Search Results (1,870)

Retinal diseases such as age-related macular degeneration (AMD) and diabetic retinopathy (DR) are major causes of visual impairment and are closely associated with oxidative stress, inflammation, vascular dysfunction, and metabolic imbalance. Increasing evidence suggests that gut microbiota also contributes to retinal homeostasis, supporting the emerging concept of the gut–eye axis. In this context, dietary anthocyanins—with blueberry anthocyanins serving as a primary representative model—have attracted attention as potential adjunctive nutritional modulators of ocular health. However, their biological effects are strongly influenced by their limited bioavailability and extensive gastrointestinal metabolism. The objective of this review is to analyze the gastrointestinal fate of dietary anthocyanins and to discuss how their absorption, enzymatic transformation, and microbial biotransformation may influence ocular protection through the gut–eye axis. The review summarizes current knowledge regarding anthocyanin stability in the oral cavity, stomach, small intestine, and colon, as well as the formation of circulating phenolic metabolites generated by the host and through microbial metabolism. In addition, the molecular mechanisms through which anthocyanins and their metabolites may support retinal health are examined, including antioxidant, anti-inflammatory, vasoprotective, and neuroprotective actions. Overall, dietary anthocyanins, illustrated through the rich profile of blueberries, represent promising adjunctive compounds for supporting ocular health, although further clinical and mechanistic studies are still required. Full article

Thai shallot (Allium cepa L. var. aggregatum) is rich in quercetin glycosides, which can be enzymatically hydrolyzed into aglycone forms with potentially higher bioavailability. However, whether this structural modification enhances metabolic efficacy in vivo remains unclear. This study aimed to compare the metabolic and histopathological effects of enzymatic (ESE) and non-enzymatic (NES) Thai shallot extracts in a high-fat diet (HFD)-induced obese mouse model. Male C57BL/6 mice were fed HFD for 12 weeks to induce obesity, followed by a 12-week treatment with NES or ESE (1000 and 2000 mg/kg/day). Metabolic parameters, lipid profiles, oxidative stress markers, hepatic enzyme activities, and histopathological changes were evaluated. Enzymatic hydrolysis significantly increased the proportion of quercetin aglycone without altering total quercetin content. Both NES and ESE improved fasting glucose, insulin resistance, lipid profiles, and oxidative stress markers compared with HFD controls. Histological examination showed attenuation of hepatic steatosis and preservation of tissue architecture in treated groups. However, no consistent superiority of ESE over NES was observed across metabolic or histopathological outcomes. Despite substantial modification of flavonoid composition, enzymatic processing did not enhance the measured metabolic efficacy of Thai shallot extract under the conditions tested. Because circulating quercetin and metabolite levels were not assessed, this finding should be interpreted as comparable metabolic efficacy rather than evidence of equivalent bioavailability. These findings suggest that factors beyond aglycone content may play a key role in determining biological activity, with implications for the development and cost-effectiveness of functional food products. Full article

Marine algae are emerging as important biological resources for the discovery and development of bioactive compounds with applications across food, pharmaceutical, cosmetic, agricultural, aquaculture, environmental, and biotechnological systems. This review critically synthesizes current knowledge on macroalgae and microalgae as sources of sulfated polysaccharides, carotenoids, phenolic compounds, proteins, peptides, vitamins, mycosporine-like amino acids, and polyunsaturated fatty acids. Emphasis is placed on the relationship between algal source, cultivation conditions, compound structure, extraction strategy, formulation, and biological activity. Key mechanisms of action are discussed, including antioxidant defense, modulation of inflammatory signaling, inhibition of metabolic enzymes, antimicrobial and antiviral activity, interactions with the gut microbiota, and regulation of cell-cycle-related pathways. Recent progress in biotechnological production, green extraction, purification, analytical characterization, bioaccessibility, bioavailability, and delivery systems is evaluated in the context of real product development. The review further highlights the use of algal bioactives in functional foods, nutraceuticals, pharmaceuticals, cosmeceuticals, aquafeeds, crop biostimulants, and environmental remediation. Current limitations, including biomass variability, compound instability, limited human validation, regulatory complexity, safety concerns, and scale-up costs, are also addressed. Overall, marine algae provide a sustainable and multifunctional platform for developing bioactive products when discovery, processing, validation, and commercialization are integrated. Full article

Theranostics is a novel approach that integrates diagnostic and therapeutic efficacy on a single platform, holding great promise for precision medicine by enabling real-time monitoring of disease progression and therapeutic response. Despite significant advances, the successful development and delivery of theranostic systems are critically limited by multiple biological barriers present at systemic, tissue, cellular, anatomical, and immunological levels. These barriers restrict bioavailability, target accessibility, and therapeutic efficacy, while often increasing off-target accumulation and adverse effects. This review provides a comprehensive overview of the major biological barriers encountered in theranostic development, including physiological barriers such as plasma protein binding, renal clearance, and hepatic metabolism; anatomical barriers like endothelial linings, the blood–brain barrier (BBB), and the tumor microenvironment; cellular barriers involving membrane permeability, intracellular trafficking, and endo-lysosomal entrapment; and immunological barriers such as immune recognition, inflammatory responses, and complement activation. Special emphasis is placed on the BBB, highlighting its structural complexity, transport mechanisms, and strategies such as molecular Trojan-horse technology, receptor-mediated and adsorptive-mediated transcytosis, and nanocarrier-based approaches to enhance central nervous system delivery. The review further discusses targeted delivery challenges, including receptor heterogeneity and multidrug resistance, and critically evaluates current strategies to overcome these barriers through surface functionalization, stimuli-responsive systems, biomimetic carriers, and controlled-release mechanisms. Finally, recent advances, clinical challenges, and future perspectives—including personalized theranostics, artificial intelligence—assisted design, and next-generation barrier-penetrating systems—are explored. Overall, this review aims to provide a structured understanding of biological barriers in theranostics and highlight innovative approaches to improve their translational potential. Full article

Background: Effective strategies for delivering neuroprotective agents to the brain remain a major challenge due to the poor solubility, rapid metabolism, and low bioavailability of promising molecules, such as 7,8-dihydroxyflavone (7,8-DHF). This small-molecule TrkB receptor agonist exhibits significant antioxidant, neuroprotective properties, and additional effects on metabolic regulation, but its therapeutic potential is limited by unfavorable pharmacokinetic characteristics. Nanotechnology-based delivery systems are increasingly explored to improve drug stability, enhance bioavailability, and facilitate direct nose-to-brain transport following intranasal administration. In this study, lipid nanoparticles encapsulating 7,8-DHF were developed using a fish-oil-based lipid core enriched with ω-3 polyunsaturated fatty acids (DHA and EPA) and naturally derived excipients, including soybean lecithin and ε-polylysine. Methods: The formulation was optimized using a Design of Experiments (DoE) approach based on a 2³ full factorial design, evaluating drug concentration, lecithin concentration, and surfactant type (Pluronic^® F127 or Tween^® 80). The main formulation responses considered were particle size, polydispersity index (PDI), zeta potential, and encapsulation efficiency. Results: The optimized nanoparticles exhibited nanometric dimensions (<250 nm); spherical morphology, confirmed by TEM; low polydispersity (PDI < 0.3); and adequate encapsulation efficiency. Stability studies in simulated biological fluids indicated good physicochemical stability for up to 48 h, while interaction studies with mucin suggested a good interaction within the mucus environment. ROS scavenging capacity was confirmed through the DPPH chemical assay, and in vitro experiments on olfactory ensheathing cells, selected as a biologically relevant model for their anatomical localization along the olfactory pathway, showed reduced cytotoxicity of the encapsulated drug compared with the free form. Conclusions: Collectively, these results support the potential application of the developed nanoformulation in the intranasal delivery of 7,8-DHF. Full article

Background: The oral microbiome has emerged as a potential contributor to cardiovascular physiology through its role in the enterosalivary nitrate–nitrite–nitric oxide pathway. Oral nitrate-reducing bacteria convert dietary nitrate into nitrite, which can subsequently be reduced to nitric oxide, a signaling molecule associated with vascular tone, endothelial function, platelet activity, and blood pressure regulation. Disruption of this pathway has been associated with reduced nitric oxide bioavailability and impaired vascular responses. Methods: This narrative review summarizes current evidence regarding the relationship between the oral microbiome, nitrate metabolism, and cardiovascular function. Relevant literature was identified through searches of PubMed/MEDLINE and Google Scholar up to May 2026. Evidence from mechanistic, observational, and interventional human studies was reviewed and synthesized thematically. Results: Available evidence suggests that oral nitrate-reducing bacteria may influence nitric oxide bioavailability and vascular function. Studies have reported associations between oral microbiome disruption and changes in blood pressure, endothelial responsiveness, plasma nitrite concentrations, and other surrogate cardiovascular markers. However, findings remain heterogeneous and are influenced by factors such as diet, oral hygiene practices, smoking status, medication use, oral health, and underlying cardiometabolic conditions. Most studies are limited by small sample sizes, short intervention durations, and reliance on surrogate outcomes rather than major cardiovascular events. Conclusions: The oral microbiome may influence cardiovascular health through its role in nitrate metabolism and nitric oxide bioavailability. However, current evidence is largely limited to surrogate vascular outcomes, while data on major cardiovascular events remain scarce. Further longitudinal and interventional studies are needed to clarify causality and evaluate microbiome-targeted interventions. Full article

Background/Objectives: In this study, we present an analysis of ayahuasca, a psychedelic preparation containing N,N-dimethyltryptamine (DMT) and β-carbolines, such as harmine (HRM), a reversible monoamine oxidase A (MAO-A) inhibitor that enables the oral bioavailability of DMT. CYP2D6 is a highly polymorphic enzyme associated with interindividual variability in drug exposure, but its influence on the pharmacokinetics of ayahuasca alkaloids remains poorly understood. Methods: Using physiologically based pharmacokinetic (PBPK) modeling, we simulated scenarios for poor (PM), normal (NM), and ultra-rapid (UM) metabolizers by adjusting CYP2D6 enzyme expression for each phenotype. Results: PMs showed increased systemic exposure to DMT (AUC +53.3%; Cmax +40.5%) and HRM (AUC +30.6%; Cmax +22.8%), while UMs exhibited reduced exposure to both compounds. Conclusions: These findings highlight the significant impact of CYP2D6 polymorphisms on the pharmacokinetics of DMT and HRM, reinforcing the value of PBPK modeling for predicting interindividual variability and potential clinical risks. Full article

Selenium (Se) is a beneficial element involved in plant growth, metabolism, stress adaptation, and crop quality improvement, but its effects are strongly influenced by chemical form, application dose, plant species, growth stage, and environmental conditions. To integrate mechanistic understanding with global research trends, this study combines a concise mini-review with a bibliometric analysis of Se research in plants from 2000 to 2025. The mini-review summarizes Se speciation and bioavailability in the soil–plant–microbe system, root uptake and long-distance transport, metabolic assimilation and detoxification, physiological regulation, stress tolerance, biofortification, and nano-Se applications. Bibliographic data were retrieved from the Web of Science Core Collection and analyzed using CiteSpace, VOSviewer, and Scimago Graphica. A total of 3451 valid publications were identified, showing a sustained increase in annual output, especially after 2018. The field has expanded from early studies on Se speciation, uptake, assimilation, and antioxidant responses toward broader themes involving crop biofortification, molecular regulation, stress physiology, foliar application, nano-Se applications, green synthesis, and phytoremediation. Overall, plant Se research has evolved into an interdisciplinary field linking mechanistic studies with safe agricultural application. Future work should emphasize standardized experimental frameworks, causal mechanism validation, precise biofortification, field-based evaluation, and safety assessment of emerging Se-based technologies. Full article

Anemia represents one of the most frequent systemic complications of inflammatory bowel disease (IBD), with a consistently higher prevalence reported in patients with Crohn’s disease (CD) compared with ulcerative colitis (UC). While chronic inflammation, impaired iron absorption, and intestinal blood loss are recognized contributors, microbiome-mediated mechanisms influencing host iron availability remain insufficiently explored. Emerging evidence indicates that CD-associated dysbiosis is characterized by an increased abundance of siderophore-producing bacteria, particularly members of the Enterobacteriaceae family. Because siderophores are high-affinity iron-chelating molecules capable of competing with host iron acquisition systems and partially escaping lipocalin-2-mediated sequestration, their expansion may contribute to reduced luminal iron bioavailability. In this systematic review, we analyzed comparative microbiome studies published between 2016 and 2026 that directly evaluated microbial differences between CD and UC. CD microbiota consistently demonstrated enrichment in siderophore-associated taxa relative to UC. Based on these findings, we propose that microbiome-driven iron competition may represent an additional mechanistic contributor to the increased prevalence and persistence of anemia observed in CD. Although direct in vivo quantification of siderophore activity in IBD remains limited, the convergence of ecological, functional, and strain-level microbiome evidence supports a biologically plausible interaction between microbial iron-scavenging strategies and host iron metabolism. Full article

Leishmaniasis is a neglected tropical disease caused by parasites of the genus Leishmania. Curcumin (CUR) is a polyphenol with several biological properties, including antimicrobial effects. However, its low bioavailability remains a challenge, and nanoencapsulation may represent a useful strategy to overcome this limitation. This study aimed to evaluate, in vitro, the antipromastigote activity of free CUR and the antiamastigote effect of CUR nanoparticles and their association with antimoniate, as well as to elucidate possible mechanisms of action. Free CUR directly inhibited promastigote proliferation, with an IC₅₀ of 25 µM at 24 h. CUR induced mitochondrial hyperpolarization, increased the production of reactive oxygen species (ROS) and nitric oxide (NO), and enhanced lipid peroxidation and the accumulation of lipid droplets in promastigotes. These alterations were associated with autophagic and apoptotic processes, morphological and ultrastructural changes, DNA fragmentation, and cell cycle arrest. Free CUR also reduced the viability of BALB/c peritoneal macrophages, and this effect was attenuated after nanoencapsulation. Free CUR, CUR nanoparticles, and their association with antimoniate (AM) reduced both the percentage of infected macrophages and the number of intracellular amastigotes at all tested concentrations, with increased NO production observed at the highest concentrations of free CUR. Altogether, our findings suggest that CUR exerts leishmanicidal activity against promastigotes by disrupting oxidative metabolism and triggering autophagic and apoptotic pathways, while amastigote elimination appears to occur through mechanisms independent of oxidative stress. Full article

Flavonoids are a structurally diverse class of plant-derived polyphenolic compounds widely recognized for their pleiotropic biological activities, including antioxidant, anti-inflammatory, and anticancer effects. In oncology, these compounds have demonstrated the ability to modulate key signaling pathways involved in cell proliferation, apoptosis, angiogenesis, and metastasis, highlighting their potential as multitarget therapeutic agents. However, their clinical translation remains significantly limited by unfavorable pharmacokinetic properties, such as poor aqueous solubility, extensive first-pass metabolism, rapid systemic clearance, and consequently low oral bioavailability. In this context, nanotechnology has emerged as a promising strategy to overcome these limitations. This review provides a comprehensive and critical analysis of current nanocarrier-based delivery systems for flavonoids, including polymeric nanoparticles, lipid-based nanocarriers (liposomes, solid lipid nanoparticles, and nanoemulsions), micelles, and cyclodextrin complexes, emphasizing their role in improving drug stability, enhancing cellular uptake, and enabling targeted delivery to tumor tissues through both passive mechanisms, such as the enhanced permeability and retention effect, and active targeting approaches. In addition, recent in vitro and in vivo studies demonstrating the superior antitumor efficacy of nanoencapsulated flavonoids compared to free compounds are discussed. Finally, the major translational challenges, safety considerations, and future perspectives for the clinical application of flavonoid-based nanomedicines in cancer therapy are highlighted. Full article

Background/Objectives: Neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) represent a growing public health concern. Both disorders are driven by mitochondrial dysfunction, oxidative stress, impaired autophagy, neuroinflammation, and neuronal loss. Single-target therapeutics have failed to halt disease progression, highlighting the need for multi-target interventions that address the complex and interconnected nature of neurodegeneration. Natural health products (NHPs) such as curcumin (CUR), coenzyme-Q10 (CoQ10), and Ashwagandha (ASH) possess antioxidant, anti-inflammatory, neuroprotective, and neurotrophic properties that may collectively address this complex pathology. However, poor bioavailability and hydrophobicity have limited clinical translations. Novel formulations, including nanomicellar Ubisol-Q10 (UQ) and water-solubilized ASH (PTS-ASH), have demonstrated enhanced metabolic uptake and neuroprotective efficacy in preclinical models. Moreover, co-administered NHPs, such as CUR + CoQ10 and CoQ10 + ASH, may provide further benefits by diversified targeting of disease pathways. Methods: This review presents an integrative interpretation of a combined UQ + ASH “tonic” in transgenic AD and paraquat-induced PD animal models using previously published qualitative immunohistochemical and functional results. This report constructs a proposed mechanistic model illustrating how these compounds may interact across multiple stages of disease AD and PD progression. Results: Based on comprehensive interpretation of the previous published reports, consistent trends suggest UQ stabilizes mitochondrial energetics and suppresses oxidative damage upstream, whereas ASH promotes downstream repair and synaptic modulation. Combined administration remained as providing balanced neuroprotective and functional outcomes. Conclusions: These interpretations of published reports and proposed mechanistic models aim to improve the translation and support the therapeutic potential of multi-component natural interventions for neurodegenerative diseases and highlight the importance of bioavailability-enhancing formulations in future preclinical and clinical research. Full article

This review examines the emerging role of machine learning (ML) in pharmaceutical chemistry, with emphasis on molecular design, synthetic feasibility, and structure–property–performance (SPP) relationships. By enabling pre-synthesis prediction of physicochemical properties, reaction pathways, and pharmaceutical performance, ML can reduce empirical trial-and-error experimentation and support more efficient exploration of chemical space. A structured narrative review design with PRISMA-aligned systematic search elements was used to evaluate 101 studies, enabling transparent literature identification, eligibility screening, and thematic synthesis across heterogeneous ML applications in pharmaceutical chemistry. This review examines structure–property relationships (SPRs) and property–performance relationships (PPRs), with emphasis on key pharmaceutical endpoints such as solubility, permeability, stability, dissolution, and bioavailability. An integrated SPP framework is proposed to connect molecular structure, intermediate properties, and final performance outcomes while incorporating retrosynthetic analysis and experimental feedback and closed-loop optimization. Recent frontier developments are also discussed, including molecular foundation models, multimodal language–graph models, diffusion-based molecular generation, E(3)-equivariant models, and MolMIM-like latent-space optimization. This review also covers co-folding and joint ligand–protein modeling, Boltz-2-like affinity prediction, AlphaFold 3-related biomolecular interaction modeling, and absorption, distribution, metabolism, excretion, and toxicity (ADMET) prediction. Key limitations include dataset leakage, benchmark inconsistency, assay variability, conformational and protonation-state effects, reproducibility challenges, regulatory constraints, and the gap between computational prediction and prospective experimental validation. Future progress is expected to depend on hybrid physics–ML models, uncertainty-aware prospective validation, autonomous experimentation, explainable artificial intelligence, and sustainability-aware molecular design. Overall, ML is evolving from a predictive tool into a chemically informed decision-support framework for rational, synthesis-aware, and experimentally validated pharmaceutical development. Full article

This study evaluated the structural, electronic, pharmacokinetic, and receptor-binding properties of three bisphosphonate derivatives, alendronate, risedronate, and zoledronate, to investigate their therapeutic relevance in osteoporosis and breast cancer. Density Functional Theory (DFT) calculations at the B3LYP/6-31G(d,p) level showed that risedronate exhibited the highest kinetic stability (ΔE = 6.7468 eV), whereas zoledronate displayed greater chemical reactivity (ΔE = 2.9669 eV) and the strongest nonlinear optical response (β = 1.20 × 10⁻³⁰ esu). ADMET analysis indicated acceptable safety profiles for all compounds, although high polarity and low lipophilicity may limit oral bioavailability. Molecular docking against 11 breast cancer- and bone metabolism-related targets revealed favorable binding affinities, particularly for zoledronate and risedronate. Zoledronate showed strong interactions with ESR2, VEGFR/KDR, GGPS1, and FPPS, whereas risedronate exhibited notable affinity for BRCA2 and MMP9. Bioinformatics analyses identified significant dysregulation of GGPS1, FDPS, TNFSF11, ESR1, MMP9, and BRCA2 in breast cancer tissues, while survival analysis linked elevated FDPS, MMP9, and BRCA2 expression to poor prognosis. Network analyses highlighted pathways related to mevalonate metabolism, hormone signaling, angiogenesis, extracellular matrix remodeling, and the RANK/RANKL/OPG axis. These findings support the potential repurposing of bisphosphonates, particularly zoledronate, for breast cancer-associated bone disease. Full article

Honokiol (HNK), a bioactive compound found in Magnolia species, is a promising, multifunctional agent with therapeutic effects on breast cancer (BrCa). Preclinical evidence, including in vitro and in vivo studies, suggests that HNK inhibits essential oncogenic pathways and reduces oxidative stress, inflammation, metabolic reprogramming, and cancer stemness. HNK demonstrates synergistic activity with chemotherapy, endocrine therapy, targeted therapy, and immune checkpoint inhibitors, increasing sensitivity to treatment across models of ER+, PR+, and HER2+ BrCas, as well as triple-negative breast cancers (TNBC). Nanotechnological delivery systems enhance the solubility, bioavailability, and intratumoral accumulation of HNK, increasing its translational capacity. Although clinical data remain very limited, current evidence in humans is insufficient to draw definitive conclusions regarding the safety and efficacy of HNK. This review summarizes mechanistic, preclinical, and emerging clinical data, highlights challenges in formulation and pharmacokinetics, and anticipates future trends in incorporating HNK into multimodal therapy for BrCa. Full article