Search Results (129)

Listeria monocytogenes poses health threats due to its resilience and potential to cause severe infections, especially in vulnerable populations. Plant extracts and/or phytocomplexes have demonstrated the capability of natural compounds in mitigating L. monocytogenes virulence. Here we explored the suitability of a computational pipeline envisioned to identify the molecular determinants for the recognition between the bacterial protein internalin A (InlA) and the human E-cadherin (Ecad), which is the first step leading to internalization. This pipeline consists of molecular docking and extended atomistic molecular dynamics simulations to identify key interaction clusters between InlA and Ecad. It exploits this information in the screening of chemical libraries of natural compounds that might competitively interact with InIA and hence impede the formation of the InIA–Ecad complex. This strategy was effective in providing a molecular model for the anti-adhesive activity of punicalagin and disclosed two natural phenolic compounds with a similar interaction pattern. Besides elucidating key aspects of the mutual recognition between InIA and Ecad, this study provides a molecular basis about the mechanistic underpinnings of the anti-adhesive action of punicalagin that enable application against L. monocytogenes. Full article

Tuberaria lignosa (Sweet) Samp. (Cistaceae) is a herbaceous species native to southwestern Europe, traditionally used to treat wounds, ulcers, and inflammatory or infectious skin conditions. This study aimed to characterize the phytochemical profile of its aqueous leaf extract and evaluate its skin-related in vitro biological activities. The phenolic composition was determined using UHPLC-HRMS/MS, HPLC-DAD, and quantitative colorimetric assays. Antioxidant activity was assessed against synthetic free radicals, reactive oxygen and nitrogen species, transition metals, and pro-oxidant enzymes. Enzymatic inhibition of tyrosinase, hyaluronidase, collagenase, and elastase were evaluated using in vitro assays. Cytocompatibility was tested on human keratinocytes and NIH/3T3 fibroblasts using MTT and resazurin assays, respectively, while wound healing was evaluated on NIH/3T3 fibroblasts using the scratch assay. Antifungal activity was investigated against several Candida and dermatophyte species, while antibiofilm activity was tested against Epidermophyton floccosum. The extract was found to be rich in phenolic compounds, accounting for nearly 45% of its dry weight. These included flavonoids, phenolic acids, and proanthocyanidins, with ellagitannins (punicalagin) being the predominant group. The extract demonstrated potent antioxidant, anti-tyrosinase, anti-collagenase, anti-elastase, and antidermatophytic activities, including fungistatic, fungicidal, and antibiofilm effects. These findings highlight the potential of T. lignosa as a valuable and underexplored source of bioactive phenolic compounds with strong potential for the development of innovative approaches for skin care and therapy. Full article

Background: Punicalagin (Pg), a major ellagitannin derived from pomegranates, possesses antimicrobial, antioxidant, and immunomodulatory properties, suggesting its potential as an adjunctive therapy for sepsis. Objectives: This study investigated the synergistic effects of punicalagin and meropenem in a murine model of sublethal sepsis induced by cecal ligation and puncture (CLP). Methods: Mice were treated with punicalagin and meropenem, and multiple parameters were analyzed, including hematological indices, bacterial burden, lymphoid organ cellularity, cytokine profiles (IL-2, IL-4, IL-6, IL-10, IL-17, IFN-γ, TNF-α), nitric oxide (NO) production, and organ histopathology. Results: Punicalagin enhanced NO-mediated antimicrobial responses, increased neutrophil migration, preserved lymphoid cellularity, and significantly reduced the bacterial translocation. Combined therapy with meropenem improved systemic IL-10 levels and mitigated histopathological damage in the liver, kidney, intestine, and lung. Importantly, punicalagin did not induce thrombocytopenia. Conclusions: These results support the potential of punicalagin as an adjunctive agent to antibiotics for sepsis treatment, offering both antimicrobial and immunoregulatory benefits. Further studies are required to explore its clinical applicability. Full article

The increasing prevalence of bacterial resistance to conventional disinfectants and antibiotics has intensified the search for effective, natural alternatives in the dairy industry. This study evaluates the bactericidal efficacy of Punica granatum L. (pomegranate) peel ethanolic extract, focusing on its application in pre- and post-dipping procedures for mastitis prevention. The extract exhibited potent activity against Escherichia coli and Staphylococcus aureus, two major mastitis pathogens. At a concentration of 10 mg/mL, the extract induced significant membrane disruption within 30 s of exposure, as evidenced by propidium iodide uptake and elevated extracellular DNA levels (Escherichia coli: 64.25 ng/μL; Staphylococcus aureus: 83.25 ng/μL) compared to controls (11.20 ng/μL and 35.20 ng/μL, respectively; p < 0.05). Complete growth inhibition (100%) was achieved within 30 s at 25 and 50 mg/mL, matching the efficacy of commercial chlorhexidine and high-concentration hypochlorite. Phytochemical analysis identified punicalagin as the predominant bioactive compound. These findings establish Punica granatum peel extract as a fast-acting bactericidal agent, exhibiting an efficacy comparable to or exceeding that of conventional disinfectants. Its rapid action and plant-based origin highlight its potential as a viable alternative for the prevention and control of bovine mastitis in dairy farming. Full article

This study aimed to investigate the effects of adding different levels of punicalagin or oleuropein to TRIS diluent on the quality of frozen–thawed semen from Najdi rams. Semen was diluted using TRIS-based diluter with 15% egg yolk (control group); supplemented with 0.1, 0.5, or 1 mg/100 mL punicalagin (in Experiment 1); or supplemented with 1, 2.5, or 5 mg/100 mL oleuropein (in Experiment 2). The collected semen was evaluated and cryopreserved, with the motility and concentration of sperm assessed using a CASA system. The results showed that the total motile spermatozoa (TMS), percentage of progressive motile spermatozoa (PMS), curvilinear velocity (VCL), rectilinear velocity, average path velocity (VAP), linearity coefficient, straightness index, minor defects, and sperm vitality were higher in the 0.1 mg/100 mL punicalagin group (p < 0.05) than in other groups. HOST% post-thawing was significantly higher in all punicalagin groups compared to the control group (p < 0.001). The percentages of PMS, TMS, VCL, minor defects, and sperm vitality were higher in the 1 mg/100 mL oleuropein group (p < 0.05) than in other groups. Oleuropein supplementation at 5 mg/100 mL decreased VAP in cooled sperms, while all levels increased VAP post-thawing. HOST-positive sperms% post-thawing was higher in all oleuropein-treated groups than the control group (p < 0.001). Moreover, oleuropein nonsignificantly increased the acrosome integrity in cooled sperms, while higher studied concentrations of oleuropein (2.5 and 5 mg/100 mL) decreased the acrosome integrity in frozen sperms. In conclusion, adding punicalagin (0.1 mg/100 mL) or oleuropein (1 mg/100 mL) to TRIS diluent improved the quality of frozen–thawed semen from rams. Full article

ADAMTS-5 (aggrecanase-2) is a major metalloprotease involved in regulating the cartilage extracellular matrix. Due to its role in removing aggrecan in the progression of osteoarthritis (OA), ADAMTS-5 is often regarded as a potential therapeutic target for OA. Punicalagin (PCG), a polyphenolic ellagitannin found in pomegranate (Punica grunatum L.), and ellagic acid (EA), a hydrolytic metabolite of PCG, have been widely investigated as potential disease-modifying osteoarthritis drugs (DMOADs) due to their potent antioxidant and anti-inflammatory properties, but their interaction with ADAMTS-5 has yet to be determined. In this study, molecular docking simulations were used to predict enzyme–inhibitor binding interactions. The results suggest that both compounds may be able to bind within the active site via the formation of H bonds and interactions between the ligand’s aromatic rings and hydrophobic residue in the enzyme with inhibition constants of 183.3 µM and 1.13 µM for PCG and EA, respectively. Biochemical activity against recombinant human ADAMTS-5 was assessed using a dimethylmethylene blue-based assay to determine residual sulfated glycosaminoglycan (sGAG) in porcine articular cartilage. Although its loss could not be attributed to ADAMTS-5, sGAG was effectively persevered by PCG and EA. The potential conversion of PCG to EA by enzyme-catalyzed hydrolysis activity was then investigated using liquid chromatography–mass spectroscopy to determine the potential for the use of PCG and EA as a prodrug–proactive metabolite pair in the development of drug delivery systems to arthritic synovial joints. Full article

Background/Objectives: Toxoplasmosis is a zoonotic disease caused by Toxoplasma gondii. The parasite infection in humans continues to rise due to an increasing seroprevalence rate in domestic and wild warm-blooded animals that serve as a major reservoir of the parasite. There are fewer drugs available for the treatment of toxoplasmosis. However, these drugs are limited in efficacy against tachyzoites and bradyzoites. Also, there are clinical side effects and geographical barriers to their use, especially in immunocompromised patients, children, and pregnant women. Tannins, a class of natural products, are known to have antimicrobial properties. However, little is known about the effects of Corilagin (CG) and Punicalagin (PU), which are classified as tannins, on T. gondii growth and their possible mechanism of action in vitro. We hypothesize that CG and PU could inhibit T. gondii growth in vitro and cause mitochondria membrane disruption via oxidative stress. Methods: Here, we investigated the anti-T. gondii activity of the two named tannins using a fluorescent-based reporter assay. Results: The 50% effective concentrations (EC_50s) values for CG and PU that inhibited T. gondii parasites growth in vitro were determined to be 3.09 and 19.33 µM, respectively. Pyrimethamine (PY) was used as a standard control which gave an EC₅₀ value of 0.25 µM. Interestingly, CG and PU were observed to cause high reactive oxygen species (ROS) and mitochondrial superoxide (MitoSOX) production in tachyzoites. This resulted in a strong mitochondria membrane potential (MMP) disruption in T. gondii tachyzoites. Conclusions: Therefore, the possible mechanism(s) of action of CG and PU against T. gondii is associated with the disruption of the mitochondria redox biology. Thus, the high ROS and MitoSOX produced as a result of these compounds created high oxidative stress, leading to mitochondrial dysfunction. Full article

Reducing the punicalagin content is an effective strategy for eliminating the astringency of pomegranate juice. In this study, pomegranate juice was used as the raw material, and tannase was applied to convert punicalagin into ellagic acid and gallic acid. The effects of tannase concentration, reaction time, and temperature on juice deastringency were evaluated, along with the antioxidant and physicochemical properties of the treated juice. The results demonstrated that, under optimal conditions (33.9 U/100 mL tannase, 30 °C, 90 min reaction time), the punicalagin content decreased by 27.8%, while the ellagic acid and gallic acid levels increased by 24.2% and 32.3%, respectively, effectively reducing the juice’s astringency. Under these conditions, the total phenolic content reached 110 mg/100 g, with a free radical scavenging capacity of 69.8%, significantly enhancing the juice’s antioxidant properties. These results suggest that tannase treatment of pomegranate juice enhances the polyphenol content, thereby improving its health benefits without compromising the product quality. Full article

This study aimed to evaluate the feasibility of producing and characterizing Cistus creticus L. powders obtained through spray drying and freeze drying using maltodextrin and inulin as carriers. Quantitative and qualitative analysis of polyphenols by high-performance liquid chromatography with diode-array detection (HPLC-DAD) and high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) identified key bioactive compounds, including punicalagin isomers and their galloyl esters, as well as flavonoids (myricetin-3-galactoside, myricetin-3-rhamnoside, quercetin-3-galactoside, and tiliroside). Phenolics in powders produced by both drying techniques ranged from 73.2 mg to 78.5 mg per g of dry matter. Inulin proved to be as effective as maltodextrin in spray drying, offering a promising alternative for plant-based powder formulation. Antioxidant capacity measured by Trolox equivalent antioxidant capacity assay with 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (TEAC ABTS) and ferric reducing antioxidant power (FRAP) assay indicated that spray-dried powders with inulin exhibited antioxidant properties comparable to those with maltodextrin. The results demonstrated that Cistus creticus L. powders obtained with inulin can serve as valuable sources of bioactive compounds with potential health benefits similar to those obtained with maltodextrin. Moreover, from a technological perspective, inulin proved to be an equally efficient carrier in terms of production-process parameters such as moisture content and water activity, making it a viable alternative to maltodextrin in plant-based powder formulations. Full article

Background: Within the solar ultraviolet (UV) spectrum, ultraviolet A rays (UVA, 320–400 nm), although less energetic than ultraviolet B rays (UVB, 280–320 nm), constitute at least 95% of solar UV radiation that penetrates deep into the skin The UV rays are associated with both epidermal and dermal damage resulting from the generation of reactive oxygen species (ROS). Among them, the longest UVA wavelengths (UVA1, 340–400 nm) can represent up to 75% of the total UV energy. Therefore, UVA radiation is linked to various acute and chronic conditions, including increased skin pigmentation and photoaging. Despite many advances in the skin photoprotection category, there is still a growing demand for natural daily photoprotection active ingredients that offer broad protection against skin damage caused by UVA exposure. In our quest to discover new, disruptive, next generation of photoprotective ingredients, we were drawn to pomegranate, based on its diverse polyphenolic profile. We investigated the pericarp of the fruit, so far considered as byproducts of the pomegranate supply chain, to design a novel patented extract “POMAOX” with a desired spectrum of phenolic components comprising of αβ-punicalagins, αβ-punicalins and ellagic acid. Methods: Antioxidant properties of POMAOX were measured using in-tubo standard tests capable of revealing a battery of radical oxygen species (ROS): peroxyl radical (ORAC), singlet oxygen (SOAC), superoxide anion (SORAC), peroxynitrite (NORAC), and hydroxyl radical (HORAC). In vitro, confirmation of antioxidant properties was first performed by evaluating protection against UVA-induced lipid peroxidation in human dermal fibroblasts (HDF), via the release of 8 iso-prostanes. The protection offered by POMAOX was further validated in a 3D in vitro reconstructed T-Skin^TM model, by analyzing tissue viability/morphology and measuring the release of Matrix Metallopeptidase 1 (MMP-1) & pro-inflammatory mediators (IL-1α, IL-1ra, IL-6, IL-8, GM-CSF, and TNF-α) after UVA1 exposure. Results: POMAOX displayed strong antioxidant activity against peroxynitrite (NORAC) at 1.0–3.0 ppm, comparable to the reference vitaminC, as well as singlet oxygen (SOAC) at 220 ppm, and superoxide radicals with a SORAC value of 500 ppm. Additionally, POMAOX demonstrated strong photoprotection benefit at 0.001% concentration, offering up to 74% protection against UVA-induced lipid peroxidation on HDF, in a similar range as the positive reference, Vitamin E at 0.002% (50 µM), and with higher efficacy than ellagic acid alone at 5 µM. Moreover, our pomegranate-derived extract delivered photoprotection at 0.001%, mitigating dermal damages induced by UVA1, through inhibition of MMP-1 and significant inhibition of pro-inflammatory mediators release (including IL-1α, IL-1ra, IL-6, IL-8, GM-CSF, and TNFα) on an in vitro reconstructed full-thickness human skin model with a similar level of protection to that of Vitamin C tested at 0.035% (200 µM). Conclusions: Overall, the novel pomegranate-derived extract “POMAOX” significantly reduced the impact of UVA on human skin, due to its broad-spectrum antioxidant profile. These findings suggest that POMAOX could offer enhanced protection against the detrimental effects of UV exposure, addressing the growing consumer demand for strong photoprotection with skincare benefits. Full article

Two different produced and packaged commercial typologies of pomegranate juice were analyzed for their physicochemical, nutritional, and biological properties. The effects of classical pasteurization (PJ) and high-pressure processing (HP), applied during the productive cycle, were evaluated through several advanced analytical methods, such as CIEL*a*b* colorimetry, HPLC-DAD, DI-ESI-MS and MS/MS, and NMR analyses. Moreover, the exerted biological activity of the two pomegranate juices was monitored through Total Phenolic and Total Flavonoid Contents, antiradical, antioxidant and chelating activity. The potential inhibition of key enzymes of degenerative processes (cholinesterases, tyrosinase) and diabetes (amylase, glucosidase), the allelopathy toward Cichorium intybus, Dicondra repens, and Diplotaxis tenuifolia, and the in vivo toxicity on brine shrimp were also evaluated. The two different applied processing techniques analyzed impacted the bioactive compound’s preservation differently, modifying the phytocomplex profile. HP significantly degrades punicalins and punicalagins, better preserving anthocyanins, if compared to PJ’s impact. Sensory qualities, antioxidant activity, enzymatic inhibition, and ecotoxicological potential were differently impacted by the two applied processes. The obtained results can be beneficial for finding the optimal processing conditions that balance microbial safety with nutritional value preservation, contributing to the development of healthy pomegranate juice products. Full article

Cistus monspeliensis L. (C. monspeliensis) is used in Italian folk medicine. This study was performed to determine genotoxic and antigenotoxic effects of C. monspeliensis leaf extract against mitomycin C (MMC) using an in vitro cytokinesis-block micronucleus assay (CBMN) in the Chinese Hamster Ovarian K1 (CHO-K1) cell line. The phytochemical composition of C. monspeliensis extract was evaluated using an untargeted metabolomic approach by employing UPLC-PDA-ESI/MS. The automated in vitro CBMN assay was carried out using image analysis systems with a widefield fluorescence microscope and the ImageStreamX imaging flow cytometer. The phytochemical profile of C. monspeliensis extract showed, as the most abundant metabolites, punicalagin, myricetin, gallocathechin, and a labdane-type diterpene. C. monspeliensis, at the tested concentrations of 50, 100, and 200 μg/mL, did not induce significant micronuclei frequency, thus indicating the absence of a genotoxic potential. When testing the C. monspeliensis extract for antigenotoxicity in the presence of MMC, we observed a hormetic concentration-dependent effect, where low concentrations resulted in a significant protective effect against MMC-induced micronuclei frequency, and higher concentrations resulted in no effect. In conclusion, our findings demonstrate that C. monspeliensis extract is not genotoxic and, at low concentration, exhibits an antigenotoxic effect. In relation to this final point, C. monspeliensis may act as a potential chemo-preventive against genotoxic agents. Full article

Pomegranate (Punica granatum L.) has long been recognised for its rich antioxidant profile and potential health benefits. Recent research has expanded its therapeutic potential to include antiangiogenic properties, which are crucial for inhibiting the growth of tumours and other pathological conditions involving aberrant blood vessel formation. This review consolidates current findings on the antiangiogenic effects of pomegranate extracts. We explore the impact of pomegranate polyphenols, including ellagic acid, punicalagin, anthocyanins, punicic acid and bioactive polysaccharides on key angiogenesis-related pathways and endothelial cell function. Emphasis is placed on the effects of these extracts as phytocomplexes rather than isolated compounds. Additionally, we discuss the use of pomegranate by-products, such as peels and seeds, in the preparation of extracts within a green chemistry and circular economy framework, highlighting their value in enhancing extract efficacy and sustainability. By primarily reviewing in vitro and in vivo preclinical studies, we assess how these extracts modulate angiogenesis across various disease models and explore their potential as adjunctive therapies for cancer and other angiogenesis-driven disorders. This review also identifies existing knowledge gaps and proposes future research directions to fully elucidate the clinical utility of pomegranate extracts in therapeutic applications. Full article

Different solvents water, ethanol and ethanol/water (6:4 v/v), were compared in the extraction of pomegranate peels and seeds (PPS) in terms of recovery yields, antioxidant properties, and antimicrobial action against typical spoilage bacterial and fungal species. The best performing extract (ethanol/water (6:4 v/v) was shown to contain mostly ellagic acid and punicalagin as phenolic compounds (5% overall) and hydrolysable tannins (16% as ellagic acid equivalents) and was able to inhibit the growth of the acidophilic Alicyclobacillus acidoterrestris at a concentration as low as 1%. The preservation of the organoleptic profile of A. acidoterrestris-inoculated apple juice with extract at 1% over 20 days was also observed thanks to the complete inhibition of bacterial growth, while the extract at 0.1% warranted a significant (40%) inhibition of the enzymatic browning of apple smoothies over the first 30 min. When incorporated in whey proteins’ isolate (WPI) at 5% w/w, the hydroalcoholic extract conferred well appreciable antioxidant properties to the resulting coating-forming hydrogel, comparable to those expected for the pure extract considering the amount present. The WPI coatings loaded with the hydroalcoholic extract at 5% were able to delay the browning of cut fruit by ca. 33% against a 22% inhibition observed with the sole WPI. In addition, the functionalized coating showed an inhibition of lipid peroxidation of Gouda cheese 2-fold higher with respect to that observed with WPI alone. These results open good perspectives toward sustainable food preservation strategies, highlighting the potential of PPS extract for the implementation of WPI-based active packaging. Full article

Background: Oxidative stress and chronic inflammation, at both the systemic and the central level, are critical early events in atherosclerosis and Alzheimer’s disease (AD). Purpose: To investigate the oxidative stress-, inflammation-, and Tau-phosphorylation-lowering effects of pomegranate polyphenols (PPs) (punicalagin, ellagic acid, peel, and aril extracts). Methods: We used flow cytometry to quantify the protein expression of proinflammatory cytokines (IL-1β) and anti-inflammatory mediators (IL-10) in THP-1 macrophages, as well as M1/M2 cell-specific marker (CD86 and CD163) expression in human microglia HMC3 cells. The IL-10 protein expression was also quantified in U373-MG human astrocytes. The effect of PPs on human amyloid beta 1-42 (Aβ_1-42)-induced oxidative stress was assessed in the microglia by measuring ROS generation and lipid peroxidation, using 2′,7′-dichlorofluorescein diacetate (DCFH-DA) and thiobarbituric acid reactive substance (TBARS) tests, respectively. Neuronal viability and cell apoptotic response to Aβ_1-42 toxicity were assayed using the MTT (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide) assay and the annexin-V-FITC apoptosis detection kit, respectively. Finally, flow cytometry analysis was also performed to evaluate the ability of PPs to modulate Aβ_1-42-induced Tau-181 phosphorylation (pTau-181). Results: Our data indicate that PPs are significantly (p < 0.05) effective in countering Aβ_1-42-induced inflammation through increasing the anti-inflammatory cytokines (IL-10) in U373-MG astrocytes and THP1 macrophages and decreasing proinflammatory marker (IL-1β) expression in THP1 macrophages. The PPs were also significantly (p < 0.05) effective in inducing the phenotypic transition of THP-1 macrophages and microglial cells from M1 to M2 by decreasing CD86 and increasing CD163 surface receptor expression. Moreover, our treatments have a significant (p < 0.05) beneficial impact on oxidative stress, illustrated in the reduction in TBARS and ROS generation. Our treatments have significant (p < 0.05) cell viability improvement capacities and anti-apoptotic effects on human H4 neurons. Furthermore, our results suggest that Aβ_1-42 significantly (p < 0.05) increases pTau-181. This effect is significantly (p < 0.05) attenuated by arils, peels, and punicalagin and drastically reduced by the ellagic acid treatment. Conclusion: Overall, our results attribute to PPs anti-inflammatory, antioxidant, anti-apoptotic, and anti-Tau-pathology potential. Future studies should aim to extend our knowledge of the potential role of PPs in Aβ_1-42-induced neurodegeneration, particularly concerning its association with the tauopathy involved in AD. Full article