Bioactive Compounds in Health and Disease - Online ISSN: 2574-0334
The Bioactive Compounds in Health and Disease (BCHD) journal is a peer-reviewed, open-access publication dedicated to cultivating a deeper understanding of how bioactive compounds impact health and disease across diverse fields of science. It is indexed in the following databases: Scopus, Index Copernicus, Crossref, and Google Scholar. In particular, Scopus has listed the BCHD journal since October 2021, with a current CiteScore of 3.9 (Calculated on January 5th, 2026). The primary objective of this journal is to develop research in an effort to better understand bioactive compounds and their role in reducing the risk of chronic diseases such as cancer, diabetes, and cardiovascular diseases. Through the investigation of bioactive compounds from the standpoint of functional foods, we have defined these compounds as: “Food bioactive compounds are primary and secondary metabolites of nutritive and non-nutritive natural components that generate bioactive impacts on the body, thereby contributing to overall human health.” The BCHD journal addresses the definition of food bioactive compounds (FBCs), where they are located, and how they affect particular molecular pathways. Readers can expect to find current research on the implications of FBCs for human health, as well as their potential to relieve symptoms of chronic diseases. The evaluation of the interplay between FBCs at subcellular, cellular, tissue, and whole-body levels may reveal changes in biological activity that directly impact biomarkers. Furthermore, the publication contains a broad range of research pertaining to the sources and identification of food bioactive compounds (i.e., prebiotic and probiotic compounds, sterols, minerals, vitamins, anthocyanins, dietary fiber, flavonoids, flavonols, isoflavones, lipids, omega-3 fatty acids, polyphenols, phytochemicals, and more). It investigates how the consumption of certain functional foods contributes to human health, such as the anticancer effects of garlic (a plant food) or the impact of fermented milk products (animal products) on gut microbiota. The journal serves as an excellent resource for students, professors, public health professionals, medical doctors, dieticians, nutritionists, and the general public. It presents valuable insights into modern advancements that promote optimal health, reduce the risk of chronic or viral diseases, and support symptom management through bioactive compounds. Scopus Metrics: [Bioactive Compounds in Health and Disease - Scopus Page] You can submit your manuscripts here or directly to the Editorial Office at editor@ffhdj.com as an email attachment. Please also submit a Cover Letter. You can find a BCHD Cover Letter here.
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Early detection of tomato bacterial canker (Cmm) using quantitative PCR (qPCR)
Background: Tomato (Solanum lycopersicum L.) is not only one of the key vegetable crops worldwide but also an important source of bioactive compounds, including lycopene, vitamin C, and polyphenols, which are associated with antioxidant and health-promoting properties. In the Republic of Armenia, the intensive development of greenhouse vegetable production contributes to increased crop productivity; however, it simultaneously increases the risk of bacterial diseases. One of the most problematic diseases is Bacterial canker of tomato, caused by Clavibacter michiganensis subsp. michiganensis (Cmm), which can lead to massive plant losses and significant yield reduction. Early diagnosis using quantitative polymerase chain reaction (qPCR) is crucial for effective disease control and the prevention of epiphytotics in greenhouses. Objective: To study the manifestation of bacterial canker of tomato under commercial greenhouse conditions and to evaluate the effectiveness of a qPCR method for the early and latent detection of the Cmm pathogen. Methods: The studies were conducted in commercial hydroponic greenhouses of the Kotayk and Ararat regions of Armenia. DNA was extracted from infected tomato stems and leaves using the CTAB method with Genetic Analysis Strategies S.L. kits and was spectrophotometrically analysed (A260/280 =1.78-1.92). Identification of Cmm was performed by qPCR using species-specific primers, and quantitative assessment of the pathogen was carried out using a standard curve based on serial tenfold dilutions. The reliability of the method was confirmed by analysis of sensitivity, linearity, repeatability, and reproducibility (Efficiency 98.1%, R² =1.0, LOD 3.1±0.4 × 10¹ copies/µl). Results: In commercial greenhouses, the first manifestations of bacterial canker in tomato include unilateral leaf wilting, darkening and necrosis of the stem vascular system, as well as alterations in fruit structure. The qPCR method enabled the detection of Cmm in all 12 examined samples with high amplification efficiency (97.5%). Samples with low Ct values (12.5-17.5) corresponded to a high number of pathogen DNA copies and exhibited pronounced visual disease symptoms. In contrast, samples with higher Ct values (26.7-36.8) contained low pathogen concentrations and, in most cases, showed no symptoms, indicating a latent stage of infection. Application of qPCR for early diagnosis reduced the proportion of infected plants from 13.2-14.9% to 4.8-5.1%, and yield losses from 9.4-10.1% to 3.5-3.9%. In addition to yield reduction, bacterial infection may affect the physiological processes of fruit development. In particular, the present study revealed a decrease in average fruit weight from 165.4 to 134.2 g, corresponding to a reduction of 18.9%. At the same time, accelerated fruit ripening was observed. The obtained results show that qPCR ensures effective early detection of infection and limits its spread under protected cultivation conditions, leading to reduced production losses and contributing to the production of healthier and high-quality plant products. Novelty: This study presents, for the first time, a comprehensive diagnosis of Cmm in commercial greenhouses in Armenia using qPCR to detect both symptomatic and latent tomato infections. The data demonstrates a direct correlation between bacterial load and symptom severity and confirms that early molecular detection of the pathogen can significantly reduce yield losses. The results highlight the practical value of implementing qPCR in greenhouse monitoring systems and provide a basis for developing a rapid phytosanitary control strategy, which has not previously been documented for the study region. Conclusion: The qPCR method demonstrated high efficiency for the early diagnosis of bacterial canker in tomato, enabling the detection of the pathogen at latent stages and preventing widespread infection. Early detection of Cmm allows timely implementation of protective measures, minimizes yield losses, and enhances the resilience of greenhouse tomato production. Thus, early molecular detection of Cmm is important not only for plant disease management but also for preserving the bioactive compounds and functional food value of tomato. Keywords: tomato, Clavibacter michiganensis subsp. michiganensis, bacterial canker, qPCR, greenhouse, early detection
Copyright (c) 2026 Iryna Vardanian, Gayane Sargsyan, Miguel A. Aranda, Armenuhi Pahlevanyan, Dmitri Sukhudyan, Hayk Martirosyan https://creativecommons.org/licenses/by/4.0
Whey as a meat quality improver in porcine metastrongylosis
Background: Breeding pigs under free-range forest conditions is considered one of the most effective ways to ensure the production of high-quality, environmentally clean meat with relatively low costs. However, free-range pig farming also carries certain risks, particularly the likelihood of infection with invasive diseases, among which metastrongylosis is the most common. Milk from cows is mainly processed into semi-dried salty cheese, and the whey produced in this process is traditionally used as a fresh feed additive for pigs. Additionally, the cheese whey may improve the chemical composition and biochemical parameters of muscle tissues in pigs infected with metastrongylosis. Objectives: To study the effect of cheese whey on the hematological composition of blood and biochemical indicators of muscle tissues in healthy and metastrongylosis-infected pigs, and to evaluate the compliance of the obtained pork with the requirements of functional food. Methods: The research was conducted in 2025–2026 in the northeastern mountainous-forest zone of Armenia, in abattoirs, and at the Research Center of Veterinary Medicine and Veterinary Sanitary Expert Examination of the Armenian National Agrarian University. The studies were conducted on 28 pigs aged 3 months to 1.5 years kept on the farm. To improve metabolic processes, fresh whey obtained during semi-dry Chanakh cheese production was used as a feed supplement. Hematological and biochemical analyses were performed using automated analyzers. Results: In porcine metastrongylosis, the organism is under stress and exposed to toxic metabolic by-products. Given these conditions, the use of cheese whey helps to alleviate pathological processes. As a result, protein restoration and anabolic processes are activated, and the organism begins to provide the structural materials necessary for maintaining and restoring muscle tissue. Conclusion։ The inclusion of cheese whey in the diet of healthy and metastrongylosis-infected pigs is an effective feed supplement. It promotes muscle growth, strengthens the muscular system, and improves the quality of meat obtained. Novelty of study: For the first time, the effectiveness of cheese whey as a natural, biologically active feed additive in pigs with metastrongylosis has been studied. The research results have shown that the inclusion of cheese whey in the pig diet improves blood parameters in both healthy pigs and those with pig metastrongylosis, as well as chemical and biochemical parameters of muscle tissue. Keywords: cheese whey, bioactive compounds, porcine metastrongylosis, functional food production, hematological and biochemical biomarkers, muscle tissue quality, livestock nutrition
Copyright (c) 2026 Valeri Grigoryan, Danik Martirosyan, Zhanna Melkonyan, Spartak Yeribekyan, Viktor Abrahamyan, Mariam Sargsyan, Ruzanna Grigoryan, Denis Le, Liana Grigoryan https://creativecommons.org/licenses/by/4.0
Use of freeze-dried fruit, berry, and vegetable powders in waffle cones for ice cream: Quality, ecological, and hygienic safety properties
Background: The primary raw material used to form the structure of ice cream waffle cones is bakery-grade wheat flour, which possesses specific technological characteristics. High levels of simple carbohydrates, primarily starch (up to 76.22 g/100 g of product), significantly increase the caloric content of finished waffle products. As a result, the product cannot be considered dietary, and its application is limited to certain consumer groups. The nutritional value and organoleptic characteristics of waffle cones can be enhanced while maintaining the required technological properties by partially replacing wheat flour with various fortifying ingredients in the recipe. Therefore, the production of waffle products with specified structural, mechanical, and technological characteristics is a modern and relevant area of research and development. Objective: To investigate the technological feasibility of using freeze-dried fruit, berry and vegetable powders in the recipe for ice cream waffle cones as a partial replacement for wheat flour. Methods: The moisture content of the powders was determined thermogravimetrically. The content of water-soluble pectin substances was determined using the calcium-pectate method, and crude fiber was determined using the intermediate filtration method. Ashing and determination of the amount of organic residue were carried out gravimetrically. The organoleptic, physicochemical (moisture content, alkalinity, wettability), and structural-mechanical (product strength) parameters of model samples and finished wafer products were evaluated. The moisture content was determined by drying the product sample for 30 minutes at the temperature of 130°C to the constant dry mass. Alkalinity was determined by titration. The strength of wafer products was determined using the Structurometer-ST2 device with microprocessor control using the ST2-07 method. The ST2-07 method is based on determining the ultimate load using the Knife No. 1 indenter. Results: The addition of vegetable, fruit, and berry powders to the waffle batter at levels of 4% to 6% resulted in a more flexible, less viscous, denser, and more structured batter. As a result, the fragility of the finished waffle cones decreased. These changes in the structural and mechanical properties of the finished waffle products can be seen as a positive effect of partially replacing traditional wheat flour with freeze-dried vegetable, fruit, and berry powders, which may ultimately make the product more appealing to consumers. Conclusions: Replacing some of the wheat flour (4 to 6% of the dry matter) with freeze-dried fruit, berry, and vegetable powders had no negative impact on the technological characteristics of the waffle cones. The resulting product exhibited acceptable organoleptic, physicochemical, and structural-mechanical properties. The vitamin-enriched formulation, due to its natural plant-based components, may contribute to the nutritional value of the product. The advantage of the developed technology is that it does not require retooling the waffle cone production line. Novelty of the Study: The results of the study can be used in the design of waffle cones with targeted functionality and specified structural and mechanical characteristics, including those with an extended shelf life. Keywords: waffle cones; plant resources; vegetable and fruit and berry powders; organoleptic properties; biochemical properties; rheological properties; quality assessment; quality products; ecological and hygienic safety; health preservation.
Copyright (c) 2026 Maxim Viktorovich Larionov, Anna Simonenkova, Ekaterina Demina, Valentina Rumyantseva, Oksana Safronova, Lusine Gagikovna Matevosyan, Rimma Hayk Osipova, Gagik Santrosyan https://creativecommons.org/licenses/by/4.0
A functional carrot-based food product in the prevention of post-weaning stress in piglets
Background: Post-weaning stress in piglets is characterized by the development of diarrhea, intestinal dysbiosis, systemic inflammation, and significant economic losses in pig farming. Limiting the use of feed antibiotics stimulates the search for safe functional products capable of modulating intestinal homeostasis. The historical protocol of E. Moreau (1908) for long-boiled carrots has demonstrated anti-adhesive and prebiotic potential but has not been considered as an element of systemic prevention in industrial pig farming. Objectives: To develop and scientifically substantiate the use of a functional carrot-based food product (Moro soup) in the prevention of post-weaning stress and associated diarrhea in piglets. Methods: The experiment was conducted on 60 piglets of a large white breed (28-35 days old, live weight 7.2 ± 0.5 kg). The animals are divided into 4 groups: 1st – control (standard diet); 2nd – antibiotic (colistin); 3rd – probiotic (Bacillus subtilis); 4th – experimental (Moro soup at a dose of 5-7 ml/kg 3 times a day, 5 days before, and 7 days after weaning). The Moro soup's main ingredients of 1 kg carrots, 2 liters of water, and 1.5 g of salt were cooked for 2 hours, after which 5% oat broth was added. The frequency and severity of diarrhea, body weight gain, large intestinal microbiota (PCR-RV), IL-6, secretory IgA (ELISA) levels, and jejunum histology were evaluated. Results: Moro soup supplementation resulted in a 67% decrease in the incidence of diarrhea (p<0.01) compared with the control group and reduced the duration of diarrhea syndrome to 1.6 ± 0.3 days. The average daily weight gain during the 14 days after weaning in the experimental group exceeded that of the control group by 18.4% (p<0.05) and was comparable to the antibiotic group. Microbiological analysis revealed a 2.3-fold increase in Lactobacillus spp. and a 70% decrease in enteropathogenic E. coli. The level of the pro-inflammatory cytokine IL-6 decreased by 40% (p<0.05), and the concentration of sIgA in the intestinal contents increased by 1.7 times. Morphometry of jejunum villi showed an increase in villi height of 22% and crypt depth by 12%, indicating a regenerative effect. Conclusion։ Moro soup is an effective functional food product that provides systemic prevention of post-weaning stress in piglets due to its combined anti-adhesive, prebiotic, anti-inflammatory, and reparative effects. Including the product in standard feeding protocols reduces reliance on antibiotics, increases livestock safety, and improves productivity. Next steps should focus on developing a free-dried form of Moro soup for industrial production and on incorporating it into commercial pre-starter feeds. Novelty of study: This is the first study to develop a functional carrot-based food product (Moro soup) and examine efficacy in the prevention of post-weaning stress in piglets. Additionally, this study is the first to obtain comprehensive data on the effects of Moro soup on the microbiota, immune response, and morphofunctional state of piglets' intestines, compared with antibiotics and probiotics. Keywords: post-weaning stress, functional animal food product, Moro soup, oligogalacturonides, intestinal microbiota, alternatives to antibiotics.
Copyright (c) 2026 Zhanna Melkonyan, Danik Martirosyan, Liana Grigoryan, Valeri Grigoryan, Albert Vardanyan, Mariam Sargsyan, Spartak Yeribekyan, Ruzanna Grigoryan, Hrachuhi Balasanyan, Denise Le, Viktor Abrahamyan https://creativecommons.org/licenses/by/4.0
Nutritional composition of shiitake mushrooms and their antioxidant and anti-inflammatory effects in LPS-stimulated C2C12 myoblasts
Background: Shiitake mushrooms (Lentinula edodes) are valued for their nutritional and medicinal properties, including antioxidant and anti-inflammatory effects. However, their impact on skeletal muscle health at the cellular level remains underexplored. Investigating their bioactive potential may reveal natural therapeutic strategies for reducing muscle inflammation and oxidative stress while promoting cell viability. Objective: This study aims to investigate the nutritional composition, bioactive compounds, and therapeutic potential of shiitake extract on muscle cells. Methods: Shiitake mushrooms were freeze-dried, powdered, and extracted with 70% ethanol. Nutritional and amino acid profiles were analyzed using standard methods and LC-MS/MS. identified by HPLC, and antioxidant activity was evaluated by measuring the radical scavenging activity using the DPPH assay. C2C12 myoblast cells were treated with the extract at concentrations of 125–1000 µg/mL. Cellular responses, including cell viability (MTS assay), IL-6 secretion (ELISA), ROS production, apoptosis, and cell cycle distribution (flow cytometry), were subsequently evaluated. Results: Nutritional analysis revealed that shiitake mushrooms provide 356 calories per 100 grams, with a high protein content (27.43 g), low fat (1.5 g), and abundant carbohydrates (58.2 g), including significant dietary fiber (34.98 g). The amino acid profile was dominated by glycine, L-Aspartic acid, and L-Leucine, along with various essential and non-essential amino acids. Bioactive compounds, such as gallic acid, p-Coumaric acid, and methyl gallate, were identified in the extract, which also exhibited potent antioxidant activity (314.04 mg Trolox/100g). In vitro experiments demonstrated that the extract reduced oxidative stress and inflammation in LPS-stimulated myoblast cells, as evidenced by decreased IL-6 secretion and ROS production. Moreover, the extract enhanced cell viability and reduced apoptosis at concentrations of 125–500 µg/mL, while concentrations above 1000 µg/mL showed toxicity. Conclusion: The findings suggest that shiitake extract has favorable potential as a therapeutic agent for promoting muscle health, and cell survival in muscle cells, as well as reducing inflammation and oxidative stress. Novelty of the Study: This study is unique in that investigates the therapeutic potential of Lentinula edodes (shiitake) extract on muscle cells, focusing on its protective effects against inflammation and oxidative stress in LPS-stimulated myoblasts. Unlike prior studies, it highlights specific bioactive compounds and demonstrates improved cell viability and reduced apoptosis, suggesting its potential as a natural agent for muscle health support. Keywords: Anti-inflammation, Antioxidant activity, Bioactive compounds, C2C12 cells, Nutritional composition, Shiitake mushroom
Copyright (c) 2026 Kwanchanok Hunthayung, Sassy Bhawamai https://creativecommons.org/licenses/by/4.0
Optimal dose of Moringa oleifera Lam for hematopoietic recovery in aluminum-induced hematotoxicity
Background: Aluminum-induced hematotoxicity disrupts hematopoiesis and leads to anemia primarily through oxidative stress mechanisms. Natural antioxidants such as Moringa oleifera have shown potential protective effects; however, the optimal therapeutic dose remains unclear. Objective: This study aimed to evaluate the dose-dependent effects of Moringa oleifera leaf extract and determine the optimal dose to improve hematological parameters in aluminum-induced hematotoxicity. Methods: Twenty-four male Wistar rats were randomly assigned into four groups (n = 6): control, AlCl₃ + 200 mg/kg Moringa oleifera, AlCl₃ + 100 mg/kg Moringa oleifera, and Moringa oleifera (200 mg/kg) only. Hematological parameters, including hemoglobin concentration, red blood cell count, hematocrit, and differential leukocyte counts, were measured over 14 days. Statistical analysis was performed using one-way ANOVA, with p ≤ 0.05 considered significant. Results: Treatment with Moringa oleifera significantly improved hematological parameters compared to the AlCl₃-exposed group (p ≤ 0.05). The 100 mg/kg dose demonstrated superior efficacy, with higher hemoglobin (12.00 g/dL), red blood cell count (7.23 × 10⁶/µL), and hematocrit (41.50%) compared to the 200 mg/kg dose. Additionally, an increase in lymphocyte percentage was observed. The dose-response relationship indicated a hormetic effect, where moderate dosing produced greater benefits than higher dosing. Conclusion: Moringa oleifera exhibits significant protective effects against aluminum-induced hematotoxicity, with 100 mg/kg identified as the most effective dose. These findings highlight its potential as a natural therapeutic agent for improving hematological health under toxic conditions Novelty of the study: This study identifies an optimal dose (100 mg/kg) of Moringa oleifera for hematological recovery in aluminum-induced toxicity and provides evidence of a hormetic dose-response effect in hematopoietic protection. Keywords: Aluminum chloride; anemia; dose–response; erythropoiesis; Moringa oleifera; hematopoietic recovery; bioactive dose.
Copyright (c) 2026 Rafiah Awad Mohamed Adam, Azhari A. Mohammed Nour, Ream Hassan Ahmed, Hanan Elamin Ibrahim, Mohamad Awad Elkarim Mohamad Ibrahim, Mohammed A. Shanwaz, Wisal A. Babiker, Ibrahim Elhag Elmahdi, Soltan J. Algamdi, Abdulmajeed AA Sindi, Raed A Alharbi, Hanan E Alyahyawi, Hanan E Alyahyawi, Abdulmohsen M Alruwetei https://creativecommons.org/licenses/by/4.0
Evaluation of Glutathione peroxidase activity and Angiotensin II as monitoring biomarkers of long-term therapy in Iraqi patients with prostate cancer
Introduction: Prostate cancer is the second most common cancer in men worldwide. The current therapeutic approaches include the use of hormonal manipulation, particularly agents like Goserelin acetate and Bicalutamide. Objective: The present study sought to explore the combination of Goserelin acetate and Bicalutamide therapy on aldosterone, angiotensin II, glutathione, and glutathione peroxidase activity in prostate cancer patients, before treatment and after three years of therapy. Methods: A total of 100 participants were collected, including 30 prostate cancer patients before treatment (G2), 40 participants were collected after treatment with Goserelin acetate as monotherapy (G4), and 30 participants with Goserelin acetate and Bicalutamide as combine therapy (G5). Results: The results showed significantly in all parameters when compared to newly diagnosed except GSH in monotherapy. Notably, ROC curve analysis demonstrated an excellent discriminative ability, with an AUC of 0.914 for G4 and 1.000 for G5 in Ang II hormone, also in GSH-Px enzyme activity was 1.000 for group G4 and 0.968 for group G5. This highlighting Ang II and GSH-Px activity as a highly sensitive and specific monitoring biomarker for long-term treatment response assessment. Conclusion: This study highlights a strong association between alterations in steroid hormones and prostate cancer progression under combination hormonal therapy, suggesting their potential role as biomarkers for monitoring therapeutic efficacy. Novelty of the Study։ This study provides the first comparative evaluation of Glutathione peroxidase activity and Angiotensin II as monitoring biomarkers of long-term therapy in Iraqi patients with prostate cancer. Keywords: Aldosterone, Angiotensin II, Glutathione peroxidase activity, Goserelin acetate, Bicalutamide.
Wejdan Salman Hashim Wejdan Salman Hashim
Copyright (c) 2026 Wejdan Salman Hashim, Yasser A.H. Al-Issa https://creativecommons.org/licenses/by/4.0
Polyphenol-based antioxidant strategies for personalized prevention of hereditary cancer
Hereditary cancer syndromes, accounting for approximately 5–10% of all malignancies, are caused by germline mutations in high-penetrance genes such as BRCA1/2, TP53, and mismatch repair genes, leading to an increased risk of early-onset and aggressive cancers. Accurate prognostic biomarkers are essential for risk stratification and personalized prevention in individuals with genetic predisposition. This review focuses on the prognostic relevance of oxidative stress and redox-dependent mechanisms in hereditary cancers. Redox imbalance, characterized by excessive reactive oxygen species (ROS) and impaired antioxidant defense, promotes genomic instability, tumor progression, and therapy resistance. Key redox-sensitive pathways, including transcription factors nuclear factor erythroid 2–related factor 2 (NRF2), nuclear factor-κB (NF-κB), and hypoxia-inducible factor-1α (HIF-1α), are discussed alongside emerging molecular and liquid biopsy biomarkers. Importantly, several dietary polyphenols, such as resveratrol, epigallocatechin gallate (EGCG), and curcumin, exhibit antioxidant, anti-inflammatory, and epigenetic effects that may help counteract mutation-associated oxidative damage. Integrating prognostic biomarker profiling with polyphenol-based, biomarker-guided functional food strategies represents a promising, non-invasive approach to personalized prevention in hereditary cancer. Novelty of Study: This review is novel in that it integrates oxidative-stress–related prognostic biomarkers with polyphenol-based dietary interventions within the structured framework of functional food science, specifically applying the Functional Food Centre’s 17-step development model to hereditary cancer prevention, thereby proposing a biomarker-guided, personalized nutrition strategy that bridges molecular oncology and functional food applications. Keywords: Hereditary cancer syndromes; Prognostic biomarkers; Oxidative stress; Redox signaling; dietary polyphenols; Personalized cancer prevention; Functional food science
Copyright (c) 2026 Davit Chkhikvishvili, Tamar Sanikidze, Nana Kipiani, Nato Nakudashvili, Zaza Nakudashvili, Tea Gabunia, Irakli Chkhikvishvili, Nunu Gogia, Manana Esaiashvili https://creativecommons.org/licenses/by/4.0
Ascophyllum nodosum extract modulates stem cell and immune cell surveillance in an acute placebo-controlled cross-over trial: Implications for healthy aging
Background: Aging is accompanied by chronic, low-grade inflammation and immune dysfunction, highlighting a need for preventative interventions that boost the body’s immune protection and innate repair mechanisms. Bioactive phytochemicals from functional foods, produced using clean, standardized technologies, are increasingly recognized and in need of scientific validation of effects in humans upon consumption. Objective: This study evaluated acute effects of a single serving of a brown seaweed extract, PolySea, from sustainable organic wild-harvested seaweed Ascophyllum nodosum on immune activation, anti-inflammatory regulation, and stem cell surveillance in healthy adults. The extract was isolated by green chemistry and had a high content of polyphenols, fucoidan, and the beta-glucan laminarin. Methods: In a randomized, double-blind, placebo-controlled, cross-over trial, twenty participants in good health consumed 50 mg of PolySea, 300 mg of PolySea, or placebo on three separate visits with at least one week’s wash-out period between visits. Blood draws performed at baseline, 1 hour, and 2 hours post-consumption were analyzed for serum cytokines and changes to immune cell numbers and stem cell numbers. Results: Consuming a single serving of PolySea rapidly activated innate immune functions at 1 hour, where pro-inflammatory cytokines (e.g., interferon-γ, interleukin-6) were significantly elevated compared to the levels after consuming placebo. Similar effects on cytokine levels were seen for the 50 mg dose and the 300 mg dose. Concurrently, increased levels of the interleukin-1 receptor antagonist suggested anti-inflammatory restoration. One hour after consuming 50 mg PolySea, there was a mild (4%), transient, and statistically significant increase in the number of monocytes when compared to changes after consuming placebo. A similar increase in the number of non-NK non-T cells was seen at one hour reaching a statistical trend, and at 2 hours, reaching significance. One hour after consuming 50 mg PolySea, the numbers of CD31++CD34- endothelial stem cells were significantly higher in the blood circulation, whereas by 2 hours, CD45dimCD34⁺ pluripotent and progenitor stem cell numbers were significantly reduced, suggesting relocation into tissues. Novelty of the study: The study’s novelty lies in quantifying the speed and extent of acute physiological and immunological shifts induced by a single 50 mg serving of the natural seaweed extract within hours, effects that are distinct from and exceed normal circadian dynamics confirmed during the placebo visit. Conclusion: A single serving of PolySea triggered a coordinated immune and regenerative response by rapidly triggering immune cell surveillance and selective changes to serum cytokine levels, restoring immune balance through anti-inflammatory activity, and selectively affecting different types of stem cells engaged in tissue repair. This biologically integrated response suggests meaningful potential for supporting regenerative physiological functions relevant for healthy aging. Keywords: Anti-inflammatory; cytokine; fucoidan; immune modulation; laminarin; phlorotannin; polyphenol; senescence.
Copyright (c) 2026 Earvin A. F. Grinage, Krista Sanchez, Dina Cruickshank, Sage V. McGarry, Gitte S. Jensen https://creativecommons.org/licenses/by/4.0
Targeting cortisol dysregulation through bioactive compounds: implications for stress, sleep, and mental wellness
Stress and sleep disturbances have emerged as significant global health challenges, intricately linked through the hypothalamic–pituitary–adrenal (HPA) axis. Cortisol, the primary stress hormone, serves as a key biomarker of HPA axis activity, influencing metabolism, immune response, and sleep regulation. Chronic elevation of cortisol disrupts circadian rhythm, inhibits melatonin synthesis, and contributes to insomnia, anxiety, and fatigue. Therefore, identifying bioactive compounds capable of modulating cortisol and restoring HPA axis balance offers a natural strategy for improving stress resilience and sleep quality. This review consolidates scientific evidence on several plant-derived and microbial bioactive compounds with cortisol-lowering and sleep-promoting effects. Bioactive compounds that modulate the HPA axis, therefore, represent a multidimensional therapeutic opportunity, acting not only on endocrine regulation but also on neurochemical balance and immune modulation. Integrating these compounds into dietary or nutraceutical interventions could provide a preventive and restorative approach for individuals experiencing chronic stress or sleep disorders. Withania somnifera (ashwagandha) exhibits adaptogenic properties via withanolides that downregulate cortisol and improve sleep onset. Panax ginseng contains ginsenosides that modulate stress hormone release and enhance neural adaptability. Ganoderma lucidum (reishi mushroom) triterpenoids exert anxiolytic and sedative effects, promoting restorative sleep. Centella asiatica triterpenes, including asiaticoside and madecassoside, contribute to cortisol regulation and neuroprotection, improving REM sleep architecture. Matricaria chamomilla flavonoids, notably apigenin, interact with GABAergic receptors and reduce HPA hyperactivation. Emerging evidence also highlights postbiotics, such as those from Limosilactobacillus fermentum PS150 and Bifidobacterium breve BB091109, which influence the gut–brain axis by enhancing neurotransmitter balance, reducing systemic inflammation, and lowering cortisol. The novelty of this study lies in presenting an integrated linkage between plant-derived bioactive compounds and postbiotics in the regulation of stress and sleep through modulation of the HPA axis. This framework highlights their potential influence on cortisol dynamics, providing valuable insights for the future development of functional products aimed at stress reduction and the promotion of mental wellness. Future research should focus on clinical validation, pharmacokinetic profiling, and formulation optimization to translate these natural agents into evidence-based functional foods and nutraceuticals capable of safely supporting stress regulation and sleep health. Keyword: Cortisol modulation, Sleep quality, Hypothalamic-pituitary-adrenal (HPA) axis regulation, Adaptogenic bioactive compounds, Gut-brain axis, Neuroendocrine regulation
Copyright (c) 2026 Kamon Chaiyasit, Kanokpong Muangsri, Songsuda Kwanpracha, Varit Srisukthaveerat https://creativecommons.org/licenses/by/4.0
Apigenin as a bioactive compound for longevity: Targets and mechanisms in senescent cells
Bioactive compounds have emerged as a focal point in contemporary health and biomedical research due to their potential in disease prevention, health promotion, and longevity enhancement. With the global rise of the longevity movement, attention has increasingly shifted toward understanding how functional foods and bioactive compounds influence molecular mechanisms associated with aging. This review focuses on apigenin, a naturally occurring flavonoid found in many fruits, vegetables, and herbs. Although apigenin exhibits poor bioavailability due to limited solubility and rapid metabolism, it has been shown to exert multiple effects due to its longevity and cellular health. In terms of cellular senescence, apigenin exhibits senomorphic activity, modulating the senescent cell phenotype rather than directly inducing their death. Specifically, it suppresses the senescence-associated secretory phenotype (SASP) by inhibiting key inflammatory signaling pathways such as NF-κB and p38-MAPK, thereby reducing chronic inflammation and tissue degeneration. However, evidence for its senolytic activity remains inconclusive, as current findings have not shown direct senolytic effects in senescent cell models. Interestingly, studies in other cellular systems show that apigenin can modulate molecular pathways associated with apoptosis, including the regulation of Bcl-2 family proteins and caspase activation, which may indirectly support cellular renewal processes. Given these findings, apigenin stands out as a promising candidate for further development as a functional ingredient in longevity-focused nutrition. Its potential role as a bioactive modulator of senescent cell behavior highlights new opportunities for future research in nutraceuticals and functional food innovation aimed at promoting healthy aging. Novelty of the study: This review highlights apigenin as a longevity-oriented functional food bioactive that targets senescent cells through senomorphic mechanisms and NAD⁺ modulation via CD38 inhibition, distinguishing it from previously reported conventional senolytic compounds. Keywords: apigenin, NAD+ metabolism, CD38 inhibitor, cellular senescence, Senescence-associated secretory phenotype (SASP)
Copyright (c) 2026 Kamon Chaiyasit, Kadesanee Likitkriengkri, Kanokpong Muangsri, Varit Srisukthaveerat https://creativecommons.org/licenses/by/4.0
Effects of a 4-week supplementation with novel bioactives N-Trans Caffeoyltyramine (NCT) and N-Trans Feruloyltyramine (NFT) on parameters of continuous glucose monitoring in individuals with prediabetes
Background: Beyond dietary modification, bioactive compounds have emerged as modulators of glycemic regulation. Silico analysis has identified N-trans-caffeoyltyramine (NCT) and N-trans-feruloyltyramine (NFT) as potent modulators of hepatocyte nuclear factor 4α (HNF4α), thereby favorably regulating blood glucose metabolism. Objective: To evaluate the effects of a proprietary dietary supplement containing novel bioactives, NCT and NFT, on parameters of continuous glucose monitoring in individuals with prediabetes. Conclusions: Overall glycemic burden, as measured using various CGM parameters, was significantly improved in response to treatment with NCT/NFT. Select measures of insulin resistance were also improved. These findings confirm the utility of a proprietary dietary supplement containing NCT/NFT to support glycemic control in individuals with dysglycemia. Novelty of the Study: This trial is among the first to investigate the effects of novel bioactives NCT and NFT supplementation on glycemic regulation in adults with prediabetes using CGM endpoints. Unlike prior studies relying primarily on point-in-time measures (e.g., fasting glucose or serum insulin), this study integrates both cross-sectional (fasting glucose) and continuous (continuous glucose monitoring) endpoints to enable a more comprehensive evaluationof glycemic control. This second manuscript extends the initial report by focusing specifically on continuous glucose monitoring outcomes alongside previously published findings. Keywords: glucose regulation, continuous glucose monitoring dietary supplements, Type 2 diabetes, post-prandial glucose, N-trans-Caffeoyltyramine, N-trans-Feruloyltyramine, NCT, NFT, prediabetes, HNF4α
Copyright (c) 2026 Seema Gulati, Anoop Misra, Rajneesh Tiwari, Michelle L. Zuelch, Swati Kalgaonkar https://creativecommons.org/licenses/by/4.0
Antioxidant activity of Mentha longifolia aromatic oils and theirapplication in extending beef burger shelf life
Background: Lipid oxidation is a major factor affecting the chemical stability and shelf life of processed meat products during frozen storage. Natural plant oils rich in bioactive compounds have gained attention as effective alternatives to Mentha longifolia antioxidants. These compounds can reduce oxidative deterioration and improve product quality. Objective: This study aimed to evaluate the effect of different concentrations of Mentha longifolia oil on the chemical properties and oxidative stability of processed burger patties during frozen storage. Materials and Methods: Crude Mentha longifolia oil was extracted using a Clevenger apparatus. Burger samples were divided into four treatments: control (T1) without oil addition, and T2, T3, and T4, each supplemented with 1, 2, and 3 g of Mentha longifolia oil, respectively. Chemical analyses were conducted before freezing and during 60 days of frozen storage at −18 °C, with testing performed twice per month. Fatty acid composition and flavonoid profiles were determined using GC–MS and HPLC, while oxidative stability was evaluated by measuring free fatty acids (FFA), peroxide value (PV), and thiobarbituric acid (TBA). Results: Mentha longifolia oil exhibited a high content of essential fatty acids and 38 identified flavonoid compounds, dominated by caffeic acid, apigenin, quercetin, and 4-hydroxy derivatives. No significant differences (P ≥ 0.05) were observed among treatments before freezing. During frozen storage, oxidative indices increased in all samples; however, oil-treated burgers showed significantly lower FFA, PV, and TBA values, with treatments T3 and T4 recording the lowest values compared to the control. Keywords: antioxidant activity; natural antioxidants; flavonoids; Mentha longifolia aromatic oils; beef burger; shelf-life extension
Copyright (c) 2026 Suhair Ali Hussein, Sari Ali Hussien, Firas Najm Ismael https://creativecommons.org/licenses/by/4.0
Laser-primed wheat as a source of phenolic bioactive compounds with antioxidant and cytoprotective potential
Background: Wheat is a major dietary staple and an important source of phenolic bioactive compounds with antioxidant and cytoprotective properties. However, environmental stress and conventional farming methods can limit the accumulation of these beneficial compounds and affect their functional quality. A promising strategy to enhance the natural synthesis of bioactive compounds is still under investigation. The functional relevance of laser-induced phenolic enrichment in human cell systems remains largely unexplored. Objective: To determine the effect of CO₂ laser seed priming on wheat phenolic content and functional (antioxidant and cytoprotective) activity. Methods: This study assessed the effects of continuous-wave CO₂ laser seed priming in the wheat cultivar “Red Doly” at three developmental stages: grain, germination, and green sprouts. Total free and bound phenolics, as well as phenolic profiles, were determined using High-Performance Liquid Chromatography (HPLC). Antioxidant capacity was evaluated through radical-scavenging assays. Cytoprotective activity was examined in Jurkat T lymphocytes under oxidative stress induced by hydrogen peroxide. Results: Laser priming enhanced germination and early growth (5–25% increase vs. control). Total free phenolic content increased significantly, particularly in green sprouts (p < 0.01). The antioxidant capacity increased at all developmental stages and correlated strongly with phenolic content (r = 0.81, p = 0.0004). Caffeic acid was most abundant in the free fractions, while ferulic acid dominated in the bound fractions. Phenolic extracts from laser-treated sprouts significantly improoved Jurkat cell viability and reduced oxidative cytotoxicity (p < 0.001), with more pronounced effects observed for free-phenolic–enriched fractions. Conclusions: This study establishes a functional connection between laser-induced metabolic activation and the protection of human cells by integrating compound identification, biomarker validation, and preclinical cellular efficacy testing (Steps 1, 2, 5, 6, and 8 of the Functional Food Development Model). CO₂ laser priming offers a scalable, chemical-free approach to producing phenolic-enriched functional wheat ingredients. Notably, this research is one of the first to demonstrate that phenolic enrichment induced by CO₂ laser priming results in measurable cytoprotective effects in a human cell-based model. Novelty: This study is one of the first to establish a connection between CO₂ laser priming-induced phenolic enrichment in wheat and a functional biological outcome. It demonstrates significant cytoprotection of human Jurkat T lymphocytes under oxidative stress. The research also includes detailed phenolic profiling using HPLC and validation of antioxidant biomarkers. Keywords: CO₂ laser seed priming; Wheat phenolics; Antioxidant capacity; Cytoprotective activity; Functional foods; Wheat sprouts; Oxidative stress
Copyright (c) 2026 Tamar V. Sanikidze, Andre D.L. Batako, Baoxiu Qi, Juan Ahuir Torres, Irakli Chkhikvishvili, Nana Bakradze, Eka Shekiladze, Aleksander Sharashenidze, Maia Enukidze, Marine Machavariani, Nunu Gogia, Marina Tsimakuridze, Lela Chkhitauri, Teimuraz Dumbadze, Sophio Kalmakhelidze https://creativecommons.org/licenses/by/4.0
Evaluation of the biological efficacy of neem oil against some pathogens
Background: The neem tree (Azadirachta indica) is an evergreen species native to regions such as India and Pakistan and is also cultivated in parts of the Americas. Products derived from neem have numerous applications, particularly in skin, hair, and nail care, as well as in food preservation, due to their ability to inhibit the growth of various microorganisms. Objective: Three organic solvents, hexane, ethanol, and petroleum ether (80-‎‎100°C), were used to extract neem oil from dried, ground seeds using the Soxhlet extraction method. High-performance liquid chromatography (HPLC) was employed to determine the fatty acid composition of the extracted oil. The antibacterial activity of neem seed oil was evaluated against four bacterial strains (Staphylococcus aureus, Bacillus spp., Pseudomonas aeruginosa, and Escherichia coli) and one yeast (Candida spp.) at three different concentrations. Results: The extraction yields were 44.89% using petroleum ether, 42.63% using hexane, and 39.17% using ethanol. Analysis revealed that long-chain fatty acids accounted for 19.77% of the neem seed oil composition, including palmitoleic acid (14.23%), oleic acid (2.49%), palmitic acid (1.50%), stearic acid (0.90%), linoleic acid (1.50%), and linolenic acid (0.05%). Neem seed oil exhibited strong antibacterial activity. Staphylococcus aureus showed inhibition zones of 36, 30, and 28 mm at concentrations of 1000, 500, and 250 µg/mL, respectively. Bacillus spp. demonstrated inhibition zones of 28 , 26 , and 24 mm at the same concentrations. Escherichia coli exhibited inhibition zones of 26 , 22 , and 10 mm, respectively. Lower inhibitory effects were observed against Pseudomonas aeruginosa, with inhibition zones of 18 , 19 , and 3 mm. Novelty: Neem seed oil represents an effective, sustainable, and environmentally friendly alternative to synthetic antimicrobial agents. Conclusion: Neem seeds are a valuable source of oil rich in long-chain fatty acids with significant therapeutic potential. The oil demonstrated notable antibacterial and antifungal activity, emphasizing its potential importance for medical and pharmaceutical applications. Keywords: Neem tree, Oil extraction, Fatty acid and Antimicrobial, antifungal activity, long-chain fatty acids.
Copyright (c) 2026 Aseel Abdulsattar Gburi, Ayyad Wajeh Raof Al-Shahwany, Sara Thamer Hadi https://creativecommons.org/licenses/by/4.0
Chemical melioration of saline soils and its residual effect on the quality and quantity of nutrients in corn grain
Background: Soil salinization reduces the availability of micronutrients, which are essential for producing functional foods such as corn. This makes it increasingly difficult to grow food in saline soils that meet the required nutritional standards for human health. Therefore, improving soil quality through the adoption of proper farming practices is vital to ensure the continued production of functional foods and their associated health benefits. Objective: The research was conducted from 2021 to 2024 in the Mrgashat community of the Metsamor region, Armavir marz, RA, under field conditions. The desalination and dealkalization processes and their impact on germination, growth, yield, qualitative characteristics, chemical composition, and functionality of the "Turbo" corn subtype were studied under varying flushing water standards. Methods: The study focused on improving saline-alkaline soils through chemical melioration with sulfuric acid, using different amounts of flushing water (25%, 50%, and 100% of the calculated norm). The effects of these treatments on the soil and the qualitative properties and chemical composition of corn were assessed. Results: With the full sulfuric acid dose (7.1 kg) and 25% flushing water (9.6 m³), a decrease in soil chemical indicators was observed. Still, the corn seeds did not germinate, suggesting an insufficient combination of ameliorant and water for effective desalination. These data can serve as a basis for assessing the extent of flushing water's effect on desalination efficiency. When 50% flushing water (19.2 m³) was used, topsoil amelioration occurred, but significant salt accumulation remained in the deeper soil layers. Partial seed germination indicated that this amount of flushing water was not enough for complete salt removal. Using 100% flushing water (38.3 m³) with the full sulfuric acid dose (7.1 kg) resulted in complete desalination and alkalinization. A marked increase in calcium (Ca) in the adsorption complex was observed, enhancing plant growth and yield. In the first year of sowing, the yield reached 29.0 qt/ha, indicating that a higher flushing water dose significantly improved soil conditions and increased yield. Novelty: This research is the first in the RA to examine the effects of different flushing water amounts on the efficiency of saline-alkaline soil amelioration and on corn growth, germination, yield, and functionality. The study emphasizes that proper selection of flushing water volume is crucial for effective salt removal, and that the combination of the ameliorant and water should be optimized to maximize desalination efficiency and high-functioning food production. Conclusion: The research demonstrates that varying amounts of flushing water significantly influence the efficiency of soil desalination and alkalinization. The use of 100% flushing water ensures complete desalination, improves soil chemical composition, and increases both corn yield and quality. These findings provide a basis for selecting optimal melioration practices to improve saline-alkaline soils and enhance functional food production. Keywords: Soil salinization, desalination, dealkalization, flushing water, melioration, sulfuric acid, corn, functional food.
Copyright (c) 2025 Marina Barseghyan, Gayane Gasparyan, Inga Beglaryan, Tatevik Jhangiryan https://creativecommons.org/licenses/by/4.0
Chemical, polyphenolic, and technological characterization of the Sev Areni grape variety and its clones: Implications for wine quality parameters
Background: The Areni grape (Vitis vinifera L.) is an indigenous Armenian variety renowned for its adaptation to local terroir and historical significance in winemaking. Its genetic diversity, particularly among clones, offers valuable resources for enhancing wine quality through variations in phenolic compounds, chemical composition, and technological traits. Understanding these differences is crucial for selecting optimal genotypes in viticulture and enology, especially in regions like Armenia, where traditional varieties contribute to unique wine profiles. Objective: To assess the chemical, polyphenolic, and color variations among three Areni grape genotypes and their impact on wine quality indicators. Methods: Analyses of grapes and wines produced under microvinification conditions were performed according to OIV standards, using spectrophotometry and HPLC to determine organic acids, physicochemical parameters, total phenolics, anthocyanins, flavonoids, and color indices. Results: Nosr Areni displayed the highest pigment content in the fruit, Areni clone 15 produced wines with the highest total phenolics, and Sev Areni wines exhibited the greatest color intensity. Chemical parameters varied depending on the specific genotype characteristics. Conclusion: Areni genotypes exhibit pronounced biochemical and technological diversity, which significantly influences wine composition and color development. Areni clone 15 stands out for its high phenolic potential, making it a promising raw material to produce high-quality red wines. Novelty of the Study։ This study provides the first comparative evaluation of Sev Areni and its clones in terms of polyphenolic composition and wine quality, identifying clones with high phenolic potential and technological suitability for winemaking. Keywords: Sev Areni grape, Vitis vinifera, polyphenols, anthocyanins, flavonoids, organic acids, wine color, clonal selection
Copyright (c) 2026 Elina Grigoryan, Karen Kazumyan, Zara Harutyunyan, Mariam Zakharyan, Gohar Mikayelyan, Armenuhi Petrosyan, Nune Simonyan, Kristine Khanamiryan, Syuzanna Abrahamyan, Armen Solomonyan, Narine Hovhannisyan, Bella Grigoryan, Julietta Baghdasaryan, Agnessa Samvelyan, Garush Samvelyan, Mikayel Mikayelyan, Lilia Samvelyan, Gevorg Datumyan https://creativecommons.org/licenses/by/4.0
Manufacturing functional biscuits fortified with dill (Anethum graveolens L.) and assessing its physical and sensory properties and microbial activity
Background: Natural substances derived from dill (Anethum graveolens) are characterized by broad antimicrobial activity against numerous human pathogens, attributable to their rich content of bioactive compounds and strong antioxidant and antimicrobial properties. Consequently, dill may be considered both a valuable nutritional supplement and a promising source of herbal medicinal agents. Objective: This research aimed to develop high-fiber biscuits through partial replacement of wheat flour with dill powder levels at 5% and 10%, and to evaluate the effects on chemical composition, antioxidant capacity, and antibacterial activity against selected pathogenic microorganisms. Results: Chemical analysis of dill revealed carbohydrate, protein, fat, crude fiber, and ash contents of 9.02%, 3.26%, 2.10%, 3.12%, and 0.96%, respectively. The moisture content was 81.34%, indicting a high water-retention capacity that may positively influence both sensory and functional properties. Phytochemical analysis demonstrated a diverse profile of phenolic and aromatic compounds, as well as amino acids. Microbiological analysis confirmed that all biscuit samples were free of coliform bacteria. Additionally, the alcohol extract of dill exhibited strong inhibitory activity against the tested bacteria, including E. coli, Salmonella, and Staphylococcus. Sensory evaluation indicated that dill incorporation improved taste, aroma, texture, and overall acceptability of the biscuits compared with the control formulation. Novelty: This study is the first to systematically incorporate dill powder into high-fiber biscuits while simultaneously evaluating its nutritional enhancement, antioxidant capacity, and antimicrobial activity against foodborne pathogens. Unlike previous studies that have focused on dill extracts or on bakery product fortification in isolation, the present work demonstrates the dual functionality of dill as both a natural preservative and a functional food ingredient within a ready-to-eat bakery product. Conclusion: Dill exhibits valuable nutritional properties, including appreciable protein and lipid contents, in addition to serving as a rich natural source of phytonutrients. These findings highlight the multifaceted potential of dill as a source of bioactive compounds, supporting its application in the functional food industry as a natural antioxidant and preservative. Consequently, dill may serve as a safe and effective ingredient for enhancing both the nutritional value and sensory quality of food products. Keywords: Dill powder; Functional food; Natural preservative; Plant-based fortification; High-fiber biscuits; Antimicrobial activity; Antioxidant capacity
Copyright (c) 2026 Noor Jumhaa Fadhil, Baraa A. Almairza, Abeer Majeed, Sara Thamer Hadi https://creativecommons.org/licenses/by/4.0
Saponins from Astragalus membranaceus and Panax notoginseng improve intestinal barrier function and probiotic adhesion in human intestinal Caco-2 cells
Background: Intestinal barrier function is critically important for human health. Despite the promising biological properties of herbal extracts, limited research has addressed the effects of Astragalus membranaceus and Panax notoginseng saponin (APS) extracts on intestinal barrier function and probiotic adhesion, particularly under conditions of inflammatory stress. In the present study, we investigated the effects of APS on Caco-2 cell monolayers challenged with LPS as an in vitro model of intestinal inflammation. Objective: This study aimed to evaluate the anti-inflammatory effects of Astragalus membranaceus and Panax notoginseng saponin (APS) extracts in preserving the intestinal epithelial barrier in a lipopolysaccharide (LPS)-stimulated human Caco-2 cell monolayer model. Methods: Caco-2 monolayers were exposed to LPS to induce barrier dysfunction. Subsequently, the monolayers were treated with APS. Barrier function was evaluated by measuring transepithelial electrical resistance (TEER), FITC-dextran flux permeability, tight junction protein (Claudin-1, Occludin, ZO-1) expression, and cellular ATP levels. In addition, the growth and adhesion of Lactobacillus rhamnosus to Caco-2 cell monolayers were assessed. Results: APS treatment significantly increased TEER values, decreased FITC-dextran permeability, restored the expression of tight junction proteins (Claudin-1, Occludin, and ZO-1), and recovered intracellular ATP levels compared to the LPS group. Furthermore, APS significantly enhanced the growth and adhesion of Lactobacillus rhamnosus to Caco-2 cell monolayers, even under inflammatory conditions. Novelty: This study identifies a previously uncharacterized synergistic role of Astragalus membranaceus and Panax notoginseng saponins in coordinating intestinal barrier protection and probiotic adhesion under inflammatory stress. These findings provide new mechanistic insight into the integrated actions of combined botanical saponins in maintaining intestinal homeostasis. Conclusion: These findings suggest that APS exerts protective effects on intestinal barrier function and promotes probiotic adherence against LPS-induced intestinal injury in human epithelial cells. APS may be considered a valuable nutritional and therapeutic supplement for maintaining gastrointestinal health. Keywords: Astragalus membranaceus and Panax notoginseng extracts; Inflammatory bowel disease; Intestinal probiotics; Tight junction proteins.
Copyright (c) 2026 Su-Fen Huang, Han-Wen Yang, Ching-Hui Ou, I-Chu Tang, Wen-Liang Chang, Tsu-Chung Chang https://creativecommons.org/licenses/by/4.0
Microbial diversity and probiotic potential of traditionally fermented African locust bean condiment (Dawadawa) from Kogi State, Nigeria
Background: Dawadawa, a protein-rich condiment from African locust bean (Parkia biglobosa), remains poorly characterized in North-Central Nigeria despite widespread consumption and traditional claims of health benefits. Objectives: This study investigated the microbial diversity, probiotic potential, and safety profile of traditionally fermented Dawadawa from Kogi State, Nigeria. Methods: Thirty Dawadawa samples were collected from Anyigba, Dekina, and Ankpa local government areas. Comprehensive microbiological characterization used culture-dependent methods, biochemical identification, and 16S rRNA gene sequencing. Probiotic attributes, including gastric acid tolerance, bile salt resistance, cell surface hydrophobicity, and adhesion capacity, were evaluated. Antimicrobial activity and safety assessments were performed using standardized protocols. Results: Total viable counts ranged from 7.42 to 8.91 log CFU/g, with lactic acid bacteria (LAB) dominating at 7.15-8.34 log CFU/g. Sixteen bacterial species were identified, with Bacillus subtilis (47%) and Lactobacillus plantarum (23%) predominating. Selected LAB isolates demonstrated gastric acid tolerance of 73-89% at pH 3.0, bile salt tolerance of 68-84% at 0.3% oxgall, and strong adhesion to intestinal epithelial cells (2.8-8.4 CFU/cell). Antimicrobial assays revealed inhibition zones of 12-24 mm against pathogenic indicators. All samples were negative for Salmonella and Listeria monocytogenes and showed no acquired antibiotic resistance. Conclusion: Dawadawa from Kogi State harbors diverse beneficial microorganisms with significant probiotic potential, supporting its development as a functional food and source of indigenous probiotic strains. This study represents the first comprehensive probiotic characterization of Dawadawa from North-Central Nigeria, identifying indigenous L. plantarum strains with exceptional functional properties suitable for probiotic development. Keywords: Dawadawa, Parkia biglobosa, lactic acid bacteria, probiotic potential, fermented condiment, functional food, Nigerian indigenous food
Copyright (c) 2025 Abdulbasit Anoze Aliyu, Momoh Theophilus Boniface, Egbeja Tsobaza Idris, Agah Dorathy, Iyeh Peter, Sulaiman Muhammed Saleh, Alfa Muhammed Salisu, Okala Yunusa Yusufu, Amodu Salisu Ameh, Okeme Ukwumonu Patrick, Idris Mustapha Omenesa, Zakari David Adeiza, Inah Blessing Mabeh, Abiodun Sunday Olusegun, Ebere Adaeze Onyebueke, Azeez Zainab, Musa Oiza Aishat, Yabefa Jeremiah Akpodoitei, Suleiman Mohammed Salisu, Godwin Amoka Audu, Adefila Adebimpe Moyosore, Joseph Abraham-Oyiguh https://creativecommons.org/licenses/by/4.0
Proline Rich Peptide-Linked Albumin Particles in Experimental Oxidative Brain Damage Model
Background: The leading contributors to death and disability are cardiovascular diseases (CVDs) and stroke. PRP-1 (Proline Rich Peptide) is a peptideisolated from the bovine hypothalamus and identified in the human brain. It was shown that this peptide may have antioxidant and neuroprotective properties. However, the circulation time of peptides in the bloodstream is limited; therefore, coupling PRP-1 with albumin nanoparticles might prolong its stability and bioavailability. The purpose of the study was to evaluate PRP-1 conjugated with albumin nanoparticles in an experimental brain injury model induced by hydrogen peroxide. Methods: We used Transmission Electron Microscopy (TEM; Philips CM10) and Dynamic Light Scattering (DLS) to evaluate particle size and zeta potential. The brain injury model was created using hydrogen peroxide as a source of free radicals, which induced disruption of the blood–brain barrier (BBB). BBB disruption was quantified by measuring Evans Blue dye accumulation in the brain parenchyma. Results: Through sedimentation and filtration procedures, we obtained stable nanoparticles (NPs). PRP-1–coupled NPs degraded more slowly in the presence of trypsin than control NPs. Furthermore, PRP-1/NPs partially prevented BBB disruption in the experimental model. Conclusion: PRP-1/albumin NPs protected the BBB under experimental brain injury conditions. Keywords: PRP-1, neurohormone, experimental stroke, albumin, nanoparticles, blood–brain barrier
Copyright (c) 2025 Kristine Edgar Danielyan, Nazeli Zaqaryan, Rita Khallouf, Maria Kojoyan, Kristine Tspnetsyan, Arpi Manukyan, Astghik Tsokolakyan, Mkrtich Alexan Yeranosyan, Samvel G. Chailyan https://creativecommons.org/licenses/by/4.0
Effect of supplementation with n-trans caffeoyltyramine and n-trans feruloyltyramine on glycemia in prediabetic individuals:Randomized, double-blind, placebo-controlled trial
Background: The global prevalence of elevated blood glucose levels is at an all-time high. For many people, reversal to normoglycemia is possible with diet and lifestyle modification. Dietary bioactives, in the form of functional food formulations or supplements, have attracted interest for their potential to improve glycemic control. In silico prediction, validated by preclinical research, has identified novel bioactives, N-trans-Caffeoyltyramine (NCT) and N-trans- Feruloyltyramine (NFT), as potent HNF4α agonists with gluco-regulatory effects. While promising, clinical studies are needed to validate these findings in humans. Objective: To evaluate the effects of a proprietary dietary supplement containing 120 mg of NCT/NFT on fasting blood glucose and other biomarkers of glycemia in an otherwise healthy population with prediabetes. Methods: A randomized, double-blind, placebo-controlled parallel arm trial was conducted in Asian Indian adults (Age: 18-50 years; BMI: 25-30 kg/m2) with prediabetes (fasting blood glucose >100 mg/dL and <126 mg/dL) and abdominal adiposity (waist circumference >80 cm for females and >90 cm for males). A total of 126 participants were randomized to receive either 120 mg/d NCT/NFT (n=63) or placebo (n=63) for 4 weeks. Outcomes were measured at day 0 and day 28. The primary endpoint was fasting blood glucose. Secondary endpoints included fasting insulin, postprandial glucose response, and time spent within and outside of the ideal glucose range (<140 mg/dL) as assessed by continuous glucose monitoring (CGM). Additional outcomes related to CGM will be presented in a subsequent publication. Glycated hemoglobin (HbA1c), serum lipids, and anthropometrics were also measured. Results: Supplementation with a proprietary sustained-release formula of 120 mg/d NCT/NFT for 4 weeks resulted in significant improvements in the primary outcome measure, fasting blood glucose (NCT/NFT: -4.1 ± 7.1 mg/dL vs. Placebo: -0.7 ± 7.0 mg/dL; p=0.0026). Fasting insulin, postprandial glucose response, and time spent outside of the ideal glucose range were also significantly improved with treatment (p=0.0147, p=0.0036, and p=0.0138, respectively). No changes were observed in other markers of glycemia, lipid profile, or anthropometric measures. Conclusions: Naturally occurring bioactive compounds, NCT and NFT, act as potent HNF4 α agonists for the part that they play in blood glucose regulation and should be considered as part of a comprehensive approach to support glycemic and overall metabolic health. Novelty of the Study: This study is among the first randomized, double-blind, placebo-controlled clinical trials to evaluate the effects of N-trans caffeoyltyramine (NCT) and N-trans feruloyltyramine (NFT) supplementation on blood glucose regulation in prediabetic adults. While prior research has focused on outcomes that provide a snapshot in time (e.g. fasting glucose or insulin), this study uniquely integrates both cross-sectional (fasting levels) and continuous endpoints (continuous glucose monitoring), providing a comprehensive assessment of bloglucose regulation through novel bioactive compounds. The findings introduce a new direction for bioactive supplementation targeting individuals with looking to maintain healthy blood glucose regulation. This trial was registered at clinicaltrials.gov as NCT06417840. Keywords: dietary supplements, N-trans caffeoyltyramine, N-trans feruloyltyramine, prediabetes, Type 2 Diabetes, glucose regulation, HNF4α, NCT, NFT
Copyright (c) 2025 Swati Kalgaonkar, Seema Gulati, Anoop Misra, Rajneesh Tiwari, Michelle L. Zuelch https://creativecommons.org/licenses/by/4.0
Blueberries and raspberries as endocrine modulators: Mechanisms, clinical evidence, and translational guidance
Endocrine pathways are increasingly recognized as important targets for preventive and adjunctive care. Blueberries (Vaccinium spp.) and raspberries (Rubus spp.) are particularly rich in anthocyanins, ellagitannins, and related flavonoids with hormone-modulating properties. Recent evidence from mechanistic and clinical studies, particularly in 2023–2024, suggests that berry-derived bioactives impact estrogen receptors, insulin signaling, and the hypothalamic–pituitary–adrenal (HPA) axis. Yet issues of bioavailability, microbiome conversion, and dosing remain insufficiently integrated. Key findings highlight selective estrogen receptor modulator–like activity that improves estrogen metabolism and menopausal health; enhanced insulin sensitivity via AMPK activation, insulin receptor signaling, and α-amylase/α-glucosidase inhibition; and HPA axis modulation with reduced cortisol exposure and improved circadian rhythms. Clinical trials in peri- and postmenopausal women report better sleep, mood, and hot-flash outcomes, while pilot studies in polycystic ovary syndrome (PCOS) suggest improved insulin sensitivity and lower androgen levels. Preliminary data also indicate antioxidative and immune-modulatory effects on thyroid function. Whole berries (≈150–200 g/day) or standardized freeze-dried equivalents consistently deliver endocrine-relevant benefits with excellent tolerability. Although plasma levels of parent anthocyanins are low, microbiome-derived metabolites such as urolithins and inter-individual variability in metabolism likely shape clinical responses. Blueberries and raspberries act as multi-target endocrine modulators through receptor, enzyme, neuroendocrine, and microbiome-mediated mechanisms. Their routine dietary inclusion represents a practical, safe strategy to support hormonal balance across life stages. Large-scale trials remain essential to define effective dosing, compare whole fruits versus extracts, and explore personalized nutrition approaches. Novelty: This study is among the first to integrate mechanistic, clinical, and translational evidence on blueberries and raspberries as endocrine modulators. Unlike prior research focusing on single pathways, we highlight their combined effects on estrogen receptors, insulin signaling, and the HPA axis, while also considering microbiome-derived metabolites such as urolithins. By synthesizing recent 2023–2024 findings, this work reframes these berries as clinically relevant functional foods with the potential to support menopausal health, PCOS, and broader hormonal balance. Keywords: flavonoids; anthocyanins; ellagitannins; endocrine function; blueberries; raspberries; phytochemicals; insulin sensitivity; stress hormones
Copyright (c) 2025 FFC/Bioactive Compounds in Health and Disease https://creativecommons.org/licenses/by-nc/4.0
Oxidative stress induced by some preservatives and the protective effects of dietary bioactive compounds
Food preservatives such as nitrites, nitrates, sodium benzoate, and synthetic phenolic antioxidants are widely used to enhance the safety, stability, and sensory properties of foods. Despite these benefits, increasing evidence indicates that chronic or high-dose exposure to preservatives may induce oxidative stress, which plays a central role in the pathogenesis of cancer, metabolic disorders, and reproductive dysfunction. This review summarizes findings from animal, in vitro, and human studies on the relationship between preservatives and oxidative stress, with a focus on nitrites in processed meats and sodium benzoate. Experimental data consistently demonstrate increased lipid peroxidation, suppression of endogenous antioxidant enzymes, mitochondrial dysfunction, and apoptosis following high-dose preservative exposure, although these doses often exceed typical human dietary intake. Epidemiological studies support the association between nitrite-derived N-nitroso compounds and colorectal carcinogenesis, aligning with the International Agency for Research on Cancer (IARC) classification of processed meats as Group 1 carcinogens. In contrast, dietary bioactive compounds such as garlic oil, honey, Nigella sativa, curcumin, berberine, omega-3 fatty acids, and polyphenols have shown protective effects by modulating oxidative pathways and restoring redox balance. However, most of these benefits are observed at pharmacological levels, raising concerns about their practical relevance in human diets. Unlike previous reviews that focus solely on the toxicity of preservatives, this study uniquely integrates the mechanistic evidence of preservative-induced oxidative stress with the mitigating potential of functional food-based dietary strategies. Overall, preservatives may act as pro-oxidants under certain conditions, while antioxidant-rich dietary patterns may offer protective potential. Further human-based studies at realistic exposure levels are essential to strengthen risk assessment and guide public health recommendations. Keywords: Preservatives; Oxidative Stress; Antioxidants; Bioactive Compounds; Nutrition.
Copyright (c) 2025 Ece Celik Atalay, Adviye Gulcin Sagdicoglu Celep, Francesco Marotta, Roberto Catanzaro https://creativecommons.org/licenses/by/4.0
Microalgae-derived compounds against Helicobacter pylori: antibacterial, antioxidant, and anti-inflammatory evidence
Helicobacter pylori is a Gram-negative bacterium that colonizes the human gastric mucosa and affects more than half of the world´s population. It is associated with gastritis, peptic ulcers, and gastric cancers. Despite antibiotics being long effective, increasing multi-resistance to key drugs has led to lower eradication rates, highlighting the need for alternative approaches. Natural bioactive compounds from microalgae have increased attention due to their antioxidant, antibacterial, and anti-inflammatory properties. Microalgae produce a wide variety of metabolites, such as photosynthetic pigments, fatty acids, peptides, and carbohydrates, many of which show promising activity against H. pylori. Antioxidants like astaxanthin and polyphenols help neutralize reactive oxygen species, protect gastric epithelial cells, and modulate inflammatory signaling. Sulfated polysaccharides and antibacterial peptides can interfere with bacterial adhesion, damage the cell membrane, and inhibit virulence factors such as cagA and vacA. Additionally, omega-3 fatty acids (EPA and DHA) and phycocyanin have strong immunomodulatory effects, reducing NF-κB activation and lowering pro-inflammatory cytokines like IL-6 and TNF-α. In contrast to previous reviews that discuss microalgal bioactivities separately, this article takes an integrated view, connecting specific microalgal compounds with H. pylori virulence mechanisms and host inflammatory responses. Using different approaches at once, microalgal metabolites can help limit bacterial growth, reduce oxidative stress, and mitigate chronic inflammation. Overall, microalgae represent a sustainable and innovative source of bioactive compounds that could complement current therapies for H. pylori infection. Incorporating these compounds into functional foods or nutraceuticals may improve treatment outcomes, protect the gastric mucosa, and reduce the use of antibiotics. Future work should focus on improving extraction methods, enhancing bioavailability, and confirming their efficacy and safety through preclinical and clinical studies. Microalgal compounds offer a promising, safe, and environmentally friendly strategy for preventing and managing H. pylori-related diseases. Keywords: H. pylori, microalgae, bioactive compounds, antibacterial activity, antioxidant activity, anti-inflammatory activity
Copyright (c) 2026 Marta Majchrzak, Laura Alonso-Pintre, Pilar Gómez-Cortés, Jose Manuel Silvan, Adolfo J. Martinez-Rodriguez, Blanca Hernández-Ledesma https://creativecommons.org/licenses/by/4.0
Testing a patented fermented papaya preparation on key aging redox and functional markers in middle-aged individuals. A 10-month randomized, single-blind, crossover study
Objectives: Physical activity and cardiovascular system efficiency are known to be inversely associated with all-cause mortality. Thus, efforts are focused on preventative strategies for middle-aged and elderly subjects who lead sedentary lifestyles and may be further burdened. This is associated with a decay in mitochondrial efficiency and capacity for adenosine triphosphate (ATP) production, which is associated with decreased performance and overall bioenergetics. Methods: After having confirmed their eligibility, 160 (45-72 years old, m/f: 50/110 participants were admitted into a double blind, 4-month crossover, separated by a one-month washout period, trial, and random assignment to one of two study treatments using a patented fermented papaya preparation (FPP®), endowed with antioxidant properties. Subjects took two sachets per day, each one containing synthetic vitamins (Vitamin C, Vitamin E, alpha-lipoic acid, and dextrose). At the beginning, 1, 2, and 4 months, biochemical assays of oxidized LDL (oxLDL) and nitric oxide (NO) were performed on peripheral blood plasma or red blood cells (RBC) (ATP) on sample aliquots stored at −80°C. Results: FPP® intervention showed a statistically significant increase in RBC-ATP (0.05 vs Multivitamin) at 2 and 4 months of observation. Both treatments significantly improved Total Antioxidant Capacity (TAC) at the 4-month observation with an earlier 2-month increase in the FPP® group (p<0.01). Despite an overall wide scattering of OxLDL values, by clustering the 52-71-year-old participants, this group has significantly higher values than the younger counterpart. Both treatments, particularly FPP® (expressed as percentage change from baseline), led to a significant decrease (p<0,05). While Multivitamin treatment was ineffective in improving FMD or NO levels, these parameters significantly increased during FPP® treatment. Conclusion: The present research study shows that a specific fermented functional food (FPP®) may offer an interesting interventional strategy to tentatively counteract age-related endothelial dysfunction, redox dysregulation, and bioenergetic decline, compared with a synthetic multivitamin mixture. Keywords: Fermented papaya, aging redox, endothelial dysfunction, redox dysregulation, bioenergetic decline
Copyright (c) 2025 J. Cervi, R. Catanzaro, R. Rastmanesh, F. Marotta, M. Castillo-Garzon , M. Osato , A. Nardin, C. Aperio, A. Moghadam Ahmadi https://creativecommons.org/licenses/by/4.0
Native cacao from southern Mexico: polyphenol profiling and its impact on inflammation and lipid metabolism modulation
Background: Cacao (Theobroma cacao L.) is well known for its polyphenolic profile, which confers antioxidant and anti-inflammatory properties. This investigation provides remarkable evidence on the functional potential of the native Criollo cacao variety Rojo Samuel (RS), a poorly characterized cultivar from southern Mexico, particularly regarding its effects on macrophage-mediated inflammation and lipid metabolism. Methods: Phenolic compounds were extracted, quantified, and characterized from cacao beans. TNFα expression and nitric oxide production (NO) were measured in RAW 264.7 macrophages treated with cacao phenolic extracts. The lipid accumulation in adipocytes (3T3-L1) was evaluated using Oil Red O stain and triglyceride accumulation during the differentiation process. PPARγ and fatty acid synthase (FAS) expression were determined by Western blot in mature adipocytes treated with native cacao extracts. Results: In RAW 264.7 macrophages, treatment with cacao phenolic extracts significantly reduced NO production by 20-75%; however, TNF-α expression was not significantly affected by the treatment. In 3T3-L1 adipocytes, treatment with 150 µg extract/mL during adipocyte differentiation significantly decreased lipid accumulation (20.6%), intracellular triglyceride content (41.3%), PPARγ expression (81.2%), and FAS expression (40.2%). These effects are likely attributable to the presence of a variety of phenolic compounds in the cacao extracts, including epicatechin, catechin, procyanidins, and others. Novelty of the Study: Unlike prior research that focused primarily on cacao for industrial applications, this study demonstrates that phenolic extracts from the Criollo cacao variety Rojo Samuel (RS) exhibit antioxidant properties, modulate macrophage-mediated inflammation, and influence lipid metabolism in adipocytes. These findings highlight the potential of this native variety as a valuable source of functional food substances. Conclusion: Phenolic compounds from RS cacao showed biological activity relevant to inflammation and lipid metabolism regulation, in addition to their antioxidant effects. Furthermore, this study highlights the importance of this native underexplored cacao variety as a promising source of functional food substances. Keywords: Criollo cacao, polyphenols, inflammation, lipid metabolism.
Effects of extraction, purification, and drying on the antioxidant capacity of wheat bran extracts
Background: Antioxidants (AO) present in wheat bran (WB) contribute to the prevention of chronic diseases such as cancer and type 2 diabetes. The choice of extraction technology is critical for obtaining biologically active compounds from plant material. Depending on the processing conditions, extracts obtained from the same raw material may vary in compositions, which directly affect their antioxidant potential (AOP). Objective: This study aimed to evaluate the effect of different extraction, purification, and freeze-drying methods on the antioxidant potential (total antioxidant capacity – TAC, total phenolic compounds – TPC, total flavonoid compounds – TFC), as well as on protein and reducing sugar contents of wheat bran extracts, in order to identify the most effective approach for producing antioxidant-rich dry extracts. Methods: Wheat bran extracts were prepared via maceration (MM, aqueous and ethanol), ultrasound-assisted extraction (UAE, aqueous and ethanol), and enzymatic aqueous extraction (EAE). TAC was evaluated using FRAP, ORAC and DPPH assays; , TPC by the Folin-Ciocalteu method, and TFC by the aluminum chloride method. Extracts were purified by either nylon-membrane filtration or ethanol (96%) precipitation and then freeze-dried with or without maltodextrin (MD). Reducing sugars and proteins were quantified using the sulfuric acid method and Lowry/Bradford assays, respectively. Statistical analysis was conducted with STATISTICA 10.0. Results: Enzymatic aqueous extraction (EAE) produced the highest TACFRAP (1,64 ± 0,03 μmol-eq. Q/ g of bran, p < 0.05) and the highest TPC (1.39 ± 0.12 μmol-eq. G/g of bran). The ethanolic UAE exhibited the highest TACORAC and TACDPPH (8,12 ± 0,27 and 0,89 ± 0,001 μmol-eq. Q/g of bran, respectively, p < 0.05) but had lower TPC and TFC compared to other extracts. Ethanol precipitation reduced protein content by 84-92% and sugars by 40% (p < 0.05), while increasing TACFRAP and TACORAC by over 60% (p < 0.05). Freeze-drying preserved high TAC values in both control and filtered extracts, regardless of maltodextrin (MD) addition Conclusion: The choice of extraction method strongly affects the recovery of antioxidants from wheat bran. Enzymatic extraction combined with ethanol precipitation and freeze-drying produces extracts with enhanced antioxidant potential, reduced impurities, and preserved bioactivity, representing an effective strategy for obtaining antioxidant-rich wheat bran extracts for functional food and nutraceutical applications. This study provides the first comprehensive evaluation of this combined approach, offering a practical method for producing high-quality, antioxidant-rich wheat bran extracts. Keywords: plant antioxidants, phenolic compounds, ultrasonic extraction, enzymatic extraction, freeze-drying, ethanol precipitation, optimization, functional food, nutraceutical applications
In vitro protease digestion affects protein-derived bioactive compound content in functional ingredients
Background: Proteins in food are degraded by proteases in the digestive tract, and their products may exhibit physiological activities. In vitro protease digestion mimics digestion of food protein in the body. When crude herbal drugs used in Japanese Kampo medicines are subjected to in vitro protease digestion, which mimics in vivo processes, decarboxylated amino acids (biogenic amines) are detected in the digest. The protease-resistant dipeptide, pyroglutamyl leucine (pyroGlu-Leu), is present in fermented foods. In vitro protease digestion of functional foods and ingredients has not yet been studied. Objective: To identify protein-derived compounds by in vitro protease digestion of three functional ingredients that possess anti-inflammatory effects: a standardized extract of Asparagus officinalis stem (EAS), a standardized extract of cultured Lentinula edodes mycelia (ECLM), and a standardized oligomerized-polyphenol from Litchi chinensis fruit extract (OPLFE). Methods: Functional ingredients were treated with endoproteinases and exopeptidases. To detect decarboxylated amino acids, amino groups were derivatized with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC), and a precursor ion scan was performed using liquid chromatography separation–tandem mass spectrometry (LC–MS/MS) to target the product ions. AQC-derivatized amines were identified, and decarboxylated amino acids and pyroGlu-Leu in the digests were analyzed and quantified using LC–MS/MS in the multiple reaction monitoring (MRM) mode. Undigested functional ingredients were analyzed by LC–MS/MS and used as the negative control. Results: Decarboxylated amino acids with anti-inflammatory activity were detected in both undigested functional ingredients and their protease digestion. Tyramine was abundant in OPLFE, but its content was significantly decreased after in vitro protease digestion. 2-Methylbutylamine and isoamylamine were present in both undigested ECLM and its digest, whereas trace amounts of isobutylamine were also detected. In addition, pyroGlu-Leu, which also exhibits anti-inflammatory effects, was highly abundant in undigested ECLM, and its content was significantly increased after in vitro protease digestion. Conclusion: We first reported that decarboxylated amino acids and pyroGlu-Leu are present in undigested functional ingredients and/or formed from their proteins by in vitro protease digestion. When functional ingredients are ingested, these protein-derived compounds may exert anti-inflammatory and other beneficial effects. This methodology may be applied to other functional foods and ingredients, leading to understanding of their effects in the body. Keywords: Functional food, bioactive compound, decarboxylated amino acid, trace amine, in vitro protease digestion, LC–MS/MS.
Copyright (c) 2026 Saki Shirako, Satoshi Miyauchi, Kenji Sato, Mikio Nishizawa https://creativecommons.org/licenses/by/4.0
Aspartame, saccharin, sucralose, and stevia: Oxidative stress pathways and functional food perspectives
Background: The increasing consumption of non-caloric sweeteners has raised concerns regarding their potential effects on oxidative stress and related health outcomes. Emerging evidence suggests that artificial sweeteners, particularly aspartame and saccharin, may induce oxidative stress in a dose-, duration-, and tissue-dependent manner. In contrast, natural sweeteners, such as stevia, may offer protective effects. This review synthesizes current findings on the oxidative and metabolic effects of non-caloric sweeteners, outlining key methodological limitations and the need for long-term clinical investigations. It further integrates mechanistic insights to distinguish the differential redox effects of artificial versus natural sweeteners and explores how antioxidant-rich functional foods might mitigate these impacts. This review comprehensively integrates mechanistic, experimental, and dietary evidence linking non-caloric sweeteners to oxidative stress while introducing functional food–based strategies to mitigate redox imbalance. It provides an updated synthesis relevant to evidence-based dietary guidance and regulatory evaluation. Keywords: non-caloric sweeteners, aspartame, saccharin, stevia, antioxidants, oxidative stress, food additives, functional foods, bioactive compounds
Copyright (c) 2025 Ece Celik Atalay, A. Gulcin Sagdicoglu Celep, Roberto Catanzaro, Francesco Marotta https://creativecommons.org/licenses/by/4.0