Search Results (494)

In this study, we combine experimental and computational approaches to elucidate a density functional theory (DFT)-derived mechanism for superoxide scavenging by resveratrol, piceatannol, and oxyresveratrol. Using rotating ring–disk electrode (RRDE) hydrodynamic voltammetry, the superoxide radicals are generated in situ, allowing direct measurement of antioxidant activity. Data show that the catechol-containing piceatannol is approximately four times more active than resveratrol, while resveratrol and oxyresveratrol exhibit similar efficiencies, indicating that the additional 2′-OH group in oxyresveratrol has minimal impact. Vitamin C (ascorbic acid) facilitates scavenging by acting as a proton donor for resveratrol, piceatannol, and 4′-OH oxyresveratrol, but it is unable to deprotonate the 2′OH group of oxyresveratrol. The experimental results suggest a superoxide dismutase (SOD)-like mechanism, obtained from energetically feasible DFT calculations, in which these stilbenes convert two superoxide anions into H₂O₂ and O₂, helped by vitamin C. Mechanistically, the first superoxide is reduced by abstracting a hydroxyl-group hydrogen atom, while the second undergoes oxidation via π–π interaction with the aromatic system, releasing O₂. Notably, resveratrol can be regenerated through a catalytic cycle involving vitamin C. These data underscore the SOD-mimicking properties of dietary polyphenols and suggest a need to reevaluate resveratrol’s clinical utility regardless of its low bioavailability. Full article

The gut microbiota and its metabolites, as components of the gut–bone axis, play a pivotal role in regulating skeletal homeostasis through the bidirectional communication network. In this systematic review, evidence was collected from mainstream databases following standardized inclusion/exclusion criteria for screening, to comprehensively retrieve and screen eligible studies from multiple mainstream databases according to standardized inclusion and exclusion criteria, and systematically summarize current research progress on plant-derived bioactive compounds targeting the gut–bone axis for skeletal health regulation. This review systematically explores the underlying mechanisms of the gut–bone axis and critically evaluates the regulatory effects and therapeutic potential of plant-derived bioactive compounds. Particular attention is given to targeted interventions involving prebiotics, probiotics, synbiotics, and plant-rich diets or functional foods. Among these interventions, synbiotics represent the most successful strategy and show the most prominent therapeutic possibilities in bone-related disorders. Different from single prebiotics (only nourish endogenous intestinal microbes), individual probiotics (easy to be degraded in gastrointestinal tract with poor colonization) and ordinary plant-rich diets (unfixed effective dosage and weak targeting property), synbiotics combine prebiotic carriers and viable probiotic strains to produce complementary advantages, which is the core reason for its outstanding therapeutic prospect against bone diseases. Synbiotics exert synergistic effects on gut microecology, mineral absorption, and immune regulation, leading to more robust and consistent improvements in bone health than single prebiotics, probiotics, or general plant-rich diets. They have been verified in preclinical and clinical studies to ameliorate osteoporosis and related skeletal diseases via the gut–bone axis. These strategies offer novel insights into the prevention and treatment of bone metabolic disorders, such as osteoporosis, by targeting the gut–bone axis with phytochemicals. Key outcomes of this review include that synbiotics, soy isoflavones, naringin, curcumin, and resveratrol effectively improve bone mineral density, restore gut microbiota balance, and inhibit pathological bone resorption via the gut–bone axis. Collectively, the above bioactive substances realize bone protection mainly by reshaping gut flora, elevating mineral uptake and suppressing excessive osteoclast activity. Representative cases include soy isoflavones mitigating estrogen-deficient bone loss in OVX models, naringin improving the trabecular microarchitecture, and probiotic BL-11 promoting longitudinal bone growth in children. Future directions will focus on clarifying dose–response relationships, developing standardized synbiotic formulations, constructing microbiome-guided precision diets, and conducting large-sample randomized controlled trials to translate plant-derived compounds into clinical therapies. Full article

Background/Objectives: This review aimed to provide an updated synthesis of the evidence on the effects(s) of grapes, blueberries, and their constituent bioactives on cardiovascular health. Cardiovascular disease remains one of the most prevalent non-communicable diseases globally. Methods: A systematic literature search was conducted using PubMed, Science Direct, and Semantic Scholar. Eligible publications were restricted to studies published since 2015 focusing on grapes, blueberries, and related bioactives. A total of 37 studies were included (17 meta-analyses/systematic reviews and 20 randomised controlled trials). Compositional data on polyphenols, anthocyanins, and stilbenes (including resveratrol) from a new hybrid variety of red-fleshed table grape were also discussed in context. Results: The evidence indicates that grape- and blueberry-derived bioactives, particularly polyphenols and resveratrol, produce modest but consistent improvements in cardiovascular risk markers, particularly endothelial function. Effects were more pronounced in higher-quality trials and in metabolically at-risk populations. Certain varieties, including red-fleshed table grapes (red berry grapes), may represent effective dietary sources of these bioactives. Conclusions: Cardiovascular disease remains a common public health challenge. Increasing attention is being given to dietary and lifestyle strategies for its prevention and management. Within this context, and alongside existing recommendations to increase fruit and vegetable intake, there is scope for more specific guidance emphasising the consumption of dark-pigmented grapes, berries, and red-fleshed table grapes abundant in bioactives such as polyphenols. Full article

Treating autosomal dominant polycystic kidney disease (ADPKD) has always been a challenge because the disease is too complex for single-target drugs, which are often held back by side effects. This narrative review explores a different strategy: using plant-derived polyphenols to target multiple disease pathways at the same time. Looking at research from 2005 to 2026, we break down how key compounds like resveratrol, curcumin, naringenin, quercetin, and epigallocatechin-3-gallate (EGCG) actually work. Preclinical studies show these molecules can slow down cyst growth by tackling inflammation, rapid cell division, and tissue scarring all at once, while also resetting the skewed energy metabolism of cystic cells. Some mechanisms are strikingly specific, such as naringenin’s direct interaction with polycystin-2 and quercetin’s ability to clear senescent cells. Yet, the real-world hurdle is poor absorption; a recent clinical trial with standard curcumin fell short simply because the compound could not reach the kidneys in high enough concentrations. Moving forward, the field needs to focus on testing these compounds in realistic animal models, designing smart nanoformulations to improve bioavailability, and exploring combinations that could safely complement current therapies like tolvaptan. Full article

Background: Synaptic plasticity in neurodegenerative disorders (NDs), cognitive impairment, and mental health conditions is regulated by brain-derived neurotrophic factor (BDNF). Even healthy individuals have different levels, which are affected by complex epigenetic, inflammatory, and metabolic regulation. BDNF expression changes are associated with both typical and abnormal aging, as well as mental health conditions. These changes affect brain areas that are crucial for memory, such as the hippocampus and the parahippocampal cortex. Neurotrophins (NTs), including nerve growth factor (NGF) and BDNF, are essential for neuronal differentiation via tropomyosin receptor kinase B (TrkB) and the p75 neurotrophin receptor (p75NTR). Dysregulated NTs signaling contributes to synaptic dysfunction and neuroinflammation. Objective: This systematic review synthesizes preclinical evidence of the potential of naturally derived compounds to modulate NTs for neuroprotection and their incorporation into novel foods. Methodology: A review of major databases found studies that examined the impact of dietary polyphenols and other bioactive substances on NT signaling oxidative stress, inflammation, and neuronal plasticity. Results: Compounds such as epigallocatechin gallate, resveratrol, curcumin, quercetin, and flavanols, can positively impact NTs, reducing reactive oxygen species/reactive nitrogen species, enhancing cell survival, and increasing the expression of trophic factors such as nuclear factor erythroid 2-related factor 2 (Nrf2), NGF, and vascular endothelial growth factor in neural stem cells. However, their bioavailability, optimal dosage, and dietary interactions require further research. Conclusions: The consumption of BDNF-promoting foods can potentially stimulate BDNF synthesis, support optimal neurotransmission, and fortify neural plasticity. Evidence supports a polyphenol-rich diet for preventing NDs and promoting brain health. Observational studies consistently support the protective effects of polyphenols on brain health through their impact on the gut–brain axis. Full article

Cancer is still one of the world’s major causes of morbidity and mortality; thus, safer and more efficient treatment approaches are required. The structural variety, multitargeted mechanisms, and generally good safety profiles of plant-derived polyphenols have made them attractive anticancer medicines. Flavonoids (like quercetin), stilbenes (like resveratrol), phenolic acids and curcuminoids (like curcumin) are major classes that have shown strong anticancer action against a variety of cancers, including prostate, colorectal and breast cancers. Through targets including PI3K/Akt, MAPK, NF-κB, and p53 signaling networks, these substances influence important molecular pathways involved in tumor initiation and development, including oxidative stress, inflammation, apoptosis, cell cycle control, angiogenesis and metastasis. The clinical translation of polyphenols is still constrained by poor bioavailability, fast metabolism, low aqueous solubility and inefficient pharmacokinetic characteristics, which lead to insufficient systemic exposure and therapeutic efficacy despite strong preclinical data. Their therapeutic applicability is further complicated by variations in absorption and possible dose-related restrictions. To overcome these limitations, the anticancer efficacy of polyphenols has been enhanced via delivery technologies like polymeric nanoparticles, lipid-based carriers, nanoemulsions and phytosome complexes, which have shown improved stability, increased bioavailability and targeted delivery to tumor tissues. This review provides a comprehensive and integrative analysis of plant-derived polyphenols by linking molecular mechanisms, pharmacokinetic limitations and emerging delivery strategies within a translational framework. By bridging these interconnected domains, this review highlights the potential of polyphenols as viable candidates in next-generation cancer therapeutics and underscores the need for well-designed clinical studies to facilitate their successful integration into oncology practice. Full article

Plant-derived bioactive compounds, such as polyphenols and saponins, possess significant pharmacological value. However, conventional extraction methods often suffer from low efficiency, poor bioavailability, and environmental burdens. Aspergillus-based biotransformation has emerged as a superior platform for overcoming these limitations due to their robust secretomes, versatile metabolic networks, and the GRAS (Generally Recognized as Safe) status of specific industrially relevant species (e.g., A. oryzae and A. niger). Existing literature frequently focuses on isolated compounds or general fungal processes. To fill this gap, this review systematically links specific Aspergillus enzymatic systems to an “enzymatic hydrolysis–transformation–synthesis” closed-loop framework, which is essential for industrial-scale valorization. In this review, we summarize recent advances in the biotransformation of phytochemicals by A. niger, A. oryzae, and A. nidulans. These fungi utilize specialized enzymes—including β-glucosidases, cellulases, and glycosidases—to enable precise hydrolysis, deglycosylation, and detoxification under mild conditions. We highlight representative transformations that demonstrate markedly enhanced bioactivity and solubility. Key examples include the conversion of polydatin to resveratrol (>90% yield) and ginsenoside Rb1 to ginsenoside compound K (94.4% conversion rate). Although industrial applications span the food, pharmaceutical, and cosmetic sectors, significant challenges persist in solid-state fermentation (SSF) scale-up, strain stability, target compound over-degradation, and downstream purification. Genetic engineering, process optimization and hybrid bioprocessing are highlighted as promising strategies to overcome these limitations and realize sustainable, high-value production of natural bioactive metabolites. Full article

Oxidative stress is a central pathogenic mechanism in acute and chronic respiratory diseases, including asthma, chronic obstructive pulmonary disease (COPD), acute lung injury (ALI), acute respiratory distress syndrome (ARDS), and pulmonary fibrosis. Excessive production of reactive oxygen and nitrogen species (ROS/RNS), combined with impaired antioxidant defenses, contributes to epithelial and endothelial injury, inflammation, mitochondrial dysfunction, airway remodeling, and progressive loss of lung function. Plant-derived polyphenols and polyphenol-rich herbal mixtures have emerged as promising candidates for respiratory protection due to their multimodal activity. They exert effects through direct antioxidant action, enhancement of glutathione-dependent and enzymatic defenses, activation of the Nrf2/HO-1 pathway, and suppression of NF-κB, MAPK, inflammasome, and profibrotic signaling. Experimental studies have demonstrated protective effects of compounds such as quercetin, resveratrol, rosmarinic acid, epigallocatechin gallate, and phenolic-rich extracts. However, clinical translation remains limited by poor bioavailability, variability of botanical preparations, lack of standardization, and insufficient high-quality human studies. This review summarizes key mechanisms of oxidative lung injury and critically evaluates the therapeutic potential and translational challenges of herbal polyphenolic mixtures in respiratory diseases. Full article

Background: Resveratrol is a plant-derived polyphenol with reported anti-inflammatory activity, and the MCP-1/CCL2 axis is a key mediator of monocyte recruitment and inflammatory tissue remodeling. Although individual preclinical studies have examined resveratrol effects on MCP-1/CCL2-related outcomes, the overall in vivo evidence has not been quantitatively synthesized. This systematic review and meta-analysis evaluated whether resveratrol treatment is associated with reduced MCP-1/CCL2-related inflammatory readouts in animal models. Methods: The protocol was registered in PROSPERO (CRD420261339126), and reporting followed the PRISMA 2020 statement. PubMed was searched from inception to 12 March 2026, with additional reference-list screening. Eligible studies were in vivo animal experiments comparing resveratrol-treated and control groups with extractable quantitative MCP-1/CCL2-related outcomes. Effect sizes were calculated as Hedges’ g with 95% confidence intervals and pooled using random-effects models fitted by restricted maximum likelihood. Subgroup, sensitivity, cumulative, influence, funnel-plot, dose meta-regression, and SYRCLE-based risk-of-bias analyses were conducted. Results: Twenty-seven studies contributing 29 analyzable datasets were included. The overall pooled effect was −3.74 (95% confidence interval, −4.50 to −2.98), indicating lower MCP-1/CCL2-related readouts in resveratrol-treated groups than in controls, with substantial heterogeneity (I2 = 78.9%). The negative association was driven mainly by rat and mouse datasets, whereas the piglet estimate was directionally opposite and the rabbit estimate came from a single dataset. Funnel-plot inspection suggested asymmetry, and dose meta-regression did not significantly explain between-study variation (slope = −0.17, p = 0.482). Leave-one-out and cumulative analyses indicated directional stability but did not resolve the underlying heterogeneity. Conclusions: These preclinical data indicate lower MCP-1/CCL2-related readouts after resveratrol treatment, but high heterogeneity, PubMed-only retrieval, and pharmacokinetic limitations limit direct clinical inference. Full article

Mushrooms have been used for centuries in traditional folk medicine for the treatment of various diseases and are valued for their health-promoting properties. This long-standing use has sparked growing scientific interest in mushrooms as a source of bioactive compounds. While mushrooms contain a wide range of biologically active substances, including terpenoids, alkaloids, and glycoproteins, this review focuses specifically on polysaccharides derived from mushroom and their potential anti-aging effects at the cellular level. The evidence presented here summarizes current knowledge based on both in vitro and in vivo studies. Additionally, this review highlights the emerging potential of mushroom-derived polysaccharides as natural carriers in advanced drug delivery systems. Although several studies have investigated the use of fungal polysaccharides in combination with therapeutic agents—such as bovine serum albumin, resveratrol, paclitaxel, and quercetin—the potential of combining fungal polysaccharides with senotherapeutics remains unexplored. To fully realize the potential of mushroom-derived polysaccharides in promoting everyday health, combating cellular aging and obtaining synergistic anti-ageing effect via using mushroom polysaccharides as carriers for senolytics, further research is needed. Full article

Cardiometabolic diseases are increasingly recognized as disorders of chronic low-grade systemic inflammation and gut barrier dysfunction that mutually reinforce one another. Each condition amplifies the other through progressive injury to the intestinal epithelium. Compromise of the mucus layer, altered tight junction dynamics, dysbiosis, and impaired epithelial restitution promote intestinal permeability and enable the translocation of lipopolysaccharide and other microbial products into the circulation, thereby inducing metabolic endotoxemia. This gut derived inflammatory signal activates Toll like receptor 4, nuclear factor kappa B, and inflammasome associated pathways, linking barrier dysfunction to insulin resistance, hepatic steatosis, adipose tissue inflammation, endothelial activation, and vascular injury. Here, we examine the gut barrier as an immunometabolic interface and synthesize current evidence connecting its disruption to endotoxin driven cardiometabolic pathology. We further evaluate selected natural bioactive compounds, including curcumin, resveratrol, quercetin, epigallocatechin gallate, berberine, anthocyanins, omega 3 polyunsaturated fatty acids, and dietary polysaccharides, as gut targeted interventions capable of reinforcing junctional integrity, restoring mucus and microbial homeostasis, lowering endotoxin burden, and attenuating inflammatory signaling. Finally, we highlight the principal translational barriers that currently limit clinical implementation, including pharmacokinetic variability, microbiota dependent biotransformation, source standardization, and the lack of robust, standardized biomarkers of barrier restoration and metabolic endotoxemia. Full article

Metabolic disorders such as obesity, type 2 diabetes, and lipid disorders are major health challenges worldwide. There is increasing interest in the role of food-derived antioxidants in the context of metabolic disorders due to their documented antioxidant activity. Antioxidants such as flavonoids and polyphenols neutralize reactive oxygen species and reduce oxidative stress, which can affect cell function and metabolic processes. Anthocyanins, curcumin, and resveratrol exhibit physiological and pharmacological properties such as antioxidant, anti-inflammatory, anti-cancer, anti-obesity, and anti-diabetic effects. The main aim of this systematic review is to comprehensively evaluate and synthesize the current scientific evidence on the role of anthocyanins, curcumin, and resveratrol in the prevention and management of metabolic disorders, with a focus on obesity, type 2 diabetes, and dyslipidemia. Databases such as PubMed and Embase were searched, and the final selection included 105 studies that met the inclusion criteria. The analyzed studies demonstrated that anthocyanin supplementation (up to 320 mg/day) was associated with reductions in inflammatory markers such as IL-6 and TNF-α, improvements in HDL cholesterol, and modest reductions in HbA1c (~0.3–0.5%). Curcumin supplementation was associated with decreases in body weight (up to 0.82 kg), BMI (up to 0.30 kg/m²), triglycerides, total cholesterol, and fasting glucose levels. Resveratrol showed mixed but potentially beneficial effects on insulin sensitivity, oxidative stress markers, and lipid metabolism, although the clinical outcomes remained inconsistent across studies. These findings suggest that the antioxidant effects of anthocyanins, curcumin, and resveratrol may be related to their ability to suppress oxidative stress and inflammatory processes, thereby contributing to improvements in glucose and lipid metabolism. The conclusions from this analysis may contribute to a better understanding of the role of antioxidants in the management of metabolic health and indicate directions for future research in this area. Full article

Grape pomace, the main solid by-product of winemaking, is a promising feedstock for the recovery of trans-resveratrol, a high-value stilbene of increasing interest for food, nutraceutical, and pharmaceutical applications. However, its efficient isolation remains challenging because of matrix complexity, the co-occurrence of structurally related stilbenes and polyphenols, and the chemical instability of trans-resveratrol. This review critically examines recent advances in the recovery of trans-resveratrol from grape pomace, while also incorporating relevant findings from other grapevine-derived matrices to distinguish matrix-specific recovery potential and to place grape pomace within the broader context of grapevine by-product valorization from extraction intensification and selective purification to analytical determination. Various extraction technologies, including ultrasound-, microwave-, and enzyme-assisted extraction, natural deep eutectic solvents, and subcritical water extraction, are assessed alongside conventional solvent extraction with emphasis on yield, selectivity, solvent compatibility, and process feasibility. Downstream separation methods such as liquid–liquid partitioning, solid-phase isolation, adsorbent resins, counter-current chromatography, molecularly imprinted polymers, and foam fractionation are compared in terms of selectivity, enrichment efficiency, solvent demand, and scale-up potential. Although significant progress has been achieved, major challenges remain regarding process integration, solvent sustainability, product stability, and industrial feasibility. Combining mild extraction with selective downstream purification is essential for producing stable, high-purity trans-resveratrol fractions suitable for future use in functional ingredients, natural preservation strategies, and other value-added applications within sustainable food systems. Full article

Plant-derived compounds exhibit well-documented osteogenic and anti-resorptive activities; however, their translation into consistent skeletal benefits remains limited. This review proposes a transformation-state-dependent framework in which the efficacy of plant-based interventions is interpreted through the exposure architectures they generate rather than solely through intrinsic molecular activity. By integrating plant matrix organization, gastrointestinal processing, microbial biotransformation, and formulation-driven pharmacokinetics with the temporal dynamics of bone remodeling, the review addresses a critical gap in the current literature, which largely evaluates phytochemicals independent of their delivery context. Across a continuum ranging from intact plant matrices to isolated compounds and advanced delivery systems, distinct pharmacokinetic regimes emerge, characterized by differences in release kinetics, metabolic transformation, systemic persistence, and target-site exposure. Representative interventions showing promising pharmacokinetic and skeletal findings include curcumin phytosome systems, resveratrol nanoformulations, icariin-loaded delivery platforms, and matrix-associated polyphenol systems capable of promoting sustained or metabolite-mediated exposure. Evidence indicates that sustained, metabolite-mediated exposure profiles are more compatible with the prolonged, cumulative nature of bone remodeling, whereas transient exposure often limits efficacy despite mechanistic activity. Formulation strategies, including phospholipid complexes, bioenhancers, and nano- or vesicle-based systems, can partially overcome these limitations by modulating exposure behavior. By reframing plant-based interventions as dynamic exposure systems, this framework provides a unifying basis for interpreting variability across studies and offers a rational foundation for designing strategies that align pharmacokinetic behavior with skeletal biology, thereby improving translational potential. Full article

Pterostilbene (Pts), a small molecule stilbenoid and a dimethyl analogue of the star molecule resveratrol, exerts significant blood–brain barrier protection on cerebral ischemia-reperfusion injury and has received extensive attention. This study performed structural optimizations on Pts to obtain a series of derivatives and investigated their anti-ischemic activities both in vitro and in vivo, aiming to identify candidates with high safety and improved efficacy compared with Pts. The ADMET method was used to predict the drug-likeness of a series of Pts derivatives, and in vitro MTT cell viability analysis was conducted on neuroblastoma cells (SH-SY5Y) and brain microvascular endothelial cells (BMECs) after oxygen-glucose deprivation/reperfusion (OGD/R) injury. On the basis of the cytotoxicity results, four derivatives (NO. 1, NO. 3, NO. 5, and NO. 7) were selected for subsequent in vitro and in vivo biological activities evaluation. These compounds exhibited significantly higher TI values (18.29–30.61) in OGD/R-injured hBMECs compared with Pts (7.63) and effectively suppressed apoptosis, promoted cell migration, and enhanced tube formation capacity. In vivo, NO. 3 (5 mg/kg, ip., 7 d) demonstrated superior efficacy compared to Pts in improving cerebral blood flow, reducing infarction volume, enhancing neurological function, and modulating serum biomarker levels in middle cerebral artery occlusion/reperfusion (MCAO/R) rats, whereas NO. 1 and NO. 7 showed comparable efficacy to Pts. The acute intraperitoneal toxicity of NO. 3 was conducted and showed that the LD₅₀ of NO. 3 was estimated to be more than 300 mg/kg. In this study, the rational design and comprehensive evaluation of Pts derivatives were reported. Compound NO. 3 demonstrated superior pharmacological efficacy to Pts both in vitro and in vivo, and it may be a promising therapeutic candidate for ischemic stroke intervention. Full article