Functional Foods in Health and Disease - Online ISSN: 2160-3855; Print ISSN: 2378-7007
The Functional Foods in Health and Disease (FFHD) is a peer-reviewed, open-access international journal which serves as the journal of the Academic Society for Functional Foods and Bioactive Compounds (ASFFBC). Journal Citation and Indexing The FFHD journal has been indexed in the Web of Science since 2011 with a current Impact Factor of 1.04. In addition, FFHD is indexed in the Emerging Sources Citation Index (ESCI) since 2015 and in Scopus since 2020. All articles from 2011 on have been accepted and indexed in web of Science. The acceptance into both Scopus and Web of Science shows the strength of the journal and the authors as well as helps to expand the reach of our published articles. The articles we publish include cutting-edge biomedical research and development of functional foods. The goal is to provide research that can lead to the development of functional food products. The actual definition for these functional foods, as provided by the Functional Food Center (FFC) is as follows: “Natural or processed foods that contain biologically-active compounds, which, in defined, effective, non-toxic amounts, provide a clinically proven and documented health benefit utilizing specific biomarkers, to promote optimal health and reduce the risk of chronic/viral diseases and manage their symptoms." The journal also serves as an excellent resource for Ph.D. students, professors, public health professionals, medical doctors, dieticians, nutritionists, government representatives (FDA, NIH, USDA), and the general public for information regarding the latest advancements for promoting optimal health and reducing the risk of chronic/viral diseases and managing their symptoms using functional foods and bioactive compounds including antioxidants, vitamins, and many more. The FFHD journal has been published under the title Functional Foods in Health and Disease since February 2011. You can submit your manuscripts and cover letter here or directly to the Editorial Office at editor@ffhdj.com as an e-mail attachment. Additional information about submission guidelines can be found here and an example cover letter can be found here. Scopus Metrics: [Functional Foods in Health and Disease - Scopus Page] The FFHD journal is also indexed in the following databases: Scopus, CrossRef, Index Copernicus International (ICI), Chemical Abstract, EBSCO, and Google Scholar. Functional Food in Health and Disease journal has been indexed in the following databases: Scopus, Index Copernicus, CrossRef, and Google Scholar. The FFHD journal has been indexed in Scopus since 2020 with a current CiteScore of 3.1 (Calculated on December 5th, 2025). Journal H-index is 30. While SJR currently lists FFHD in Quartile 3 (Q3), a direct search on the Scopus website shows that the journal is now ranked in Quartile 2 (Q2), reflecting recent citation improvements.
Authors retain the copyright of their articles and grant the Functional Food Center (FFC) and its journals the right of first publication under the terms of the Creative Commons Attribution 4.0 International License. This license permits unrestricted use, distribution, and reproduction in any medium, including commercial use, provided the original author(s) and source are properly credited. Authors may post and share their published work freely, provided that the original publication in this journal is acknowledged. By submitting to this journal, authors confirm that their manuscripts are original, not under consideration elsewhere, and that they hold the necessary rights to grant this license. The Functional Food Center encourages open scientific exchange and allows derivative and extended works, provided attribution to the original publication is maintained.
Activation of tryptophan metabolism in cardiometabolic disorders: Prognostic role of IDO and TDO enzymes
Background: Cardiometabolic disorders, including cardiovascular disease and type 2 diabetes mellitus (T2DM), represent a major global health burden and are closely associated with metabolic abnormalities such as obesity, dyslipidemia, and impaired glucose regulation. Disease progression is strongly influenced by chronic low-grade inflammation and dysregulated immune responses. Tryptophan, an essential amino acid, plays an important role in immune regulation and maintenance of inflammatory homeostasis. Overactivation of the kynurenine pathway leads to the accumulation of toxic metabolites, which promote inflammation and increase the risk of atherosclerosis, pulmonary arterial hypertension (PAH), and non-alcoholic fatty liver disease (NAFLD). Methods: This study was conducted between October 2024 and February 2025 and included total 150 participants. Ninety patients with cardiometabolic disorders were enrolled, including 30 patients with coronary artery disease (CAD) combined with T2DM, 30 patients with CAD combined with PAH, and 30 patients with CAD combined with NAFLD. Sixty apparently healthy individuals served as a control group. Venous blood samples were collected from all participants. Hematological parameters were evaluated using an automated complete blood count analyzer. Serum levels of indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) were determined using enzyme-linked immunosorbent assay techniques. CD8+ T cell expression was determined using flow cytometry. All patients had angiographically confirmed coronary artery disease. Results: Serum IDO levels were significantly elevated in patients with CAD combined with T2DM (4.85 ± 1.21 ng/mL), CAD combined with PAH (4.32 ± 1.08 ng/mL), and CAD combined with NAFLD (5.01 ± 1.34 ng/mL) compared to the control group (2.13 ± 0.74 ng/mL; P < 0.01). Similarly, serum TDO levels were significantly higher in CAD + T2DM (3.76 ± 0.98 ng/mL), CAD + PAH (3.54 ± 0.87 ng/mL), and CAD + NAFLD (3.92 ± 1.05 ng/mL) than in controls (1.89 ± 0.63 ng/mL; P < 0.01). CD8⁺ T-cell proportions were also significantly increased in CAD + T2DM (32.4 ± 5.8%), CAD + PAH (30.7 ± 5.1%), and CAD + NAFLD (31.9 ± 6.0%) compared to healthy controls (21.3 ± 4.2%; P < 0.01). Novelty of the Study: This study is among the first to simultaneously evaluate CD8⁺ T cell expression and IDO and TDO enzyme activity in several cardiometabolic disorders, highlighting their combined prognostic significance in inflammation-driven metabolic pathology. Conclusions: These findings suggest that inflammation-related activation of tryptophan metabolism through the kynurenine pathway plays an important role in immune disturbances and disease progression in cardiometabolic disorders. IDO and TDO enzymes may serve as valuable diagnostic biomarkers and potential therapeutic targets in inflammation-induced metabolic diseases. Keywords: Chronic inflammation; Tryptophan metabolism; IDO and TDO enzymes; Kynurenine pathway; Cardiometabolic disorders; Functional food biomarkers
Copyright (c) 2026 Anwar Jasib Almzaiel, Jihad Yaser Kshash https://creativecommons.org/licenses/by/4.0
Physiological and biochemical responses of Vicia faba L. to folic acid treatments and their relation to Aphis fabae infestation
Background: This study investigated the effects of foliar-applied folic acid (FA) on the growth and biochemical responses of faba bean (Vicia faba L.) under black bean aphid (Aphis fabae) infestation. Objective: This study aimed to evaluate the effect of foliar-applied folic acid on the growth, biochemical composition, and antioxidant defense system of faba bean (Vicia faba L.) and to determine its relationship with black bean aphid (Aphis fabae) infestation. Methods: Faba bean plants were treated with folic acid at concentrations of 0, 50, 100, and 150 mg/L under greenhouse conditions. Growth parameters, photosynthetic pigments, metabolites, and antioxidant enzyme activities were measured, and aphid infestation trials were conducted to assess plant resistance responses. Folic acid significantly improved plant growth, photosynthetic pigments and biochemical composition, with the highest concentration (150 mg/liter) producing the strongest effect. Aphid infestation markedly reduced biomass and pigment content; FA at 100–150 mg/L partially restored these parameters. FA treatments also increased secondary metabolites and antioxidant enzyme activities, infected plants showed a strong defense response, indicating a priming effect against biotic stress. Results: Folic acid application significantly improved growth parameters of both healthy and aphid-infested green bean plants, with 150 mg/L producing the highest fresh and dry weights. It partially alleviated aphid-induced stress by restoring growth performance compared with untreated infested plants. Treatment also enhanced plant water status and height, indicating improved physiological activity and hormone-like effects. These findings support the potential of folic acid as a biostimulant for sustainable crop productivity and stress tolerance. Novelty of the study: This study demonstrates a dual role of folic acid as both a growth-promoting biostimulant and defense-promoting agent against Aphis fabae in Vicia faba. Unlike previous studies focused primarily on abiotic stress, this work integrates physiological, biochemical and insect-related responses, supporting folic acid as a sustainable tool to increase crop productivity and resistance under biotic stress. Conclusion: Folic acid acts as an effective biostimulant that improves growth, photosynthetic efficiency and antioxidant defense in faba bean while reducing aphid-induced damage. These findings support its use as a sustainable strategy to enhance pest tolerance and increase crop productivity. Keywords: Vicia faba, folic acid, Aphis fabae, antioxidant enzymes, metabolites, plant resistance.
Copyright (c) 2026 Ahmed Khaleel Kafori, Mohamed Ali Triki https://creativecommons.org/licenses/by/4.0
Safety and efficacy of a proprietary Asparagus racemosus root extract on ovarian morphology, androgen balance, and insulin resistance in women diagnosed with polycystic ovary syndrome
Background: Polycystic ovary syndrome (PCOS) is a common endocrine-metabolic disorder characterized by ovarian dysfunction, androgen imbalance, and insulin resistance (IR). Current treatments often target isolated symptoms and may have tolerability limitations, suggesting the need for safe, multi-targeted therapeutic alternatives. Asparagus racemosus (Shatavari), which contains steroidal saponins, demonstrates phytoestrogenic and metabolic regulatory activities and may offer potential benefits in PCOS. Objective: To evaluate the efficacy and safety of CL22205, a standardized A. racemosus root extract, on ovarian morphology, reproductive hormones, hyperandrogenic drive, insulin sensitivity, and anthropometric outcomes in women suffering from PCOS. Methods: In a randomized, double-blind, placebo-controlled study, 60 women (age 20–35 years) suffering from PCOS were assigned to receive either CL22205 (200 mg/day) or a placebo over a period of 84 consecutive days. The primary outcome was the change in ovarian volume from baseline. Secondary outcomes included ovarian volume, cyst size, follicle count, and menstrual cycle regularity, hirsutism score, acne severity, serum endocrine factors, insulin resistance, and anthropometric measurements. Safety was assessed through hematology, serum biochemistry, urinalysis, and monitoring of adverse events. Results: Fifty-nine participants completed the trial. CL22205 demonstrated significant reductions (p < 0.05, vs. baseline) in ovarian volume (18.7%), cyst size (39.0%), and average follicle count (19.7%), and improved menstrual regularity (10.8%) at the end of the study. Hirsutism score (41.8%) and acne severity (40.7%) decreased remarkably. CL22205 significantly increased (p < 0.05 vs. baseline) serum levels of sex hormone binding globulin, reduced total testosterone, and lowered the luteinizing hormone: follicle-stimulating hormone ratio. Post-trial, homeostatic model assessment for IR decreased by 13.2% (p < 0.0001 vs. baseline), indicating enhanced insulin sensitivity. Reductions in body weight and waist and hip circumferences further supported the metabolic benefits. No major adverse effects were observed. Conclusion: CL22205 exhibited reproductive, endocrine, and metabolic benefits with excellent tolerability, demonstrating its potential as a phytoceutical intervention for the management of PCOS. Keywords: Asparagus racemosus, Clinical trial, Hyperandrogenism, Insulin resistance, Phytoceutical, Polycystic ovary
Copyright (c) 2026 Sridevi Kondamudi, Sravanthi Sadu, Sujatha Deva, Aishwarya Yalamanchi, Amulya Yalamanchi https://creativecommons.org/licenses/by/4.0
Sakulora™ (Lacticaseibacillus paracasei strain Shidare) improves bowel function: A randomized, double-blind, placebo-controlled trial
Introduction and objective: Heat-killed lactic acid bacteria with postbiotic effects have emerged as promising functional food ingredients for promoting intestinal health. SakuloraTM, which consists of heat-killed Lacticaseibacillus paracasei strain Shidare (strain Shidare) isolated from weeping cherry blossom, may exert postbiotic effects on the gut microbiota. However, its impact on the intestinal environment and intestinal mobility remains unclear. Therefore, the present study investigated the efficacy of SakuloraTM on intestinal serotonin and fecal IgA concentrations in mice and bowel function in healthy adults through a randomized, double-blind, placebo-controlled trial. Methods: In the pre-clinical phase, mice were administered heat-killed strain Shidare, and intestinal serotonin and fecal IgA concentrations were assessed. Forty-four healthy adults with mild constipation were then randomly assigned to receive either SakuloraTM (containing 50 billion cells of the heat-killed strain Shidare) or a placebo daily for 2 weeks. The frequency of bowel movements in one week was used as the primary outcome. Results: In murine models, the administration of heat-killed strain Shidare significantly increased intestinal serotonin and fecal IgA concentrations. In the clinical trial, the weekly frequency of bowel movements was significantly higher in the SakuloraTM group than in the placebo group. No significant improvements were observed in the secondary endpoints, including the gut microbiota and fecal short-chain fatty acids. No serious adverse events developed throughout the study period. Novelty of the Study: The bowel movement-improving effect of the heat-killed strain Shidare was demonstrated for the first time, and its mechanism was suggested to be an increase in intestinal serotonin and IgA levels. Conclusions: SakuloraTM containing heat-killed strain Shidare effectively improved the bowel function, supporting its potential as a safe functional food ingredient for maintaining digestive health in healthy individuals. Trial Registration: UMIN-CTR: UMIN000054746 Keywords: Lacticaseibacillus paracasei; postbiotics; bowel function; intestinal environment
Copyright (c) 2026 Tsuyoshi Takara, Naoko Suzuki, Kazuo Yamamoto, Shin-ichiro Iio, Hayata Noguchi, Toshihiro Kakinuma, Asami Baba, Hiroshi Shimoda, Takumi Watanabe, Akari Yoneda, Yuriko Namatame, Tetsuro Kan, Masafumi Nagata, Shogo Takeda https://creativecommons.org/licenses/by/4.0
Biogenic silver–copper oxide nanocomposites as functional food safety agents for pathogenic microbial control in aquatic food systems
Background: Multidrug-resistant (MDR) pathogens pose a significant threat to aquatic food systems and water safety. In response, functional food science increasingly focuses on bioactive compounds derived from natural sources for food preservation and safety applications. Objectives: This study aims to investigate the antimicrobial efficacy of biogenic silver-copper-oxide nanocomposites (Ag-CuO NCs) as functional food safety agents. Methods: Biogenic Ag-CuO nanocomposites were synthesized using aqueous extracts from locally sourced botanicals at Prince Abubakar Audu University. Antimicrobial activity was evaluated against six multidrug-resistant (MDR) environmental pathogens commonly found in aquatic ecosystems (Vibrio parahaemolyticus, Escherichia coli, Salmonella enterica, Listeria monocytogenes, Pseudomonas aeruginosa, and Staphylococcus aureus) using minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays. Synergistic effects with conventional food preservation methods were also assessed. Biomarker analysis included quantification of reactive oxygen species (ROS) production and assessment of membrane integrity disruption using flow cytometry and scanning electron microscopy (SEM). Results: Biogenic Ag-CuO nanocomposites demonstrated significant antimicrobial activity, with MIC values ranging from 2.5–15 μg/mL across all tested pathogens. The nanocomposites exhibited predominantly bactericidal activity. V. parahaemolyticus was the most susceptible (MIC: 2.5 μg/mL), whereas S. aureus displayed the highest resistance (MIC: 15 μg/mL). ROS quantification revealed a significant elevation in treated bacterial cells (p < 0.001), indicating oxidative stress-mediated antimicrobial mechanisms. SEM imaging confirmed cellular membrane disruption in all treated organisms. Furthermore, synergistic applications with a mild thermal treatment (50°C) enhanced antimicrobial efficacy by 3.8-fold, positioning these nanocomposites as adjuvant agents for food safety. Conclusions: Biogenic Ag-CuO nanocomposites exhibit promising functional antimicrobial properties relevant to food safety applications in aquatic food systems. Their natural derivation, dual-metal composition, and non-toxic profile at therapeutic concentrations suggest viability as bioactive food-grade safety compounds. Novelty of the Study: This study is among the first to systematically evaluate biogenic silver-copper oxide nanocomposites as functional food safety agents against multidrug-resistant aquatic pathogens, combining traditional food safety science with green nanotechnology to create novel bioactive food preservation solutions. The integration of mechanistic characterization (ROS quantification and cellular imaging), pathogen panel testing (six clinically relevant MDR organisms), and synergistic evaluation with mild thermal processing represents an original contribution advancing functional food antimicrobial applications. Keywords: functional foods, biogenic nanocomposites, antimicrobial agents, aquatic pathogens, food safety, bioactive compounds, multidrug-resistant bacteria
Copyright (c) 2026 David Adeiza Zakari, Egbeja Tsobaza Idris, Godwin Amoka Audu, Precious Adejoh Idakwoji, Joseph Abraham-Oyiguh, Hassan Amoto Abdullahi, Godwin Omuya Aliyu, Onwuatuegwu Joseph Chukwuma Taiwo, Kadiri Dickson Adejoh, Nwobodo Humphrey Afam, Ifeanyi Anthony Ezugwu, Onuh Kenneth Ikwulono, Abiodun Sunday Olusegun, Yebafa Jeremiah Akpodoitei, Abdulbasit Anoze Aliyu, Adebimpe Moyosore Adefila https://creativecommons.org/licenses/by/4.0
Antibiotic resistance profiling and histological characterization of Lactobacillus isolated from traditional dairy products
Background: Lactobacillus bacteria play a significant role in improving public health, due to their potential impact on both public health and food safety. They play a crucial role in enhancing food digestion and nutrient absorption in the intestines. This has contributed to increased public awareness of the benefits of probiotics and functional foods, and consequently, the need to evaluate their antibiotic resistance. Objectives: This research aims to study and evaluate the antibiotic resistance and histological characteristics of Lactobacillus strains isolated from conventional dairy products. Methodology: The research involved collecting samples of various dairy products available to consumers in local markets, such as milk, yogurt, and cheese. The necessary analyses were performed, and Lactobacillus bacteria were isolated using a suitable culture medium. Specific techniques were applied to isolate the desired strains. Results: The research showed high bacterial concentrations in the studied samples. The bacterial growth rate varied with the degree of dilution, indicating high bacterial density. These results demonstrate the potential for Lactobacillus bacteria to grow and thrive in diverse environments, underscoring the importance of ongoing assessment of their antibiotic resistance. Conclusion: The study's findings highlight the significance of understanding the role of Lactobacillus isolated from dairy products in antibiotic resistance, as well as the importance of continuing to investigate their impact to ensure food safety and address health challenges. Keywords: Lactobacillus, Traditional dairy products, Probiotics, Antibiotic resistance, Functional dairy foods, Histological characterization, Lactic acid bacteria, Food safety.
Copyright (c) 2026 Alaa Eid Ali ALkharabsheh, Zainab Mohammad Farhan, Ban Nadhum Abdul-Fatah, Aida Aboud Hussein Al-Hudairi, Mohamed Abouyounes, May Abdul Hafed Abdul Kader, Omar Saddam Fadhil https://creativecommons.org/licenses/by/4.0
A natural nootropic for cognitive enhancement: A case study on the standardized mango leaf extract Zynamite®
The demand for natural nootropics to enhance cognitive function has grown significantly. Mangifera indica L. (mango) leaves, with a long history of use in traditional medicine, have recently emerged as a promising candidate. Historically used as a tonic to combat fatigue and exhaustion, mango leaves are now the subject of rigorous scientific investigation. This review synthesizes the ethnobotanical background, phytochemical profile, and neuropharmacological activities of mango leaf extract and its principal bioactive compound, mangiferin. We delve into the mechanisms by which mangiferin impacts the central nervous system (CNS), including its antioxidant, anti-inflammatory, and neurotransmitter-modulating properties. A central component of this review is a detailed case study on Zynamite®, a standardized mango leaf extract. We examine preclinical and clinical evidence supporting its efficacy in enhancing cognitive domains such as reaction time, attention, and memory, particularly under conditions of stress and mental fatigue. To further optimize clinical outcomes, we detail the development of Zynamite® S, a version engineered to improve solubility and address pharmacokinetic hurdles. While previous literature has broadly discussed the diverse bioactivities of mango leaves, this article represents the first comprehensive review to specifically synthesize its effects on CNS and cognitive performance. By bridging the gap between traditional wisdom and modern science, this work provides a unique translational perspective on mango leaf extract as an evidence-based natural nootropic. Keywords: Mango Leaf Extract, Cognitive Enhancement, Solubility, Zynamite®
Copyright (c) 2026 Ana Beltrán-Arranz, David Fuentes-Ríos, Rubén Pérez-Machín, Laura López-Ríos https://creativecommons.org/licenses/by/4.0
Development and nutritional evaluation of sorghum-chickpea-baobab based complementary foods for infants in Sudan
Background: Protein-energy malnutrition (PEM) remains a critical public health concern in Sudan, particularly among children under two years—a period marked by rapid growth and transition from exclusive breastfeeding to complementary feeding. Effective complementary foods must be rich in protein, energy, and micronutrients while maintaining acceptable sensory qualities. Objective: This study aimed to develop and evaluate sorghum-based complementary food formulations supplemented with chickpea and baobab powder to improve nutritional quality, protein digestibility, and sensory acceptability. Methods: Four blends were formulated using malted or decorticated sorghum flour, chickpea flour (20–30%), baobab powder (10%), milk powder (5%), and sugar (5%). Proximate composition, vitamin C content, and in vitro protein digestibility (IVPD) were assessed using standard AOAC methods. Sensory evaluation was conducted with 15 mothers using a five-point hedonic scale. Data were analyzed using ANOVA and Duncan’s test at p ≤ 0.05. Results: Chickpea supplementation significantly improved protein content (up to 15.56%) and IVPD (up to 71.54%). Baobab enhanced vitamin C content (up to 15.74 mg/100g). Sensory scores were highest for Blend A (20% chickpea, decorticated sorghum), particularly in color, taste, and overall acceptability. All blends showed acceptable moisture levels and enhanced nutrient density compared to a commercial formula. Conclusion: Chickpea and baobab fortification significantly improved the nutritional and sensory properties of sorghum-based complementary foods. These locally sourced formulations demonstrate strong potential as functional foods to improve infant nutrition and reduce PEM prevalence in Sudan. Novelty of the study: This study introduces a complementary food prototype integrating sorghum, chickpea, and baobab—ingredients not previously combined in this proportion for infant feeding in Sudan. Chickpea enhances protein density and digestibility, while baobab naturally enriches vitamin C, improving functional properties. Keywords: complementary food, sorghum, chickpea, baobab, protein-energy malnutrition, Sudan, infant nutrition, sensory evaluation.
Copyright (c) 2026 Rabaa Musa Hamad Ali, Alafia Basheer Alsadig Musa, Mona Moddathir Gad Almoula, Obada Adam Daowd Mahammed, Amira Gali Abdulla Adam, Hanan Elamin Ibrahim, Azhari A. Mohammed Nour, Mohamed Awad Elkarim Mohamed Ibrahim, Sultan Qasem Mashnafi, Wisal Abass Mohammed Babiker, Lobna Saad Mohammed Abd Elmeged, Soltan Jabir Algamdi https://creativecommons.org/licenses/by/4.0
Pasteurized Akkermansia muciniphila AKK ONE improves aging-related phenotypes and increases lifespan in zebrafish models
Background: Aging is a biological process characterized by progressive compositional and functional alterations in the gut microbiota. Akkermansia muciniphila, a commensal bacterium of the human intestine, has been shown to confer significant metabolic and health benefits, particularly in the context of aging-associated physiological decline. Objective: The primary objective of this study was to further evaluate the potential anti-aging effects of pasteurized Akkermansia muciniphila AKK ONE using aged zebrafish models. Methods: Three aging models were established in zebrafish through exposure to aluminum chloride hexahydrate, D-galactose, and hydrogen peroxide, respectively. Behavioral and physiological parameters were assessed, including light-dark transition time difference, total locomotor distance, movement distance within the blue region, telomere length, relative expression of the spns1 gene, and survival rate. Results: Administration of pasteurized AKK ONE significantly improved mobility as indicated by enhanced light-dark transition time difference and increased total moving distance. Additionally, after pasteurized AKK ONE treatment, the moving distance in the blue region of aged zebrafish rose compared to that of the normal control group, showing substantial improvements in learning and memory. At the epigenetic level, both telomere length and the relative expression of the spns1 gene were significantly improved after administration of pasteurized AKK ONE. Noteworthy is the increased survival rate in the pasteurized AKK ONE group. Conclusions: Pasteurized AKK ONE effectively ameliorated aging-related phenotypes in aspects of mobility, cognition, and epigenetics, and remarkably increased lifespan in aged zebrafish models. Keywords: pasteurized Akkermansia muciniphila AKK ONE, zebrafish, lifespan, aging, mobility, cognition, telomere, spns1 gene.
Copyright (c) 2026 Yangwenshan Ou, Haotian Feng, Nan Li https://creativecommons.org/licenses/by/4.0
Effects of Leu-Asp-Gln-Trp-enriched whey protein hydrolysate on mood and fatigue in healthy adults: A randomized, double-blind, placebo-controlled trial
Background: Mental health concerns and fatigue are increasingly prevalent among healthy adults. Objective: This study evaluated the effects of whey protein hydrolysate (WPH) enriched with the functional tetrapeptide Leu-Asp-Gln-Trp (LDQW) on mood state and fatigue. Methods: A randomized, double-blind, placebo-controlled, parallel-group comparative study was conducted on 112 healthy adults aged 18 to 64 years. Participants were randomly assigned to receive either an active food containing 1.0 g of MWPH (WPH with 0.1% of LDQW) or a placebo food daily for 12 weeks. The primary outcome was mood state using the Profile of Mood States-Short Form 2nd Edition (POMS2-SF), and the secondary outcome was fatigue, evaluated using the Visual Analog Scale (VAS). Results: The active group showed significant improvements in several POMS2-SF scores (Total Mood Disturbance, Depression-Dejection, Fatigue-Inertia, and Friendliness) compared with the placebo group at 12 weeks. Notably, the active group showed significant improvements in the Vigor-Activity score of POMS2-SF compared to the placebo group, at as early as 4 weeks, which persisted throughout the study. The VAS score for shoulder discomfort also significantly improved in the active group compared with the placebo group at 4 weeks and beyond. No adverse events related to the test foods were observed. Conclusions: Daily intake of the WPH enriched with LDQW improved mood state, reduced fatigue, and relieved shoulder discomfort, providing benefits for both mental and physical health. Trial registration: The study protocol was registered with UMIN-CTR (ID: UMIN000054349). Keywords: whey protein hydrolysate; mood; fatigue; shoulder discomfort; LDQW; functional peptides
Copyright (c) 2025 Mayu Nakatsuka, Kazumi Nabeshima, Ryo Sakiyama, Soichiro Sato, Manabu Nakano, Miyuki Tanaka, Masahiko Nakamura https://creativecommons.org/licenses/by/4.0
Ultra-low-dose lactulose modulates the gut microbiota in healthy adults: A double-blind, randomized, placebo-controlled crossover trial
Background: Gut health, particularly the composition and function of the gut microbiota, is increasingly recognized as essential for overall well-being. Non-digestible oligosaccharides are established prebiotics that stimulate beneficial gut bacteria; however, excessive intake may cause gastrointestinal discomfort. This study aimed to determine the minimum effective dose of lactulose using 16S rRNA gene sequencing to support safe and sustainable dietary applications. Methods: In a double-blind, randomized, placebo-controlled crossover trial, 100 healthy Japanese adults received lactulose (500 mg/day) or placebo for 28 days, separated by a 14-day washout period. The relative abundance of Bifidobacterium was analyzed using a linear mixed model with centered log-ratio transformation. Results: As a result of the analyses conducted on the PPS (Per Protocol Set, n = 78) and FAS (Full Analysis Set, n = 99), lactulose intake significantly increased the relative abundance of Bifidobacterium. Overall alpha diversity remained unchanged, although participants with low baseline alpha diversity enterotypes showed a trend toward restoration of alpha diversity. No adverse events or gastrointestinal symptoms, such as bloating or diarrhea, were observed, confirming the safety of lactulose. Conclusions: These findings provide novel evidence that even minimal doses of lactulose can beneficially modulate the gut microbiota, notably by increasing the relative abundance of Bifidobacterium without inducing laxative effects. Ultra-low-dose lactulose may serve as a practical and safe functional food ingredient to support long-term gut health, and continued research on its incorporation into functional food matrices will be important. Trial registration: The study protocol was registered with UMIN-CTR (ID: UMIN000055862). Keywords: Lactulose; Prebiotics; Bifidobacterium; Improving gut microbiota, Gastrointestinal health
Copyright (c) 2025 Ryo Sakiyama, Seiya Miyashita, Manabu Nakano, Miyuki Tanaka https://creativecommons.org/licenses/by/4.0
Glycemic benefits of a bitter melon-based multi-herbal extract supplement in adults predisposed to metabolic syndrome
Background: Herbal plants are rich in nutrients and bioactive compounds that contribute to health promotion and are associated with a reduced risk of metabolic syndrome. However, evidence from human clinical trials remains limited and inconsistent, particularly regarding the combined effects of multiple herbal species. Objective: This study aimed to evaluate the effects of consuming a dietary supplement containing extracts from various medicinal herbs on nutritional status, blood pressure, and key biochemical markers in adults predisposed to metabolic syndrome. Methods: A total of 70 adult participants aged 30-59 years who were at risk of metabolic syndrome were enrolled in a 12-week randomized, double-blind, placebo-controlled trial. Participants were randomly assigned into two groups: the experimental group (n=35), which received a bitter melon–based multi-herbal extract supplement (BMMH), and the placebo group (n=35). Pre-and post-intervention outcomes were compared, including waist circumference, body composition, glucose metabolism, lipid profiles, and inflammatory biomarkers. Dietary intake and physical activity were also assessed. Results: All seventy participants completed the study. After 12 weeks, participants who consumed BMMH extract supplement exhibited significant reductions in fasting blood glucose and HbA1c levels (p = 0.011 and p = 0.036, respectively). In addition, a significant decrease in the LDL-C to HDL-C ratio was observed (p = 0.014), whereas no comparable changes occurred in the placebo group. No statistically significant effects were observed for other lipid parameters or inflammatory markers, including IL-6, TNF-α, and hs-CRP. Conclusion: Bioactive compounds present in medicinal herbs, particularly bitter melon, may support glucose homeostasis by enhancing glucose utilization and thereby reducing blood glucose levels. These compounds may help reduce the risk of cardiovascular disease. Thus, consumption of dietary supplements derived from herbal extracts may serve as a supportive factor in improving metabolic syndrome outcomes and potentially preventing the development of non-communicable diseases. Trial registration: Thai Clinical Trials Registry TCTR20241122004 Keywords: functional foods, bioactive compounds, bitter melon, fasting blood glucose, metabolic syndrome
Copyright (c) 2026 Chanchira Phosat, Atchariya Chuenchom, Puyada Yaempannarai, Jirayu Lainampetch https://creativecommons.org/licenses/by/4.0
Assessment of toxic liver cirrhosis and its prevention through herbal hepatoprotectors with a proposed innovative strategy
Background: In contemporary medicine, effective andnosologically less harmful approaches for the prevention and treatment of liver cirrhosis remain insufficient, as indicated by the projected increase in mortality over the next decade. In recent years, the discovery and development of herbal medicine have surged. Therefore, a critical need of our time is to identify more comprehensive and novel strategies for studying liver cirrhosis to develop more effective prevention and therapy, such as those in this scientific paper. Objective: This study aims to observe the progressive dynamics of toxic liver cirrhosis using a novel preliminary diagnostic approach centered on the morphofunctional interrelationship of the liver, lungs, and kidneys and subsequently to formulate therapy strategies employing the proposed Flasil herbal combination. Methods: CCl₄-induced liver cirrhosis model was used in this prospective investigation. Mixtures (Flasil 1 and 2) prepared from active compounds of Helichrysum rubicundum (C. Koch.) flowers and S. marianum seeds grown in Armenia. At the end of the experiment, H&E staining was used to assess histological abnormalities in the liver and adjacent organs. Results: Research has demonstrated that toxic liver disease can manifest signs of pulmonary and renal disorders in the pre-cirrhotic state. Histopathological analysis showed that both Flasil formulations exhibited hepatoprotective effects while concurrently reducing pathological changes in pulmonary and renal tissues. Flasil 2 was more effective in promoting liver and kidney repair through enhanced hepatocyte regeneration, whereas Flasil 1 demonstrated greater efficacy in supporting lung tissue regeneration during the acute-to-chronic transition of liver cirrhosis. . However, non-invasive tests are needed to demonstrate both the feasibility of the proposed strategy and the different biological activities of the new Flasil combination according to the dose. Novelty: A liver-lung-kidney morphofunctional correlation tactical approach for the initial diagnosis of cirrhosis was assessed for the first time. FLASIL is the first natural product shown to affect liver-lung-kidney dysfunction in a CCl₄ model. Conclusion: This new approach (diagnosing through the liver-lung-kidney morphofunctional linkage) enables early detection and, based on it, prevention of cirrhosis by regulating its dynamics and giving varying dosages of the Flasil combination as an innovative herbal hepatoprotector. However, they necessitate the investigation of further diagnostic criteria. Keywords: liver cirrhosis, new approach, liver-lung-kidney linkage, herbal medicine, Flasil
Copyright (c) 2026 Lilit Arshakyan https://creativecommons.org/licenses/by/4.0
The second-meal effect of Undaria pinnatifida sporophylls (mekabu) in healthy young women: An open-label crossover study
Background: Postprandial hyperglycemia is an early indicator of impaired glucose tolerance and an established risk factor for the development of type 2 diabetes mellitus (T2DM). While low–glycemic index (GI) foods and soluble dietary fibers have shown efficacy in modulating postprandial glycemia, their capacity to influence glycemic responses to subsequent meals—referred to as the "second-meal effect"—remains underutilized in dietary interventions. Objective: This study aimed to investigate whether breakfast consumption of Undaria pinnatifida (mekabu), a seaweed rich in soluble fiber and sulfated polysaccharides, could attenuate postprandial glycemic response at a subsequent meal in healthy young women. Methods: An open-label, two-period, crossover study was conducted among healthy female participants. Subjects consumed a test breakfast with or without mekabu, followed by a standardized lunch. Capillary blood glucose levels were measured at multiple time points post-lunch to assess second-meal glycemic modulation. Results: The findings indicated that mekabu consumption at breakfast significantly reduced postprandial blood glucose levels after lunch, compared to the control condition. These effects may be mediated, at least in part, through delayed gastric emptying and enhanced GLP-1 secretion. Conclusion: Breakfast intake of mekabu may enhance glycemic stability over successive meals by eliciting a second-meal effect. These findings support the potential utility of mekabu as a functional dietary intervention for the early prevention of T2DM. Keywords: Mekabu (Undaria pinnatifida), Second-meal effect, Soluble dietary fiber, Postprandial glycemia, Glucagon-like peptide-1 (GLP-1), functional foods, bioactive compounds
Copyright (c) 2025 Masaki Taga, Kazuma Yohizumi, Hitomi Kobayashi, Naoki Iwamoto https://creativecommons.org/licenses/by/4.0
Microalgae and the gut microbiome: Insights from animal models to human trials
ABSTRACT: The gut microbiota is a vast consortium of microorganisms living in the gastrointestinal tract that plays essential roles in host metabolic, nutritional, and immune functions. However, this delicate ecosystem is susceptible to disruptions, or dysbiosis, which have been associated with conditions such as inflammatory bowel disease, obesity, and metabolic syndrome. The consumption of Western diets disrupts gut function; however, functional foods are essential for healthy microbiota. Microalgae, known for their ecological sustainability and rich nutritional profile, are increasingly considered promising sources of bioactive compounds, with growing evidence suggesting they may support the growth of beneficial gut microbes and help restore microbial balance. Microalgal-rich diets have shown promise by modulating fatty acid metabolism, inhibiting gut inflammation, and improving gut health. Despite previous investigations, the specific effects of microalgae on the gut microbiome remain underexplored, and the available data are dispersed. This review aims to unite and apprise the current scientific literature on the effects of microalgae-based dietary interventions on the gut microbiome by examining studies conducted in animal models, evidence from human-based approaches, including in vitro gut models and clinical trials, and identifying critical knowledge gaps in this research area. By highlighting the most relevant findings and outlining areas requiring further investigation, this review underscores the emerging potential of microalgae as microbiome-modulating agents and their promising role in next-generation functional foods for human health. Keywords: microalgae, gut microbiome, animal models, clinical trials, prebiotics
Copyright (c) 2025 Samuel Paterson, Tosin A. Olasehinde, Pilar Gómez-Cortés, Blanca Hernández-Ledesma https://creativecommons.org/licenses/by/4.0
Anti-type 2 diabetes mellitus activity of Citrus reticulata-derived materials: Mechanistic insights from integrated network pharmacology, molecular docking, and in vitro assays
Background: Citrus reticulata-derived materials (CRDMM) are representative medicinal and edible resources, yet their systematic evaluation for anti-type 2 diabetes mellitus (T2DM) potential remains to be fully elucidated. Objective: This study aimed to investigate the anti-T2DM potential of CRDMM and explore the underlying mechanisms of action using an integrated experimental and computational approach. Results: In vitro assays demonstrated significant α-glucosidase inhibitory activity across 16 CRDMM extracts, with Guangchenpi exhibiting the strongest potency (IC₅₀: 2.5–3.8 mg/mL). Network pharmacology analysis identified 10 active compounds and 74 potential targets, among which AKT1, TP53, PPARG, and PTGS2 were highlighted as core targets via protein-protein interaction analysis. Pathway enrichment suggested involvement in lipid metabolism and inflammatory pathways. Molecular docking confirmed strong binding affinities (< –7.0 kcal/mol) between key flavonoids (e.g., neohesperidin_qt and nobiletin) and the core targets. ADMET predictions indicated favorable drug-likeness, despite potential nephrotoxicity risks. Novelty: This study is the first to integrate multi-approach validation—combining in vitro bioactivity, network pharmacology, molecular docking, and ADMET profiling—to systematically reveal that CRDMM exerts anti-T2DM effects via a multi-component, multi-target mechanism. Conclusion: The results provide a scientific basis for developing CRDMM as functional food ingredients or dietary supplements for blood glucose management in T2DM. Keywords: Citrus reticulata, type 2 diabetes mellitus, α-glucosidase inhibition, network pharmacology, molecular docking, functional food, medicinal-food homology, nobiletin
Copyright (c) 2025 Hanhua Wang, Mingyue Li, Yanyue Wang https://creativecommons.org/licenses/by/4.0
Superiority of the body roundness index over BMI in linking central adiposity with vitamin D3: A cross-sectional study in Iraqi adults
Background: Body mass index is a poor measure of central adiposity. The Body Roundness Index may be a better measure, although data for Middle Eastern adults are limited. Objectives: To investigate the association of animal-fat consumption with adiposity indices as well as vitamin D3, and compare BRI with BMI as a marker of body fat in Iraqi adults. Methods: We used dietary questionnaires, anthropometry, and bioelectrical impedance to estimate visceral fat area and serum vitamin D3 in a cross-sectional study of 527 adults. Correlation and regression analyses were performed. Results: There was no association between animal-fat intake and the adiposity indices or vitamin D3. In contrast with BMI, BRI presented a quite strong inverse correlation with vitamin D3 (r = –0.497, p < 0.001). Visceral fat area was not predicted by any of the indices. Novelty explicit: In this adult sample from Iraq, BRI is more helpful than BMI for detecting central adiposity, which is associated with vitamin D3 insufficiency; as a result, BRI may be a better screening tool in a clinical and epidemiological context. Conclusion: BRI was a better indicator of metabolic risk associated with adiposity than BMI. In both clinical and epidemiological settings, it might be a beneficial screening tool for central adiposity and Vitamin D deficiency. Keywords: Body Roundness Index; Vitamin D3; Visceral fat; Body Mass Index; Adiposity.
Copyright (c) 2025 Functional Foods in Health and Disease - Online ISSN: 2160-3855; Print ISSN: 2378-7007 https://creativecommons.org/licenses/by-nc/4.0
Effect of homogenization and ultra-high-pressure homogenization on the activity of dairy by-products against gastrointestinal pathogens
Background: The growing emphasis on agri-food sustainability and the circular economy has promoted the valorization of dairy by-products, particularly whey, which has an estimated annual global production of approximately 200 million tons. Whey is a valuable source of proteins with nutritional and bioactive properties, and nearly half of its volume is processed into whey protein concentrate (WPC) and whey protein isolate (WPI). During WPI production, whey protein phospholipid concentrate (WPPC) is generated; however, its functional properties remain poorly characterized. The incorporation of bioactive compounds from bovine milk and its by-products into infant formulas and specialized products may contribute to gut, brain, and immune system health. Objective: This study aimed to characterize WPPC obtained from bovine whey and to evaluate its activity against Cronobacter sakazakii and rotavirus, as well as to assess the impact of conventional homogenization (CH) and ultra-high-pressure homogenization (UHPH) on this bioactivity. Methods: WPPC was obtained from industrial cheese whey through ultrafiltration and microfiltration. The resulting fractions were characterized by SDS-PAGE, laser diffraction (Mastersizer), and proteomic analysis, and were further compared with commercial WPPC. Conventional homogenization (25 MPa) and UHPH treatments (100–200 MPa) were applied using pilot plant-scale equipment. Antibacterial activity against C. sakazakii was evaluated by measuring bacterial growth and adhesion to Caco-2/TC7 cells, while antiviral activity against bovine rotavirus strain WC3 was assessed in MA104 cells using indirect immunofluorescence. Results: WPPC at a protein concentration of approximately 5 mg/mL inhibited C. sakazakii growth and adhesion to Caco-2/TC7 cells by ~40-50%, with both CH and UHPH enhancing the inhibitory activity of non-commercial WPPC by ~40%. WPPC achieved complete inhibition of rotavirus at concentrations above 0.25 mg/mL. The observed bioactivities appear to be mainly attributable to compounds with molecular weights greater than 30 kDa. Conclusion: WPPC exhibits significant antibacterial and antiviral activities, with antibacterial effects enhanced by homogenization treatments. UHPH emerges as a promising alternative to thermal pasteurization. These findings further expand current knowledge of WPPC functional properties and support its potential application as a functional ingredient in health-oriented food formulations. Keywords: cheese whey, WPPC, homogenization, ultra-high-pressure homogenization, rotavirus, Cronobacter sakazakii
Copyright (c) 2026 Laura García, Laura Carmona, Rodrigo Casado, María Dolores Pérez, Antonio J. Trujillo-Mesa, M. Manuela Hernández-Herrero, Artur X. Roig-Sagués, Laura Grasa, Lourdes Sánchez https://creativecommons.org/licenses/by/4.0
Cerebrovascular and antihyperlipidemic properties of sour cherry (Prunus cerasus) fruit
Background: Ischemic diseases are major global health burden, contributing significantly to cardiovascular and cerebrovascular disorders, with ischemic stroke being a leading cause. The main risk factors for ischemia are vascular wall damage, atherosclerosis progression, lipid metabolism disturbances, and increased platelet aggregation. Current medications targeting these mechanisms may lead to side effects, especially when they are used for prevention, driving interest in plant-derived compounds with cardiovascular and cerebrovascular benefits. Sour cherry (Prunus cerasus) has attracted attention for its high levels of polyphenols, anthocyanins, flavonoids, and organic acids, known for their blood pressure-regulating, anti-inflammatory, and sleep-modulating properties. These compounds protect the vascular system by reducing oxidative stress, inflammation, and endothelial dysfunction. Investigation of sour cherry cerebrovascular and anti-hyperlipidemic properties may contribute to integrating plant-based therapies into existing cardiovascular treatment strategies, offering new opportunities for disease prevention and management. Objectives: The purpose of this observation was to investigate the antihyperlipidemic activity and discover the new cerebrovascular effects of sour cherry fruits. Results: Obtained data evidenced that cholesterol levels in blood samples after 7 days of fruit intake were decreased by 2.74±1.52% compared with baseline parameters (day 0). Continued sour cherry fruit intake for 14 days led to further reduction in cholesterol levels by 8.1±3.30%, nearly three times exceeding the reduction level registered on day 7. Assessment of sour cherry fruits on triglyceride levels showed a significant reduction on days 7 and 14 by 17.86 ± 5.57% and 21.01 ± 9.25%, respectively, compared to baseline. No notable changes were observed in high-density lipoprotein (HDL) levels following sour cherry fruit intake. In contrast, low-density lipoprotein (LDL) levels decreased by 8.1 ± 4.24% after 14 days of consumption compared with control values. Registration of brain blood flow enabled the discovery of cerebrovascular activity in sour cherry fruits. It is noteworthy that its ability of sour cherry fruits to increase the cerebral blood flow (CBF) appears especially in case of cerebral blood flow impairment. Thus, under the normal condition, cerebral blood flow after intraperitoneal injection of 2.5 g/kg freeze-dried sour cherry fruit solution was not changed significantly. After the ligation of right common carotid artery, when CBF was decreased by 31.07±3.96% (p<0.05) intraperitoneal administration of the freeze-dried sour cherry fruits solution (2.5 g/ kg) was accompanied by the elevation of CBF, being above from occlusion levels by 13.6±5.19% ( p<0.05) at 30 minutes, and by 33.8±6.06% -at 80 minutes, compared to occlusion values. Notably, by the end of the experiment, CBF levels exceeded not only the occlusion level by 40.04±12.51%, as well as the baseline level. Conclusion: The findings of this study suggest that sour cherry fruits possess cerebrovascular and antihyperlipidemic activity, as based on their ability to improve impaired cerebral blood flow and reduce cholesterol and triglyceride levels. These results highlight the potential of sour cherry as a natural and effective plant-based agent for reducing cardiovascular disease risk factors, including hypercholesterolemia. Keywords: common carotid artery occlusion, new cerebrovascular activity, lipid spectrum changes, freeze-dried sour cherry.
Active medicinal-food homologous complex nutrients (AMCN) enhance immune systems in zebrafish
Background: Immunosuppression, whether caused by disease, stress, or medical treatments, compromises host defense by disrupting both innate and adaptive immune responses. Natural compounds such as Ganoderma lucidum, polygonatum, and mulberry leaves have long been used in traditional medicine for their immune-enhancing properties, yet their efficacy is often limited by low bioavailability. Biotransformation offers a promising approach to enhance the bioactivity of these medicinal-food homologous substances, but its potential in restoring immune function has not been fully explored. Objective: The objective of this study was to investigate whether active medicinal-food homologous complex nutrients (AMCN) formulation containing Ganoderma lucidum, polygonatum, and mulberry leaf could restore immune function in an immunodeficient zebrafish model. Specifically, we aimed to evaluate its effects on both innate and adaptive immune cell populations, including neutrophils, macrophages, and T cells, as well as its ability to modulate key immune-related cytokines. Methods: AMCN was prepared by culturing Ganoderma lucidum mycelia, followed by enzymatic biotransformation with polygonatum and mulberry leaf powders and subsequent fermentation with Lactobacillus plantarum. Transgenic zebrafish larvae were used as an in vivo model to evaluate immunomodulatory effects. Immune suppression was induced using cyclophosphamide, and larvae were exposed to AMCN to assess immune recovery. Changes in innate and adaptive immune cell populations and key cytokine expression were analyzed to determine the efficacy of AMCN. Results: AMCN treatment significantly restored immune cell populations in immunodeficient zebrafish, increasing neutrophils, macrophages, and T cells compared with the model group. It also upregulated key pro-inflammatory cytokines, including tnf-α, il-12a, and ifn-γ. Conclusion: AMCN effectively restores both innate and adaptive immune cell populations in an immunodeficient zebrafish model, highlighting its potential as a natural immunomodulatory agent. Novelty of the study: This study is the first to show that a biotransformed complex of AMCN can restore both innate and adaptive immune cell populations in an immunodeficient zebrafish model. AMCN exhibited broad immunostimulatory effects, upregulating key cytokines and highlighting biotransformation as a strategy to enhance the bioactivity of medicinal-food homologous substances for mitigating immunosuppression. Keywords: AMCN, biotransformation, immunomodulation, zebrafish model.
A functionally sustainable approach to producing pure agricultural products
Background: Functional foods address dietary needs and promote health by harnessing bioactive compounds. Peppers, a staple crop worldwide, are vital for nutrition and the economy. Biohumus enhances soil microbial activity, improves plant nutrition, and stimulates the activation of bioactive components in crops.​ Objective: This study evaluates the effectiveness of microbial biohumus, developed by the "Hrant Petrosyan Scientific Center," in increasing the yield and quality of three pepper varieties: Loshtak, Arajnek, and Jermatnayin Hska.​ Methods: Seedlings of the pepper varieties, provided by the “Vegetable and Technical Crops Scientific Center” CJSC of the RA Ministry of Economy, were cultivated in vegetative containers with 85 kg of soil at the “Hrant Petrosyan Scientific Center of Soil Science, Agrochemistry and Melioration,” a branch of the ANAU Foundation. Growth and development parameters were measured throughout the experiments, and the contents of ascorbic acid and chlorophylls a and b were determined.​ Novelty: This study introduces an organic fertilizer tailored for sustainable agriculture. Biohumus not only boosts yield but also enhances the functional and nutritional quality of crops, aligning with global trends in functional food production.​ Results: The application of biohumus as a biofertilizer significantly increased the yield of the three pepper varieties:​ Arajnek: 33.3% increase (304 c/ha) compared to the control (228 c/ha).​ Jermatnayin hska: 51.3% increase (237 c/ha) compared to the control (191 c/ha).​ Loshtak: 50.04% increase (360 c/ha) compared to the control (239.8 c/ha).​ Combining biohumus with inorganic fertilizers (NPK) resulted in even higher yields:​ Arajnek: 82% increase (415 c/ha).​ Jermatnayin hska: 75.05% increase (342 c/ha).​ Loshtak: 81.8% increase (436 c/ha).​ Additionally, biohumus application enhanced chlorophyll content (a+b: 18.78 mg/l) compared to the control (15.0 mg/l) and increased ascorbic acid levels, particularly in Jermatnayin hska fruits treated with N60P60K60.​ Conclusion: The application of biohumus offers a sustainable approach to agricultural practices. It improves yield while reducing the need for chemical fertilizers, thereby supporting the production of functional foods. Keywords: Pepper varieties, biohumus, food functionality, yield, quality​
Copyright (c) 2026 Tatevik Jhangiryan, Gayane Gasparyan, Marina Barseghyan, Inga Beglaryan, Sevak Daveyan, Surik Hunanyan https://creativecommons.org/licenses/by/4.0
Differential protective effects of whole and skimmed whey on LPS-induced barrier dysfunction and inflammation in Caco-2/TC7 cells
Background: Lipopolysaccharide (LPS) from Gram-negative bacteria disrupts intestinal epithelial integrity and promotes inflammation, contributing to the pathogenesis of gastrointestinal disorders. Dairy-based whey products are rich in bioactive compounds with known barrier-protective and immunomodulatory properties. Objective: This study aimed to evaluate the effects of two types of bovine whey — bovine whole whey (BWW) and bovine skimmed whey (BSW) — on LPS-induced barrier dysfunction and inflammation in the intestinal in vitro model Caco-2/TC7 cells. Methods: Caco-2/TC7 cell line was exposed to 20 µg/ml LPS for 24h to induce epithelial barrier disruption. Additionally, cells were treated with 5 mg/ml BWW or 5 mg/ml BSW alone, or in combination with 20 µg/ml LPS. Transepithelial electrical resistance (TEER), FITC-dextran permeability, and mRNA expression of tight junction (TJ) proteins (ZO-1, claudin-1, claudin-3, occludin) and inflammation-related genes (IL-1R, COX-2, iNOS) were assessed. Results: LPS significantly reduced TEER without increasing macromolecular permeability or altering TJ gene expression. Both whey fractions restored TEER to control levels, with BSW also enhancing baseline barrier integrity. BWW and BSW upregulated ZO-1 and claudin-1 mRNA expression, though claudin-1 was downregulated when BSW was combined with LPS. Importantly, only BWW normalized LPS-induced overexpression of IL-1R, COX-2, and iNOS, indicating better anti-inflammatory properties likely due to its retained lipid components. Conclusion: Both whey fractions reinforce epithelial barrier function under LPS challenge, but only whole whey (BWW) provides dual protection by also attenuating inflammatory responses. These findings support the potential of whole whey as a functional food ingredient for intestinal health by targeting both physical and immunological aspects of barrier dysfunction. Keywords: bovine whey, LPS, intestinal permeability, tight junction proteins, inflammation
Copyright (c) 2025 Elena Layunta, Laura García, Sofía Gimeno, Jaime Martínez, Lourdes Sánchez, Laura Gras https://creativecommons.org/licenses/by/4.0
Acceptability and tolerability of a Hibiscus sabdariffa L. beverage and effect on biomarkers of pregnant women: Phase I pilot trial
Background: Hibiscus sabdariffa L. (HS) is a plant in the Malvaceae family, known as roselle, whose calyces contain compounds with antioxidant and anti-inflammatory properties. Various studies have demonstrated its antihypertensive, antihyperlipidemic, and glycemic control effects. During pregnancy, women also experience metabolic and biochemical changes that allow them to adapt to the development of a new human being. Among these metabolic changes are increased plasma concentrations of glucose and fatty acids, which can serve as substrates for fetal growth. However, if not adequately controlled, they can lead to gestational diabetes and dyslipidemia. One of the main complications of pregnancy is hypertensive disorders, which affect 10% of worldwide pregnancies and are the leading cause of maternal and fetal morbidity and mortality. Objective: This work aimed to evaluate the acceptability and tolerability of a Hibiscus sabdariffa beverage and its effect on biomarkers in women in the second trimester of pregnancy. Methods: A four-week phase I pilot trial was conducted in women in their second trimester of pregnancy. Participants consumed a daily dose of HS beverage, which provides 9.6 mg of total anthocyanins, and several metabolic parameters were recorded (diastolic and systolic blood pressure, plasma glucose, cholesterol, triglycerides, and creatinine concentrations, as well as urinary protein levels). Measurements were taken before the start of the trial and at the end of the 4 weeks following beverage consumption. Results: The protocol for this study was approved by the Research Ethics Committee of the Centro de Desarrollo de Productos Bióticos. Ten women participated in the trial. Diastolic and systolic blood pressure values did not change significantly between the initial and final measurements. Plasma markers also showed no significant differences between the two measurements, although there was a slight decrease in glucose (from 80.5 ± 8.4 to 74.8 ± 9.6 mg/dL) and triglycerides (from 110.7 ± 24.5 to 105.7 ± 14.4 mg/dL). The limitations of this work were the number of participants and the study time, however, as it was a phase I pilot trial, the aim was to identify the acceptability and tolerability of the beverage and to obtain preliminary information regarding the biomarkers to apply them in a study with a larger number of participants over an extended period. Novelty: The originality of this work is the use of an HS beverage made from ground calyces, instead of a traditional infusion or extracts, to determine whether its use is feasible during pregnancy, as well as to obtain preliminary information about its effects on blood pressure and biomarkers. This pilot is the first to evaluate a ground-calyx Hibiscus sabdariffa beverage (not an infusion or extract) providing 9.6 mg/day total anthocyanins specifically in second-trimester pregnant women, focusing on acceptability, tolerability, and preliminary cardiometabolic biomarkers. Conclusion: HS beverage demonstrated acceptability and tolerability. Although the number of women included in this preliminary trial is low, it may be expected to have at least one case of an increase in blood pressure, but none presented these symptoms. The prevention of hypertension in all cases is a promising result. The HS beverage could be evaluated in longer-term clinical trials to confirm the maintenance of blood pressure and biochemical indicators at adequate values for pregnant women according to World Health Organization throughout the pregnancy. Keywords: Hibiscus sabdariffa, acceptability, tolerability, hypertensive disorders of pregnancy
Expression ratio of PD-1 on the T cell surface and TGF-β levels in acute and chronic brucellosis: A marker of immune evasion
Background: Brucellosis is considered a zoonotic disease characterized by the ability of Brucella spp. to evade host immune responses and establish chronic infections. Key immune-regulatory molecules, such as transforming growth factor-beta (TGF-β) and programmed death-1 (PD-1), may play a central role in this immune evasion. Objective: The present study had a gold target to compare the expression of PD-1 on CD4⁺ and CD8⁺ T cells, as well as serum levels of TGF-β level between patients with acute or chronic brucellosis relative to those in healthy controls. It also aimed to assess their prospective roles as immunological markers of advancing and persistent disease. Methods: In the present study, we recruited a total of 60 confirmed brucellosis patients , about 30 of both acute and chronic, as well as 30 healthy controls. The enzyme-linked immunosorbent assay was reliant on the measurement of serum TGF-β levels, and flow cytometry assisted in the identification of PD-1 expression among CD4 ⁺ and CD8 ⁺ T cells. Correlation analyses were conducted to explore the relationship between TGF-β levels and PD-1 expression. Results: Patients with acute brucellosis exhibited significantly higher levels of PD-1 on CD4⁺ and CD8⁺ T lymphocytes than that of chronic patients and healthy individuals (P < 0.05). Patients with chronic brucellosis also showed increased PD-1 levels compared with controls. No significant difference was found between both acute and chronic brucellosis stages but serum level of TGF-β in both cases differed significantly from control (P < 0.05). Plasma TGF-β was highly positively correlated with PD-1 expression (r = 0.99, P < 0.0001) indicating that they could act co-operatively to suppress immunity. Novelty: The present study sheds novel light on the immunological basis of brucellosis infection, especially about immune escape. It illustrates the correlation of PD-1 expression with TGF-β levels, as a biomarker for disease monitoring and also as a therapeutic target. These results provide a new insight into the host–pathogen interplay that may contribute to designing therapeutic interventions for reactivating antimicrobial immune responses in chronic brucellosis. Conclusion: The ultimate conclusions of our study are that the immune suppression in patients infected with brucellosis infections is due to the product of higher levels serum TGF-β and increased expression levels of PD-1 on CD4⁺ and CD8⁺ T cells. The strong association of TGF-β and PD-1 suggests a controlling program that facilitates Brucella persistence. The examined markers look to be promising targets for therapy of immunological dysfunction in chronic brucellosis and could serve as the indicators for the monitoring of disease. Keywords: Brucellosis, chronic infection (CI), immune evasion, PD-1, TGF-β, T cell exhaustion.
Clove bud extract inhibits glycation of bovine serum albumin: Insights from in vitro and molecular dynamics simulation analysis
Background: Glycation is a non-enzymatic reaction between amino groups within proteins and reducing sugars, leading to advanced glycation end products (AGEs). AGEs can induce protein cross-linking and accumulate in various tissues. Their buildup contributes to complications associated with chronic disease. Although antiglycation agents like aminoguanidine are well documented, there is a significant need for more effective AGE inhibitors to address various pathogeneses and complications. Syzygium aromaticum, commonly known as clove, has several medicinal properties, including antimicrobial and antioxidant effects that contribute to reduced oxidative stress. However, its impact on glycation and related biochemical parameters has not been thoroughly investigated. Objectives: This study aims to evaluate the impact of clove bud extract on BSA glycation and elucidate its mechanism of action through molecular simulations. Methods: The antiglycation effects of clove bud extract were evaluated by quantifying glycation-induced changes in BSA structure and aggregation following glucose-mediated glycation and subsequent treatment with varying extract concentrations. UV spectroscopy and fluorescence-based assays (Congo red and Thioflavin T) were used to assess these changes. At the same time, molecular docking and dynamics simulations explored the underlying molecular interactions between clove bud components and BSA. Results: The results demonstrated that clove bud extract at a 600 µg/ml concentration significantly decreased the browning intensity by 54.38%. When combined with glycated BSA, the extract reduced the aggregation index and mitigated glycation-induced alterations in BSA's secondary structure, indicating its potential to inhibit glycation and prevent AGE formation. Increasing the dosage of clove bud extract resulted in a decrease in Thioflavin T-specific fluorescence in the samples. Molecular docking studies revealed several compounds within the clove extract interact with glycation-prone residues on BSA, specifically lysine and arginine. Molecular simulation studies further confirmed that all tested compounds form stable complexes with BSA when simulated under aqueous conditions, which mirror physiological environments. Novelty of the Study: This study presents novel findings on the inhibitory effects of clove bud extract on the glycation process of bovine serum albumin (BSA), demonstrating its potential as a natural inhibitor of glycation. Conclusion: These findings underscore the potential of clove bud as a natural inhibitor of glycation and glycation-induced protein aggregation. Keywords: Clove; glycation; Oxidative stress, aggregation; BSA; molecular docking; molecular dynamics simulation, Pathogenesis.
Regulation of a synbiotic herbal-probiotic formula (HBF) on alcohol metabolism in human: A randomized controlled trial
Background: Excessive alcohol intake is a global health concern. Short-term alcohol consumption can lead to unpleasant hangover experiences, while long-term excessive intake is associated with liver injury, neurological disorders, cancer, and various other diseases. Herbal and probiotic interventions have shown promise in modulating alcohol metabolism, but the effects of combined synbiotic formulas remain underexplored. Methods: This study aimed to investigate the effects of a novel herbal–probiotic formula (HBF), composed of Pueraria lobata (30%), Hovenia dulcis (30%), Lactobacillus rhamnosus Alcoker0067 (20%), and Lactobacillus plantarum ZQ15 (20%), on alcohol metabolism in healthy male volunteers. In a randomized, placebo-controlled trial, 20 participants were assigned to either the HBF or placebo group. Following HBF or placebo administration and subsequent alcohol consumption, blood samples were collected at multiple time points (0.5–8 h) to measure ethanol, acetaldehyde, and acetic acid concentrations, as well as ADH and ALDH activities. Liver function (ALT, AST), oxidative stress markers (MDA, SOD, GPx), and inflammatory factors (TNF-α, IL-1β) were also evaluated. Results: HBF significantly (p < 0.05) accelerated ethanol clearance and enhanced serum ADH and ALDH activities at 0.5 and 1.5 h. Compared to the placebo group, HBF administration led to lower serum ethanol and MDA levels, elevated SOD activity, and reduced TNF-α and IL-1β concentrations, especially at 0.5 h and 3 h. ALT and AST levels were also decreased, indicating a hepatoprotective effect. Conclusion: The HBF formula effectively promotes alcohol metabolism and alleviates oxidative stress and inflammation associated with alcohol consumption, supporting its potential as a safe and effective anti-hangover intervention. Keywords: anti-hangover, alcohol, Pueraria lobata, Hovenia dulcis, Lactobacillus rhamnosus Alcoker0067, Lactobacillus plantarum ZQ15.
Apricot leaf: A new source of bioactive compounds – an overview
Background: Growing awareness of the health benefits of functional foods has fueled interest in products rich in bioactive compounds. Fruits and berries are well-established sources of phytochemicals such as polyphenols, terpenes, pectin, fiber, minerals, and vitamins. More recently, plant leaves have emerged as promising alternative reservoirs of these bioactive compounds. Several berry leaves are already included in the European Commission’s Novel Food Catalogue or are traditionally consumed in herbal teas. Within this context, the leaves of apricot (Prunus armeniaca L.) represent a valuable yet largely underexplored resource. Objectives: This review summarizes current knowledge on the biochemical composition, phytochemical diversity, and health-promoting effects of apricot leaves, highlighting their potential applications in functional foods and natural health products. Results: Apricot leaves contain abundant polyphenols, flavonoids, phenolic acids, tannins, essential oils, and vital macro- and microelements. Key phenolic compounds include chlorogenic acid, catechin, rutin, and naringin, while condensed tannins dominate the tannin fraction. ORAC, ABTS, FRAP, and chemiluminescent assays confirm strong free-radical-scavenging capacity. Quercetin-3-O-rutinoside, 5-O-caffeoylquinic acid, and 3-O-caffeoylquinic acid exhibit anti-obesity effects through pancreatic lipase and COX-1 inhibition. Essential oils rich in phytol show notable antioxidant and neuroprotective activity, including acetylcholinesterase inhibition. Apricot leaf extracts display hepatoprotective, antimicrobial (notably against Staphylococcus aureus and Salmonella typhimurium), and antifungal properties without cytotoxicity. Minerals such as potassium, calcium, magnesium, iron, and zinc further enhance their nutritional value. Conclusions: With their rich phytochemical and mineral profile, apricot leaves offer promising applications in herbal teas, oral care, skincare, and as natural flavoring agents. Their antioxidant, antimicrobial, and hepatoprotective effects support their potential as functional food ingredients and natural health-promoting products. Novelty: This is the first comprehensive review dedicated to the phytochemistry, pharmacological potential, and food-industry applications of apricot leaves. Keywords: apricot leaves, bioactive compounds, functional food, bioactive properties, applications in functional
Genetic Changes In Common Dandelion (Taraxacum officinale) Induced by High Concentrations of Heavy Metals in Soil
Background: Heavy metal contamination poses a significant environmental threat in developing regions such as the Syunik Province of Armenia, where agricultural lands coexist with metal mining operations. Heavy metals are genotoxic, therefore, the study of genetic changes in wild and cultivated edible plants here is essential for evaluating the safety of traditional plant-based foods (“zhengyal,” honey, herbal teas, etc.). Taraxacum officinale (dandelion) is notable for its use in traditional diets and the accumulation of micronutrients. Thus, it’s prospective for both environmental monitoring and functional food development. Context and purpose of this study: The relation between heavy metal contamination of environment and DNA polymorphisms of T. officinale from Syunik, Armenia was studied. Results: Significant genetic variation was observed among the samples, with the highest polymorphism (95.46%) in Artsvanik Village and the lowest (73.24%) in Ttujur District. Increased soil concentrations of Fe and Mn were correlated with greater DNA polymorphism, suggesting a higher mutation rate in contaminated areas. These results point to a direct relationship between heavy metal exposure and genome instability in dandelion plants. Conclusions: Significant genetic changes were observed in samples from all surveyed locations in Syunik. T. officinale is able to accumulate heavy metals and may be used in ecotoxicological and remediation research as bio-indicator. Also, it could be recommended for further research as potential source for bioactive supplements and functional foods elaboration with diuretic, antioxidant, anti-inflammatory, anti-aging, and immunomodulatory properties. Keywords: Taraxacum officinale, food safety, heavy metals, soil contamination, PCR, polymorphism
The effect of different growth conditions on the content of bioactive compounds and gross β-radioactivity of some wild edible plants in the Republic of Armenia
Background: Nowadays, people prefer using edible plants over synthetic drugs for the prevention and treatment of diseases. These plants are rich in bioactive compounds (BC), such as vitamins, carotenoids, proteins, carbohydrates, organic acids, flavonoids, tannins, and more. Humans have used them for thousands of years as both food and medicine. Through the rational use of edible plants, people aim to enhance the body’s immunity and prevent diseases. In this context, the need to obtain edible plants that are both rich in BC and radioecologically safe has become an urgent concern. Objective: To identify the optimal conditions for obtaining BC-rich radioecologically safe plant products, we studied the comparative characteristics of BC (protein, tannins, flavonoids) content and their gross β-radioactivity in several wild edible plants-WEP (sickleweed - Falcaria vulgaris Bernh., eryngium - Eryngium caucasicum Trautv., and rhubarb - Rheum rhabarbarum L.) under outdoor hydroponics and soil cultivation conditions. The research was conducted at the Institute of Hydroponics Problems (IHP) in the Ararat Valley; an area located within a 30 km radius of the Armenian Nuclear Power Plant (ANNP). Methods: Total protein content was assessed using the Kjeldahl method, and tannin content was determined using a titrimetric method, while the total flavonoid content was quantified using a spectrophotometric method. Gross β-radioactivity of samples was defined with radiochemical methods through the radiometer UMF-1500 with low background. Results: The cultivation method (hydroponics, soil) did not significantly affect the content of total flavonoids and tannins in sickleweed leaves. In hydroponics, the protein content in sickleweed increased by 1.3 times, while the flavonoid content in eryngium leaves and the tannin content were 1.2 times higher than those in soil-grown plants. The concentration of the nutrient solution (0.75N, 1.0N, 1.25N) significantly affected the flavonoid and tannin content in the petioles of rhubarb. The minimum flavonoid and tannin content in rhubarb petioles was recorded at 0.75N (0.2% and 2.1%, respectively), while the maximum content was observed at 1.25N (0.4% and 2.8%, respectively). Food plants, in order of gross β-radioactivity levels in hydroponics and soil, form the following descending order: sickleweed > eryngium > rhubarb. The gross β-radioactivity of plants varied between 780-910 Bq/kg in hydroponic systems, compared to 650-760 Bq/kg in soil. Novelty: This study is the first to integrate biochemical profiling of BC with radiological safety assessment in WEP (sickleweed, eryngium, and rhubarb) cultivated under hydroponic and soil conditions. It demonstrates that hydroponics not only enhances protein, flavonoid, and tannin yields but also ensures radio-ecological safety, confirming WEP as promising functional food ingredients and medicinal resources. Conclusion: In the raw materials of WEP, the content of certain BC in hydroponics exceeded that in soil. The raw materials of plants grown under different conditions are considered radio-ecologically safe because their gross β-radioactivity does not exceed the radio-ecological safety threshold set by the World Health Organization (< 1000 Bq/kg). Regardless of cultivation conditions, edible plants can be used as a functional food. Keywords: Falcaria vulgaris Bernh., Eryngium caucasicum Trautv., Rheum rhabarbarum L., protein, tannin, total flavonoids, radio-ecological safety.
Integrative effects of an oral supplement mixture containing melon, yeast extract, and licorice on skin pigmentation reduction: Insights from a zebrafish model and a randomized double-blind controlled pilot human trial
Introduction: Intrinsic aging (e.g., genetic and metabolic changes) and extrinsic factors (e.g., sun exposure and environmental pollution) contribute to skin pigmentation and aged facial appearance. Plant extracts, known for their antioxidant properties, may influence skin pigmentation both directly and indirectly through pigment metabolism in the liver, potentially mitigating the effects of aging. Objective: This study investigates the effects of a mixture of melon, yeast extract, and licorice (Mix) oral supplement on liver metabolism and skin pigmentation. Methods: A zebrafish model of chemical liver injury was established using acetaminophen (APAP). Liver and yolk sac areas were analyzed, and uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) activity and total bilirubin content were measured to assess the supplement’s protective effects. Additionally, a zebrafish pigmentation model was induced with menadione, and yolk sac pigmentation intensity was analyzed. A pilot randomized, double-blind, placebo-controlled clinical trial was conducted with 22 healthy female volunteers randomly assigned to either the experimental or placebo group. Participants consumed 700 mg of the mixture (Mix) daily for 8 weeks. Skin brightness (L*), yellowness (b*), individual typology angle (ITA°), and melanin index (MI) were measured using a skin colorimeter (CL 400), melanin meter (MX 18), and VISIA 7 at baseline, 4 weeks, and 8 weeks. Results: In the zebrafish liver injury model, the mixture group（Mix Group）showed a significant increase in liver surface area, a decrease in yolk sac area, increased UGT1A1 activity, and reduced total bilirubin levels compared to the model control group. In the zebrafish pigmentation model, yolk sac pigmentation intensity was lower in the mixture group（Mix Group）. The pilot human trial demonstrated that participants taking the mixture (Mix) experienced significant improvements in skin brightness (L*) and ITA°, along with reductions in skin yellowness (b*) and melanin index (MI) after 4 and 8 weeks. Conclusion: An oral supplement comprising bioactive compounds from melon, yeast extract, and licorice effectively reduce skin pigmentation and supports liver pigment metabolism. This formulation, with its demonstrated functional food properties, suggests potential as an anti-aging intervention. Keywords: Skin pigmentation; Liver; Oral supplements; Plant extracts; Antioxidants; Zebrafish