish a DHT-induced AGA mouse model, whereas DPCs were used to establish a DHT-induced cellular model. Thereafter, we investigated the therapeutic mechanism of action of EA via immunofluorescence, western blot analysis, immunohistochemistry, electron microscopy, and molecular docking. RESULTS: EA stimulated hair regeneration in mice and reversed DHT-induced increases in iron content, lipid peroxidation, and DHT-induced mitochondrial dysfunction by activating the Wnt/ß-catenin signaling pathway. Further, ß-catenin knockdown suppressed the inhibitory effect of EA on DHT-induced ferroptosis in DPCs. CONCLUSION: EA inhibits DHT-induced ferroptosis and promotes hair regrowth in mice by activating the Wnt/ß-catenin signaling pathway. Thus, it has potential for use as a treatment option for AGA.

Dietary supplementation with ellagic acid improves the growth performance, meat quality, and metabolomics profile of yellow-feathered broiler chickens.

The aim of this research was to explore the effects of ellagic acid (EA) on growth performance, meat quality, and metabolomics profile of broiler chickens. 240 healthy yellow-feathered broilers were randomly divided into 4 groups (6 replicates/group and 10 broilers /replicate): 1) a standard diet (CON); 2) CON+0.01% EA; 3) CON+0.02% EA; 4) CON+0.04% EA. Compared with the CON group, dietary 0.02% EA increased linearly and quadratically the ADG and lowered F/G ratio from 29 to 56 d and from 1 to 56 d of age (P < 0.05). The EA groups had higher spleen index and showed linear and quadratic improve thymus index (P < 0.05). A total of 0.02% EA linearly and quadratically increased the leg muscle percentage and quadratically increased the breast muscle percentage (P < 0.05). Compared to the control diet, 0.02% EA decreased quadratically the L* and increased a* of breast muscle at 45 min postslaughter (P < 0.05), and quadratically decreased (P < 0.05) the b* and increased linearly and quadratically (P < 0.05) drip loss. Additionally, EA improved linearly and quadratically (P < 0.05) serum total protein concentration and reduced linearly and quadratically (P < 0.05) serum blood urea nitrogen concentration. A total of 0.02% EA quadratically increased catalase activity and decreased malondialdehyde concentration in breast muscle compared with the control diet (P < 0.05). 0.02% and 0.04% EA could linearly and quadratically increase (P < 0.05) the concentrations of histidine, leucine and essential amino acids (EAA), 0.02% EA could linearly and quadratically increase (P < 0.05) the concentrations of threonine, glutamate, and flavored amino acids in breast muscle. 0.02% EA linearly and quadratically improved the C20:3n6, C22:6n3, polyunsaturated fatty acid (PUFA) concentrations, and the ratio of PUFA to saturated fatty acids (SFA), but reduced the C16:0 and the SFA concentrations in breast muscle than the CON group (P < 0.05). The EA diet linearly increased (P = 0.035) and quadratically tended (P = 0.068) to regulate the C18:2n6c concentration of breast muscle. Metabolomics showed that alanine metabolism, aspartate and glutamate metabolism, arginine and proline metabolism, taurine and hypotaurine metabolism, and glycerophospholipid metabolism were the most differentially abundant. These results showed that EA supported moderate positive effects on growth performance, meat quality, and metabolomics profile of broilers.

Network pharmacology, computational biology integrated surface plasmon resonance technology reveals the mechanism of ellagic acid against rotavirus.

The target and mechanism of ellagic acid (EA) against rotavirus (RV) were investigated by network pharmacology, computational biology, and surface plasmon resonance verification. The target of EA was obtained from 11 databases such as HIT and TCMSP, and RV-related targets were obtained from the Gene Cards database. The relevant targets were imported into the Venny platform to draw a Venn diagram, and their intersections were visualized. The protein-protein interaction networks (PPI) were constructed using STRING, DAVID database, and Cytoscape software, and key targets were screened. The target was enriched by Gene Ontology (GO) and KEGG pathway, and the 'EA anti-RV target-pathway network' was constructed. Schrodinger Maestro 13.5 software was used for molecular docking to determine the binding free energy and binding mode of ellagic acid and target protein. The Desmond program was used for molecular dynamics simulation. Saturation mutagenesis analysis was performed using Schrodinger's Maestro 13.5 software. Finally, the affinity between ellagic acid and TLR4 protein was investigated by surface plasmon resonance (SPR) experiments. The results of network pharmacological analysis showed that there were 35 intersection proteins, among which Interleukin-1ß (IL-1ß), Albumin (ALB), Nuclear factor kappa-B1 (NF-κB1), Toll-Like Receptor 4 (TLR4), Tumor necrosis factor alpha (TNF-α), Tumor protein p53 (TP53), Recombinant SMAD family member 3 (SAMD3), Epidermal growth factor (EGF) and Interleukin-4 (IL-4) were potential core targets of EA anti-RV. The GO analysis consists of biological processes (BP), cellular components (CC), and molecular functions (MF). The KEGG pathways with the highest gene count were mainly related to enteritis, cancer, IL-17 signaling pathway, and MAPK signaling pathway. Based on the crystal structure of key targets, the complex structure models of TP53-EA, TLR4-EA, TNF-EA, IL-1ß-EA, ALB-EA, NF-κB1-EA, SAMD3-EA, EGF-EA, and IL-4-EA were constructed by molecular docking (XP mode of flexible docking). The MMGBS analysis and molecular dynamics simulation were also studied. The Δaffinity of TP53 was highest in 220 (CYS → TRP), 220 (CYS → TYR), and 220 (CYS → PHE), respectively. The Δaffinity of TLR4 was highest in 136 (THR → TYR), 136 (THR → PHE), and 136 (THR → TRP). The Δaffinity of TNF-α was highest in 150 (VAL → TRP), 18 (ALA → GLU), and 144 (PHE → GLY). SPR results showed that ellagic acid could bind TLR4 protein specifically. TP53, TLR4, and TNF-α are potential targets for EA to exert anti-RV effects, which may ultimately provide theoretical basis and clues for EA to be used as anti-RV drugs by regulating TLR4/NF-κB related pathways.

Ellagic acid protected the gingival tissue via fibroblast and epidermal growth factors in rats.

PURPOSE: To investigate the effect of ellagic acid (EA) in gingival tissues injury in rats. METHODS: Twenty rats were categorized into two groups. In burn group, an excisional wound area was created by removing a 4-mm diameter flap from the left molar region in the mucoperiosteal region of the gingiva. In burn + ellagic acid group, 1.2 mg/mL EA was administered as irrigation for one week. Animals was sacrificed under anesthesia at the end of experiment. Malondialdehyde (MDA), myeloperoxidase (MPO) and glutathione (GSH) level were measured. Hematoxylin and eosin, fibroblast growth factor (FGF) and epidermal growth factor (EGF) immunostainings were applied to tissues. RESULTS: MDA, MPO, inflammation and leukocyte infiltration were high in burn group. Degeneration epithelium, edema and inflammatory cell infiltration in connective tissue areas, and dilatation and congestion in blood vessels were observed in burn group. In burn + EA group, the gingival epithelium improved, collagen fiber production increased and organized dermis were observed. After burn injury, FGF and EGF activity was increased in EA treated groups. CONCLUSIONS: We suggest that EA have the potential for better healing outcomes in oral wounds. EA seems to have promising therapeutic efficacy to enhance oral wound healing.

Ellagic acid protects against angiotensin II-induced hypertrophic responses through ROS-mediated MAPK pathway in H9c2 cells.

The early myocardial response of hypertension is an elevation of angiotensin-II (Ang-II) concentration, leading to heart failure and cardiac hypertrophy. This hypertrophic event of the heart is mediated by the interaction of Ang type 1 receptors (AT-R1), thereby modulating NADPH oxidase activity in cardiomyocytes, which alters redox status in cardiomyocytes. Ellagic acid (EA) has anti-inflammatory and anti-oxidative capacities. Thus, EA has potential preventive effects on cardiovascular diseases and diabetes. In the last decades, because the protective effect of EA on Ang-II-induced hypertrophic responses is unclear, this study aims to investigate the protective effect of EA in cardiomyocytes. H9c2 cells were treated to Ang-II 1 µM for 24 h to induce cellular damage. We found that EA protected against Ang-II-increased cell surface area and pro-hypertrophic gene expression in H9c2. EA reduced Ang-II-caused AT-R1 upregulation, thereby inhibiting oxidative stress NADPH oxidase activation. EA mitigated Ang-II-enhanced p38 and extracellular-signal-regulated kinase (ERK) phosphorylation. Moreover, EA treatment under Ang-II stimulation also reversed NF-κB activity and iNOS expression. This study shows that EA protects against Ang-II-induced myocardial hypertrophy and attenuates oxidative stress through reactive oxygen species-mediated mitogen-activated protein kinase signaling pathways in H9c2 cells. Thus, EA may be an effective compound for preventing Ang-II-induced myocardial hypertrophy.

Protective effects and mechanisms of ellagic acid on intestinal injury in piglets infected with porcine epidemic diarrhea virus.

The present study was conducted to decipher the protection effects of ellagic acid (EA) on piglets infected with porcine epidemic diarrhea virus (PEDV). Thirty 7-day-old piglets were randomly assigned to three treatment groups: control, PEDV, and EA + PEDV groups. After a 3-day period of adaption, piglets in the EA + PEDV group were orally administered with 20 mg/kg·BW EA during days 4-11 of the trial. On day 8, piglets were orally administered with PEDV at a dose of 106 TCID50 (50% tissue culture infectious dose) per pig. Additionally, intestinal porcine epithelial (IPEC-1) cells infected with PEDV were used to investigate the anti-PEDV effect of EA in vitro. The results showed that EA at a dose of 10-40 µmol/L increased the viability of PEDV-infected IPEC-1 cells, and EA administration mitigated intestinal edema in piglets challenged with PEDV. Further studies indicated that EA treatment significantly increased the proportion of white blood cells in blood and concentrations of IL-6, IL-1ß, and IL-10 in the serum, but decreased the TNF-α content and gene expression of IL-6, IL-1ß, TNF-α, and CXCL2 in the jejunum. Moreover, EA intervention considerably elevated the activity of total superoxide dismutase (T-SOD), but decreased the H2O2 concentration in the ileum of piglets. Importantly, EA suppressed the increased expression of antiviral-related genes and proteins (including MXI, ISG15, HSP70, and p-IRF7) induced by PEDV challenge in the jejunum. Furthermore, PEDV infection increased the protein abundance of p-JAK2 and p-STAT3, which were further enhanced by EA supplementation. In conclusion, our results revealed that EA could promote the restoration of intestinal homeostasis by regulating the interferon pathway that was interrelated with the activation of JAK2/STAT3 signaling. These findings provide theoretical basis for the use of EA as a therapy targeting PEDV infection in piglets.

Gordonibacter faecis sp. nov., producing urolithin C from ellagic acid, isolated from feces of healthy Korean subjects.

A Gram-stain-positive, anaerobic, motile, and short rod-shaped bacterium, designated KGMB12511T, was isolated from the feces of healthy Koreansubjects. Phylogenetic analysis based on the 16S rRNA gene sequence showed that strain KGMB12511T was closely related to Gordonibacter pamelaeae 7-10-1-bT (95.2%). The draft genome of KGMB12511T comprised 33 contigs and 2,744 protein-coding genes. The DNA G + C content was 59.9% based on whole-genome sequences. The major cellular fatty acids (>10%) of strain KGMB12511T were C18:1 cis9, C18:1 cis9 DMA (dimethylacetal), and C16:0 DMA. The predominant polar lipids included a diphosphatydilglycerol, four glycolipids, and an unidentified phospholipid. The major respiratory quinones were menaquinone 6 (MK-6) and monomethylmenaquinone 6 (MMK-6). Furthermore, HPLC analysis demonstrated the ability of strain KGMB12511T to convert ellagic acid into urolithin. Based on a comprehensive analysis of phenotypic, chemotaxonomic, and phylogenetic data, strain KGMB12511T represents a novel species in the genus Gordonibacter. The type strain is KGMB12511T (= KCTC 25343T = NBRC 116190T).

In vitro conversion of ellagic acid to urolithin A by different gut microbiota of urolithin metabotype A.

The metabolite urolithin A, a metabolite of the dietary polyphenol ellagic acid (EA), has significant health benefits for humans. However, studies on the gut microbiota involved in ellagic acid metabolism are limited. In this study, we conducted in vitro fermentation of EA using human intestinal microbiome combined with antibiotics (vancomycin, polymyxin B sulfate, and amphotericin B). Liquid chromatography-mass spectrometry (LC-MS/MS) analysis demonstrated that the production capacity of urolithin A by gut microbiota co-treated with polymyxin B sulfate and amphotericin B (22.39 µM) was similar to that of untreated gut microbiota (24.26 µM). Macrogenomics (high-throughput sequencing) was used to analyze the composition and structure of the gut microbiota. The results showed that the abundance of Bifidobacterium longum, Bifidobacterium adolescentis, and Bifidobacterium bifidum in the gut microbiota without antibiotic treatment or co-treated with polymyxin B sulfate and amphotericin B during EA fermentation was higher than that in other antibiotic treatment gut microbiota. Therefore, B. longum, B. adolescentis, and B. bifidum may be new genera involved in the conversion of EA to urolithin A. In conclusion, the study revealed unique interactions between polyphenols and gut microbiota, deepening our understanding of the relationship between phenolic compounds like EA and the gut microbiota. These findings may contribute to the development of gut bacteria as potential probiotics for further development. KEY POINTS: • Intestinal microbiome involved in ellagic acid metabolism. • Gram-positive bacteria in the intestinal microbiome are crucial for ellagic acid metabolism. • Bifidobacterium longum, Bifidobacterium adolescentis, and Bifidobacterium bifidum participate in ellagic acid metabolism.

Irvingia gabonensis baill. (African Mango): A comprehensive review of its ethnopharmacological significance, unveiling its long-standing history and therapeutic potential.

ETHNOPHARMACOLOGICAL RELEVANCE: Irvingia gabonensis (Aubry-Lecomte ex O'Rorke) Baill. (IG) is a multipurpose tree native to tropical Africa such as Equatorial Guinea, Nigeria, Gabon, and Cameroon with high ethnomedicinal values. AIM OF THE STUDY: This review emphasizes the ethnopharmacological significance, phytochemical, and functional properties of African mango, focusing on its potential for human health and industrial applications. MATERIALS AND METHODS: Literature published on IG was traced by different databases, including the Egyptian Knowledge Bank database (EKB), ScienceDirect, PubMed, Google Scholars, Research Gate, Web of Science, Elsevier, and Scopus. Numerous keywords were used to achieve an inclusive search in the databases, like 'African Mango', 'Bush Mango', 'Irvingia gabonensis', 'Wild Mango', 'Dika Nut', 'Phytochemistry', 'Traditional uses', 'Functional foods', 'Polyphenols', 'Ogbono', 'Ellagic acid and its derivatives', and 'Pharmacological activities'. RESULTS: Different parts of IG have been employed in traditional medicine and recorded a great success. The ripe fruit pulp was consumed fresh or processed into juice and wine documented for anti-diarrheal, anti-diabetic, anti-ulcer, hepatoprotective, antimicrobial, and anti-inflammatory properties. The kernels, which are widely traded and incorporated into traditional dishes, remain an integral part of culinary traditions. Seeds have folkloric uses for weight loss and are popular as blood thinners and anti-diabetics. Where the bark is reported for dysentery, colic, scabies, toothache, and various skin conditions. In Senegal, the stem bark is employed for gonorrhea, hepatic disorders, and gastrointestinal ailments. The leaves possess the potential to enhance renal and hepatic functions, safeguarding these vital organs against the detrimental effects of toxic substances. Pulp is rich in vitamin C, carbohydrates, and proteins. Oil is the major constituent of the seed, which is mainly composed of myristic and lauric acids. The defatted extracts are characterized by flavonoid glycosides and ellagic acid derivatives. Despite their widespread use, IG extracts are still inadequately characterized phytochemically and merit further investigation within the realm of scientific research. Encouragingly, toxicity studies have demonstrated the relative safety of IG extract at the administered doses. CONCLUSION: The review extends our knowledge of the health benefits of IG, where these effects could be attributed to the phytochemicals present.

Improvement of Urolithin A Yield by In Vitro Cofermentation of Streptococcus thermophilus FUA329 with Human Gut Microbiota from Different Urolithin Metabotypes.

Streptococcus thermophilus FUA329 converts ellagic acid (EA) to urolithin A (Uro-A), which is not autonomously converted by the gut microbiota to produce highly bioavailable and multibiologically active Uro-A in urolithin metabotype 0 (UM-0) populations. We consider that Streptococcus thermophilus FUA329 has the potential to be developed as a probiotic. Therefore, we utilized S. thermophilus FUA329 for in vitro cofermentation with gut microbiota. The results revealed that strain FUA329 increased the production of EA-converted Uro-A during in vitro cofermentation with the human gut microbiota of different urolithin metabotypes (UMs), with a significant increase in the production of Uro-A in the experimental group of UM-0. In addition, changes in the in vitro cofermentation microbial community were determined using high-throughput sequencing. Strain FUA329 modulated the structure and composition of the gut microbiota in different UMs, thereby significantly increasing the abundance of beneficial microbiota in the gut microbiota while decreasing the abundance of harmful microbiota. Of greatest interest was the significant increase in the abundance of Actinobacteria phylum after the cofermentation of strain FUA329 with UM-0 gut microbiota, which might be related to the significant increase in the production of Uro-A.

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.

Chestnut Wood Tannins in Broiler Diets: Pharmacokinetics, Serum Levels during Rearing, and Intestinal Absorption Pattern of Gallic Acid.

Studies on the bioavailability, serum levels, and absorption of hydrolyzable tannin compounds are lacking. In this study, we performed a pharmacokinetic trial, measured the serum levels of compounds in broilers that were reared with different feed added or not with tannins, and tested the digestibility of tannins throughout the intestinal tract. Only gallic acid and 4-O-methyl gallic acid were found in the serum. Moreover, gallic acid showed a 41.8% absolute oral bioavailability and a 72.3% relative bioavailability of gallic acid from chestnut extract compared to the standard. The rapid metabolization caused alternating serum levels during the day and night. These patterns were not affected by the feed type or the previous addition of tannins in the feed. The absorption and metabolization in the intestines occurred gradually throughout the intestinal tract. The latter was true for gallic acid as well as ellagic acid, which was not found in the serum. We can conclude that components from chestnut tannins are absorbed throughout all components of the intestinal tract and are eliminated quickly with little interaction from the feed and previous addition of tannins. Moreover, ellagic acid seems to be absorbed but would remain accumulated in the intestinal tissue or be metabolized by the microbiome.

Oral administration of ellagic acid mitigates perioperative neurocognitive disorders, hippocampal oxidative stress, and neuroinflammation in aged mice by restoring IGF-1 signaling.

This study investigates the potential of ellagic acid (EA), a phytochemical with antioxidant and anti-inflammatory properties, in managing perioperative neurocognitive disorders (PND). PND, which represents a spectrum of cognitive impairments often faced by elderly patients, is principally linked to surgical and anesthesia procedures, and heavily impacted by oxidative stress in the hippocampus and microglia-induced neuroinflammation. Employing an aged mice model subjected to abdominal surgery, we delve into EA's ability to counteract postoperative oxidative stress and cerebral inflammation by engaging the Insulin-like growth factor-1 (IGF-1) pathway. Our findings revealed that administering EA orally notably alleviated post-surgical cognitive decline in older mice, a fact that was manifested in improved performance during maze tests. This enhancement in the behavioral performance of the EA-treated mice corresponded with the rejuvenation of IGF-1 signaling, a decrease in oxidative stress markers in the hippocampus (like MDA and carbonylated protein), and an increase in the activity of antioxidant enzymes such as SOD and CAT. Alongside these, we observed a decrease in microglia-driven neuroinflammation in the hippocampus, thus underscoring the antioxidant and anti-inflammatory roles of EA. Interestingly, when EA was given in conjunction with an IGF1R inhibitor, these benefits were annulled, accentuating the pivotal role that the IGF-1 pathway plays in the neuroprotective potential of EA. Hence, EA could serve as a potent candidate for safeguarding against PND in older patients by curbing oxidative stress and neuroinflammation through the activation of the IGF-1 pathway.

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.

Synergistic antibacterial activity of Phyllanthus emblica fruits and its phytocompounds with ampicillin: a computational and experimental study.

Phyllanthus emblica L. (syn. Emblica officinalis), popularly known as amla, Indian gooseberry, or the King of Rasyana, is a member of Phyllanthaceae family and is traditionally used in Ayurveda as an immunity booster. The present study aimed to investigate the synergistic interaction of Phyllanthus emblica (FPE) fruits and its selected phytocompounds with ampicillin against selected bacteria. Further, an in silico technique was used to find if major phytocompounds of FPE could bind to proteins responsible for antibiotic resistance in bacterial pathogens and enhance the bioactivity of ampicillin. FPE and all the selected phytocompounds were found to have synergistic antibacterial activity with ampicillin against tested bacteria in different combinations. However, ellagic acid and quercetin interactions with ampicillin resulted in maximum bioactivity enhancement of 32-128 folds and 16-277 folds, respectively. In silico analysis revealed strong ellagic acid, quercetin, and rutin binding with penicillin-binding protein (PBP-) 3, further supported by MD simulations. Ellagic acid and quercetin also fulfill Lipinski's rule, showing similar toxicity characteristics to ampicillin. FPE showed synergistic interaction with ampicillin, possibly due to the presence of phytocompounds such as gallic acid, ellagic acid, quercetin, and rutin. Molecular docking and MD simulations showed the strong interaction of ellagic acid and quercetin with PBP-3 protein. Therefore, these compounds can be explored as potential non-toxic drug candidates to combat bacterial antimicrobial resistance.

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.

High variability in Factor IX one-stage assay in samples spiked with nonacog beta pegol among different pairs of reagent/detection system.

INTRODUCTION: Haemophilia B (HB) is an X-linked hereditary bleeding disorder characterized by coagulation factor IX (FIX) deficiency. To improve the quality of life of patients and adherence to treatment, recombinant factor concentrates modified to extend their half-life have been developed, called extended half-life factors (EHL: extended half-life). Nonacog beta pegol (N9-GP) is a glycopegylated recombinant human FIX molecule that has a half-life of 93 h with a single dose and has shown a higher recovery percentage than other molecules. To diagnose and monitor the treatment of haemophiliac patients, FIX activity is determined with the one-stage clotting assay (OSA) and/or the chromogenic assay. The objective of this work, carried out in three centres, was to measure the recovery of N9-PG with 10 different activated partial thromboplastin time (APTT) reagents on three platforms, in samples spiked in vitro with N9-GP, at four different concentration levels. METHODS: It was measured the recovery of N9-GP with 10 different APTT reagents (polyphenol, ellagic acid, silice dioxide, colloidal silica as APTT activator on three platforms, in sample spiked in vitro with N9-GP. RESULTS: The results show heterogeneity in the activity of N9-GP measured by OSA with the different APTT reagents when the calibrations were performed with the specific calibrator of each coagulometer. A recovery percentage between 87% and 108% was obtained only with polyphenol and ellagic acid as activator in the three platforms evaluated. The other reagents studied overestimate or underestimate, with no clear profile. When a calibration curve was performed with a calibrator prepared from the N9-GP vial, all APTT reagents met the established recovery requirement. CONCLUSION: APTT reagents with polyphenol or ellagic acid as activator would be the only ones appropriate when using the commercially available OSA with specific calibrator to monitor patients treated with N9-GP.