Search Results (3,813)

Background: Epimedium is a natural herb with immunomodulatory potential, but its vaccine adjuvant properties remain poorly understood. Objective: The aim of this study was to elucidate the adjuvant effects of Epimedium and the underlying molecular mechanisms. Methods: Network pharmacology was used to identify bioactive compounds and targets of Epimedium from the TCMSP database, and immunomodulation-related targets from GeneCards and OMIM. PPI networks, KEGG/GO enrichment, molecular docking, and molecular dynamics (MD) simulations were performed. In vivo, female BALB/c mice were immunized with the Staphylococcus aureus (S. aureus) vaccine subunit HI antigen, either alone or with low- or high-dose icariin (ICA). Serum antibody responses (IgG, IgG1, IgG2a, IgG2b) were measured by ELISA. Survival against lethal S. aureus USA300 challenge was monitored. Results: Network pharmacology predicted 488 targets and 13 pathways. Core targets included IL6, TP53, EGFR, CTNNB1, HIF1A, HSP90AA1, JUN, MTOR, SRC, and AKT1. KEGG/GO analysis indicated involvement of T cell receptor and NOD-like receptor signaling pathways in inflammatory responses. Molecular docking and MD simulations confirmed stable ligand-target binding. Experimental validation showed that ICA significantly enhanced HI-specific antibody responses and induced a Th2-biased humoral immune response (IgG1/IgG2a ratio > 1), which is particularly relevant for vaccines targeting extracellular pathogens such as S. aureus. ICA also improved survival after lethal bacterial challenge. Conclusions: This study identifies potential bioactive compounds, core targets, and key pathways of Epimedium as a vaccine adjuvant. Experimentally, ICA, as a representative component, enhanced HI-specific antibody responses and conferred protection against lethal S. aureus challenge. Together, these findings offer a computational–experimental basis that may guide further mechanistic investigation. Full article

Sargassum filipendula is a widely distributed, edible brown alga that possesses a rich nutritional profile. Several studies have demonstrated that the components/extracts of S. filipendula (SFE) possess diverse pharmacological potential against both infectious and non-infectious diseases. These include antibacterial and antifungal properties, as well as antioxidant, anti-aging, anti-osteoporosis, antiviral, antiprotozoal, and immunomodulatory effects. Furthermore, SFE has shown significant anticancer activity across various malignant cell lines. The unique phytochemical profile of this species, characterized by the presence of sulfated polysaccharides (primarily fucoidan), carotenoids, phenols, glycolipids, and phlorotannins, serves as the foundation for these wide-ranging pharmacological activities. Studies have demonstrated that SFE can modulate key molecular targets, such as glycogen synthase kinase-3 beta, and activate the mitochondrial-dependent apoptosis pathway, providing a robust mechanistic basis for the observed pharmacological activities. Recent evaluations of nutritional parameters and techno-functional properties confirm the rich nutritional profile of S. filipendula, supporting its application in a diverse range of food products. Despite its diverse bioactive phytochemicals and broad efficacy against infectious and non-infectious diseases, research on S. filipendula remains largely restricted to in vitro preclinical studies. The lack of a comprehensive compilation of its pharmacological activities, phytochemical profiles, and molecular targets hinders its development as a therapeutic agent. This review aims to bridge this gap by compiling the existing knowledge, identifying research deficiencies, particularly the lack of in vivo data and safety assessments for high-dose therapeutic applications, while proposing suggestions for transitioning S. filipendula into a viable therapeutic or functional supplement. Full article

Kratom (Mitragyna speciosa) is a botanical candidate for pain management with potentially reduced opioid-related risks, partly through modulation of neuroimmune pathways involving Toll-Like Receptor 4 (TLR4). This study aimed to characterize the phytochemical profile of kratom ethanol extract and evaluate its effects on TLR4 signalling, neuroinflammatory cytokines, analgesic activity, withdrawal behaviours, and organ safety in morphine-dependent mice. Metabolite profiling was conducted using UHPLC–Q-Exactive Orbitrap HRMS, followed by molecular docking of major constituents to the TLR4 complex. In vivo assessments included flow cytometry and gene expression analyses of TLR4-mediated cytokines (NF-κB, IL-1β, IL-6), behavioural assays for antinociception, endurance, and withdrawal symptoms, and histopathological and biochemical evaluation of liver, kidney, and spleen tissues. More than 100 metabolites were identified, including mitragynine and flavonoids such as rutin and isoquercetin, which showed interactions with key TLR4 residues. Selected fractions suppressed pro-inflammatory cytokine expression, increased tail-pinch latency comparable to morphine, reduced withdrawal manifestations, and demonstrated nephroprotective and immunomodulatory effects, although mild reversible hepatic alterations were observed in specific fractions. Overall, kratom ethanol extract exhibited fraction-dependent analgesic and anti-neuroinflammatory activities associated with TLR4 modulation, supporting its potential as a botanical analgesic candidate while emphasizing the importance of safety optimization and standardized fraction development. Full article

Atopic dermatitis (AD) is a chronic inflammatory skin disease with a complex pathogenesis involving epidermal barrier dysfunction, microbiome dysbiosis, and immune dysregulation. Despite significant advances in therapy, including biologics and targeted treatments, their use may be limited by adverse effects, highlighting the need for safe adjunctive strategies. Polyphenols are naturally occurring bioactive compounds that are abundant in plant-based foods and are known for their anti-inflammatory, antioxidant, and immunomodulatory properties, making them promising candidates for supportive AD management. This review integrates current evidence on the effects of polyphenols on epidermal barrier lipids, microbiome interactions, and key inflammatory pathways, including NF-κB and JAK/STAT signaling. Additionally, the role of polyphenols in modulating dendritic cell and neutrophil activity, and reducing reactive oxygen species (ROS) production and neutrophil extracellular trap (NET) formation, as well as their potential involvement in mitophagy regulation, is discussed. Polyphenols support epidermal barrier integrity by modulating the expression of key structural proteins, including filaggrin, involucrin, and loricrin, leading to a reduction in transepidermal water loss (TEWL). Furthermore, they interact bidirectionally with the gut microbiome, acting as metabolic substrates for beneficial bacteria and promoting the growth of short-chain fatty acid (SCFA)-producing species such as Lactobacillus, Bifidobacterium, and Akkermansia, while simultaneously inhibiting pathogenic strains. These findings highlight the role of polyphenols in maintaining microbiome homeostasis and supporting epidermal barrier integrity. The review encompasses findings from clinical studies, animal models, and mechanistic investigations, while also addressing limitations related to polyphenol bioavailability. Overall, polyphenols may represent a valuable adjunctive approach in AD management; however, further well-designed clinical and mechanistic studies are required to confirm their therapeutic potential. Full article

Astaxanthin (ASX) is a xanthophyll carotenoid widely studied for its beneficial properties in humans, mainly related to its local or systemic antioxidant, cytoprotective and immunomodulatory effects. Particularly, ASX can donate electrons to neutralize reactive oxygen species (ROS), thereby mitigating oxidative stress, a key factor in the onset of several chronic and degenerative diseases. Thanks to these valuable properties, ASX has attracted considerable interest in the pharmaceutical, nutraceutical and cosmetic sectors. Despite its promising biological potential, the application of ASX is limited by several physicochemical factors. It is a highly lipophilic molecule, unstable when exposed to light, heat and oxygen, which leads to rapid degradation, and is characterized by low bioavailability. To overcome these limitations, various formulation strategies have been developed, particularly encapsulation-based approaches aimed at improving stability, solubility and therapeutic applications. This review provides an overview of the conventional and innovative dosage forms of ASX developed to enhance bioavailability and preserve the chemical and biological properties of this powerful antioxidant, by focusing on the different administration routes. Special attention is given to the advantages and limitations of the different formulation strategies and their implications for human health according to the different administration routes. Although oral administration remains the most explored route, further studies are needed to develop formulations suitable for alternative routes of administration. Full article

Background/Objectives: Oral cancer remains a major global health challenge, with persistent limitations in treatment efficacy and significant therapy-related morbidity. Probiotics, owing to their immunomodulatory, anti-inflammatory, and microbiota-regulating properties, have emerged as potential therapeutic and adjuvant agents. This scoping review aimed to systematically map and critically appraise preclinical and clinical evidence regarding the therapeutic and supportive effects of probiotics in oral cancer. Methods: A comprehensive literature search was conducted across PubMed, Scopus, Web of Science, and Google Scholar without temporal restrictions, including studies published up to February 2026. Eligible studies comprised in vitro, in vivo, and clinical investigations evaluating the effects of live or non-viable probiotic interventions on oral cancer biology and related clinical outcomes. Results: Twenty-one studies were included: 13 in vitro, 3 in vivo, and 6 clinical studies. Preclinical evidence indicates that strains such as Lactiplantibacillus plantarum, Lactobacillus acidophilus, and Lacticaseibacillus paracasei exert selective antiproliferative effects (up to 85% inhibition) via apoptosis induction, modulation of PTEN/MAPK and NF-κB signaling, and reduction in pro-inflammatory mediators. In vivo models demonstrated tumor growth suppression and improved survival without significant toxicity. Clinically, probiotics reduced treatment-induced oral mucositis, improved salivary function, and enhanced microbiota stability and patient-reported outcomes. However, evidence on direct oncological endpoints remains limited. Conclusions: Probiotics demonstrate biologically plausible, strain-specific antitumor and supportive effects, with the strongest evidence supporting their role as adjunctive agents, particularly in managing treatment-related complications. Further well-designed in vivo and clinical studies are required to define optimal strains, dosing strategies, and integration with standard oncologic treatments. Full article

Background: Surfactant Protein D (SP-D) is a critical immunomodulatory collectin maintaining alveolar homeostasis. Obstructive sleep apnea (OSA)-related intermittent hypoxia (IH) disrupts pulmonary surfactant integrity; however, severity-dependent SP-D dynamics remain incompletely characterized. This study explores SP-D as a potential indicator of IH-induced alveolar stress and evaluates whether Galectin-3 (Gal-3) inhibition modulates surfactant homeostasis. Methods: Forty adult male Sprague-Dawley rats (8 per group) were randomized to Control (normoxia), Moderate IH (MIH; 15–30 events/hour), Severe IH (SIH; 30–60 events/hour), MIH + Gal-3 inhibitor (Modified Citrus Pectin, 800 mg/kg/day), or SIH + Gal-3 inhibitor. IH exposure lasted 8 h/day for 10 days. Outcomes included circulating SP-D, Surfactant Protein B (SP-B), inflammatory markers, physiological parameters, and histopathological lung injury scores assessed via American Thoracic Society guidelines. Results: SP-D levels showed numerical reductions with increasing IH severity (Control: 1969.07 pg/mL [IQR: 262.15]; SIH: 1404.30 pg/mL [IQR: 351.88]), representing a 28.6% decrease. However, between-group variability resulted in non-significant omnibus testing (Kruskal–Wallis p = 0.187). Gal-3 inhibition elevated SP-D levels, particularly in severe IH (2133.95 pg/mL [IQR: 1240.70]), though high inter-individual variability was observed (CV = 58.1%). SP-B showed significant suppression under moderate IH (p = 0.019) with restoration by treatment. Exploratory correlation analysis revealed moderate positive associations between SP-D and heart rate (r = 0.587) and respiratory rate (r = 0.419) in severe IH, though these did not reach statistical significance (p = 0.126 and p = 0.301, respectively). Histologically, severe IH induced diffuse alveolar damage (total lung score: 19.67 ± 0.82). Gal-3 inhibition produced context-dependent effects: protective in severe IH but paradoxically exacerbating inflammation under moderate IH (29.20 ± 4.64 vs. 20.00 ± 4.34; p < 0.05). Gal-3 inhibition significantly attenuated cardiac injury (injury score: 0.00 ± 0.00 vs. 7.17 ± 0.75 in severe IH; p < 0.001, η² = 0.859). Conclusions: SP-D demonstrates severity-associated alterations consistent with alveolar epithelial stress during IH, though high variability limits definitive biomarker validation in this sample. Gal-3 inhibition modulates surfactant homeostasis and attenuates cardiopulmonary injury in a context-dependent manner. These findings support further investigation into SP-D as a component of multimodal severity stratification in OSA and highlight Gal-3 inhibition as a context-dependent anti-inflammatory strategy, pending validation in larger cohorts with tissue-level confirmation. Full article

Background/Objectives: The worldwide occurrence of ulcerative colitis (UC) is increasing, but existing treatments frequently suffer from limited effectiveness and notable side effects. walnut green husk polysaccharide (WGHP) has been shown to exhibit anti-inflammatory and immunomodulatory activities; however, its specific potential and mechanisms of action against colitis remain unclear. This study aimed to evaluate the effectiveness of purified WGHP on (dextran sulfate sodium) DSS-induced UC and elucidate the underlying mechanisms. Methods: WGHP-2-2, a primary acidic polysaccharide fraction, was extracted from crude WGHP and analyzed through chromatography and spectroscopy. The therapeutic efficacy of WGHP-2 was assessed using a murine model of DSS-induced UC. Assessments included disease severity (DAI, colon length, histopathology), inflammatory markers (tissue IL-6, TNF-α, IL-10), and intestinal barrier integrity (Claudin-5, Occludin, ZO-1). Results: WGHP-2-2 is an acidic polysaccharide with a molecular weight of 15.29 kDa. Its composition includes glucosamine, rhamnose, glucuronic acid, galacturonic acid, glucose, galactose, and arabinose, with respective molar ratios of 0.55, 8.48, 3.06, 65.99, 4.49, 10.86, and 6.57. Methylation and NMR analyses revealed a backbone mainly composed of →4)-α-D-GalpA-(1→ and →2)-α-D-Rhap-(1→ linkages, with side chains or terminal residues such as T-Rhap, T-Galp, T-Glcp, and T-Araf. In vivo, WGHP-2 significantly mitigated DSS-induced UC symptoms in a dose-dependent manner. Specifically, the high-dose group (123 mg/kg) markedly attenuated colon shortening and improved histological architecture, including the restoration of colonic crypts. WGHP-2 effectively reduced pro-inflammatory cytokines IL-6 and TNF-α in colon tissues, while increasing the anti-inflammatory cytokine IL-10. Conclusions: WGHP-2 mitigates DSS-induced UC by inhibiting pro-inflammatory cytokines (IL-6, TNF-α), increasing IL-10 levels, and improving intestinal barrier integrity through the upregulation of tight junction proteins. These results position WGHP-2 as a promising lead compound for developing functional foods for UC. Full article

Mogrosides, the primary bioactive compounds of Siraitia grosvenorii, are natural, non-caloric sweeteners with promising therapeutic potential for diabetes. They provide a dual advantage: delivering sweetness without impacting blood glucose levels, while simultaneously exerting beneficial antidiabetic effects. This review systematically synthesizes current knowledge on mogrosides, covering their extraction methods, metabolic pathways, and underlying antidiabetic mechanisms. We first detail key extraction techniques and examine their metabolic fate, which is primarily characterized by gut microbiota-mediated deglycosylation leading to the formation of mogrol. Subsequently, the antidiabetic efficacy of mogroside-rich extracts and pivotal monomeric derivatives is critically evaluated, with an emphasis on mechanistic insights such as AMP-activated protein kinase (AMPK) pathway activation, anti-inflammatory and antioxidant activities, immunomodulatory effects, and the regulation of gut microbiota. It is important to note that due to the limitation of clinical trial data, most of the evidence reviewed derives from in vitro studies or animal models. Finally, their emerging role as functional ingredients within the food industry was discussed. Collectively, this review aimed to establish a robust scientific foundation for the development of mogrosides as safe, plant-derived sweeteners endowed with enhanced health-promoting properties for the prevention and management of diabetes. Full article

Coffee is a very popular psychoactive beverage with a complex composition. Besides its stimulant effect due to caffeine, it contains several bioactive compounds with antioxidant properties and potent metabolic activity. Its clinical efficacy is fundamentally determined by the bioavailability and metabolic fate of its constituents. The bioactive components of coffee, such as polyphenols, melanoidins, phytosterols, biogenic amines, and carotenoids, have notable antioxidant, anti-inflammatory, and immunomodulatory effects. This review aims to present the main bioactive components of coffee, their biological effects, mechanisms of action, and the influence of preparation methods and individual variability on metabolic outcomes in common chronic diseases. The data are synthesized from clinical, prospective, and interventional studies to examine how processing variables and biological metabolism influence the health-promoting potential of coffee antioxidants. Brewing methods like hot filtration optimize the extraction of these antioxidants. Individual clinical outcomes are further modulated by genetic polymorphisms and gut microbiota variability, which influence the activation of the cellular Nrf2 antioxidant defense pathway. Full article

Microbiome-based therapies are reshaping the therapeutic landscape for ulcerative colitis (UC), offering new avenues for disease management beyond conventional immunomodulatory and biologic treatments. UC remains a chronic, relapsing condition with significant unmet clinical needs, as many patients fail to achieve sustained remission or experience adverse effects with current therapies. The gut microbiome has emerged as a central contributor to UC pathogenesis, influencing epithelial barrier integrity, immune homeostasis, and metabolic signaling. Interventions such as fecal microbiota transplantation (FMT) and defined microbial consortia have demonstrated proof-of-concept efficacy in early-phase clinical trials, each leveraging distinct mechanistic strategies. FMT, as a broad ecological intervention, restores microbial diversity and functional redundancy, potentially addressing multiple pathogenic mechanisms simultaneously. In contrast, defined consortia enable precise targeting of specific metabolic and immunological pathways, including short-chain fatty acid production, bile-acid remodeling, epithelial barrier reinforcement, immune modulation, and succinate degradation. Recent clinical evidence suggests that consortia with broader mechanistic coverage may achieve more consistent biological activity than narrowly focused designs. This review synthesizes mechanistic and clinical insights across broad and defined microbial consortia, integrates evidence from randomized controlled trials and early-phase LBP studies, and outlines a precision-medicine framework to guide therapy selection. We highlight the importance of aligning therapeutic mechanisms with patient-specific microbial, metabolic, and immune profiles, and discuss future directions including biomarker-guided stratification, hybrid consortia, and adaptive trial designs. Advancing both broad and defined approaches, while incorporating ecological principles, mechanistic understanding, and patient stratification, will be essential to realizing the full therapeutic potential of microbiome-based therapies in UC. Full article

The immune system plays a pivotal role in the maintenance of homeostasis and protection from pathogens. With increasing public interest in immune health, functional foods and herbal formulations are gaining attention as potential immunomodulators. Therefore, we aimed to investigate the combined immune-enhancing effects of HemoHIM (HIM) and Hwaljingigo (HGG) through combination treatment based on the recommended daily intake in RAW 264.7 macrophages. Cell viability, nitric oxide (NO) production, and cytokine (tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6) expression levels were assessed using the XTT, Griess, and enzyme-linked immunosorbent assay (ELISA), respectively. Immunoblotting was conducted to confirm changes in protein expression. Neither HIM nor HGG was cytotoxic at any of the tested concentrations. Both the single and combination treatments increased NO production and cytokine expression in a concentration-dependent manner. Furthermore, the combination of HIM (one sachet) and HGG (three sachets) resulted in the highest levels of NO and cytokine production. Bliss Independence analysis revealed synergistic interactions for IL-1β and IL-6, while NO and TNF-α showed additive effects. These findings suggest that the combination of HIM and HGG enhances immune responses by stimulating macrophage activity, thereby supporting the potential application of multi-herbal formulations as functional immunomodulatory agents. Full article

Sjögren’s disease (SjD) is a chronic autoimmune disorder characterized by progressive dysfunction of the exocrine glands, driven primarily by aberrant T- and B-cell activation. Current therapeutic strategies remain largely symptomatic and are frequently limited by off-target effects and long-term toxicity, underscoring an urgent need for safer, mechanism-based adjunctive approaches. In recent years, nutritional interventions and medicinal herbs have emerged as promising complementary strategies, owing to their capacity to modulate immune–metabolic pathways and restore immune homeostasis. Nutrients such as n-3 polyunsaturated fatty acids (PUFAs) and short-chain fatty acids (SCFAs) exert well-documented anti-inflammatory effects and influence immune cell differentiation via immunometabolic reprogramming. Concurrently, bioactive constituents derived from medicinal herbs offer multi-target regulation of inflammatory signaling and lymphocyte function. This review synthesizes current advances in the immunomodulatory roles of dietary components and edible herbs in the context of SjD, focusing on their mechanistic convergence on T-cell subsets, B-cell responses, and the gut–immune axis. By integrating traditional knowledge with contemporary immunological insights, this article aims to provide a conceptual framework for the rational integration of nutritional and herbal strategies into the clinical management of SjD. Full article

The utilization of immunomodulatory nanomaterials, i.e., leveraging their unique properties to enhance immune responses, represents a transformative approach for the treatment of various diseases. Recent advancements in nanotechnology have enabled the design of nanomaterials capable of delivering immunomodulatory agents in a targeted manner, such as cytokines, antibodies, and nucleic acids, to specific cells or tissues involved in immune regulation. These nanomaterials, including nanoparticles, liposomes, nanogels, nanoemulsions, dendrimers, MXenes and extracellular vesicles, have been increasingly tailored to modulate immune responses with precision and efficacy. This targeted approach not only enhances therapeutic outcomes but also reduces off-target effects, minimizing systemic toxicity. In this review, an overview of immunomodulatory nanomaterials and their biomedical applications are highlighted. Herein, we have discussed different types of nanomaterials and their design strategies, interactions with different immune system components (macrophages, dendritic cells (DCs), neutrophils, T lymphocytes (CD4⁺ helper T-cells, CD8⁺ cytotoxic T-cells, regulatory T-cells/Tregs, and memory T-cells), and B lymphocytes), and immunomodulation mechanisms. Furthermore, nanomaterial-based immunomodulation strategies to enhance cancer immunotherapy, wound healing, and bone regeneration and the treatment of infectious diseases, autoimmune diseases, and allergy and are discussed in detail. In addition to therapeutic applications, selected nanomaterial platforms demonstrate significant potential in pharmaceutical formulations by improving drug stability, controlled release, and bioavailability, as well as in cosmetology through skin-targeted delivery, anti-inflammatory activity, immune protection, and enhanced tissue regeneration. Finally, clinical trial updates, challenges and future prospects are outlined. Key findings indicate that lipid-based, polymeric, inorganic nanoparticles and dendrimers provide complementary advantages for immunomodulation, including efficient delivery, controlled release, multifunctionality, and precise immune targeting. Despite safety, regulatory, and scalability challenges, these systems show strong potential for advancing precision and personalized medicine. Taken together, these innovations hold great promise for personalized medicine approaches, wherein nanomaterials can be tailored to individual patient profiles for more effective and precise disease treatment and prevention strategies. This review focuses primarily on the mechanistic interactions between immunomodulatory nanomaterials and immune cells, including macrophages, dendritic cells, neutrophils, T lymphocytes, and B lymphocytes, rather than providing an exhaustive treatment of physicochemical optimization parameters such as particle size or surface modification chemistry, which fall outside the defined scope of this work. Full article

Graft-versus-host disease (GVHD) remains the most severe complications following allogeneic hematopoietic cell transplantation (allo-HCT). Mesenchymal stromal cells (MSCs) have shown therapeutic potential in GVHD due to their immunomodulatory properties. However, their clinical application is constrained by safety concerns, including ectopic engraftment, microvascular obstruction, rejected by host, and potential tumor-supportive effects. Increasing evidence suggests that MSC-derived exosomes (MSC-Exos), as cell-free mediators, retain many of the beneficial effects of MSCs while exhibiting improved safety and stability profiles. MSC-Exos carry diverse bioactive cargo, including nucleic acids, lipids, and proteins, and can modulate immune responses, promote tissue repair, and restore barrier integrity. In this review, we place particular emphasis on both immunoregulation and tissue barrier protection as dual mechanisms underlying MSC-Exos efficacy in GVHD. We further discuss emerging preclinical and clinical evidence, as well as key challenges in translation. Full article