Nutraceuticals, Volume 5, Issue 4 (December 2025) – 10 articles

Cancer remains a persistent global health challenge, continuously driving the search for novel and effective therapeutic strategies. In the case of breast cancer, treatment decisions are primarily guided by factors such as the disease stage, histological grade, molecular receptor status, and the presence of genetic mutations. Understanding these parameters is crucial for tailoring interventions and improving clinical outcomes. To enhance prognostic and diagnostic accuracy, attention has increasingly turned to identifying molecular targets that play key roles in breast cancer development. Currently, standard treatments include surgery, chemotherapy, and radiotherapy. However, these approaches are often associated with significant side effects and a diminished quality of life. As a result, many breast cancer patients are turning to complementary therapies—including phytotherapy, nutritional interventions, and dietary supplements—to support conventional treatment, alleviate adverse effects, and improve overall well-being. Within the vast realm of medicinal flora, anticancer plants represent a compelling area of study, serving as a rich reservoir of bioactive compounds. These compounds have demonstrated significant promise in the ongoing battle against cancer. Often highlighted in traditional medicinal practices, these plants harbor a wide array of phytochemicals, such as alkaloids, flavonoids, polyphenols, and terpenoids. These phytochemicals manifest diverse biological activities, notably exhibiting pronounced anticancer properties. The exploration of these natural compounds has opened new avenues for developing innovative and targeted therapeutic strategies in cancer treatment. They achieve definitive chemotherapeutic and chemopreventive roles by integrating with specific molecular signals. Their multiple biological functions include antimutagenic, antiproliferative, antimetastatic, anti-angiogenesis, anti-inflammatory, antioxidant, and immunomodulatory properties, which collectively enable them to control cancer progression and intervene at various stages of cancer cell development. Moreover, these compounds are involved in regulating the cell cycle and microRNA, ultimately leading to cancer cell death by promoting apoptosis and autophagy, often mediated through ROS signaling. Thus, based on a large theoretical revision, we conclude that high-quality evidence is necessary in order to advise these products concerning their efficacy and safety. Also, clinical evidence should be supported by a comprehensive individual diagnosis and adequate research protocols in order to evaluate whether the benefits of these plant-produced interventions can outweigh their harms. Full article

The present study used a syngeneic mouse model of malignant melanoma to evaluate the inhibitory efficacy of continuous xylitol administration via a subcutaneous osmotic minipump. The B16F10 syngeneic model for malignant melanoma consisted of 6–8-week-old C57BL/6 male mice subcutaneously injected with 5 × 10⁵ B16F10 cells suspended in 100 μL PBS in the right flank. The mice were randomly assigned to two groups: Group 1 was the treatment group, which received 10% w/v xylitol in saline-loaded pumps (n = 10), while Group 2 was the control group, which received saline-loaded pumps (n = 10). ALZET 2004 minipumps were implanted subcutaneously in the left flank of B16F10-injected mice once more than 50% of all mice developed palpable tumors. After pump implantation surgery, the mice were monitored daily and weighed 2–3× times per week. Tumor sizes were measured with calipers 2–3× per week, and all mice were euthanized when their tumors became too large (20 mm on any axis or 2000 mm³). The tumor size growth was reduced by approximately 35% by volume in the xylitol-treated group which was not statistically significant. The xylitol group had a longer survival time, but this was not statistically significant (Kaplan–Meier), as was the case with the survival analysis by the Cox proportional hazards model. The metabolomic analysis suggests that xylitol significantly alters the tumor’s metabolism, potentially affecting the host immune response. Full article

This randomized, double-blind, placebo-controlled study investigated Ageratum conyzoides (A. conyzoides) for alleviating osteoarthritis symptoms and improving quality of life. Conducted in Australia between 2021 and 2024, the study included 70 adults aged ≥45 years with clinically diagnosed osteoarthritis. Participants consumed 250 mg of pyrrolizidine alkaloid-free A. conyzoides extract or a placebo daily for 12 weeks. Pain and function were assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) every three weeks. Secondary measures included pain assessed by the Visual Analogue Scale (VAS), the SF-36 quality-of-life questionnaire, inflammatory markers, and safety parameters. A. conyzoides supplementation resulted in significant reductions in total WOMAC scores at weeks 9 and 12 (p < 0.05) compared to placebo. VAS pain scores were significantly lower at weeks 9 and 12 (p < 0.05). SF-36 scores improved significantly in the pain and role limitations due to physical health domains (p < 0.05). Plasma inflammatory markers IL-6 and IL-8 showed significant reductions compared with placebo (p < 0.05). No between-group differences were observed for adverse events. These findings demonstrate that A. conyzoides supplementation is a safe and effective option for reducing osteoarthritis symptoms, with significant improvements observed in pain, function, and inflammatory markers. Full article

Palmitoylethanolamide (PEA) is a naturally occurring fatty acid amide and an endocannabinoid-related lipid that has been extensively studied for its analgesic, immunomodulatory, antimicrobial, and anti-inflammatory properties. It has demonstrated efficacy in various applications and is currently utilized as a nutraceutical for its antinociceptive, neuroprotective, and immunomodulatory effects, particularly in supporting brain and joint health and in mitigating inflammatory processes. Background/Objectives: Despite its significant therapeutic potential, the clinical effectiveness of PEA is limited by its poor water solubility and, consequently, low oral bioavailability. Additionally, degradation in the acidic gastrointestinal environment further compromises its absorption. To address these challenges, several technological strategies have been explored to improve its pharmacokinetic profile, including conventional micronization and ultra-micronization techniques. The objective of this study was to characterize a novel liposomal formulation based on PEA and evaluate its intestinal permeation and absorption. Methods: Comparative permeation studies of PEA were conducted using ex vivo models to evaluate its absorption characteristics across gastrointestinal mucosae. The experiments were performed in a Franz diffusion cell system using a porcine colon mucosa in two physiologically relevant media: Simulated Gastric Fluid (SGF) and Fasted State Simulated Intestinal Fluid (FaSSIF). Results: Liposomal PEA showed a more efficient and continuous release over time, reaching higher concentrations of PEA permeated through the membrane. Conclusions: Our findings demonstrate a significant improvement in PEA’s permeability and absorption in an ex vivo simulated gastrointestinal environment. Liposomal PEA appears to be more affine to biological membranes. These results suggest that liposomal PEA may represent a promising therapeutic strategy for managing chronic pain and inflammatory conditions such as chronic pelvic pain. Full article

Bacteriocins from lactic acid bacteria have attracted considerable attention as natural alternatives to conventional antimicrobial agents. Weissellicin LM85, a bacteriocin purified from Weissella confusa LM85, has been less extensively studied in terms of its mechanism of action and potential applications. In this study, purified weissellicin LM85 exhibited potent inhibitory effects against Gram-positive bacteria, with minimum inhibitory and bactericidal concentrations determined against Micrococcus luteus MTCC106. Time-kill assays and fluorescence staining indicated a concentration-dependent reduction in cell viability, accompanied by membrane disruption. Further analyses revealed potassium ion efflux, dissipation of membrane potential (Δψ) and pH gradient (ΔpH), genomic DNA fragmentation, and pronounced morphological alterations in target cells. These findings are strongly suggestive of membrane-targeted bactericidal activity, likely involving pore-forming effects. In addition, weissellicin LM85 inhibited both growth and biofilm formation of Salmonella enterica subsp. enterica serovar Typhimurium ATCC13311 and Staphylococcus aureus subsp. aureus ATCC25923. Mechanistic analyses revealed the disruption of cell membrane integrity, leakage of potassium ions, cytoplasmic contents, and non-specific DNA degradation, indicating a multifaceted antibacterial mode of action. These findings highlight weissellicin LM85 as a promising natural antimicrobial with potential applications in food preservation and the control of foodborne pathogens and biofilm-associated infections. Further studies on cytotoxicity and in vivo efficacy are required to advance its practical application. Full article

Protein supplements are popular nutritional supplements consumed primarily by physically active individuals with increased protein demands. Despite the increasing consumer demand for protein supplements in Greece, detailed and comparative data on the nutritional profile of such products is scarce. The purpose of this study was to determine the nutritional quality of protein powder supplements available in the Greek market and to compare animal- with plant-based products. Data was extracted from the websites of the major retailers (n = 28). In total, 216 products were identified and grouped as animal- and plant-based, depending on the protein origin. Animal-based products were predominantly (84.0%) produced from whey. Protein content was significantly higher (p < 0.05) in animal-based products, providing 43.5% of the reference intake (RI) for men and 53.2% for women per serving. The content of essential amino acids (EAAs), branched amino acids (BCAAs) and alanine (Ala) was significantly higher (p < 0.05) in animal-based products (median: 11.0, 5.3 and 1.2 g/serving) compared with plant-based alternatives (median: 8.4, 4.0 and 1.0 g/serving size). Plant-based protein supplements contained significantly higher (p < 0.05) content of fiber, fat and salt and were more energy-dense per 100 g. Mean serving size was larger for animal-based products (29.9 ± 0.4 g) compared with the plant-based ones (28.1 ± 0.5 g). Animal-based supplements were more expensive to purchase by 4.3 € per kg. Overall, animal-based protein powder supplements show a more desirable nutritional profile regarding protein content and quality. Results of this study can serve as a tool for consumers to make informed and healthy choices and for health professionals to provide effective and personalized guidance based on the nutritional content of products. Full article

The olive fruit is recognized for being a significant source of phenolic compounds, including hydroxytyrosol (H-tyr), tyrosol (Tyr), oleuropein (Ole), and verbascoside (Verb). The maturity index (MI) significantly influences the phenolic profile, which is a cultivar-specific trait. A study was conducted to assess the evolution of the phenolic profile in seven olive cultivars during ripening: ‘Galega vulgar’ (Gv), ‘Azeiteira’ (Az), ‘Cobrançosa’ (Cob), ‘Picual’ (Pic), ‘Carrasquenha’ (Car), ‘Redondil’ (Red), and ‘Arbequina’ (Arb). The results indicate a declining trend in total phenolic compounds (TPC) across all cultivars, with Cob and Car exhibiting the highest values, over 60 g GAE kg⁻¹ at T1 and above 30 g GAE kg⁻¹ at T7, respectively. In Ole quantitation, Red demonstrated the highest values, recording 39 g kg⁻¹ in T1 and 15 g kg⁻¹ at T7, with per olive fruit unit measurements ranging from 19.7 mg at T1 to 22.7 mg at T7. These findings underscore olive fruit as an exceptional source of bioactive compounds and their advantageous health-promoting effects, which might be utilized as a functional food source, validating the unique phenolic profiles of each cultivar in relation to ripening. Full article

The human gut microbiota helps maintain metabolic balance, supports immune function, and defends against opportunistic pathogens that can disrupt the microbiota ecosystem. An imbalance or dysbiosis in microbial composition is linked to various diseases, including inflammatory bowel disease, metabolic syndromes, and neurodegenerative disorders. Using microbiota modulation with prebiotics and postbiotics is a practical approach to address these imbalances. Prebiotic compounds are defined as substrates that promote metabolic activity and restore microbial patterns. Postbiotics include short-chain fatty acids (SCFAs), microbial cell lysates, and extracellular compounds. This research aims to investigate how the gut microbiota can be modulated in vitro using the prebiotic ColonX and a postbiotic derived from Kombucha fermentation within a controlled GIS1 in vitro system. These products demonstrate potential for modulation, as they support selective bacterial growth and enhance microbial diversity. Prebiotics help stabilize gut pH, while postbiotics play a crucial role in biofilm formation. Together, they provide an innovative approach to treating dysbiosis and enhancing overall gut health. The findings highlight the importance of utilizing prebiotics and postbiotics to modulate gut microbiota in chronic diseases characterized by dysbiosis. This paper is especially relevant for elderly populations, as gut dysbiosis is common, and microbiota modulation supports healthy aging. Full article

Urinary tract infections (UTIs) are common and create significant clinical challenges. Most UTIs are caused by uropathogenic Escherichia coli (UPEC) and affect 50 to 70% of women at some point in their lives. Of this population, 25% will have a recurrent urinary tract infection (rUTI) within 3 to 12 months of the first episode. High rates of rUTIs may occur because UPEC can enter a non-proliferative or quiescent state within the urothelium of the bladder. This state allows UPEC to evade the host’s immune response and antibiotic treatment. We utilized a library of plant extracts derived from the URI Heber W. Youngken Jr. Medicinal Garden to determine if they reversed UPEC quiescence with a novel in vitro quiescence assay using the classic UPEC endemic lineage ST73 strain CFT073. We found an overall active extract hit rate of 69% (79/114 active) and that active extracts contained high levels of polyphenolic compounds. Further testing showed that polyphenols with adjacent hydroxyl groups on a benzene ring (catechol moiety) were the most effective and potent in reversing quiescence. The ability to reverse quiescence was also linked to the compound’s ability to bind iron (e.g., epigallocatechin gallate and rosmarinic acid were the most potent reversing agents—0.1 mM—and they both had the strongest iron-binding activity as determined via CAS assay). These findings reveal a new class of metabolites that can reverse quiescence in UPEC strains. Full article

DHMBA, a novel antioxidant derived from oyster, exhibits dual properties that block oxidative stress by acting as a radical scavenger in various cells. DHMBA has been shown to play a pharmacological role by exerting anti-macrophage and anti-cancer effects. Gallic acid, which is widely distributed in edible plants, exhibits a potent antioxidant activity. In this study, we compared the effects of DHMBA and gallic acid using inflammatory macrophages (RAW264.7 cells) and human lung cancer cells (A549 cells) in vitro. In these cells, we demonstrated that DHMBA at comparatively lower concentrations (1 or 10 µM) significantly affected cell proliferation and stimulated cell death, resulting in a decrease in cell number. Gallic acid at 1 and 10 μM did not affect the proliferation or death of RAW264.7 and A549 cells. DHMBA may be a potent antioxidant that regulates cell function. Despite having the same molecular weight, the chemical structure of DHMBA and gallic acid exerted different effects. Notably, the combined DHMBA and gallic acid with comparatively lower concentrations (1 and 10 μM) showed potent effects in suppressing the proliferation of RAW264.7 and A549 cells. However, this combination did not induce a significant effect on cell death. Thus, the effects of DHMBA were potentiated in the presence of the antioxidant gallic acid. This finding suggests a potential effect induced by the combined antioxidants. This study provides a new strategy for disease prevention using the strong antioxidants DHMBA and gallic acid. Full article