2026-03-27
Yinan Yuan, Fuqiao Xu, Hanluo Li, Sini Kang, Yiming Wen, Heng Liu, Xiaoze Ren, Lan Yuan
Background : Aging is a complex biological process characterized by progressive cellular and molecular deterioration, including oxidative stress accumulation, telomere attrition, and cellular senescence. Active medicinal–food homologous complex nutrients (AMCN) are bioactive compounds derived from natural sources with potential anti-aging effects, but their mechanisms remain poorly understood. Objective: To investigate the anti-aging effects of AMCN and their underlying molecular mechanisms using a zebrafish aging model. Methods: Zebrafish were subjected to an aging model and treated with varying concentrations of AMCN. Aging biomarkers were assessed, including β-galactosidase activity, intracellular reactive oxygen species (ROS), telomerase protein concentration, and telomere length. Results: AMCN treatment significantly decreased β-galactosidase staining intensity as well as ROS levels in a dose-dependent manner. Telomerase protein concentration was elevated, and telomere length was partially restored, particularly at moderate and higher AMCN concentrations. Novelty of Study: This study demonstrates, for the first time in a whole-organism vertebrate model, that active medicinal–food homologous complex nutrients (AMCN) exert coordinated, multi-target anti-aging effects in a zebrafish model by reducing oxidative stress, attenuating cellular senescence, and preserving telomere integrity. By establishing a functional association between redox regulation and telomere maintenance, this study provides mechanistic evidence supporting the role of AMCN in modulating key processes involved in aging. The use of zebrafish as a translational vertebrate model enables in vivo evaluation of these effects and enhances the physiological relevance of AMCN, supporting their application in the development of nutraceuticals and functional foods aimed at mitigating age-related decline and maintaining physiological homeostasis. These findings highlight AMCN as a promising multi-component dietary intervention targeting interconnected hallmarks of aging. Conclusions: AMCN exerts protective effects against aging-related cellular dysfunction by reducing oxidative stress, suppressing senescence, and maintaining telomere stability. These results provide scientific support for the potential use of AMCN as a functional dietary intervention to promote healthy aging and prevent age-related functional decline. Keywords: A ctive medicinal–food homologous complex nutrients, functional food, zebrafish model, anti-aging, reactive oxygen species, telomerase, telomere, oxidative stress , cellular senescence
2026-02-28
Eriko Nakatani, Shimako Tanaka, Takayuki Yonezawa, Je Tae Woo, Shizuo Yamada, Takashi Okura
Background: Nobiletin, a polymethoxyflavonoid found in citrus fruits, exhibits neuroprotective potential in disorders of the central nervous system. However, the precise mechanism governing its passage across the blood-brain barrier (BBB) remains unclear. Objective: This study aimed to elucidate the mechanism of the brain transport of nobiletin by determining its passive transport ability, P-glycoprotein (P-gp) substrate recognition, and the effect of P-gp on its brain transport. Methods: The ability of nobiletin to traverse the BBB was assessed using an artificial lipid membrane (PAMPA-BBB) to determine passive diffusion parameters. Its interaction with P-gp was examined through ATPase activation assays and bidirectional transport studies in P-gp-overexpressing cell lines (LLC-GA5-COL300) compared with control cells (LLC-PK1). The in vivo distribution of nobiletin in mouse brain and plasma was further quantified following oral administration, with and without P-gp inhibition by elacridar. Results: Nobiletin exhibited high passive transport in artificial lipid membrane permeation assay. It increased ATPase activity in P-gp-overexpressing membranes. Significant increases in basolateral-to-apical transport were observed in P-gp-expressing cells, indicating that P-gp transports nobiletin as a substrate, similar to verapamil, but not as effectively as quinidine. When orally administered to mice, the plasma and brain concentrations of nobiletin increased simultaneously and peaked at 30 min, indicating rapid distribution between the blood and brain. The brain/plasma concentration ratio at 30 min was not significantly increased upon P-gp inhibition, indicating that P-gp does not affect the brain transport of nobiletin. Novelty: This study provides the first quantitative in vivo evidence that P-gp does not functionally restrict the brain distribution of nobiletin, establishing passive diffusion as the predominant BBB transport mechanism of nobiletin. Conclusions: These results demonstrate that nobiletin efficiently crosses the BBB primarily via passive diffusion, with minimal modulation by P-gp. These findings clarify its brain transport kinetics and reinforce its potential as a neuroprotective bioactive compound for dietary and pharmaceutical development. Keywords: Nobiletin; Blood–brain barrier; P-glycoprotein; Passive transport; Brain distribution.
2026-02-19
Anwar Jasib Almzaiel, Jihad Yaser Kshash
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
2026-02-12
Ahmed Khaleel Kafori, Mohamed Ali Triki
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.
2026-02-06
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
Introduction and objective: Heat-killed lactic acid bacteria with postbiotic effects have emerged as promising functional food ingredients for promoting intestinal health. Sakulora TM , 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 Sakulora TM 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 Sakulora TM (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 Sakulora TM 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: Sakulora TM 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
2026-01-16
Alaa ALkharabsheh, Zainab Farhan, Ban Abdul-Fatah, Aida Al-Hudairi, Mohamed Abouyounes, May Kader, Omar Fadhil
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.
2026-01-13
Yangwenshan Ou, Haotian Feng, Nan Li
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.
2026-01-10
david adeiza zakari, Egbeja Idris, Godwin Audu, Precious Idakwoji, Joseph Abraham-Oyiguh, Hassan Abdullahi, Godwin Aliyu, Onwuatuegwu Taiwo, Kadiri Adejoh, Nwobodo Afam, Ifeanyi Ezugwu, Onuh Ikwulono, Abiodun Olusegun, Yebafa Akpodoitei, Abdulbasit Aliyu, Adebimpe Adefila
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
2025-12-09
Ryo Sakiyama, Seiya Miyashita, Manabu Nakano, Miyuki Tanaka
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
2025-11-03
Yinan Yuan, Fuqiao Xu, Heng Liu, Xiaoze Ren, Lan Yuan
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.