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BACKGROUND: Sea buckthorn (Hippophae rhamnoides L.) was introduced into Canada in the early 2000s. This plant bears fruits with high commercial value in other countries due to its premium oil. Nevertheless, sea buckthorn berries are also a rich source of bioactives with nutraceutical potential, especially the variety grown in Newfoundland (Canada), which has not previously been characterized. As such, this study evaluated the composition of polyphenols in sea buckthorn pomace and seeds, as well as their prospective health‐promoting effects. RESULTS: Polyphenolic identification by high‐performance liquid chromatography–ultraviolet–mass spectrometry–time of flight revealed the presence of 24 compounds in the seeds and 16 compounds in the pomace, including phenolic acids, flavonoids, and tannins, with ellagic acid derivative IV (pomace, 52.13 μg g−1) and (+)‐catechin (seeds, 690.8 μg g−1) being the most dominant. Sea buckthorn extracts displayed in vitro antidiabetic and anti‐obesity potential by inhibiting α‐glucosidase (71.52–99.31%) and pancreatic lipase (15.80–35.61%) enzymes, respectively. The extracts also protected low‐density‐lipoprotein cholesterol (50.97–89.67%) and supercoiled DNA (35.11–79.84%) from oxidative damage. CONCLUSION: Sea buckthorn berries grown in Canada showed promising health benefits induced by their rich and diverse polyphenolic profile and need to be considered for further commercial expansion as a bioactive‐loaded superfruit. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Background: Decades of clinical research have demonstrated the efficacy of lithium in treating acute episodes (both manic and depressive), as well as in preventing recurrences of bipolar disorder (BD). Specific to lithium is its antisuicidal effect, which appears to extend beyond its mood-stabilizing properties. Lithium's clinical effectiveness is, to some extent, counterbalanced by its safety and tolerability profile. Indeed, monitoring of lithium levels is required by its narrow therapeutic index. There is consensus that adequate serum levels should be above 0.6 mEq/L to achieve clinical effectiveness. However, few data support the choice of this threshold, and increasing evidence suggests that lithium might have clinical and molecular effects at much lower concentrations. Content: This narrative review is aimed at: (1) reviewing and critically interpreting the clinical evidence supporting the use of the 0.6 mEq/L threshold, (2) reporting a narrative synthesis of the evidence supporting the notion that lithium might be effective in much lower doses. Among these are epidemiological studies of lithium in water, evidence on the antisuicidal, anti-aggressive, and neuroprotective effects, including efficacy in preventing cognitive impairment progression, Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS), of lithium; and (3) revieweing biological data supporting clinically viable uses of lithium at low levels with the delineation of a mechanistic hypothesis surrounding its purported mechanism of action. The study selection was based on the authors' preference, reflecting the varied and extensive expertise on the review subject, further enriched with an extensive pearl-growing strategy for relevant reviews and book sections. Conclusions: Clinical and molecular effects of lithium are numerous, and its effects also appear to have a certain degree of specificity related to the dose administered. In sum, the clinical effects of lithium are maximal for mood stabilisation at concentrations higher than 0.6 mEq/l. However, lower levels may be sufficient for preventing depressive recurrences in older populations of patients, and microdoses could be effective in decreasing suicide risk, especially in patients with BD. Conversely, lithium's ability to counteract cognitive decline appears to be exerted at subtherapeutic doses, possibly corresponding to its molecular neuroprotective effects. Indeed, lithium may reduce inflammation and induce neuroprotection even at doses several folds lower than those commonly used in clinical settings. Nevertheless, findings surrounding its purported mechanism of action are missing, and more research is needed to investigate the molecular targets of low-dose lithium adequately. [ABSTRACT FROM AUTHOR]

Neurological disorders (NDs) are diseases that seriously affect the health of individuals worldwide, potentially leading to a significant reduction in the quality of life for patients and their families. Herbal medicines have been widely used in the treatment of NDs due to their multi-target and multi-pathway features. Ginkgo biloba leaves (GBLs), one of the most popular herbal medicines in the world, have been demonstrated to present therapeutic effects on NDs. However, the pharmacological mechanisms of GBLs in the treatment of neurological disorders have not been systematically summarized. This study aimed to summarize the molecular mechanism of GBLs in treating NDs from the cell models, animal models, and clinical trials of studies. Four databases, i.e., PubMed, Google Scholar, CNKI, and Web of Science were searched using the following keywords: “Ginkgo biloba”, “Ginkgo biloba extract”, “Ginkgo biloba leaves”, “Ginkgo biloba leaves extract”, “Neurological disorders”, “Neurological diseases”, and “Neurodegenerative diseases”. All items meeting the inclusion criteria on the treatment of NDs with GBLs were extracted and summarized. Additionally, PRISMA 2020 was performed to independently evaluate the screening methods. Out of 1385 records in the database, 52 were screened in relation to the function of GBLs in the treatment of NDs; of these 52 records, 39 were preclinical trials and 13 were clinical studies. Analysis of pharmacological studies revealed that GBLs can improve memory, cognition, behavior, and psychopathology of NDs and that the most frequently associated GBLs are depression, followed by Alzheimer’s disease, stroke, Huntington’s disease, and Parkinson’s disease. Additionally, the clinical studies of depression, AD, and stroke are the most common, and most of the remaining ND data are available from in vitro or in vivo animal studies. Moreover, the possible mechanisms of GBLs in treating NDs are mainly through free radical scavenging, anti-oxidant activity, anti-inflammatory response, mitochondrial protection, neurotransmitter regulation, and antagonism of PAF. This is the first paper to systematically and comprehensively investigate the pharmacological effects and neuroprotective mechanisms of GBLs in the treatment of NDs thus far. All findings contribute to a better understanding of the efficacy and complexity of GBLs in treating NDs, which is of great significance for the further clinical application of this herbal medicine. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) is the most aggressive sub-type of breast cancer, mainly affecting premenopausal women. As it neither expresses hormone receptors nor overexpresses HER2 receptors, it is difficult to tackle this deadly disease effectively. It is a well-known fact that phytochemicals have remarkable therapeutic potential in the prevention and treatment of different disorders. One of the well-known phytochemicals, ellagic acid (EA) has shown better efficacy in the prevention and treatment of cancer in many preclinical and clinical settings. Therefore, in this study, ellagic acid gold nanoparticles (EA-AuNp) were synthesized and characterized to passively target TNBC cells through EPR effect. EA-AuNp were prepared using the direct reduction method and characterized by UV–Visible spectroscopy, DLS, XRD, EDX, TEM and FT-IR spectra. We found that it significantly suppressed the TNBC cell proliferation (IC 5 0 12 μ g/ml) compared to EA alone (IC 5 0 36 μ g/ml). Flow cytometry and live and dead assays revealed that EA-AuNp induced more cell death in TNBC cells compared to EA alone. Further, western blot analysis substantiated that EA-AuNp induced apoptosis by regulating the expression of Bcl-2, survivin, caspase 3 and caspase 9. In conclusion, EA-AuNp has high anti-cancer potential and additional preclinical and clinical studies are highly recommended. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) and diabetes are non-communicable diseases with global impacts. Inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are suitable therapies for AD, while α-amylase and α-glucosidase inhibitors are employed as antidiabetic agents. Compounds were isolated from the medicinal plant Terminalia macroptera and evaluated for their AChE, BChE, α-amylase, and α-glucosidase inhibitions. From 1H and 13C NMR data, the compounds were identified as 3,3′-di-O-methyl ellagic acid (1), 3,3′,4′-tri-O-methyl ellagic acid-4-O-β-D-xylopyranoside (2), 3,3′,4′-tri-O-methyl ellagic acid-4-O-β-D-glucopyranoside (3), 3,3′-di-O-methyl ellagic acid-4-O-β-D-glucopyranoside (4), myricetin-3-O-rhamnoside (5), shikimic acid (6), arjungenin (7), terminolic acid (8), 24-deoxysericoside (9), arjunglucoside I (10), and chebuloside II (11). The derivatives of ellagic acid (1–4) showed moderate to good inhibition of cholinesterases, with the most potent being 3,3′-di-O-methyl ellagic acid, with IC50 values of 46.77 ± 0.90 µg/mL and 50.48 ± 1.10 µg/mL against AChE and BChE, respectively. The compounds exhibited potential inhibition of α-amylase and α-glucosidase, especially the phenolic compounds (1–5). Myricetin-3-O-rhamnoside had the highest α-amylase inhibition with an IC50 value of 65.17 ± 0.43 µg/mL compared to acarbose with an IC50 value of 32.25 ± 0.36 µg/mL. Two compounds, 3,3′-di-O-methyl ellagic acid (IC50 = 74.18 ± 0.29 µg/mL) and myricetin-3-O-rhamnoside (IC50 = 69.02 ± 0.65 µg/mL), were more active than the standard acarbose (IC50 = 87.70 ± 0.68 µg/mL) in the α-glucosidase assay. For α-glucosidase and α-amylase, the molecular docking results for 1–11 reveal that these compounds may fit well into the binding sites of the target enzymes, establishing stable complexes with negative binding energies in the range of −4.03 to −10.20 kcalmol−1. Though not all the compounds showed binding affinities with cholinesterases, some had negative binding energies, indicating that the inhibition was thermodynamically favorable. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The phenolic compounds of four Palestinian honey samples (PH1-PH4) and their antibacterial effects as well as their cytotoxic, cytostatic, and antimigration effects in human breast cancer cell line (MDA) were evaluated here. HPLC analysis of PH2 (Cornflower), PH3 (Milk thistle), and PH4 (Ziziphus) revealed 15 phenolic compounds, namely, caffeic acid, carvacrol, chrysin, ellagic acid, galangin, gallic acid, kaempferol, p-coumaric acid, pinobanksin, pinocembrin, protocatechuic acid, quercetin, rutin, salicylic acid, and silydamin. The minimum inhibitory concentration (MIC) method applied to Pseudomonas aeruginosa (P. aeruginosa), Staphylococcus aureus (S. aureus), and Escherichia coli (E. coli). A strong positive correlation was detected between antimicrobial activity (E. coli) and p-coumaric acid, quercetin, and silydamin. IC50 values for DPPH neutralization varied from 0.19 w/w% to 10 w/w%. The potential anticancer properties of the honey samples were evaluated on MDA cells. Samples PH2 and PH3 demonstrated cytostatic activity, reducing cell viability by about 43% at non-toxic concentration of 4 mg/mL. The cytostatic effects were strongly correlated with the presence of caffeic acid, chrysin, protocatechuic acid, rutin, and salicylic acid (p < 0.01). Moreover, the cell migration rate was significantly reduced (by up to 85%) with PH2 and PH3 compared to untreated cells (p < 0.05). A strong positive correlation was observed between the cytostatic effects of the concentration of carvacrol and Pinocembrin (p < 0.01). Our findings validate honey’s antibacterial properties and suggest its anticancer benefits may stem from cytostatic and antimigration effects. [ABSTRACT FROM AUTHOR]

Background: Traditional Persian medicine has introduced effective remedies in opioid dependence care. One of the most widely used remedies is an herbal formulation containing Peganum harmala L. and Fraxinus excelsior L. (HF). This study investigated the effects of HF to attenuate the withdrawal signs and rewarding effects in morphine-dependent rats. Methods: Forty-nine male Wistar rats were randomly divided into seven groups. The control and vehicle groups received normal saline and sodium carboxymethyl cellulose, respectively. The morphine group received morphine for one week. The single and daily dose of HF groups received morphine similar to the morphine group, and HF (1.4 and 2.8 g/kg) once a day in the daily dose group and only on the last day of the experiment in the single dose of HF group. Finally, the withdrawal signs as well biochemical tests were evaluated. The behavioral parameters were assessed by conditioned place preference (CPP), elevated plus-maze and Y-maze tests. The antioxidant activity of HF was evaluated by measurement of serum contents of malondialdehyde, stable nitric oxide metabolites and total antioxidant capacity (TAC). Moreover, the protein expression of c-fos was assessed by western blotting. Results: Daily treatment with HF significantly reduced the score of CPP behavioral test, all of the withdrawal signs, TAC and the c-fos protein level. Conclusions: The results indicated that HF might be a promising complementary treatment in reducing morphine-induced physical and psychological dependence probably through modulation of c-fos protein expression. [ABSTRACT FROM AUTHOR]

The primary objective of this study was to conduct a comparative analysis of the anti-inflammatory activity between Etoricoxib (ETO) and Matcha green tea (MG) in the context of acute kidney injury (AKI) induced by ionizing gamma radiation (IR) in female rats. Furthermore, the potential impact of whole body IR exposure on the intestinal system and serum estradiol levels was investigated. Additionally, it was acknowledged that the ETO and MG treatments might have exerted favorable effects on the intestinal and hormonal responses. Six groups of rats were assigned to different treatments: control, ETO, MG, irradiation (IRR), ETO + IRR, and MG + IRR. The evaluation included measuring the total phenolic and flavonoid contents of ETO and MG, as well as assessing their antioxidant activity, radical scavenging capacity, reducing power, and total antioxidant capacity. Kidney function was assessed through serum creatinine and urea levels. Oxidative stress markers, including superoxide dismutase, glutathione, malondialdehyde, and catalase, were measured to evaluate the antioxidant effects of ETO and MG. The anti-inflammatory potential of the treatments was evaluated by measuring STAT-3 and interleukins (IL-6, IL-23, and IL-17) using an ELISA assay. Prostaglandin E2 receptor (PGE-2) mRNA expression, histopathological examination, and immunohistochemistry for NF-κB inhibitors were performed to investigate the underlying mechanisms in kidney tissue homogenates. Histopathological changes and DNA fragmentation in the intestinal tissues were determined, and the characterization of Matcha green tea was performed using liquid chromatography-mass spectrometry (LC-MS). This allowed for the identification and quantification of various compounds present in Matcha green tea. Furthermore, the study assessed the effect of IR and treatments on estrogen levels in female rats. Data showed that both ETO and MG had the potential to mitigate the adverse effects of AKI induced by IR. Notably, MG exhibited greater efficacy in attenuating oxidative stress and inflammation associated with renal injury. These findings revealed and compared the effects of ETO and MG in alleviating AKI caused by IR. MG demonstrated greater anti-inflammatory and antioxidant properties, highlighting its potential as a natural therapeutic agent. These results contribute to the growing evidence supporting the use of MG in managing IR-induced renal complications. Future studies should focus on elucidating the molecular mechanisms and optimizing the application of MG in clinical settings. This study is of significant importance as it compares the therapeutic potential of ETO and MG in mitigating AKI and intestinal damage induced by IR. The findings reveal that MG exhibits greater anti-inflammatory and antioxidant properties compared to ETO. These results provide valuable insights into the potential use of MG as a natural therapeutic agent for managing IR-induced renal and intestinal complications. As radiation therapy is commonly used in cancer treatment, identifying effective agents to protect the kidneys from radiation damage is crucial. The study contributes to the growing evidence supporting the application of MG in clinical settings, offering a promising alternative approach with potential benefits in terms of reduced side effects and improved patient outcomes. [ABSTRACT FROM AUTHOR]

The nanoporous compound SBA-15 was functionalized using (3-aminopropyl)trimethoxysilane (APTES). Then the obtained product was modified with ellagic acid (ELA), a bioactive polyphenolic compound. The structure of the prepared nanoporous composition SBA-15@ELA was extensively characterized and confirmed by various techniques, such as Fourier-transform infrared (FT-IR) spectroscopy, Energy dispersive X-ray (EDX) elemental analysis, scanning electron microscopy (SEM), thermogravimetric analysis (TGA), X-ray diffraction (XRD), transmission electron microscopy (TEM) and N2 adsorption–desorption isotherms (BET). The novel, recoverable, heterogenous SBA-15@ELA nanoporous compound was used to investigate its catalytic effect in the synthesis of 4-oxo-quinazoline derivatives (19 examples) with high yields (78–96%), as an important class of nitrogen-containing heterocyclic compounds. The use of an inexpensive mesoporous catalyst with a high surface area, along with easy recovery by simple filtration are among the advantages of this catalysis research work. The catalyst has been used in at least 6 consecutive runs without a significant loss of its activity. [ABSTRACT FROM AUTHOR]

Chebulae Fructus (CF) is known as one of the richest sources of hydrolyzable tannins (HTs). In this study, ultra-performance liquid chromatography coupled with a photodiode array detector method was established for simultaneous determination of the 12 common phenolcarboxylic and tannic constituents (PTCs). Using this method, quantitative analysis was accomplished in CF and other four adulterants, including Terminaliae Belliricae Fructus, Phyllanthi Fructus, Chebulae Fructus Immaturus, and Canarii Fructus. Based on a quantitative analysis of the focused compounds, discrimination of CF and other four adulterants was successfully accomplished by hierarchical cluster analysis and principal component analysis. Additionally, the total contents of the 12 compounds that we focused on in this study were unveiled as 148.86 mg/g, 96.14 mg/g, and 18.64 mg/g in exocarp, mesocarp, and endocarp and seed of CF, respectively, and PTCs were witnessed to be the most abundant in the exocarp of CF. Noticeably, the HTs (chebulagic acid, chebulanin acid, chebulinic acid, and punicalagin) were observed to be ultimately degraded to chebulic acid, gallic acid, and ellagic acid during sunlight-drying of the fresh fruits. As a result, our study indicated that CF and its adulterants could be distinguished by the observed 12 PTCs, which were mainly distributed in the exocarp of the fruits. The HTs were prone to degrade into the three simple phenolcarboxylic acids during drying or processing, allowing us to obtain a more comprehensive understanding of the PTCs, with great significance in the improved quality of CF and related products. [ABSTRACT FROM AUTHOR]

The oxygen evolution reaction (OER) is central to energy conversion technologies, but the high cost and scarcity of commercial noble metal catalysts limit their widespread application. Natural products exhibit great potential in preparing high‐performance electrocatalysts due to their cost‐effectiveness and sustainability. Here, a kind of 1D polymers [M‐EA (M═Co, Cu, Ni)] for oxygen evolution reaction via the complexation of ellagic acid (EA) with metal ions are reported. It is found that Ni‐EA displays a low overpotential (190 mV at 10 mA cm−2) and an ultralow Tafel slope (28 mV dec−1), with a production cost of only 3.6 × 10−2% of IrO2. Density functional theory investigations reveal the electrocatalytic mechanism of the OER. A rechargeable Zn‐Air battery using Ni‐EA+Pt/C as the air electrode shows a lower charging potential and better cycling stability than the IrO2+Pt/C‐based battery. This work provides a train for the development of state‐of‐the‐art OER catalysts. [ABSTRACT FROM AUTHOR]

The fruit processing industry generates large quantities of by-products well known to be rich in bioactive compounds with numerous nutritional properties and beneficial effects for human health. We developed a strategy to valorise raspberry seeds and obtain valuable ingredients with potential application in cosmetic skincare formulas. Cold press extraction technology was applied to extract oil, and the remaining defatted raspberry seed cake was treated with three proline based deep eutectic solvents (DES) to extract polyphenols. The most potent was proline/citric acid extract, with free and total ellagic acid content (52.4 mg/L and 86.4 mg/L), total phenolic content (TPC, 550.1 mg GAE/L) and radical scavenging activity (RSA, 4742.7 mmol TE/L). After the direct mixing of the extract and after encapsulation with starch as a carrier, the skincare emulsion and microemulsion were characterised by irritation potential (Zein test), transepidermal water loss (TEWL), red blood cell (RBC), and DPPH antioxidant test. The resulting preparations were of improved quality in comparison to the control hand cream, with a low skin irritation effect, lower TEWL, and higher antioxidant potential. This work complies with circular economy principles and green technology standards, and represents the efficient model on how to reuse natural resources through waste minimization. [ABSTRACT FROM AUTHOR]

Aims The research aimed to optimize the ultrasound-assisted extraction of secondary metabolites and the antibacterial activity of the plant species Geranium robertianum. The phytochemical profiles of the optimized extracts, as well as their antibacterial and synergistic activity with an antibiotic and their potential mechanisms of action and cytotoxicity, were examined. Methods and results Response Surface Methodology was used to optimize extraction conditions. Optimized ethanol and acetone extracts were tested via microdilution, checkerboard, time-kill kinetics, and cell membrane permeability methods. The extracts displayed broad antibacterial activity with minimum inhibitory concentrations ranging from 1.25 to 20 mg ml−1. In addition, the extract synergistically reacted with gentamicin against gentamicin-resistant strains of Escherichia coli and Staphylococcus aureus , enhancing the efficacy of the antibiotic up to 32-fold. The extracts demonstrated strain-dependent bactericidal activity in a 24-h time interval. They increase the permeability of the cell membrane, thus disrupting its normal functioning. The cytotoxic concentration (CC50) on human keratinocytes was 1771.24 ± 5.78 µg ml−1 for ethanol extract, and 958.01 ± 6.14 µg ml−1 for acetone extract. Kaempferol, ellagic acid, quercetin, and rutin were recognized as the main components in both extracts. Conclusions The findings of this study indicate that the extracts of G. robertianum can be considered as potential natural antibacterial agents in the control of microorganisms. [ABSTRACT FROM AUTHOR]

Edible insects are a promising and sustainable food source for humans due to their low environmental footprint, high feed conversion ratio, and high protein content. Furthermore, the nutritional profile of the edible insects can be modified depending on the provided diet. The aim of this study was to evaluate the growth performance, proximate composition, and ellagic acid accumulation in Tenebriomolitor larvae fed on corn flour media enriched with pomegranate peel. Corn flour and pomegranate peel were mixed in a 1:1 ratio (w/w) (PCM) and 50 T.molitor larvae were added to each jar. After 12 days of rearing, the weight of T.molitor larvae fed on PCM and the control increased by 88.35% and 58.6%, respectively, compared to their initial values. An increase in carbohydrate, protein and ash contents, along with a decrease in lipid content, was observed in the control diet after 12 days of feeding compared to the initial larvae. Conversely, the PCM diet exhibited an increase in ash and carbohydrate contents and a decrease in lipid and protein contents after 12 days of feeding compared to the initial larvae. Total phenolic content (TPC) of T.molitor larvae did not significantly vary when fed with the control group, while it increased on the fourth and twelfth days for larvae fed with the PCM diet. The CUPRAC antioxidant activity of larvae also increased on the fourth day of feeding on the PCM diet. Ellagic acid was not detected in larvae fed with control and initially, it accumulated in T.molitor larvae fed with PCM after 8 and 12 days of rearing, with concentrations of 92.54 and 115.6 µg/g larvae, respectively. This study highlights the importance of diet in changing the phenolic profile of T.molitor larvae, which can be used as a functional food ingredient to obtain value-added products from agricultural wastes. [ABSTRACT FROM AUTHOR]

Ellagic acid (EA) is a natural antioxidant found in many fruits and vegetables. However, its solubility in water is poor, which limits its application. To overcome this limitation, the surfactants Span 20 and Tween 60 are used to increase its solubility in water. FTIR, TEM and laser particle size and zeta potential analysis were used to characterize the morphology and structure of ellagic acid emulsions. The antioxidant activity of surfactant-compatible ellagic acid was determined using various antioxidant evaluation methods such as DPPH and ABTS radical scavenging, reducing power and total antioxidant activity. The results indicate that the solubility of ellagic acid in water was improved by the addition of Span 20 and Tween 60, and ellagic acid formed complex particles in combination with Span 20 and Tween 60. Compared to pure ellagic acid, the antioxidant activity of ellagic acid lotion was significantly enhanced. [ABSTRACT FROM AUTHOR]

Objective:To explore effect of polydatin on ocular surface dysfunction and pathology in dry eye disease (DED) rats and its protective mechanism. Methods:Eighteen from 90 SD rats were randomly chosen as control group, and other rats were injected subcutaneously with scopolamine hydrobromide to establish DED model. After modeling, rats were separated into model group, 0.05%polydatin group, 0.5%polydatin group, 0.5%polydatin+U0126 [mitogen-activated protein kinase kinase (MEK) inhibitor group, with 18 rats in each group; each administration group was given corresponding doses of drugs for intervention, and rats in control group and model group were given same amount of normal saline. On the 7th, 14th, 21st, and 28th day of intervention, Schirmer test was performed to measure tear secretion amount of rats in each group, fluorescein staining was performed to measure tear film breakup time (BUT) and corneal damage of rats in each group; RT-qPCR was performed to measure mRNA expression of proinflammatory factors TNF-α, IFN-γ and IL-1β in cornea and conjunctival tissues; HE staining was performed to observe histopathological changes of cornea; PAS staining was performed to evaluate number of conjunctival goblet cells; Western blot was performed to detect expressions of MEK/extracellular regulatory protein kinase (ERK) pathway related proteins. Results:Compared with control group, tear secretion amount BUT and number of conjunctival goblet cells in model group were obviously reduced (P<0.05), corneal injury score, TNF- α, IFN- γ and IL-1β mRNA levels were obviously increased (P<0.05), corneal epithelial layer was thinned, a large number of inflammatory cell infiltration and new capillaries could be seen; compared with model group, tear secretion amount, BUT, number of conjunctival goblet cells, p-MEK1/2/MEK1/2 and p-ERK1/2/ERK1/2 in 0.05%polydatin group and 0.5%polydatin group were obviously increased (P<0.05), corneal injury score, TNF-α, IFN-γ and IL-1β mRNA levels were obviously reduced (P< 0.05), pathological damage of corneal tissue was obviously relieved; U0126 could significantly attenuate protective effects of polydatin on ocular surface dysfunction and pathological changes in DED rats. Conclusion:Polydatin may improve ocular surface dysfunction and pathology of DED rats induced by scopolamine by activating MEK/ERK pathway. [ABSTRACT FROM AUTHOR]

Purpose: Dysfunctions of retinal pigment epithelium (RPE) attributed to oxidative stress and inflammation are implicated with age-related macular degeneration (AMD). A debate on the curative role of metformin in AMD has been raised, though several recent clinical studies support the lower odds by using metformin. This study aimed to determine whether metformin could exert cytoprotection against RPE oxidative damages and the potential mechanisms. Methods: A cellular AMD model was established by treating ARPE-19 cells with hydrogen peroxide (H2O2) for 24 h. The reactive oxygen species (ROS) generation, expression of antioxidant enzymes, and levels of pro-inflammatory cytokines were monitored under administrations with H2O2 with/without metformin. The expression and DNA-binding activity of transcription factor erythroid-related factor 2 (Nrf2) were determined by western blot, immunofluorescence, and electrophoretic mobility shift assay. Knockout of Nrf2 was conducted by CRISPR/Cas9 gene deletion system. Results: Metformin pretreatment significantly improved the H2O2-induced low viability of ARPE-19 cells, reduced ROS production, and increased contents of antioxidative molecules. Concurrently, metformin also suppressed levels of pro-inflammatory cytokines caused by H2O2. The metformin-augmented nuclear translocation and DNA-binding activity of Nrf2 were further verified by the increased expression of its downstream targets. Genetic deletion of Nrf2 blocked the cytoprotective role of metformin. Conclusion: Metformin possesses antioxidative and anti-inflammatory properties in ARPE-19 cells by activating the Nrf2 signaling. It supports the potential use for the control and prevention of AMD. [ABSTRACT FROM AUTHOR]

Background: During the pandemic, the interest in colorful wild small fruits increased due to their positive effects on health. Also it has become very important to offer species with high nutritional value as fresh or processed products for human consumption due to increasing world population and decreasing arable land. In this context, we characterized the horticultural characteristics of 11 rosehip genotypes grown from seeds. Results: Citric acid was determined as the main organic acid in all the genotypes investigated. The mean values of the organic acids obtained from all the genotypes were found to be as follows: citric acid (7177 mg L–1), malic acid (3669 mg L–1), tartaric acid (1834 mg L–1), oxalic acid (1258 mg L–1), carboxylic acid (631.9 mg L–1), shikimic acid (157.8 mg L–1), ascorbic acid (155 mg L–1), and acetic acid (20.9 mg L–1). Ellagic acid was the dominant phenolic compound (90.1 mg L–1 – 96.2 mg L–1) in all genotypes. The average values obtained from all genotypes for total phenolics, total flavonoids, and antioxidant activity were 37 261 mg GAE L–1, 526.2 mg quercetin L–1, and 93.6%, respectively. These characteristics had the lowest coefficients of variation, which indicated that all genotypes were similar regarding high biochemical with antioxidant effect. In addition, fruit width, fruit length, and fruit weight varied between 13.0 and 17.3 mm, 20.7 and 25.5 mm, and 1.4 and 2.7 g, respectively. Conclusions: The genotypes were categorized according to different purposes, such as suitability for wine production, making vinegar, etc. While the pomological characteristics were strongly positively correlated among themselves, they were generally found to be negatively correlated with the phytochemical characteristics. Categorizing genotypes according to different usage purposes can improve the agricultural and industrial application of rosehip and enhance their breeding efficacy. [ABSTRACT FROM AUTHOR]

Urolithiasis is a prevalent urological disorder that contributes significantly to global morbidity. This study aimed to assess the anti-urolithic effects of Cymbopogon proximus (Halfa Bar) and Petroselinum crispum (parsley) seed ethanolic extract /Gum Arabic (GA) emulsion, and its nanogel form against ethylene glycol (EG) and ammonium chloride (AC)-induced experimental urolithiasis in rats. Rats were divided into four groups: group 1 served as the normal control, group 2 received EG with AC in drinking water for 14 days to induce urolithiasis, groups 3 and 4 were orally administered emulsion (600 mg/kg/day) and nanogel emulsion (600 mg/kg/day) for 7 days, followed by co-administration with EG and AC in drinking water for 14 days. Urolithiatic rats exhibited a significant decrease in urinary excreted magnesium, and non-enzymic antioxidant glutathione and catalase activity. Moreover, they showed an increase in oxalate crystal numbers and various urolithiasis promoters, including excreted calcium, oxalate, phosphate, and uric acid. Renal function parameters and lipid peroxidation were intensified. Treatment with either emulsion or nanogel emulsion significantly elevated urolithiasis inhibitors, excreted magnesium, glutathione levels, and catalase activities. Reduced oxalate crystal numbers, urolithiasis promoters' excretion, renal function parameters, and lipid peroxidation while improving histopathological changes. Moreover, it decreased renal crystal deposition score and the expression of Tumer necrosis factor-α (TNF-α) and cleaved caspase-3. Notably, nanogel emulsion showed superior effects compared to the emulsion. Cymbopogon proximus (C. proximus) and Petroselinum crispum (P. crispum) seed ethanolic extracts/GA nanogel emulsion demonstrated protective effects against ethylene glycol induced renal stones by mitigating kidney dysfunction, oxalate crystal formation, and histological alterations. [ABSTRACT FROM AUTHOR]

Propolis extracts have been widely studied due to their popularity in traditional medicine, presenting incredible biodiversity. This study aimed to analyze propolis extracts' phytochemical, physicochemical, and biological activities from four different biogeographic zones of the Huila region (Colombia). The raw material samples were collected by the scraping method and the ethanolic extracts (EEPs) were obtained by cold maceration with ethanol (96%). The physicochemical and sensory characterization was carried out according to the protocols recommended by the Brazilian Ministry of Agriculture and the main components of the EEPs were identified by LC-HRMS analysis. The determination of total phenols and flavonoids was carried out using colorimetric techniques. The antioxidant activity, cytotoxicity, and cell cycle regulation analyses in L929 and HGnF cells were evaluated using DPPH, Alamar Blue, and 7-amino actinomycin D (7-AAD) assays. The propolis samples presented an average yield of 33.1%, humidity between 1.6 and 2.8%, melting point between 54 and 62 °C, ashes between 1.40 and 2.19%, and waxes of 6.6–17.9%, respectively. The sensory characteristics of all samples were heterogeneous, complying with the quality specifications established by international standards. The polyphenolic and total flavonoid content was representative in the samples from Quebradon (255.9 ± 9.2 mg GAE/g, 543.1 ± 8.4 mg QE/g) and Arcadia (543.1 ± 8.4 mg GAE/g, 32.5 ± 1.18 g QE/g) (p < 0.05) that correlated with high antioxidant activity (Quebradon: 37.2 ± 1.2 µmol/g, Arcadia: 38.19 ± 0.7 µmol/g). In the chemical composition analysis, 19 compounds were characterized as phenolic acids and flavonoids, the most representative being chrysoeriol-O-methyl-ether, ellagic acid, and 3,4-O-dimethylcaffeic acid. Regarding biological activity, Quebradon and Arcadia propolis presented low toxicity with IC50 of 2.83 ± 2.3 mg/mL and 4.28 ± 1.4 mg/mL in HGnF cells, respectively, and an arrest of the cell cycle in the G2/M phase of 71.6% and 50.8% compared to the control (11.9%) (p < 0.05). In general, the results of this study contribute to the identification of valid quality criteria to evaluate Colombian propolis, contributing to its study and chemical and biological characterization as a source of raw material for industrial and pharmaceutical use. In addition, Quebradon and Arcadia propolis can be important sources of bioactive molecules for the development of new drugs. [ABSTRACT FROM AUTHOR]

Summary: Burdekin plums (BP) are the fruits of Pleiogynium timoriense (DC.) Leenh, a tree native to Australia. In this study, BP fruit leathers were developed by blending BP puree with apple puree (0%–80% levels) to make five formulations of BP fruit leathers (100BP, 80BP, 60BP, 40BP, 20BP). Physicochemical parameters and microbial stability of fruit leathers were studied during six‐month storage at ambient conditions (temperature 16–25 °C, humidity 60%–77%). Results showed that BP leathers had a water activity from 0.60 to 0.64 and moisture content from 21% to 25%, and both were stable during storage. 20BP had the highest score for all colour parameters measured and had the lowest value in hardness. Reduction in redness and chroma and an increase in hue were observed in all leathers after storage. The total content of cyanidin 3‐galactoside and cyanidin 3‐glucoside decreased from 400–1600 mg/kg DW to 100–500 mg/kg DW after processing into leathers then to 9–70 mg/kg DW after storage. A decrease in catechins was also observed after puree was processed into leather and after the 6 months of storage, whereas an increase in gallic acid, ellagic acid, quercetin 3‐glucoside, trigalloylglucose was observed particularly in 20BP. Total phenolic content (ranging from 6 to 24 mg GAE/g DW) and antioxidant capacity (ranging from 80 to 240 μmol Fe2+/g DW) remained relatively stable after processing and storage with a slight reduction in 80BP and 100BP. Fruit leathers were microbiologically safe and shelf‐stable during the 6 months of storage. These results demonstrated the potential of BP to be processed into shelf‐stable fruit leathers rich in bioactive phenolics. [ABSTRACT FROM AUTHOR]

BACKGROUND: Overactive osteoclasts disrupt bone homeostasis and play a bad role in the pathological mechanisms of related skeletal diseases, such as osteoporosis, fragility fractures, and osteoarthritis. Studies have confirmed that ellagic acid and ellagtannin have the potential to inhibit osteoclast differentiation. As their natural metabolites, urolithin A has antioxidant, anti-inflammatory, anti-proliferative and anti-cancer effects, but its effect on osteoclast differentiation and its underlying molecular mechanisms remain unclear. OBJECTIVE: To explore the effect of urolithin A on osteoclast differentiation induced by receptor activator for nuclear factor-κB ligand and its mechanism. METHODS: Mouse mononuclear macrophage leukemia cells (RAW264.7) that grew stably were cultured in vitro. Toxicity of urolithin A (0, 0.1, 0.5, 1.5, 2.5 μmol/L) to RAW264.7 cells were detected by cytotoxic MTS assay to screen out the safe concentration. Different concentrations of urolithin A were used again to intervene with receptor activator for nuclear factor-κB ligand-induced differentiation of RAW264.7 cells in vitro. Then, tartrate-resistant acid phosphatase staining and F-actin ring and nucleus staining were performed to observe its effect on the formation and function of osteoclasts. Finally, the expressions of urolithin A on upstream and downstream genes and proteins in the MAPK signaling pathway were observed by western blot and RT-qPCR assays. RESULTS AND CONCLUSION: Urolithin A inhibited osteoclast differentiation and F-actin ring formation in a concentration-dependent manner and 2.5 μmol/L had the strongest inhibitory effect. Urolithin A inhibited the mRNA expression of Nfatc1, Ctsk, Mmp9 and Atp6v0d2 and the protein synthesis of Nfatc1 and Ctsk, related to osteoclast formation and bone resorption. Urolithin A inhibited the activity of osteoclasts by downregulating the phosphorylation of p38 protein to inhibit the mitogen-activated protein kinase signaling pathway. [ABSTRACT FROM AUTHOR]

Terminalia canescens DC. Radlk. (family: Combretaceae) is native to northern Australia. Species of the genus Terminalia are widely used as traditional medicines to treat diverse ailments, including bacterial infections. However, we were unable to find any studies that had examined the antimicrobial activity of T. canescens. In this study, T. canescens was screened against a panel of bacterial pathogens, including multi-antibiotic-resistant strains. Solvents with different polarities were used to extract different complements of phytochemicals from T. canescens leaves. Methanolic and aqueous extracts exhibited substantial antimicrobial activity against various pathogens, including those that are multidrug-resistant strains. When combined with some selected clinical antibiotics, some extracts potentiated the antibacterial inhibitory activity. This study identified two synergistic, eleven additive, eleven non-interactive and eight antagonistic interactions. The toxicities of the plant extracts were examined in the Artemia franciscana nauplii assay and were found to be non-toxic, except the aqueous extract, which showed toxicity. Metabolomic liquid chromatography–mass spectrometry (LC-MS) analyses highlighted and identified several flavonoids, including vitexin, quercetin, orientin and kaempferol, as well as the tannins ellagic acid and pyrogallol, which may contribute to the antibacterial activities observed herein. The possible mechanism of action of these extracts was further explored in this study. [ABSTRACT FROM AUTHOR]

BACKGROUND: Dietary interventions are crucial in modulating inflammation in humans. Strawberries are enjoyed by people of different ages as a result of their attractive phenotype and taste. In addition, the active compounds in strawberries may contribute to the reduction of inflammation. When developing new strawberry cultivars to address agricultural and environmental threats, the bioactivity of strawberries must be improved to maintain their health benefits. RESULTS: We determined the phytochemical contents of extracts from a new Korean strawberry cultivar, with the CN7 cultivar extract possessing the highest total polyphenol and flavonoid contents compared to the CN5 and Seolhyang cultivar extracts. The new Korean strawberry cultivars reduced the expression of inflammatory‐related genes in lipopolysaccharide (LPS)‐induced RAW264.7 cells via the nuclear factor‐kappa B signaling pathway, indicating an anti‐inflammatory effect. The CN7 cultivar showed greater bioactivity potential and the highest ellagic acid content; hence, we assessed the effect of the CN7 cultivar in an LPS‐stimulated mouse model. The CN7 cultivar treatment demonstrated its effectiveness in reducing inflammation via the downregulation of inflammatory cytokines secretion and gene expression. CONCLUSION: The results obtained in the present study have revealed the observable differences of the newly developed strawberry cultivars with Seolhyang in mitigating inflammation induced by LPS. The enhanced phytochemical content of the CN7 cultivar extract may contribute to its improved anti‐inflammatory effect. Therefore, it is crucial to maintain the nutritive benefits of strawberry during the development of new cultivation. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Background: Drug-induced kidney injury was among the most common renal damages, from which gentamicin occupies around 25% of this injury. Gentamicin-induced renal damage is caused by increased free radicals with subsequent amplified inflammation. Ajuga remota leaf extract has many phytochemicals with antioxidant activities, which may improve gentamicin-induced renal damage. Thus, we aimed to investigate the nephroprotective effect of Ajuga remota leaf methanolic extract on gentamicin-induced nephrotoxicity in Swiss Albino Mice. Methods: An experimental study design was used on 30 experimental mice randomly allocated in six groups: Group I, II, II, IV, and VI, among which mice were given only distilled water, only gentamicin, 600 mg/kg Ajuga remota leaf extract only, gentamicin along with 200 mg/kg extract, gentamicin with 400 mg/kg extract and gentamicin with 600 mg/kg extract, respectively. At the end of the experiment, the mice were sacrificed after being anaesthetized, and blood samples were collected through a cardiac puncture for renal function tests while the kidneys were removed for histopathological evaluation. The data were entered into Epidata version 4.6 and exported to SPSS version 25 for further analysis using one-way analysis of variance. Statistical significance was set at p < 0.05. Results: Group II mice had significantly higher levels of serum creatinine and blood urea levels compared to group I and III. The body weight of the mice in group V and group VI showed a significant increase compared with Group II. Serum creatinine and blood urea levels were reduced significantly in the Ajuga remota leaf extract administered group of mice compared to group II. Abnormal kidney architectural changes were seen among group II mice; however, those changes were improved after administration of Ajuga remota leaf methanolic extract. Conclusion: Methanol extract of Ajuga remota leaf provided effective protection against gentamicin-induced oxidative renal damage through its antioxidant effects. [ABSTRACT FROM AUTHOR]

Human glutathione transferase A4-4 (hGSTA4-4) displays high catalytic efficiency towards 4-hydroxyalkenals and other cytotoxic and mutagenic products of radical reactions and lipid peroxidation. Its role as a target for the chemosensitization of cancer cells has not been investigated so far. In this study, the inhibitory potency of twelve selected natural products and ten monocarbonyl curcumin derivatives against hGSTA4-4 was studied. Among natural products, ellagic acid turned out to be the strongest inhibitor with an IC50 value of 0.44 ± 0.01 μM. Kinetic analysis using glutathione (GSH) and 1-chloro-2,4-dinitrobenzene (CDNB) as variable substrates showed that ellagic acid behaved as a competitive inhibitor towards both GSH and CDNB, with Ki values of 0.39 ± 0.02 and 0.63 ± 0.03 μM, respectively. Among the curcumin derivatives studied, three proved to be the most potent inhibitors, in the order DM151 > DM101 > DM100, with IC50 values of 2.4 ± 0.1 μM, 12.7 ± 1.1 μΜ and 16.9 ± 0.4 μΜ, respectively. Further kinetic inhibition analysis of the most active derivative, DM151, demonstrated that this compound is a mixed inhibitor towards CDNB with inhibition constants of Ki = 4.1 ± 0.5 μM and Ki' = 0.536 ± 0.034 μM, while it is a competitive inhibitor towards GSH with a Ki = 0.98 ± 0.11 μM. Molecular docking studies were performed to interpret the differences in binding of ellagic acid and curcumin derivatives to hGSTA4-4. The in silico measured docking scores were consistent with the obtained experimental data. Hydrogen bonds appear to be the main contributors to the specific binding of monocarbonyl curcumin derivatives, while π-π stacking interactions play a key role in the enzyme–ellagic acid interaction. In vitro cytotoxicity assessment of the worst (DM148) and the best (DM151) inhibitors was performed against glioblastoma cell lines U-251 MG and U-87 MG. The results revealed that DM151 displays considerably higher cytotoxicity against both glioblastoma cell lines, while the glioblastoma cytotoxicity of DM148 was very limited. Furthermore, low and non-toxic doses of DM151 sensitized U-251 MG cells to the first-line glioblastoma chemotherapeutic temozolomide (TMZ), allowing us to propose for the first time that hGSTA4-4 inhibitors may be attractive therapeutic partners for TMZ to optimize its clinical effect in glioblastoma chemotherapy. [ABSTRACT FROM AUTHOR]

This study investigated the impact of deltamethrin (DM) toxicity on brown trout (Salmo trutta fario), examining its effects on the immune system, including the white blood cell (WBC), lymphocyte (Lym), total immunoglobulin (T. Ig), and lysozyme levels, as well as its neurotoxic consequences on the brain tissue. The neurotoxic effects encompassed oxidative stress, the activity of the antioxidant enzymes, such as the superoxide dismutase (SOD) and catalase (CAT), acetylcholinesterase (AChE) activity, and DNA damage using 8-hydroxy-2-deoxyguanosine (8-OHdG). The DM exposure led to elevated levels of malondialdehyde (MDA), and 8-OHdG, while concurrently causing a reduction in the AChE activity, protein and lipid content, WBC count, Lym, lysozyme activity, T. Ig levels, as well as the SOD and CAT levels in the brain tissues of groups 2 and 3 when compared to those in group 1. In summary, the findings of this study strongly indicate that DM induces DNA damage, immunotoxicity, and neurotoxicity in the brain tissue of brown trout, primarily due to the excessive production of reactive oxygen species (ROS). Moreover, the observed dose-dependent responses of DM to the environmental concentrations on all the investigated parameters suggest its potential utility in aquaculture risk assessment. [ABSTRACT FROM AUTHOR]

In this study, the effects of vitamin D3 (Vit. D) and a stinging nettle [Urtica dioica L. (UD)] extract were examined using histopathological and immunohistochemical methods in the stomach tissues of an experimentally created rat model of Crohn's disease (CD). The CD model was created using trinitrobenzene sulfonic acid (TNBS). The animals in the study were divided into control, TNBS, TNBS+Vit. D, and TNBS+UD groups. At the end of the experiment, the animals were euthanised and their stomach tissues were evaluated for necrosis, degeneration, apoptosis, and inflammation. Additionally, an immunohistochemical method was applied to determine the somatostatin (SSTR), aquaporin-1 (AQP-1), caspase-3, and tumour necrosis factor-alpha (TNF-a) immunoreactivity in the gastric tissues. In the evaluations, degenerative and necrotic changes and mononuclear cell infiltration areas were observed in the TNBS group, but such changes could be improved with Vit. D and UD applications. The results suggest that the combination of the Vit. D and UD extract may have a protective and therapeutic role in mitigating TNBS-induced damage to the gastric tissues, potentially through the regulation of SSTR, AQP-1, caspase-3, and TNF-a expression. This indicates a promising avenue for further research and the exploration of these compounds in the context of gastrointestinal health. [ABSTRACT FROM AUTHOR]

Experimental and clinical studies have revealed the influence of AMP-activated protein kinase (AMPK) signaling on the development of non-alcoholic liver fibrosis. Currently, the results of experimental studies demonstrate that inhibition of AMPK promotes fibrogenesis, while its activation prevents the development of liver fibrosis. The purpose of this work is to establish the effect of activation of AMP-activated protein kinase by the administration of phenformin on the content of glycosaminoglycans, oxyproline and sialic acids in the liver of rats under the conditions of long-term administration of ethanol. The study was conducted on 24 male Wistar rats. The animals were randomly divided into 4 groups of 6 animals each, on which we modeled ethanol-induced liver damage and administered phenformin hydrochloride at a dose of 10 mg/kg. The experiment lasted 63 days. In the liver of rats, the content of total glycosaminoglycans, the concentration of heparin-heparan, keratan-dermatan and chondroitin fractions of glycosaminoglycans, the content of free oxyproline and sialic acids were studied. Long-term alcoholization leads to a violation of the extracellular matrix of the liver of rats, which is evidenced by a decrease in the concentration of proteoglycans and a redistribution of their fractions in the direction of a decrease in anti-inflammatory and regenerative fractions. Chronic intake of alcohol increases the processes of desialylation of glycoconjugates and the intensity of collagenolysis. Activation of AMP-activated protein kinase by administration of phenformin under the conditions of simulating ethanol-induced liver damage leads to an increase in the concentration of glycosaminoglycans due to the growth of heparin-heparan and chondroitin fractions and reduces the intensity of desialylation of glycoconjugates and collagenolysis in the liver of rats. [ABSTRACT FROM AUTHOR]

The prevalence and incidence of obesity and the comorbidities linked to it are increasing worldwide. Current therapies for obesity and associated pathologies have proven to cause a broad number of adverse effects, and often, they are overpriced or not affordable for all patients. Among the alternatives currently available, natural bioactive compounds stand out. These are frequently contained in pharmaceutical presentations, nutraceutical products, supplements, or functional foods. The clinical evidence for these molecules is increasingly solid, among which epigallocatechin-3-gallate, ellagic acid, resveratrol, berberine, anthocyanins, probiotics, carotenoids, curcumin, silymarin, hydroxy citric acid, and α-lipoic acid stand out. The molecular mechanisms and signaling pathways of these molecules have been shown to interact with the endocrine, nervous, and gastroenteric systems. They can regulate the expression of multiple genes and proteins involved in starvation–satiety processes, activate the brown adipose tissue, decrease lipogenesis and inflammation, increase lipolysis, and improve insulin sensitivity. This review provides a comprehensive view of nature-based therapeutic options to address the increasing prevalence of obesity. It offers a valuable perspective for future research and subsequent clinical practice, addressing everything from the molecular, genetic, and physiological bases to the clinical study of bioactive compounds. [ABSTRACT FROM AUTHOR]

Objective: Inflammation and oxidative stress are major factors in the development of many disorders. Natural antioxidants present in plants can interrupt, decrease, or reduce the oxidation of components sensitive to oxidative processes by scavenging free radicals and lowering oxidative stress. Most anti-inflammatory agents used in the management of inflammatory disorders diminish oxidative damage. The biological potential of Citrus karna Raf. remains undisclosed, despite its richness in several bioactive compounds. Methods: The methanolic extract was evaluated for quantitative phytochemical analysis and antioxidative efficacy using 1,1-diphenyl-2-picrylhydrazyl radical and hydrogen peroxide scavenging activity. A carrageenan-induced paw edema model was employed to evaluate the anti-inflammatory potential as antioxidants exert anti-inflammatory effects. In silico prediction of activity spectra for substance predictions were performed to understand the possible mechanism of action of phytochemicals. Results: Citrus karna methanolic extract (CKME) showed dosedependent radical scavenging effects. The powerful scavenging activity of CKME could be due to the diverse polyphenolic compounds such as ascorbic acid, beta-carotene, and naringin. In addition, the percentage inhibition of paw edema and swelling was observed in CKME-treated rats and mice, which is the same as that of standard drug-treated groups. The Pa value of ascorbic acid, beta-bisabolene, linalool, and naringin is more than 0.7 which shows that these phytoconstituents might contribute to the anti-inflammatory action of extract samples such as CKME. Conclusions: Our findings shows that CKME possess strong antioxidant and anti-inflammatory effects. The richness of plants in polyphenolics such as flavonoids might be a contributing factor for these potential effects. [ABSTRACT FROM AUTHOR]

Cambuci (Campomanesia phaea Berg.) is a native fruit to the Atlantic Forest biome of Brazil with several bioactive compounds, ascorbic acid, phenolic compounds, volatile compounds, tannins, and carotenoids and it is used mainly to produce jellies, ice cream, juices, and alcoholic beverages. This review and bibliometric analysis establish the progress, trends, and perspectives of research on this fruit. The results show an increase in publications is related to the emergence of this new research and demonstrate the potential growth of cambuci in different studies. Between 2003 and 2022, 153 articles and 22 reviews related to cambuci were published. The bibliometric analysis revealed that the main research area was Agricultural and Biological Sciences, and the main country producing research on the cambuci fruit was Brazil, with 118 articles published. Given that most publications are associated with Brazil, the foremost institutions dedicated to cambuci research are also Brazilian. The University of São Paulo spearheads the list of affiliations and comprises eight other Brazilian organizations, including seven universities and one research institution. The author's keywords revealed that phenolic compounds, antioxidant capacity, flavonoids, antioxidant activity, bioactive compounds, and osmotic dehydration are motor themes in cambuci research. Additionally, ellagic acid is a bioactive phenolic compound in tannins, and proanthocyanidins are compounds of great relevance in cambuci and have great benefit for human health with antibacterial, antifungal, antiviral, anti-inflammatory, antidiabetic, gastroprotective, and antidepressant activity. In conclusion, the review establishes that cambuci is an interesting source for its application in the food and pharmaceutical industries. [ABSTRACT FROM AUTHOR]

Objective: This study assessed the relationship between speech and language impairment and outcome in a multicenter cohort of isolated/idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD). Methods: Patients with iRBD from 7 centers speaking Czech, English, German, French, and Italian languages underwent a detailed speech assessment at baseline. Story‐tale narratives were transcribed and linguistically annotated using fully automated methods based on automatic speech recognition and natural language processing algorithms, leading to the 3 distinctive linguistic and 2 acoustic patterns of language deterioration and associated composite indexes of their overall severity. Patients were then prospectively followed and received assessments for parkinsonism or dementia during follow‐up. The Cox proportional hazard was performed to evaluate the predictive value of language patterns for phenoconversion over a follow‐up period of 5 years. Results: Of 180 patients free of parkinsonism or dementia, 156 provided follow‐up information. After a mean follow‐up of 2.7 years, 42 (26.9%) patients developed neurodegenerative disease. Patients with higher severity of linguistic abnormalities (hazard ratio [HR = 2.35]) and acoustic abnormalities (HR = 1.92) were more likely to develop a defined neurodegenerative disease, with converters having lower content richness (HR = 1.74), slower articulation rate (HR = 1.58), and prolonged pauses (HR = 1.46). Dementia‐first (n = 16) and parkinsonism‐first with mild cognitive impairment (n = 9) converters had higher severity of linguistic abnormalities than parkinsonism‐first with normal cognition converters (n = 17). Interpretation: Automated language analysis might provide a predictor of phenoconversion from iRBD into synucleinopathy subtypes with cognitive impairment, and thus can be used to stratify patients for neuroprotective trials. ANN NEUROL 2024;95:530–543 [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) may result from the dysfunctions of various mechanisms such as protein accumulation, mitophagy, and biogenesis of mitochondria. The purpose of the study was to evaluate the molecular mechanisms in ALS development and the impact of swim training on these processes. In the present study, an animal model of ALS, SOD1-G93A mice, was used with the wild-type mice as controls. Mice swam five times per week for 30 min. Mice were analyzed before ALS onset (70 days old), at ALS 1 disease onset (116 days old), and at the terminal stage of the disease ALS (130 days old), and compared with the corresponding ALS untrained groups and normalized to the wild-type group. Enzyme activity and protein content were analyzed in the spinal cord homogenates. The results show autophagy disruptions causing accumulation of p62 accompanied by low PGC-1α and IGF-1 content in the spinal cord of SOD1-G93A mice. Swim training triggered a neuroprotective effect, attenuation of NF-l degradation, less accumulated p62, and lower autophagy initiation. The IGF-1 pathway induces pathophysiological adaptation to maintain energy demands through anaerobic metabolism and mitochondrial protection. Key messages: The increased protein content of p62 in the spinal cord of SOD1-G93A mice suggests that autophagic clearance and transportation are disrupted. Swim training attenuates neurofilament light destruction in the spinal cord of SOD1-G93A mice. Swim training reducing OGDH provokes suppression of ATP-consuming anabolic pathways. Swim training induces energy metabolic changes and mitochondria protection through the IGF-1 signaling pathway. [ABSTRACT FROM AUTHOR]

Objective: To investigate effect of Wumei Pill on colon cell apoptosis in ulcerative colitis (UC) rats by regulating miR-146a and its mechanism. Methods: A total of 50 SD rats were selected, with 10 rats in each group, and divided into control group, model group, Wumei Pill low, medium and high doses groups. Transfected with anti-miR-NC, anti-miR-146a, miR-NC, miR-146a as anti-miR-NC group, anti-miR-146a group, Wumei Pill+miR-NC group, Wumei Pill+miR-146a group. CCK-8 was used to detect cell proliferation; flow cytometry was used to detect cell apoptosis; RT-qPCR was used to detect cell miR-146a expression; ELI-SA was used to detect cell IL-1β and IL-13 contents; Western blot was used to detect expressions of B-cell lymphoma 2 (Bcl-2) and Bax proteins. Results: Compared with control group, cell survival rate, Bcl-2 protein expression in model group were decreased, while apoptosis rate, Bax protein expression, IL-lp, IL-13 contents and miR-146a expression were increased (P<0.05). Compared with model group, Wumei Pill significantly increased cell survival rate and Bcl-2 protein expression, decreased cell apoptosis rate, Bax protein expression, IL-1β, IL-13 contents and miR-146a expression (P<0.05). Inhibition of miR-146a increased cell survival rate, Bcl-2 protein expression, decreased cell apoptosis rate, IL-1β, IL-13 contents and Bax protein expression (P<0.05). Overexpression of miR-146a reversed effects of Wumei Pills on proliferation and apoptosis of colon cells in UC rats. Conclusion: Wumei Pill can reduce apoptosis of colon cells in UC rats by up-regulating expression of miR-146a. [ABSTRACT FROM AUTHOR]

Currently, natural polymer materials with bactericidal properties are extremely popular. Unfortunately, although the biopolymer material itself is biodegradable, its enrichment with bactericidal compounds may affect the efficiency of biodegradation by natural soil microflora. Therefore, the primary objective of this study was to evaluate the utility of fungi belonging to the genus Trichoderma in facilitating the degradation of chitosan film modified with cinnamic acid and ellagic acid in the soil environment. Only two strains (T.07 and T.14) used chitosan films as a source of carbon and nitrogen. However, their respiratory activity decreased with the addition of tested phenolic acids, especially cinnamic acid. Addition of Trichoderma isolates to the soil increased oxygen consumption during the biodegradation process compared with native microorganisms, especially after application of the T.07 and T.14 consortium. Isolates T.07 and T.14 showed high lipolytic (55.78 U/h and 62.21 U/h) and chitinase (43.03 U/h and 41.27 U/h) activities. Chitinase activity after incorporation of the materials into the soil was higher for samples enriched with T.07, T.14 and the consortium. The isolates were classified as Trichoderma sp. and Trichoderma koningii. Considering the outcomes derived from our findings, it is our contention that the application of Trichoderma isolates holds promise for expediting the degradation process of chitosan materials containing bactericidal compounds. [ABSTRACT FROM AUTHOR]

Introduction: Methotrexate (MTX), Moringa oleifera (MO), and Andrographis paniculata (AP) have been reported to have anti-hyperglycemic, antioxidative, and anti-inflammatory effects in diabetic rats. This study aims to investigate the single and combination effects of MTX, MO, and AP on random blood glucose levels, interleukin-6 (IL-6) levels, and trabecular density in diabetic rats. Methods: A total of 49 male rats were divided into seven groups, namely one control group and six diabetes mellitus (DM) groups. All rats in the DM groups were injected with streptozotocin-nicotinamide (STZ-NA) intraperitoneally. In addition, the DM groups were administered with a placebo daily (DG), a single dose of 500 mg/kg BW MO daily (DG+MO), a single dose of 500mg/kg BW AP daily (DG+AP), a single dose of 7 mg/kg BW MTX once a week (DG+MTX), a combination of MTX+MO, and a combination MTX+AP, respectively. The experiment lasted for 28 days. On day 29, the right and left femur of the rats were collected for IL-6 examination (ELISA) and histopathological analysis. Results: IL-6 expression levels were significantly lower in diabetic rats treated with single and combination of MTX, MO, and AP compared to untreated diabetic rats (p < 0.05). However, the random blood glucose levels and trabecular density between treated and untreated diabetic rats were not significantly different (p < 0.001, p = 0.152). In addition, IL-6 levels were not correlated with trabecular density in all groups (r = -0.057, p = 0.722). Conclusion: Single doses of MTX, MO leaf extract, and AP leaf extract could suppress IL-6 expression in the femur tissue in diabetic rats. However, the IL-6 expression was not correlated with trabecular density although it significantly affected blood glucose levels in this study. [ABSTRACT FROM AUTHOR]

Kaempferol, a flavonoid compound found in various fruits, vegetables, and medicinal plants, has garnered increasing attention due to its potential neuroprotective effects in neurological diseases. This research examines the existing literature concerning the involvement of kaempferol in neurological diseases, including stroke, Parkinson's disease, Alzheimer's disease, neuroblastoma/glioblastoma, spinal cord injury, neuropathic pain, and epilepsy. Numerous in vitro and in vivo investigations have illustrated that kaempferol possesses antioxidant, anti‐inflammatory, and antiapoptotic properties, contributing to its neuroprotective effects. Kaempferol has been shown to modulate key signaling pathways involved in neurodegeneration and neuroinflammation, such as the PI3K/Akt, MAPK/ERK, and NF‐κB pathways. Moreover, kaempferol exhibits potential therapeutic benefits by enhancing neuronal survival, attenuating oxidative stress, enhancing mitochondrial calcium channel activity, reducing neuroinflammation, promoting neurogenesis, and improving cognitive function. The evidence suggests that kaempferol holds promise as a natural compound for the prevention and treatment of neurological diseases. Further research is warranted to elucidate the underlying mechanisms of action, optimize dosage regimens, and evaluate the safety and efficacy of this intervention in human clinical trials, thereby contributing to the advancement of scientific knowledge in this field. Significance statement: Kaempferol, a flavonoid compound found in various fruits, vegetables, and medicinal plants, to serve as a natural neuroprotective agent for the prevention and treatment of neurological disorders. By conducting an extensive review of the current literature, this study underscores the varied mechanisms through which kaempferol demonstrates its neuroprotective effects, emphasizing its antioxidant, anti‐inflammatory, and antiapoptotic properties. Furthermore, the therapeutic potential of kaempferol in modulating key signaling pathways involved in neurodegeneration and neuroinflammation, such as the PI3K/Akt, MAPK/ERK, and NF‐κB pathways, is underscored. Additionally, various beneficial effects of kaempferol, including enhancing neuronal survival, attenuating oxidative stress, reducing neuroinflammation, promoting neurogenesis, and improving cognitive function, are emphasized. In summary, compelling evidence is presented supporting the use of kaempferol as a promising natural compound for the prevention and treatment of neurological diseases, thereby indicating the importance of further research to elucidate the mechanisms of action, optimize dosage regimens, and assess the safety and efficacy of kaempferol in human clinical trials. [ABSTRACT FROM AUTHOR]

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 C18:1cis9, C18:1cis9 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). [ABSTRACT FROM AUTHOR]

Annona squamosa Linn. fruit is famous for its nutritional value with a long history of medicinal benefits due to the presence of many phytochemicals, including alkaloids, diterpenes, essential oil, phytopeptides, etc. Several studies envisaged that Annona squamosa possesses cytotoxic, diuretic, antiurolithiatic, antitumor, anti-psoriatic, antioxidant, and hepatoprotective properties. This plant is traditionally used for the treatment of wound infection, dysentery, seizure, tumors, fever, vomiting, parasitic infections, hypertension, thyroid, toothache, acne, heart disease, inflammation, diabetes, hair loss, dandruff, hemorrhage, maggot-infected sores, abortifacient, and cough. However, some chemical constituents isolated from the plant have shown specific toxic effects in human and animal models, such as acute oral toxic effects, genotoxic, neurotoxic, and ocular toxic. The plant has diverse pharmacological actions, the seeds of this plant possess a genotoxic effect but on the contrary, the bark of the plant shows genoprotective activity. A large number of ethnobotanical studies reported the seed of this plant is used to induce abortion in humans, but a scientific study carried out in pregnant rats reported aqueous seed extract of the plant did not interfere with reproductive performance. The presented review summarized the traditional uses, pharmacological, and toxicological activities of the isolated compounds from this plant. Additionally, some patents and commercial products related to Annona squamosa are also brought up in this article to explore its application which would attract the scientific community to search out its hidden side. [ABSTRACT FROM AUTHOR]

Alchemilla species (Rosaceae) are popularly known as 'Lady's Mantle, Lion's claw' and are used for medicinal purposes as diuretic, laxative, tonic, and wound healing agents. Bioactivities and phenolic content of Alchemilla pseudocartalinica Juz. species have yet to be investigated. Our research focused on assessing the antioxidant characteristics of A. pseudocartalinica methanol (MEAP) and water extracts (WEAP), as well as their inhibitory effects on acetylcholinesterase (AChE), α-glycosidase (a-gly), and human carbonic anhydrase II (hCA II) enzymes. Additionally, we conducted chemical characterization using UPLC-MS/MS and investigated the correlation between major phenolic compounds and enzymes through molecular docking analysis. To assess the antioxidant activities of the MEAP and WEAP, six test systems were employed, including DPPH, ABTS, DMPD, FRAP, CUPRAC, and Fe3+ reducing assays. The outcome showed that the methanol extract of the plant generally has stronger antioxidant activity. In addition, UPLC-MS/MS analysis indicated, miquelianin (44.095 mg/g), quinic acid (17.054 mg/g), and ellagic acid (6.492 mg/g) were significant in the methanol extract. A molecular docking study revealed a significant affinity for binding between the hCAII enzyme and quinic acid, miquelianin, and AChE/α-gly enzymes. A. pseudocatalinica methanol and water extracts have high antioxidant activity and good inhibition effect against AChE, α-glycosidase, and hCA II enzymes. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Zn-ion hybrid supercapacitors (ZHCs) combining merits of battery-type and capacitive electrodes are considered to be a prospective candidate in energy storage systems. Tailor-made carbon cathodes with high zincophilicity and abundant physi/chemisorption sites are critical but it remains a great challenge to achieve both features by a sustainable means. Herein, a hydrogen-bonding interaction-guided self-assembly strategy is presented to prepare iodine-doped carbon nanocages without templates for boosting zinc-ion storage by nucleophilicity. The biomass ellagic acid contains extensional hydroxy and acyloxy groups with electron-donating ability, which interact with melamine and ammonium iodide to form organic supermolecules. The organic supermolecules further self-assemble into a nanocage-like structure with cavities under hydrothermal processes via hydrogen-bonding and π-π stacking. The carbon nanocages as ZHCs cathodes enable the high approachability of zincophilic sites and low ion migration resistance resulting from the interconnected conductive network and nanoscale architecture. The experimental analyses and theoretical simulations reveal the pivotal role of iodine dopants. The I5−/I3− doping anions in carbon cathodes have a nucleophilicity to preferentially adsorb the Zn2+ cation by the formation of C+-I5−-Zn2+ and C+-I3−-Zn2+. Of these, the C+-I3− shows stronger bonding with Zn2+ than C+-I5−. As a result, the iodine-doped carbon nanocages produced via this template-free strategy deliver a high capacity of 134.2 mAh/g at 1 A/g and a maximum energy and power density of 114.1 Wh/kg and 42.5 kW/kg. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Ellagic acid (EA) is a natural polyphenol and a free radical scavenger with antioxidant properties. This study investigated the protective effects of EA during in vitro maturation (IVM) of porcine oocytes. To determine the optimal concentration, IVM medium was supplemented with various concentrations of EA. Treatment with 10 μM EA (10 EA) resulted in the highest cleavage rate, blastocyst formation rate, and total cell number per blastocyst and the lowest percentage of apoptotic cell in parthenogenetic blastocysts. In the 10 EA group, abnormal spindle and chromosome misalignment were rescued and the ratio of phosphorylated p44/42 to total p44/42 was increased. Furthermore, the reactive oxygen species and glutathione levels were significantly decreased and increased, respectively, and antioxidant genes (Nrf2, HO-1, CAT, and SOD1) were significantly upregulated in the 10 EA group. mRNA expression of developmental-related (CDX2 , POU5F1 , and SOX2) and anti-apoptotic (BCL2L1) genes was significantly upregulated in the 10 EA group, while mRNA expression of pro-apoptotic genes (BAK , FAS , and CASP3) was significantly downregulated. Ultimately, following somatic cell nuclear transfer, the blastocyst formation rate was significantly increased and the percentage of apoptotic cell in blastocysts was significantly decreased in the 10 EA group. In conclusion, addition of 10 EA to IVM medium improved oocyte maturation and the subsequent embryo development capacity through antioxidant mechanisms. These findings suggest that EA can enhance the efficiencies of assisted reproductive technologies. • The optimal ellagic acid (EA) concentration during IVM of porcine oocytes is 10 μM. • EA treatment during IVM of porcine oocytes improves subsequent embryo development. • EA improves nuclear and cytoplasmic maturation of porcine oocytes through an antioxidant mechanism. [ABSTRACT FROM AUTHOR]

The present study investigated the effects of ellagic acid, a type of polyphenol that does not have a glycan and is composed of four hydroxyl groups and two lactone functional groups, on porcine in vitro fertilization (IVF) by focusing on its anti-hyaluronidase activity. A comparative analysis of ellagic acid and apigenin, which is commonly used as a hyaluronidase inhibitor, was performed. It compared the effects of ellagic acid and apigenin on hyaluronidase activity at different concentrations. The results showed that 10, 20, and 40 μM ellagic acid strongly reduced hyaluronidase activity (P < 0.05). The addition of 20 μM ellagic acid, but not apigenin, to porcine IVF medium effectively reduced polyspermy without decreasing sperm penetration or the formation rates of male pronuclei in cumulus-free oocytes. However, neither ellagic acid nor apigenin affected the number of sperm that bound to zona pellucida (ZP) or the induction of zona hardening and protease resistance. The percentage of acrosome-reacting sperm that bound to the ZP was markedly lower in the presence of 20 μM ellagic acid than in the untreated and apigenin-treated groups, even though the antioxidant capacity of ellagic acid was weaker than that of apigenin. Furthermore, a markedly higher percentage of embryos developed to the blastocyst stage in the ellagic acid-treated group, and the apoptotic indexes of expanded blastocysts produced by the ellagic acid treatment during IVF were significantly low. Therefore, the anti-hyaluronidase effect of ellagic acid markedly suppressed the induction of the acrosome reaction in sperm that bound to the ZP, resulting in a marked decrease in polyspermy under conditions that maintained high sperm penetrability during IVF and sustainment of the developmental potency in porcine oocytes. [ABSTRACT FROM AUTHOR]