Search Results (499)

Zearalenone (ZEN), a mycotoxin commonly found in cereal crops and foods, induces testicular damage and disrupts gut microbial composition. Curcumin (CUR), a bioactive compound derived from turmeric, is known to enhance intestinal microbial balance and exhibit anti-inflammatory properties. This study aimed to investigate the mechanism by which CUR alleviates ZEN-induced reductions in sperm quality through the modulation of the gut microbiota–testis axis. Forty-eight 6-week-old Balb/c male mice were randomly assigned to four treatment groups: control (CON), CUR (200 mg/kg body weight CUR), ZEN (40 mg/kg body weight ZEN), and ZEN + CUR (200 mg/kg CUR + 40 mg/kg ZEN). The degree of sperm damage was quantified by assessing both the survival rate and the morphological integrity of the spermatozoa. CUR was found to mitigate ZEN-induced reductions in the testosterone levels, testicular structural damage, and disrupted spermatogenesis. Exposure to ZEN markedly perturbed the gut microbiota, characterized by increased relative abundances of Prevotella and Bacteroides and a concomitant reduction in Lactobacillus. These alterations were accompanied by pronounced activation of the IL-17A–TNF-α signaling axis, as demonstrated by elevated transcriptional and translational expression of pathway-associated genes and proteins. Co-administration of CUR effectively reinstated microbial homeostasis and mitigated ZEN-induced IL-17A pathway activation. In conclusion, ZEN induces testicular inflammation and reduced sperm quality by lowering testosterone levels and disrupting gut microbial balance, which drives the testicular IL-17A signaling pathway. CUR alleviates ZEN-induced testicular inflammation and sperm quality reduction by restoring beneficial gut microbes and testosterone levels. Full article

Turmeric oleoresin (TO), a natural pigment derived from Curcuma longa rhizomes, is valued for its health benefits, which are primarily attributed to its rich curcuminoid content (curcumin, demethoxycurcumin, and bisdemethoxycurcumin). Despite these benefits, curcuminoids are known to be light-sensitive and possess photosensitizing properties. This study investigated the impact of common light sources, fluorescent light and white LED (both at 10 W/m²), on the chemical stability, antioxidant activity, cytotoxicity, and photosensitizing properties of TO. Exposure to both light sources significantly reduced TO’s color and fluorescence intensity, with white LED causing greater instability. HPLC analysis confirmed a decrease in individual curcuminoid levels, with curcumin degrading most rapidly under both conditions. The DPPH radical scavenging activity of irradiated TO decreased compared to fresh or dark-stored turmeric, whereas its ABTS radical scavenging activity increased upon light exposure. Photosensitizing potency, measured by formazan decolorization and lipid peroxide formation, declined as TO decomposed under light. Conversely, the cytotoxicity of TO against B16F10 melanoma cells was significantly enhanced under light exposure, though this effect was diminished significantly after 24 h of pre-irradiation. These findings underscore the instability of turmeric pigment under common lighting conditions, which should be a crucial consideration when processing, storing, and distributing turmeric-containing products. Full article

Curcumin is widely recognized for its various pharmacological properties, including antioxidant, anti-inflammatory, and anti-tumor activities. Nevertheless, the development of curcumin as a therapeutic agent is impeded by its limited oral bioavailability, which stems from its chemical instability, poor aqueous solubility, and rapid degradation. This study aimed to develop granule formulations incorporating poly(N-isopropylacrylamide)-grafted hyaluronic acid or HA-g-pNIPAM to enhance dissolution and protect curcumin from degradation. Three formulations were developed: F10 (HA-g-pNIPAM physically mixed with curcumin), F10 Encap (curcumin encapsulated within HA-g-pNIPAM), and F11 (curcumin granules without HA-g-pNIPAM). The stability results showed that F10 Encap effectively maintained curcumin content throughout the study period, retaining approximately 94% of its initial concentration by day 30, compared to 70% from F11 (p < 0.05) at 30 °C and 75% relative humidity. All dried curcumin granules exhibited excellent flowability, as determined by the angle of repose measurements. All three formulations exhibited a consistent particle size distribution across replicates, with a peak in the 150–180 μm size range. The sustained release observed for F10 Encap and F10 after the initial burst suggested that the HA-g-pNIPAM provided a controlled release mechanism, ensuring continuous curcumin dissolution over 240 min in gastric and intestinal conditions. These findings suggested that HA-g-pNIPAM improved dissolution and stability of curcumin. Full article

Background/Objectives: Curcumin is a promising therapy for glioblastoma but is limited by poor water solubility, rapid metabolism, and low blood–brain barrier penetration. This study aimed to evaluate curcumin and six curcumin derivatives with improved activity against a glioblastoma cell line and favorable absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties. Methods: Twenty-one curcumin derivatives were assessed and subjected to in vitro MTT cytotoxicity assays in SF268 glioblastoma and Vero cells. On the basis of the cytotoxicity results, six derivatives with the most favorable characteristics were selected for additional mechanistic studies, which included microtubule depolymerization, mitochondrial membrane potential (ΔΨm), and BAX activation assays. ADMET properties were determined in silico. Results: Compounds 2–4, 6, and 11 demonstrated better activity (IC₅₀: 0.59–3.97 µg/mL and SI: 3–20) than curcumin (IC₅₀: 6.3 µg/mL; SI: 2.5). Lead derivatives destabilized microtubules, induced ΔΨm collapse, and activated BAX. In silico ADMET prediction analysis revealed that compounds 4 and 6 were the most promising for oral administration from a biopharmaceutical and pharmacokinetic point of view. Conclusions: Strategic modifications were made to one or both hydroxyl groups of the aromatic rings of curcumin to increase its physicochemical stability and activity against glioblastoma cell line SF268. Compound 4, bearing fully protected aromatic domains, was identified as a prime candidate for in vivo validation and formulation development. Full article

Obesity is not only an aesthetic problem but also an important comorbidity in metabolic syndrome and other types of pathologies. Currently discussed adjuvants are turmeric and curcumin, used as food supplements. Starting from synthesis in turmeric plant up to the use of turmeric as a spice, a significant amount of turmeric and its derivatives are lost during the processing procedure. In oral administration, the reduced bioavailability of these compounds must be taken into account, an aspect that can be improved by using different combinations and dosages. As for their pharmacodynamic effects, through its antioxidant and anti-inflammatory properties, curcumin improves mitochondrial function and promotes the browning of white adipose tissue. Another mechanism of action of curcumin in weight loss is enzymatic modulation, leading to a decrease in the activity of key enzymes involved in lipogenesis and an increase in the activity of lipolytic enzymes. These properties are enhanced by the synergistic action of the other polyphenols present in turmeric, especially calebin A, p-coumaric acid, caffeic acid and ferulic acid. Summarizing these effects, curcumin is a promising food supplement, opening new directions for further research to discover possibilities to improve or even eliminate the calamity of obesity that is currently wreaking havoc. Full article

Microbial biofilms present a formidable challenge in ophthalmology. Their intrinsic resistance to antibiotics and evasion of host immune defenses significantly complicate treatments for ocular infections such as conjunctivitis, keratitis, blepharitis, and endophthalmitis. These infections are often caused by pathogens, including Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans, particularly in patients using contact lenses or intraocular implants—devices that serve as surfaces for biofilm formation. The global rise in antimicrobial resistance has intensified the search for alternative treatment modalities. In this regard, plant-derived antimicrobials have emerged as promising candidates demonstrating broad-spectrum antimicrobial and antibiofilm activity through different mechanisms from those of conventional antibiotics. These mechanisms include inhibiting quorum sensing, disrupting established biofilm matrices, and interfering with microbial adhesion and communication. However, the clinical translation of phytochemicals faces significant barriers, including variability in chemical composition due to environmental and genetic factors, difficulties in standardization and reproducibility, poor water solubility and ocular bioavailability, and a lack of robust clinical trials evaluating their efficacy and safety in ophthalmic settings. Furthermore, regulatory uncertainties and the absence of unified guidelines for approving plant-derived formulations further hinder their integration into evidence-based ophthalmic practice. This review synthesizes the current knowledge on the pathogenesis and treatment of biofilm-associated ocular infections, critically evaluating plant-based antimicrobials as emerging therapeutic agents. Notably, resveratrol, curcumin, abietic acid, and selected essential oils demonstrated notable antibiofilm activity against S. aureus, P. aeruginosa, and C. albicans. These findings support the potential of phytochemicals as adjunctive or alternative agents in managing biofilm-associated ocular infections. By highlighting both their therapeutic promise and translational limitations, this review contributes to the ongoing discourse on sustainable, innovative approaches to managing antibiotic-resistant ocular infections. Full article

The growing prevalence of bacterial infections and the alarming rise of antimicrobial resistance (AMR) have driven the need for innovative antimicrobial coatings for medical implants and biomaterials. However, implant surface properties, such as roughness, chemistry, and reactivity, critically influence biological interactions and must be engineered to ensure biocompatibility, corrosion resistance, and sustained antibacterial activity. This review evaluates three principal categories of antimicrobial agents utilized in surface functionalization: metal/metaloxide nanoparticles, antibiotics, and phytochemical compounds. Metal/metaloxide-based coatings, especially those incorporating silver (Ag), zinc oxide (ZnO), and copper oxide (CuO), offer broad-spectrum antimicrobial efficacy through mechanisms such as reactive oxygen species (ROS) generation and bacterial membrane disruption, with a reduced risk of resistance development. Antibiotic-based coatings enable localized drug delivery but often face limitations related to burst release, cytotoxicity, and diminishing effectiveness against multidrug-resistant (MDR) strains. In contrast, phytochemical-derived coatings—using bioactive plant compounds such as curcumin, eugenol, and quercetin—present a promising, biocompatible, and sustainable alternative. These agents not only exhibit antimicrobial properties but also provide anti-inflammatory, antioxidant, and osteogenic benefits, making them multifunctional tools for implant surface modification. The integration of these antimicrobial strategies aims to reduce bacterial adhesion, inhibit biofilm formation, and enhance tissue regeneration. By leveraging the synergistic effects of metal/metaloxide nanoparticles, antibiotics, and phytochemicals, next-generation implant coatings hold the potential to significantly improve infection control and clinical outcomes in implant-based therapies. Full article

Obesity and depression frequently coexist, sharing overlapping molecular pathways such as inflammation, oxidative stress, gut microbiota dysbiosis, and neuroendocrine dysfunction. Recent research highlights the therapeutic potential of plant-derived bioactive compounds in targeting these shared mechanisms. This scoping review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and included 261 peer-reviewed studies identified through PubMed, Scopus, and the Web of Science up to December 2024. Studies were screened based on predefined inclusion and exclusion criteria. This review synthesizes data from peer-reviewed studies, including both preclinical and clinical investigations, focusing on polyphenols, flavonoids, alkaloids, and other phytochemicals with anti-inflammatory, antioxidant, neuroprotective, and metabolic effects. Compounds such as quercetin, epigallocatechin gallate (EGCG), resveratrol, curcumin, anthocyanins, and luteolin demonstrate promise in modulating adenosine monophosphate-activated protein kinase (AMPK), brain-derived neurotrophic factor (BDNF), nuclear factor kappa B (NF-κB), and gut–brain axis pathways. Our scoping review, conducted in accordance with PRISMA guidelines, identifies promising combinations and mechanisms for integrative phytotherapy. These findings underscore the potential of botanical strategies in developing future interventions for metabolic and mood comorbidities. Full article

Young athletes face unique nutritional challenges due to their simultaneous engagement in intensive physical training and ongoing growth and development. Standard adult-based dietary recommendations often fail to meet the specific needs of this population. While the role of macronutrients and micronutrients is well recognized, increasing attention is being paid to bioactive compounds—non-essential food-derived elements with potential health benefits. This review aims to summarize current evidence regarding the efficacy, safety, and potential benefits of bioactive compounds in the nutritional management of young athletes. Methods: A narrative review of the literature published over the last 30 years was conducted across PubMed/Medline, Embase, and Scopus databases to identify relevant studies published in English. The inclusion criteria covered original research articles, clinical trials, cohort and case-control studies, and meta-analyses focusing on individuals aged 8–20 years. Studies addressing supplementation strategies, physiological effects, and safety concerns of bioactive compounds in young athletes were selected. Preclinical data and adult-based studies were also included to contextualize molecular mechanisms and support clinical findings. Results: The review highlights that bioactive compounds such as omega-3 fatty acids, curcumin, caffeine, and creatine as well as antioxidant vitamins may play a beneficial role in improving recovery, immune function, and performance in young athletes. Of these 21 studies, 8 focused on recovery and muscle soreness, 6 addressed immune function or antioxidant/anti-inflammatory effects, and 7 investigated direct performance enhancement. However, most of the available evidence derives from adult populations, and pediatric-specific data remain limited. Concerns remain about the misuse of supplements, lack of professional guidance, and potential contamination with banned substances. Conclusions: While some bioactive compounds show promising potential to support the health and performance of young athletes, current evidence is insufficient to support routine use in this population. More pediatric-specific research is necessary to establish safety, efficacy, and appropriate supplementation protocols tailored to young athletes’ unique physiological needs. Full article

DYRK1A kinase is a critical regulator in cellular signaling pathways and a promising therapeutic target for neurodegenerative diseases, diabetes and cancers. Despite its significance, the development of potent, selective and safe inhibitors remains a significant challenge. Several natural flavonoids have been reported to inhibit DYRK1A by binding in the ATP-binding pocket, exhibiting antidiabetic properties. However, a systematic screening of these structural derivatives remains lacking. In this study, we aimed to expand the pool of flavonoid-based DYRK1A inhibitor candidates for drug development against DYRK1A through targeted screening and structure-based analysis. A focused library of 13 flavonoid derivatives was screened to identify novel DYRK1A inhibitors, revealing eight new flavonol inhibitors with IC₅₀ values ranging from 149.5 nM to 737.9 nM. Among these, fisetin demonstrated the highest potency with an IC₅₀ of 149.5 nM, followed by kaempferol (296.3 nM), isorhamnetin (418 nM), morin (478.4 nM), myricetin (633.2 nM) and luteolin (797.8 nM), all exhibiting submicromolar inhibitory activity. Additional novel inhibitors, Apigenin and Kaempferide, also showed effective inhibition. As controls, the previously known inhibitors quercetin and curcumin were evaluated, yielding IC₅₀ values of 737.9 nM and 2.35 μM, respectively, which validated the assay conditions. To the best of our knowledge, fisetin is the most potent known DYRK1A inhibitor among flavonoids. Cellular assays further demonstrated that the top flavonoid hits induced dose-dependent cytotoxicity and morphological changes in HeLa cells. Structure-activity relationship and molecular simulation analysis revealed that the selected flavonols interact with key residues for DYRK1A inhibition. These results highlight flavonols as a promising scaffold for DYRK1A inhibition and provide valuable natural inhibitor leads for further optimization and therapeutic development. Full article

Plant-derived polyphenols have become a subject of scientific interest in recent decades due to their widespread occurrence in dietary sources and multi-faceted biological activity, with many of these compounds being recognized as antioxidants and anti-inflammatory agents. Several of these chemicals have, moreover, attracted further interest as their anti-tumoral capabilities were discovered, promising potential implementation in the treatment of proliferative diseases, including various cancers. Malignancies of the central nervous system, the most prevalent of which are glioblastomas, are noted for their aggressiveness, dismal prognosis and low survival rates. This review focuses on two polyphenols with the most expansive body of research on this topic, namely resveratrol and curcumin. It covers recent developments in the research, including in vitro findings, animal model studies and clinical trials on these compounds’ effects on the growth and progression of glial tumors of the central nervous system. Its aim is to present the latest findings on the subject of the mechanisms of action of these phytochemicals and their synergistic activity with conventional therapies, as well as strategies to improve their efficacy for future therapeutic applications. Full article

Background/Objectives: Drug resistance and severe side effects caused by gemcitabine (Gem) and cisplatin (CDDP) are common. This study aimed to investigate the combined effects of CU4c and Gem or CDDP on lung cancer cells in vitro and in nude mouse xenograft models. Methods: Antiproliferative activity and drug interaction were evaluated using MTT and Chou–Talalay methods, respectively. Apoptosis induction and cell cycle arrest were analyzed by flow cytometry. The expression levels of proteins were evaluated by Western blot analysis. The HDAC-inhibitory activity of CU4c was confirmed in vitro, in silico, and in A549 cells. Results: CU4c inhibited the proliferation of A549 cells in a dose- and time-dependent manner but had little effect on the growth of noncancerous Vero cells. CU4c synergistically enhanced the antiproliferative activities of CDDP (at 24 h) and Gem (at 48 and 72 h) against A549 cells. Combined CU4c and CDDP notably inhibited A549 proliferation by triggering cell cycle arrest at S and G2/M phases at 24 h with elevated levels of p21 and p53 proteins. Combined CU4c and Gem induced cell cycle arrest at both the S and G2/M phases at 48 h via upregulating the expression of the p21 protein. CU4c enhanced the apoptotic effects of CDDP and Gem by increasing the Bax/Bcl-2 ratio, pERK1/2, and Ac-H3 levels. Combined CU4c and Gem significantly reduced tumor growth while minimizing visceral organ damage in animal study. Conclusions: These results suggest that CU4c enhances the anticancer activity of CDDP and Gem and reduces the toxicity of Gem in animal studies. Full article

Background: Breast cancer (BC) is the most common cancer in women worldwide. Much progress has been made to improve treatment options for patients suffering from the disease, including a novel therapy—Poly (ADP-ribose) polymerase inhibitor (PARPi) that specifically targets tumors with deficiencies in the Homologous Recombination (HR) DNA repair pathway. To benefit better from conventional therapy, many patients seek alternative supplementation, with 20–30% of cancer patients using herbal medication on top of their regular treatment. An example of such easily available over-the-counter supplements is curcumin, a natural compound derived from turmeric (Curcuma longa). Various studies reported the potential HR deficiency (HRD) inducing effect of curcumin in cancer cells. Methods: Eight BrC and three normal cell lines and a BrC PDX model were used to evaluate the effect of curcumin on RAD51 ionizing radiation-induced focus (IRIF) formation. Three breast BrC cell lines underwent further analysis using the BRCA2 Western blot technique. To assess cell survival after treatment with curcumin and/or PARPi, a clonogenic survival assay was performed on both normal and cancerous cell lines. Results: Curcumin treatment led to a reduction in RAD51 IRIF formation capacity across all tested models. A decrease in BRCA2 levels was observed in the tested cell lines. Our findings demonstrate that HRD can be induced in both cancerous and normal cells, suggesting that curcumin treatment may increase the risk of toxicity when combined with PARPi therapy. Conclusions: The use of curcumin in combination with certain anti-cancer treatments should not be implemented without extensive monitoring for deleterious side effects. Full article

Oxidative stress is a common feature of various pathological conditions, including tissue remodeling and dysfunction. Cardiac fibroblasts, which play a key role in maintaining extracellular matrix homeostasis, are sensitive to oxidative injury. Curcumin and tetrahydrocurcumin are plant-derived polyphenols with antioxidant properties, yet their relative efficacy in preventing oxidative stress–induced dysfunction in cardiac fibroblasts remains unclear. In this study, cardiac fibroblasts were treated with curcumin or tetrahydrocurcumin prior to exposure to tert-butyl hydroperoxide (t-BHP), a widely used inducer of oxidative stress. Cell viability, apoptosis, reactive oxygen species (ROS) production, and Tgfb1 expression were assessed. Both curcuminoids significantly attenuated oxidative stress–induced cell death, decreased cell viability, and reduced Tgfb1 expression. Notably, tetrahydrocurcumin demonstrated superior protective effects across most parameters. These findings suggest that both compounds help mitigate oxidative-stress–induced cellular dysfunction in cardiac fibroblasts and highlight tetrahydrocurcumin as a potentially more effective antioxidant. Further studies are needed to explore their role in the context of tissue remodeling and fibrotic progression. Full article

Background: Curcumin, a bioactive polyphenol derived from turmeric, has demonstrated potential therapeutic effects in metabolic dysfunction-associated steatotic liver disease (MASLD) by modulating inflammation, oxidative stress, hepatic fat accumulation, and fibrosis. Objective: To evaluate the efficacy of curcumin in reducing hepatic steatosis and liver stiffness in patients with MASLD. Methods: In this randomized, double-blind, placebo-controlled trial, 78 patients with type 2 diabetes mellitus (T2DM) and MASLD were randomly assigned to receive either curcumin (1500 mg/day) or placebo for 12 months. The primary outcome was the change in tumor necrosis factor (TNF) levels. Secondary outcomes included changes in interleukin-1 beta (IL-1β), interleukin-6 (IL-6), antioxidant enzyme activities (glutathione peroxidase, superoxide dismutase), the oxidative stress marker malondialdehyde, non-esterified fatty acids, and hepatic parameters (hepatic steatosis and liver stiffness). Assessments were conducted at baseline and at 3, 6, 9, and 12 months. Results: All participants completed the study (curcumin group: n = 39; placebo group: n = 39). Curcumin significantly reduced TNF levels at all follow-up points compared to placebo (p < 0.001). IL-1β, IL-6, and malondialdehyde levels also declined significantly (p < 0.001), while antioxidant enzyme activities, including glutathione peroxidase and superoxide dismutase, increased significantly (p < 0.001), indicating improved oxidative balance. Furthermore, curcumin led to significant reductions in non-esterified fatty acids, total body fat, BMI, hepatic steatosis, and liver stiffness compared to placebo. Conclusions: Twelve months of curcumin supplementation improved glycemic control, reduced systemic inflammation and oxidative stress, and significantly improved hepatic steatosis and liver stiffness in patients with MASLD. These findings support curcumin as a promising adjunctive therapy for MASLD management. Full article