Background:

Colorectal cancer (CRC) remains a major global health challenge due to the limitations of current therapies, including systemic toxicity and inadequate tumor specificity. Natural products like nutmeg (Myristica fragrans) exhibit anticancer potential, but their clinical application is limited by poor bioavailability. Integrating nutmeg extracts into nanocarriers may overcome these barriers and enhance their therapeutic efficacy.

Methods:

Nutmeg extract was prepared using supercritical CO₂ extraction (NSFE) and encapsulated into hybrid poly(lactic-co-glycolic acid)–lipid nanoparticles (NSFE-PLGA-LN) via nanoprecipitation. Characterization included particle size (DLS), morphology (TEM), zeta potential, and encapsulation efficiency. Metabolomic profiling was performed using UHPLC-HRMS/MS. Bioactivity was predicted through network pharmacology and molecular docking against CRC-related targets (EGFR, PTGS2, STAT3, JAK2, PIK3CB). Cytotoxic effects were assessed in CRC cell lines (HT-29, HCT-116) and normal colon fibroblasts (CCD-18Co) using MTT assays.

Results:

Metabolomic analysis identified bioactive compounds including myristicin, elemicin, β-caryophyllene, and sabinene. Network pharmacology and docking simulations revealed significant interactions with CRC-related pathways, notably apoptosis, proliferation, and inflammation, with β-caryophyllene demonstrating strong affinity (Vina score ≤ –7.2 kcal/mol). NSFE-PLGA-LN exhibited selective cytotoxicity, with IC₅₀ values of 95.5 µg/mL (HT-29), 89.2 µg/mL (HCT-116), and minimal toxicity on normal CCD-18Co cells (IC₅₀=896.5 µg/mL).

Conclusions:

Hybrid PLGA–lipid nanoparticles significantly enhanced nutmeg extract’s therapeutic profile, providing selective, sustained anticancer activity. These findings support further preclinical evaluation and mechanistic studies warranted for potential clinical translation.

Anti-aging functional foods have garnered widespread attention for their ability to provide health benefits through daily diets. Picroside I is a natural compound extracted from the rhizome of Picrorhizae Rhizoma. Picrorhizae Rhizoma, a common traditional Chinese medicinal material, is also frequently used as an ingredient in health teas. Its rhizome is rich in various bioactive components. Caenorhabditis elegans, a classic model organism for aging research, holds significant importance in the study of functional foods. In this study, we used C. elegans as a model to investigate the effects of the natural compound Picroside I from traditional Chinese medicine on the lifespan and locomotor ability of the worms. The results showed that Picroside I increased the head thrashing and pharyngeal pumping rates of the worms on day 8, thereby enhancing their muscle vitality. Moreover, Picroside I at a concentration of 10 μM significantly extended the healthspan of the worms. Further network pharmacology and molecular docking analyses revealed that Picroside I may be associated with glycation end-product receptors and lipid metabolism. Additionally, it was found that the compound acts on the disulfide bond region of the asymmetric dimer of kinase domains of the EGFR protein, reducing the stability of the protein and thereby affecting downstream signaling pathways in cells, such as the PI3K/Akt pathway and the MAPK pathway, which in turn influence cellular metabolic processes. Our study indicates that Picroside I has significant potential to extend the lifespan and enhance the muscle vitality of C. elegans. It holds promise as a novel anti-aging food ingredient and is of great significance for the development of traditional Chinese medicine-based anti-aging functional foods.

Capsaicin, a natural bioactive component extracted from chili peppers, is important in food flavoring and food preparation. Currently, the global climate is changing rapidly, extreme cold wave events occur frequently, and direct cell damage and secondary ice crystal effects triggered by low-temperature stress seriously threaten the survival of organisms, so analyzing the cold tolerance mechanism is of great significance for biological protection and low-temperature medicine. As an important model organism in pharmaceutical research, Cryptococcus hidradii is of great significance in the testing of functional foods. In this study, we used Cryptobacterium hidradii as a model to investigate the protective effect of capsaicin, a natural food active ingredient, in low-temperature stress. A control group and three experimental groups (capsaicin concentrations of 10 μM, 50 μM, and 250 μM) were set up to compare the locomotor indexes of different groups of nematodes after treatment at 4°C, 30 min, and we found that different concentrations of capsaicin enhanced the locomotor ability of nematodes at low temperatures, with a significant enhancement of the head bobbing, body bending, and pharyngeal pumping rate. In the -20°C, 5 min cold shock recovery experiment, capsaicin was able to shorten the recovery time of nematodes. In three consecutive cold shock experiments, the recovery rate of nematodes increased significantly, showing adaptation to cold shock, and capsaicin was able to accelerate the adaptation of nematodes to cold shock recovery. The study showed that capsaicin could enhance the nematode's locomotor ability in the low-temperature environment, promote the nematode's recovery after cold shock, and synergize with the nematode's adaptive memory to promote the self-protection and adaptation to the nematode in the low-temperature environment.

Chickpeas have gained prominence as a sustainable source of protein, combining high nutritional value with potential health benefits. Recently, bioactive peptides derived from chickpea proteins have been investigated for their antioxidant properties, including their ability to neutralize free radicals and chelate metals. In this context, the new Cappuccino variety has emerged as a promising yet underexplored material. Preliminary studies suggest that protein hydrolysates from chickpeas may release active peptides, paving the way for applications in functional foods and nutraceuticals.

This study aimed to evaluate the release of antioxidant peptides during the simulated digestion of globulins, the major protein fraction (60–70%) of chickpeas, correlating the degree of hydrolysis with antioxidant activity. In vitro digestibility was assessed using the pepsin–pancreatin method. The amount of α-amino groups released (nmol leucine equivalents/mg protein) and antioxidant activity (µmol TROLOX equivalents—TE/mL hydrolysate) were quantified via ABTS assay.

The hydrolysis profiles indicated low protein breakdown during the gastric phase (point A), with 596.8 nmol leucine/mg protein released, whereas the intestinal phase (point C) led to a significant increase in hydrolysis, reaching 1650.83 nmol leucine/mg. Antioxidant activity showed a direct correlation with the degree of hydrolysis. For the obtained hydrolysates, antioxidant activity ranged from 854.99 to 1378.35 nmol TE/mg protein or from 2858.4 to 4838.7 µmol TE/mL hydrolysate.

These findings suggest a progressive release of peptides with higher antioxidant activity throughout simulated digestion. The in vitro digestion of globulins from the GB Cappuccino chickpea variety revealed a phase-dependent pattern of antioxidant peptide release, with a marked intensification during the intestinal phase. The correlation between protein hydrolysis and increased antioxidant activity reinforces the potential of this variety as a promising source of bioactive peptides for functional and nutraceutical formulations.

Introduction: Dietary bioactive compounds are increasingly recognized for their role in regulating epithelial homeostasis and preventing abnormal cell proliferation. Among them, polyphenol-rich byproducts of winemaking have demonstrated antiproliferative effects in various tissues, including the colon, by modulating oxidative stress, inflammation, and cell cycle control. Grape Antioxidant Dietary Fibre (GADF) is a natural product that combines high amounts of dietary fibre and phenolic antioxidants obtained by a patent procedure from red grape pomace (Vitis vinifera, var Cencibel). In this study, we studied GADF's effect on proximal colonic epithelium proliferation and its molecular mechanisms in healthy rats.

Methods: Male Wistar rats were randomly assigned to control (Standard diet) or GADF-fed groups (5% w/w GADF replacing cellulose in an isoenergetic diet) for four weeks. Proximal colonic tissues were collected, and cytosolic and nuclear extracts were obtained. Immunohistochemistry and Western blot were conducted to assess proliferation and cell cycle markers. All procedures were approved by the Animal Care Committee of Universidad Complutense de Madrid (EU Directive 86/609/EEC).

Results: A significantly lower percentage of proliferating cell nuclear antigen (PCNA)-positive nuclei in Lieberkühn’s crypts was observed in GADF-fed rats compared to controls (-30.71%, p<0,0001). GADF also induced a 24-fold increase in p53 phosphorylation at Ser392 (p < 0.0001), with localization in both the nucleus and cytoplasm. In parallel, GADF upregulated the expression of the cyclin-dependent kinase inhibitors p21^Cip1/Waf1 and p27^Kip1 by 35% and 25% (both p<0.001) and downregulated cyclin D1 and cyclin E by 26% and 17% (p<0.01), respectively.

Conclusions: This study provides novel insights into the molecular mechanisms by which GADF modulates epithelial cell dynamics in the healthy colon. By inducing a p53-dependent G1/S cell cycle arrest, GADF effectively limits epithelial proliferation, supporting its role as a promising chemopreventive dietary component for maintaining colonic health and reducing early risk factors associated with colorectal cancer.

INTRODUCTION: Gastric cancer (GC), widely known as stomach cancer, is a critical health concern across the world. Natural products have been renowned for millennia and are highly reputable as a fashionable supply of therapeutic agents. Erucin is a naturally occuring isothiocyanate found in various cruciferous vegetables, particularly in rocket (arugula) and certain types of broccoli. This study aimed to evaluate the anti-cancer effect and mechanistic role of erucin on GC cell lines.

METHODS: To understand the pharmacological potential of erucin, we employed network pharmacology, molecular docking, molecular dynamics simulations, and in-vitro studies. These methods contributed to a holistic understanding of the mechanisms, interactions, and efficacy of erucin in GC.

RESULTS: Network pharmacology analysis revealed 10 key targets including SRC, AKT1, mTOR1, BCL2, and HIF1A in the gastric cancer pathway. Molecular docking showed that erucin exhibited higher binding affinities for SRC, AKT1, and mTOR1 among these targets, with stable interactions validated by dynamics simulation for SRC and AKT1. Erucin induced concentration and time-dependent cytotoxicity in AGS cells with a 24 h IC₅₀ of 77.3 ± 6.6 µM and 48 h IC₅₀ of 52.6 ± 1.12 µM. Acridine orange/ethidium bromide (AO/EtBr) dual staining assay showed a dose-dependent increase in apoptotic cells, characterized by nuclear condensation and membrane blebbing. Erucin treatment markedly inhibited the colony formation ability of AGS cell line in a dose-dependent manner. AGS cells treated with Erucin exhibited significantly reduced migration rates compared to control cells. Western blotting showed Bax upregulation, Bcl-2 downregulation, and cytochrome c release with downregulated SRC. These findings have antiproliferative and anti-cancer effects on AGS cells.

CONCLUSION: Erucin exhibits potent anti-cancer activity in AGS gastric cancer cells by directly targeting critical oncogenic regulators including SRC, mTORC1, and AKT1. Its multi-targeted interaction profile and ability to inhibit cell proliferation, migration, and colony formation strongly support its therapeutic potential in gastric cancer management.

Introduction: Insomnia is the most common sleep disorder in women. Many metabolic processes are involved in sleep regulation and depend on nutritional status, suggesting a link between diet and sleep¹. Over the past decade, there has been increased interest in the analysis of ellagitannins—a group of polyphenols whose metabolites involve ellagic acid (EA) and urolithins (Uros). Uros are microbial-derived metabolites with high bioavailability, blood–brain barrier permeability, and documented antioxidant, anti-inflammatory, and neuroprotective properties². However, Uros have not yet been analysed in the context of insomnia. This preliminary study will aim to evaluate the associations between urine metabolites of ellagitannins and insomnia occurrence among peri- and postmenopausal women.

Methods: This preliminary cross-sectional study involved 80 women aged 50–70, including 38 women with insomnia. Due to the direct impact on insomnia, the exclusion criteria for the study included neurological and psychiatric diseases. The occurrence of insomnia was assessed using the five-point WHIIRS scale (Women's Health Initiative Insomnia Rating Scale)³. The profile of ellagitannins metabolites in urine was analysed using the LC-MS technique.

Results: Three ellagitannin metabolites were identified in all urine samples (mean concentration): EA (12.6 nM), Uros C (2.8 nM), and Uros D (7.9 nM). Women without insomnia had slightly but significantly higher Uros C concentrations compared to women with insomnia (3.0 vs. 2.5 nM; p=0.0470). Uros A (1.3 nM) and B (1.0 nM) were identified in 80% and 14% women without insomnia and 74% and 8% women with insomnia, respectively.

Conclusions: The obtained findings provide promising preliminary data to design prospective studies involving diet and microbiome analyses to confirm the inverse association between Uros C concentration and insomnia occurrence and explain the mechanisms underlying them.

Research funding: This research was funded by the National Science Centre, Poland, grant number: 2024/08/X/NZ9/00854.

References: ¹Binks et al., Nutrients 2020; ²Zhao et al. Mediators Inflamm. 2020; ³Hery et al. Sleep Health. 2020.

The use of antibiotics in human nutrition and livestock production as growth promoters in some parts of the world has faced restrictions owing to growing concerns regarding their use, necessitating research efforts and substantial funding dedicated to finding cost-effective and sustainable alternatives. This quest for sustainable alternatives to antibiotics has led to an intense research interest in probiotics. However, their widespread application remains limited owing to an incomplete understanding of their functional mechanisms. This preliminary study focused on identifying promising candidates that will be further explored for experimental validation using animal models. This study investigated the immunogenic peptides derived from the following probiotic bacterial species: Ligilactobacillus saerimneri (GVGNDRRPVNAKNIKKRRAQ, GFDTDRYFEENKNEYDWGKP, EKYHLIEAEGIKRVTEEFIW, DNKVPVHVKGVEYAANAEDS, PLVLGVLFIATGYISYATYR, DVGSLLINHVLTSTLVMKQA); Ligilactobacillus salivarius (FSKEVADRANVENIEPGLIR, TLDKLEINTEEFMDFQKAFM, VRAKNYNAAETQVKVSVIAN, LYLVEYFINNKLHNMIVRAK, QRVHITNLYGLSGVAGLAQK, ALLDELREGTLDKLEINTEE), and Lactobacillus acidophilus (MKDYRLFLIDLDGTVYRG, CKDYRLFLIDLDGTVYRG, DKDYRLFLIDLDGTVYRG, EKDYRLFLIDLDGTVYRG, FKDYRLFLIDLDGTVYRG, NKDYRLFLIDLDGTVYRG). L. saerimneri was isolated from the cecum of a 20-day-old chicken, while L. salivarius was isolated from the feces of swine. They were specifically investigated for their ability to induce interleukin-5 (IL-5), interleukin-6 (IL-6), and interferon gamma (IFN_γ) as key cytokines involved in immune modulation. The study was approved by the Ethics Committee, Monogastric Animal Management and Behaviour, Department of Animal Science, University of Ibadan, Nigeria (MAMB02Bio25). All the selected peptides induced IL-5, IL-6, and IFN_γ. The ability to induce IFN_γ in humans was highest in peptides from Ligilactobacillus salivarius (0.8367), which is statistically similar to peptides from Ligilactobacillus saerimneri (0.800). Peptides from Lactobacillus acidophilus obtained the lowest value (0.7533). L. salivarius and L. saerimneri peptides are 100% immunogenic against tumor peptides, while L. acidophilus peptides are 66% immunogenic. These results suggest their potential sustainable applications as food supplements, feed additives, and as part of vaccine development, providing promising avenues for antibiotic alternatives.

This study characterizes magarine derived from the pili nut (Canarium ovatum), a tree native to the Philippines, focusing on its potential as a plant-based milk alternative. Pili nut margarine was prepared using protocols adapted from established nut-based milk methodologies. Proximate analysis revealed high lipid and protein content, supporting its nutritional viability. Gas chromatography–mass spectrometry (GC-MS) analysis of the lipid fraction identified major fatty acid methyl esters, including oleic acid (C18:1, 48.2%), palmitic acid (C16:0, 27.5%), linoleic acid (C18:2, 13.7%), and stearic acid (C18:0, 6.8%), along with minor components such as lauric and myristic acids. These results indicate a lipid profile rich in monounsaturated and polyunsaturated fatty acids associated with positive health effects. Fourier-transform infrared (FT-IR) spectroscopy further confirmed the presence of key functional groups: strong absorption bands corresponding to O–H stretching (~3400 cm⁻¹), C–H stretching (~2920 cm⁻¹), C=O stretching (~1740 cm⁻¹), and C–O stretching (~1050 cm⁻¹), consistent with triglycerides and other lipid esters. Differential scanning calorimetry (DSC) revealed thermal transitions characteristic of margarine matrices, with endothermic peaks between 24–30 °C and 90–110 °C, indicating stable emulsified fat structures. Viscosity measurements demonstrated favorable rheological properties across various temperatures, while total acidity values supported the product’s stability and palatability. The combined compositional, structural, and functional analyses underscore the potential of pili magarine as a nutritious, locally sourced, plant-based milk alternative, supporting dietary diversity and sustainable food innovation in the Philippines.

Cardiovascular diseases continue to be among the primary causes of death worldwide. Oxidative stress and inflammatory mechanisms are deeply involved in their pathogenesis. In this context, biomarkers, such as cardiac troponins, are critical tools for assessing cardiovascular risk. Olea europaea (Oleaceae) has been proven to exert antioxidant activities. Scutellaria baicalensis, belonging to the Lamiaceae family, has demonstrated cardiovascular benefits in various therapeutic models. Policosanols, a group of long-chain alcohols derived from sugarcane, have been shown to lower cholesterol levels and combat oxidative stress. This study investigates the cardioprotective potential of a plant-based formulation composed of Olea europaea, Scutellaria baicalensis, and policosanols. Three concentrations were tested: mixture 1 (5 µg/ml, 10 µg/ml, 1.5 µg/ml); mixture 2 (50 µg/ml, 100 µg/ml, 15 µg/ml); and mixture 3 (500 µg/ml, 1000 µg/ml, 150 µg/ml). The cytotoxicity of these mixtures was evaluated on HFF-1 human fibroblasts using MTT assay, with no significant toxicity observed at concentrations up to 1000 μg/ml. Among the mixtures, the third formulation showed the most notable effects in reducing H₂O₂-induced damage and oxidative stress in H9c2 cardiomyoblasts. Additionally, in an ex vivo model of LPS-induced inflammation in murine cardiac tissue, this mixture significantly downregulated the expression of pro-inflammatory and oxidative markers such as COX-2, NF-kB, TNF-α, and iNOS. Furthermore, it led to a decrease in cardiac injury biomarkers (troponin I and BNP) and increased the levels of catalase (CAT), highlighting a protective antioxidant response. In conclusion, the results suggest that this botanical formulation may exert a protective role on cardiac tissue exposed to oxidative stress. However, additional investigations are necessary to confirm and further elucidate these effects.