Search Results (1,051)

Multiple sclerosis (MS) is a chronic autoimmune disorder of the central nervous system marked by inflammatory demyelination and progressive neurodegeneration. Although current immunomodulatory therapies can reduce relapse rates, they are often associated with limited long-term efficacy and adverse effects, highlighting the need for safer and more comprehensive complementary approaches. Dietary bioactive phytochemicals—notably, the polyphenols epigallocatechin-3-gallate (EGCG), curcumin, and resveratrol—have demonstrated potential to modulate the immune and inflammatory pathways implicated in MS pathogenesis. In addition to their immunomodulatory roles, emerging evidence suggests that these compounds also exert neuroprotective effects independent of immune modulation, including antioxidant activity, mitochondrial stabilization, and enhancement of neurotrophic signaling. Furthermore, recent studies identify the gut microbiota as a central mediator of MS pathophysiology and of how dietary phytochemicals are metabolized and exert their effects. This review examines experimental data evaluating the therapeutic potential of selected bioactive phytochemicals in MS, focusing on their mechanisms of action—including both immune-dependent and immune-independent neuroprotective effects—and interactions with the gut microbiota. Current limitations in translating findings from animal models to clinical settings are also discussed, and future directions for research in this evolving area are highlighted. Full article

Methicillin-resistant Staphylococcus aureus (MRSA), a major global public health threat due to its broad resistance, urgently requires the development of new antibiotic alternatives. (‒)‒Epigallocatechin-3-gallate (EGCG) is considered a natural bioactive compound with anti-MRSA properties. The L-Lectin module of serine-rich adhesin for platelets (SraP) is considered an important target for blocking MRSA-infected hosts. This study aims to investigate the mechanism of action of EGCG against MRSA. Surface plasmon resonance (SPR), cell adhesion and invasion, biofilm formation, checkerboard assays, RNA sequencing (RNA-seq) and quantitative real-time polymerase chain reaction (qRT-PCR) were performed. The results showed that EGCG bound to SraP L Lectin with high affinity and effectively inhibited MRSA colonization. Additionally, EGCG significantly suppressed pyrimidine metabolism and downregulated related genes, thereby potentially inhibiting bacterial growth. It also markedly reduced the expression of multiple genes associated with β-lactam resistance and inhibited biofilm formation. A strong synergistic effect was observed between EGCG and the bactericidal agent ceftriaxone (CRO). When combined with 10 μg/mL EGCG, CRO required 75% less dosage and exhibited a prolonged antimicrobial effect. In conclusion, EGCG exerts anti-MRSA effects through multiple pathways and represents a promising candidate as an alternative therapeutic agent against MRSA infections. Full article

Mixed dementia, most often caused by the coexistence of Alzheimer’s disease and vascular dementia pathologies, presents unique preventive and therapeutic challenges that may be addressed through dietary and nutraceutical interventions. Current evidence demonstrates that diets emphasizing polyphenol-rich foods like olive oil, berries, and leafy greens exert neuroprotective effects by reducing oxidative stress, inflammation, and amyloid pathology while improving cerebrovascular function. Specific bioactive compounds, including resveratrol, curcumin, quercetin, epigallocatechin gallate, N-acetylcysteine, and Huperzine A, among some others, have demonstrated therapeutic potential through their multimodal mechanisms targeting the pathogenic pathways of Alzheimer’s disease and vascular dementia, including Aβ and tau pathology, neuroinflammation, oxidative stress, and neurovascular dysfunction. However, our limited appreciation of the pharmacokinetics and pharmacodynamics of natural compounds and the inadequate extent of clinical studies underscore the need for further research. This review synthesizes current knowledge on diet and nutraceutical compounds that may be of value in the prevention and treatment of mixed Alzheimer’s disease and vascular dementia. We focus on their molecular mechanisms of action relevant to the dual pathophysiological basis of mixed Alzheimer’s disease and vascular dementia. Full article

Multifunctional hydrogels with an interpenetrated network structure have shown great potential for biomedical and tissue-regeneration applications. In this work, the biomedical hydrogel was fabricated with an interpenetrated network based on dopamine grafted gelatin (DA-Gel), and genipin crosslinked quaternary ammonium chitosan (QCS), incorporating epigallocatechin gallate (EGCG). The EDC/NHS and Schiff-base bond connections occurred in the hydrogels, as confirmed by Fourier-transform infrared (FT-IR) analysis. The properties of the fabricated hydrogels, including microstructure, degradation rate, adhesive strength, mechanical strength, and rheological behavior, can be regulated by adjusting the DA-Gel/QCS ratio or by using different crosslinking approaches. In addition, the fabricated hydrogels exhibited self-healing properties and strong adhesion to various materials and organs. Furthermore, the hydrogels performed good antibacterial activity against the typical bacteria, Escherichia coli and Staphylococcus aureus. EGCG encapsulated hydrogels displayed excellent antioxidant activities and good hemocompatibility. The hydrogels also demonstrated excellent cytocompatibility and good cell migration ability. The above results provide a facile approach to fabricate the biomedical hydrogels with a regulated network structure and multifunctional characteristics with potential in biomedical applications. Full article

Objective: Advanced glycation end-products (AGEs) contribute to oxidative stress and inflammation, leading to various disorders, including skin inflammation. Here, we investigated the anti-inflammatory effects of Aloe vera flower (AVF) extract and its active constituents, vitexin (V) and isovitexin (IV), in a glyoxal-derived AGE (GO-AGE)-induced skin inflammaging model. Methods: We evaluated the effects of AVF, V, and IV in epidermal keratinocytes (HaCaT cells) using enzyme-linked immunosorbent assay, Western blotting, quantitative real-time polymerase chain reaction, and in silico molecular docking. Results: Treatment of HaCaT cells with AVF, V, or IV significantly suppressed the secretion and expression of interleukins (IL-6 and IL-8) at both the mRNA and protein level, and reduced the expression of key inflammatory proteins, including kappa-light-chain-enhancer of activated B cells (NF-κB) and cyclooxygenase-2 (COX-2), and phosphorylation of mitogen-activated protein kinase (MAPK) pathway proteins. Notably, the inhibitory effects of V and IV on COX-2 expression were more comparable to or exceeded those of the positive control (Epigallocatechin gallate), even at a lower concentration. Conversely, the expression of sirtuin 1 (SIRT1) was upregulated by AVF, V, and IV, with IV showing 1.5-fold upregulation. Molecular docking analyses supported these findings, with IV displaying a particularly high binding affinity for COX-2 (−11.0 kcal/mol). Conclusions: These findings highlight the potential of AVF, V, and IV as novel therapeutic agents for managing skin inflammaging by modulating inflammatory pathways. Full article

Extracts from the stem bark of Stryphnodendron adstringens (barbatimão) exhibit relevant medicinal properties, such as anti-inflammatory, antioxidant, antimicrobial, and wound-healing activities, which reinforce their potential for developing herbal medicines. The $550 billion plant bioactive market (by 2030) demands safer, green-chemistry-aligned extraction methods for responsible industrial scaling. In this study, dry extracts obtained from the stem bark of S. adstringens were obtained by ultrasound-assisted maceration in one- and two-step extraction systems. Parameters such as yield, solvent evaporation time, cost, acute toxicity, epigallocatechin gallate (EGCG) concentration, cell viability, antioxidant potential, and anti-inflammatory activity were evaluated. High-EGCG two-step organic extracts were industrially difficult, needing more raw material and toxic solvents. In contrast, the single-step extracts showed a better balance between yield, cost, safety, and biological efficacy. All extracts showed cell viability above 70% at safe concentrations and significantly reduced the production of inflammatory cytokines. Thus, the results confirm that optimizing single-step extraction, with lower environmental impact solvents, enables producing safe and effective polyphenol-rich extracts, consolidating water as the main candidate for industrial-scale phytotherapeutic formulations of barbatimão, in line with its traditional use in infusions. Full article

Background: Aggregatibacter actinomycetemcomitans is a Gram-negative, facultative anaerobic, immobile oral bacterium responsible for the secretion of virulence factors, namely leukotoxin (LtxA), a large exotoxin of the RTX family that enables the bacterium to evade the immune system by destroying leukocytes, resulting in aggressive periodontitis (AP) leading to tooth loss. Methods: This study aimed to screen 106 molecules derived from Moroccan propolis in order to identify potential inhibitors of the active sites of LtxA based on molecular docking, ADMET property evaluation, and molecular dynamics (MD) simulation. Results: Epigallocatechin gallate (EGCg), used as a reference compound, showed binding energies of −6.9 kcal/mol, −6.1 kcal/mol, −6.5 kcal/mol, and −5.9 kcal/mol with the four active sites P1, P2, P3, and P4, respectively. By establishing conventional hydrogen bonds, pi-alkyl bonds, and non-covalent pi–pi bonds. Chrysin and luteolin showed favorable binding affinities with the four active sites, named as follows: P1–P4 (P1–chrysin = −7.5 kcal/mol; P2–chrysin = −7.9 kcal/mol; P3–chrysin = −8.1 kcal/mol; P4–chrysin = −6.9 kcal/mol; P1–luteolin = −7.3 kcal/mol; P2–luteolin = −7.6 kcal/mol; P3–luteolin = −8.1 kcal/mol; P4–luteolin = −7.3 kcal/mol). The binding affinity of these two propolis derivatives was stabilized by pi−sigma bonds, pi−alkyl bonds, conventional hydrogen bonds, pi-cation interactions, non-covalent pi–pi bonds, and carbon–hydrogen bonds. According to free energy calculations performed with Prime MM-GBSA, the complexes formed by chrysin demonstrated the most stable interactions due to Van der Waals and lipophilic forces. Luteolin formed significant interactions, but slightly weaker than those of chrysin. These results reveal the inhibitory potential of chrysin and luteolin with protein active sites. MD simulations corroborated the excellent stability of complexes formed by chrysin, as indicated by low RMSD values, suggesting favorable dynamic behavior. Conclusions: These results highlight the potential of chrysin as a versatile inhibitor capable of interacting with the four active sites. These findings are a strong foundation for further experimental confirmations. Full article

Alzheimer’s disease (AD) represents an increasingly severe global health challenge. Recently, the role of the gut–brain axis in AD pathogenesis has garnered significant attention. Dysbiosis of the gut microbiota can exacerbate core pathologies such as neuroinflammation, amyloid beta (Aβ) deposition, and tau hyperphosphorylation through neural, endocrine, and immune pathways. Polyphenolic compounds have emerged as a focal point in neuroprotective research owing to their pronounced anti-inflammatory and antioxidant properties. Notably, polyphenols exert effects not only by directly influencing the central nervous system (CNS) but also through indirectly modulating the composition and function of the gut microbiota, thereby impacting bidirectional gut–brain communication. This dual mechanism offers a potential avenue for their application in the prevention and treatment of AD. This review aims to compile recent research on the relationship between polyphenols and the gut microbiota. We assessed the literature from PubMed, Google Scholar, and Web of Science databases, published from the establishment of the database to 24 November 2025. The keywords used include “Polyphenols”, “Gut–brain axis”, “Gut microbiota”, “Alzheimer’s disease”, “Epigallocatechin gallate”, “Quercetin”, “Curcumin”, “Ferulic acid”, “Resveratrol”, “Anthocyanin”, “Myricetin”, “Chlorogenic acid”, etc. This review discusses the various mechanisms by which polyphenols influence AD through modulating the gut microbiota. Polyphenols and gut microbiota exhibit critical bidirectional interactions. On one hand, the bioavailability and activity of polyphenols are highly dependent on metabolic conversion by gut microbiota. On the other hand, polyphenols selectively promote the proliferation of beneficial bacteria such as bifidobacteria and lactobacilli like prebiotics, while inhibiting the growth of pathogenic bacteria. This reshapes the intestinal microecology, enhances barrier function, and regulates beneficial metabolites. Utilizing a nanotechnology-based drug delivery system, the pharmacokinetic stability and brain targeting efficacy of polyphenols can be significantly enhanced, providing innovative opportunities for the targeted prevention and management of AD. Full article

Background: Excess adiposity induces low-grade inflammation, including increased C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α). Green tea contains epigallocatechin gallate (EGCG), with anti-inflammatory potential. EGCG metabolism is influenced by individual variations in catechol-O-methyltransferase (COMT) genotypes. Objectives: To evaluate the effect of green tea extract (GTE) supplementation on circulating inflammatory cytokines among postmenopausal women with overweight or obesity and differing COMT genotypes. Methods: This study is a secondary analysis of a random subset (N = 97) from the Minnesota Green Tea Trial (MGTT), a randomized double-blinded placebo-controlled trial. The intervention was a high-dose GTE supplement (843 ± 44 mg EGCG/day) or placebo for 1 year. Serum CRP, TNF-α, and IL-6 were measured at 0, 6, and 12 months. Absolute changes in inflammatory cytokines from baseline to month 12 were evaluated using linear mixed-effects models adjusted for age, body mass index (BMI), smoking history, physical activity, and vitamin supplement use. Results: The changes from month 0 to month 12 were not statistically different between the groups for any of the inflammatory cytokines measured. The overall treatment effect was not statistically significant for CRP (p = 0.24), IL-6 (p = 0.59), TNF-α (p = 0.36), nor for the interaction between treatment group and time (all Ps > 0.40). There was no significant interaction between treatment group and COMT genotype for the stated markers. Conclusions: A high-dose GTE supplement consumed daily for one year did not significantly decrease inflammatory cytokines among postmenopausal women with overweight or obesity. The COMT genotype did not modify the effects of GTE supplementation on inflammatory cytokines. Future studies with a larger sample size among those at high risk of systemic inflammation are warranted. Full article

Epigallocatechin gallate (EGCG)—the most abundant catechin in green tea—is a promising component of advanced composite biomaterials. The pharmacological activity of EGCG is typically attenuated upon thermal processing, although the exact effects of heating free and modified EGCG in air and vacuum are unknown. To bridge this gap, we herein examined the effects of heating free and modified (in gelatin containing beta-tricalcium phosphate granules) EGCG in vacuum and air (100–220 °C, 1–16 h) on its physicochemical and antioxidant properties using water and ethanol solubility measurements, discoloration and antioxidant activity (2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid) assays, ultraviolet–visible spectroscopy, mass spectrometry, nuclear magnetic resonance spectroscopy, and attenuated total reflectance Fourier transform infrared spectroscopy. The antioxidant activity of EGCG-modified gelatin sponges was assessed in vitro using the DPPH assay and in vivo using a calvarial bone defect model in eight-week-old male Sprague–Dawley rats. Free and modified EGCG showed antioxidant activities, which were largely retained after heating in vacuum at 150 °C. These findings show that appropriate heating procedures preserve the antioxidant activity of EGCG and provide insights for the development of EGCG-based biomaterials. Full article

The worldwide burden of visual impairment is mostly attributed to ocular diseases, which include alterations of the retina, optic nerve, cornea, and ocular surface. Despite advances in medicine, the prevention and management of these conditions remain challenging, driving ongoing research into novel bioactive compounds. Among these, polyphenols—an assorted group of plant-derived compounds abundant in the human diet—have attracted significant attention due to their potential antioxidant, anti-inflammatory, and immunomodulatory properties. Increasing evidence suggests that polyphenols may help counteract oxidative stress and modulate pathways involved in ocular pathologies, assisting the conventional therapeutic strategies. This narrative review aims to analyze the current evidence about the potential therapeutic effects of the main polyphenols (e.g., curcumin, resveratrol, epigallocatechin gallate) currently recognized for the management of ocular diseases. Full article

The tea plant (Camellia sinensis) employs inducible chemical defenses against insect herbivores, yet the role of phenylalanine ammonia-lyase (PAL) in this process remains inadequately characterized. This study demonstrates that PAL is essential for tea plant’s direct resistance against the tea geometrid (Ectropis grisescens Warren). Inhibition of PAL activity using 2-Aminoindan-2-phosphonic acid significantly reduced catechins accumulation and promoted larval growth of E. grisescens. Compared to mechanical wounding alone, simulated herbivory feeding (mechanical wounding plus oral secretions) induced higher PAL activity and more pronounced upregulation of CsPAL genes. This response specifically highlighted CsPALb, CsPALd, and CsPALe as core, herbivore-responsive members. Transient silencing of CsPALb in tea leaves led to a significant reduction in the levels of catechin (-)-epigallocatechin and epigallocatechin gallate. Moreover, heterologous overexpression of CsPALb and CsPALd in tobacco (Nicotiana tabacum) enhances resistance to Spodoptera litura. Our results indicate that PAL-mediated phenylpropanoid metabolism is not only critical for herbivore resistance of tea plant, but can also provide valuable gene resources for improving herbivore resistance in other plants. Full article

Alzheimer’s disease (AD), the leading cause of dementia worldwide, is characterized by progressive neuronal loss, amyloid-β (Aβ) aggregation, tau hyperphosphorylation, oxidative stress, neuroinflammation, cholinergic dysfunction, and gut–brain axis dysregulation. Despite advances in anti-amyloid therapeutics, current interventions provide only modest symptomatic relief and face limitations in accessibility, cost, and long-term efficacy. Plant-derived bioactive compounds, rooted in traditional medicine systems such as Ayurveda and Traditional Chinese Medicine, have gained increasing attention as multi-target therapeutic agents due to their pleiotropic actions, relative safety, and ability to cross the blood–brain barrier. This review synthesizes mechanistic and translational evidence on major phytochemicals, including withanolides (Withania somnifera), curcumin (Curcuma longa), ginkgolides and bilobalide (Ginkgo biloba), bacosides (Bacopa monnieri), ginsenosides (Panax ginseng), crocin/safranal (Crocus sativus), epigallocatechin-3-gallate (Camellia sinensis), rosmarinic acid (Salvia officinalis, Melissa officinalis), and asiaticosides (Centella asiatica). These compounds exert neuroprotective effects by inhibiting Aβ aggregation, reducing tau phosphorylation, scavenging reactive oxygen species, attenuating NF-κB-mediated inflammation, modulating cholinergic signaling, enhancing synaptic plasticity via brain-derived neurotrophic factor/cAMP response element-binding protein (BDNF/CREB) activation, and regulating gut microbiota. Multi-target approach analyses underscore their synergistic potential in targeting interconnected AD pathways. However, translation remains hindered by poor oral bioavailability, rapid metabolism, and variability in clinical outcomes. Advances in delivery platforms, including liposomes, bilosomes, solid lipid nanoparticles, and nanostructured lipid carriers, are improving stability, blood–brain penetration, and therapeutic efficacy in preclinical models. Collectively, plant-derived phytochemicals serve as promising, affordable, and multi-modal candidates for reshaping AD management, bridging traditional knowledge with modern therapeutic innovation. Full article

Rheumatoid arthritis (RA) and osteoarthritis (OA) are significant global health challenges, fueling the need for innovative therapeutic strategies. Natural polyphenolic compounds, such as green tea catechins, exhibit promising anti-inflammatory, antioxidant, and immunomodulatory properties, making them potential adjuncts to rheumatic disease therapy. This review examines the effects of catechins, particularly epigallocatechin-3-gallate (EGCG), on key pathophysiological processes associated with RA and OA, such as pro-inflammatory cytokine production, oxidative stress, cartilage degradation, angiogenesis, and immune cell activation and proliferation. This study contains experimental data contained in full-text articles published in open-access indexed journals published only in English. The most important conclusions drawn from the in vitro and in vivo studies available so far, as well as studies on patients, show that green tea catechins modulate pro-inflammatory pathways, reduce the level of pro-inflammatory cytokines and improve the condition of the intercellular matrix in joint tissues, limiting the destruction of joint tissues in animals and patients and reducing pain. Although these studies suggest potential benefits, such as reduced inflammation and improved clinical parameters, the number and scale of studies are insufficient to confirm the clinical efficacy in a broad patient population. Therefore, claims of adjunctive therapy to conventional therapies should be interpreted with caution, and further well-designed and more powerful clinical trials are needed to verify the translation of the promising molecular mechanisms of green tea catechins into clinical practice. Full article

Melanoma, particularly the malignant type owing to its aggressive metastatic potential, is one of the most severe cancers. When detected early, the cure rate of melanoma is very promising and has a higher 5-year survival rate. However, it becomes very difficult to treat when it has spread to deeper layers of the skin and to other parts of the body. Despite the reduced mortality, the incidence of melanoma is on the rise due to exposure to various environmental factors, particularly UV radiation without protection. Naturally occurring dietary agents have been studied for their antitumor and chemopreventive potential against the development of various cancers including melanoma. The current review is aimed at compiling developments in the past ten years surrounding their preclinical and clinical relevance in the treatment and prevention of malignant melanoma. Various cellular pathways modulated by these phytochemicals are also examined to provide a comprehensive overview of their mechanisms involved in reducing tumor burden. Specifically, the review focuses on the most consumed foods across the world that are rich in such phytochemicals including curcumin, sulforaphane, resveratrol, quercetin and epigallocatechin gallate (EGCG) and their potential against the development of melanoma. Full article