Search Results (444)

There is a rapidly rising demand for cosmeceutical solutions for skin lightening/brightening due to the growing need for dermatologic applications and consumers’ preference to enhance the brightness of skin. Traditionally, the main ingredients for developing dermatological products were the potentially harmful and controversial hydroquinone compounds; however, in recent years, the research field experienced a transition towards safer antioxidant-based agents. The present review analyzes the application and use of antioxidants in modern cosmetics as an innovative approach, and the chemical and biological mechanisms of their functions that could revolutionize the industrial applications. The most effective ones include competitive inhibition of tyrosinase enzyme, pheomelanin switch through the help of glutathione, protection from reactive oxygen species (ROS) in order to inhibit ultraviolet (UV)-stimulated production of melanin, as well as prevention of the migration of melanosomes using niacinamide. The review identifies and analyzes several components used as ingredients, such as vitamins C, Niacinamide, vitamin E, licorice root, epigallocatechin-3-gallate (EGCG), or resveratrol, among many more. In spite of their high efficiency, there are numerous problems associated with the instability, dermal irritation, and absorption of pure antioxidants. Finally, the legal framework developed by the Food and Drug Administration (FDA) and European Union (EU), potential risks like pro-oxidation damage, and future perspectives such as personalized skincare via machine learning and artificial intelligence (AI) are discussed. Full article

Simple phenolic compounds can act as antioxidants or prooxidants depending on their structure and environmental conditions. Glutamate-induced excitotoxicity leads to neurodegeneration, astrocyte dysfunction, oxidative stress, and neuroinflammation. This study examined six phenolics: catechol, phloroglucinol, resorcinol, pyrogallol, hydroquinone, and hydroxyquinol, assessing their effects on astrocyte survival in a glutamate-excitotoxic model. Mouse astrocytes (C8-D1A) were exposed to 20 mM glutamate, with phenolics added before, during, or after treatment. Cell viability, morphology, nuclear condensation, ROS levels, and inflammatory cytokines were measured using the MTT assay, microscopy, CellROX, and RT-qPCR. Simultaneously, treatment improved astrocyte survival and preserved morphology, whereas pre- or post-treatment did not confer protection and worsened toxicity at higher doses. Resorcinol showed the strongest protective effect, followed by hydroxyquinol and hydroquinone at lower doses. Resorcinol and hydroxyquinol decreased ROS levels, whereas pyrogallol and hydroquinone increased cell survival without reducing ROS. All four lowered IL-6 and TNF-α. These findings demonstrate that the effects of phenolics, whether protective or toxic, depend on concentration, structure, and timing, underscoring their dual role in excitotoxic environments. They also identify resorcinol as a promising candidate for further preclinical study. Full article

In this paper we validate Group Contribution (GC) parameters for substituted phenols and dihydroxybenzenes including catechol, resorcinol and hydroquinone with respect to a recently developed Group Contribution method for estimating the heat of formation of organic compounds with chemical accuracy (1 kcal/mol). For the compounds studied, we found differences greater than this threshold between experimental data from different publications. Using quantum mechanical methods in conjunction with common knowledge from physical organic chemistry, we were able to validate the GC model values and thereby extend the applicability range of the previously developed model. It could be concluded that most GC-predicted values can be considered trustworthy, assuming the B3LYP correction for steric interaction between ortho t-butyl and hydroxyl groups is included. As with earlier studies, we found that G4 quantum-calculated values can serve as a reliable source of gas-phase heats of formation of organic compounds. Full article

Airborne fine particulate matter (PM_2.5) has been extensively identified as a major contributor to adverse health outcomes, including respiratory illnesses, cardiovascular diseases, and premature mortality. PM_2.5 poses an even greater threat due to the presence of environmentally persistent free radicals (EPFRs). It is, thus, important to study human exposure to EPFRs. Dust samples from residential areas in Al Ain, UAE, were tested, and free radicals were detected and quantified. ESR measurements showed distinct signals with g-factors around 2.004–2.006, typically associated with oxygen-centered EPFRs. Spin concentrations were quantified at approximately 2.64 × 10¹⁶ spins/g in Dust Sample 1 (DS1) and 2.36 × 10¹⁷ spins/g in Dust Sample 2 (DS2), values comparable to those reported in other regions. DS1 and DS2 were collected from two different locations in inhabited areas of the city of Al Ain. Fourier Transform InfraRed (FTIR) spectra revealed possible functional groups such as catechols and hydroquinones, while X-ray diffraction (XRD) confirmed mineral oxides that could stabilize these radicals. However, the spectra also displayed features consistent with the six-line hyperfine splitting of Mn. These findings confirm the presence of environmentally relevant paramagnetic species in dust, which have implications for human health. Full article

Anthracyclines such as doxorubicin (DOX) remain central components of breast cancer (BC) chemotherapy, although their efficacy is frequently limited by drug resistance. Myoglobin (MB), an oxygen-binding heme protein expressed in breast tumors, has been implicated in the detoxification of DOX in cardiomyocytes, but its role in BC remains unclear. Using MB-expressing and MB-knockout (MBKO) MDA-MB-468 BC cells, we demonstrate that MB confers hypoxia-dependent resistance to DOX. Under hypoxia, MB-expressing cells exhibited reduced intracellular DOX-associated fluorescence, enhanced superoxide generation, and decreased sensitivity to DOX, findings consistent with altered redox cycling and oxidative processing of the drug. Re-expression of MB in MBKO cells restored resistance, whereas pharmacological modulation of MB function using carbon monoxide-releasing molecule-3 and tert-butoxycarbonyl-alanine reversed MB-dependent reductions in intracellular DOX accumulation. In contrast, aclarubicin, an anthracycline lacking the hydroquinone moiety required for efficient redox cycling, failed to reproduce MB-dependent effects. Analyses of four independent neoadjuvant BC cohorts further demonstrated that elevated MB expression was consistently associated with reduced probability of achieving pathological complete response following anthracycline-containing chemotherapy. Collectively, these findings identify MB as a previously unrecognized modulator of BC response to redox-active anthracyclines and support its potential utility as both a predictive biomarker and therapeutic target. Full article

Polyphenols often oscillate between antioxidant and pro-oxidant behaviours depending on structural motifs and context, yet the field still relies heavily on test-tube antioxidant assays that poorly predict cellular and clinical outcomes. This review (2015-2025) integrates chemistry, enzymology, and human data to frame polyphenols as modulators of redox signalling rather than mere radical scavengers. We first formalize the catechol/o-quinone-hydroquinone/p-quinone cycle and the role of NQO1 and Keap1/NRF2 thresholds. We then examine bioavailability, conjugation, and microbiota-derived metabolites (metabotypes), highlighting when the “active” species is a conjugate or a microbial derivative. We discuss safety through quinone speciation and adduct chemistry, and connect food processing (e.g., PPO-driven browning) with shifts in quinone pools. Contextual “levers” (pH, O₂, Fe/Cu, oxidases) can flip antioxidant to pro-oxidant outputs, sometimes beneficial via hormesis and redox preconditioning. In humans, randomised trials and prospective cohorts point in a broadly consistent direction, although primary composite endpoints have often proved null, and observational associations should not be read as equivalent to trial evidence. Heterogeneous results across studies are largely explained by dose, adherence, metabotypes, matrix, and endpoint selection. We propose a practical dose-response framework and a reporting checklist to improve interpretation and translation. Recasting polyphenols as tuneable redox-signalling agents clarifies apparent contradictions across models and suggests precision-nutrition strategies (metabotype-aware) and food design approaches (PPO and quinone speciation) with potential in healthy ageing, muscle, and brain. Full article

Plerixafor is a clinically approved CXCR4 antagonist that mobilizes hematopoietic stem cells by disrupting CXCL12/CXCR4 retention signaling. However, its biochemical effects on melanocytes and pigmentation remain unexplored. We investigated how Plerixafor modulates CXCR4 signaling in melanocytes and evaluated its potential as a pro-melanogenic agent using in vitro and in vivo approaches. Human PIG1 melanocytes were treated with 10 nM Plerixafor with or without hydroquinone (HQ), followed by qPCR for MITF and tyrosinase expression, flow cytometry for CXCR4/CXCR7 and integrin profiling, transwell migration assays, β-arrestin siRNA knockdown, Western blotting, subcellular fractionation, and ChIP-qPCR for β-catenin binding to MITF regulatory regions. A murine HQ-induced depigmentation model was used to test topical Plerixafor on pigmentation, hair follicles, melanogenic gene expression, and systemic safety markers. Plerixafor significantly increased MITF and tyrosinase mRNA and enhanced melanocyte migration while counteracting HQ-induced suppression of melanogenic genes. In addition, it reduced cell-surface CXCR4 (consistent with β-arrestin-mediated receptor internalization) without altering CXCR7, c-KIT, or N-cadherin. β-Arrestin knockdown abolished Plerixafor-induced ERK phosphorylation and melanogenic responses, confirming β-arrestin dependence. Plerixafor promoted β-catenin nuclear translocation and direct β-catenin occupancy at MITF promoter/enhancer TCF/LEF motifs. In vivo, topical Plerixafor restored HQ-induced depigmentation, increased hair follicle number and melanin content, and upregulated cutaneous MITF and tyrosinase without hepatic, renal, or inflammatory toxicity. Plerixafor functions as a biased CXCR4 ligand in melanocytes, influencing the β-arrestin–β-catenin–MITF signaling axis to drive melanogenesis and re-pigmentation. These findings identify β-arrestin-dependent CXCR4 signaling as a tractable pharmacologic mechanism for therapeutic re-pigmentation in pigmentary disorders. Full article

Background: The World Health Organization has identified the growing ineffectiveness of antibiotics against resistant pathogens as a global threat to public health, linked to increased morbidity and mortality. In this context, Pseudomonas aeruginosa stands out as a multidrug-resistant, biofilm-forming pathogen whose biofilm formation increases its tolerance to antimicrobials, which has driven the development of anti-virulence strategies as a therapeutic alternative. In this regard, the present study aimed to evaluate extracts and compounds from Piper species in assays targeting the inhibition of biofilm and virulence factors in Pseudomonas aeruginosa, as well as their anti-quorum sensing activity using Chromobacterium violaceum as a biosensor model. Methods: For this purpose, quorum sensing interference was first assessed through inhibition of violacein production using C. violaceum ATCC 12472 as a biosensor model. The modulation of virulence-associated phenotypes in P. aeruginosa ATCC BAA-47 was subsequently examined through inhibition of biofilm formation by crystal violet staining and spectrophotometric quantification of elastase, protease and pyocyanin production. Results: It was found that extracts from P. aduncum, P. sucrense, P. grande, and P. cumanense inhibited biofilm formation in P. aeruginosa and showed potential activity against quorum sensing in the C. violaceum model, while P. ceanothifolium exhibited only antibiofilm activity. Furthermore, hydroquinone-type compounds and benzoic acid derivatives reduced biofilm formation and virulence factors in P. aeruginosa. Conclusions: The results obtained demonstrate antibiofilm and anti-virulence activity, as well as a possible modulation of quorum sensing in model systems, suggesting that Piper species represent a promising source of bioactive compounds. Full article

N-hydroxypipecolic acid (NHP) is a key mobile signal in systemic acquired resistance in plants, and its glycosylation has been proposed to regulate immune signaling. Previous studies have demonstrated that the UDP-glycosyltransferase UGT76B1, known as an SA glycosyltransferase in Arabidopsis thaliana, also catalyzes NHP glycosylation. In this study, we re-evaluated NHP glycosylation activity of UGT76B1 using an in vitro enzyme-coupled fluorescence assay that quantitatively detects UDP released during UDP-sugar-dependent glycosylation. Unexpectedly, our biochemical analyses demonstrated that UGT76B1 lacks genuine glycosylation activity toward NHP under the in vitro assay conditions tested, although this system clearly detected UGT76B1 activity toward salicylic acid (SA), as well as the activities of UGT74F1 and UGT72B1 toward SA and hydroquinone, respectively. To explore potential UGTs responsible for NHP glycosylation, we evaluated the enzymatic activities of 41 UGT candidates successfully expressed in Escherichia coli, which are selected based on transcriptomic responses to tenoxicam treatment, molecular docking simulations using AlphaFold3/AutoDock Vina, phylogenetic criteria, and previous reports. Within this selected and successfully expressed UGT panel, none exhibited authentic NHP glycosylation activity, although this does not preclude the possibility that other members of the Arabidopsis UGT family possess NHP glycosyltransferase activity. Our findings challenge the prevailing view that UGT76B1 is the primary glycosyltransferase for NHP in A. thaliana and indicate that NHP metabolism may rely on undiscovered non-canonical enzymes or distinct metabolic pathways that warrant further investigation. Full article

Melasma is a chronic hyperpigmentation disorder that significantly impacts quality of life. Given the persistent challenges in melasma management, there is a need to evaluate therapies that may offer long-term treatment. This descriptive review analyzes interventional clinical studies involving melasma patients and placebo or hydroquinone (HQ) comparators published between 2014 and 2024. Two human authors screened studies and extracted data, with artificial intelligence used as a human-supervised support tool for screening assistance, data extraction, and discussion synthesis. Study limitations were evaluated descriptively. Treatments were grouped into five categories: HQ-based Standard Treatments, Isolated Molecules as Depigmenting Therapies, Botanical and Antioxidant-Based Therapies, Regenerative and Microenvironment-Modulating Therapies, and Procedure-Assisted and Combination Treatments. HQ remained a key benchmark, although recurrence and tolerability limitations were frequently observed. Several non-HQ or adjunctive approaches demonstrated benefit when administered orally, topically, intradermally, or via iontophoresis. Botanical antioxidants, synbiotics, epidermal growth factor, and platelet-rich plasma also showed promising efficacy. Nevertheless, the evidence base was constrained by small sample sizes, heterogeneous comparators, inconsistent endpoints, mixed objective and subjective assessments, and variable follow-up durations, which prevented meta-analysis. Research on melasma treatment is growing worldwide, with several promising non-HQ and adjunctive strategies emerging. However, standardization of outcomes, comparator selection, and longer follow-up periods is needed to clarify efficacy, tolerability, and relapse prevention throughout diverse skin tones. Full article

Micron-sized plate-like TS-1 zeolites are designed to combine the mass transfer efficiency of MFI straight channels along the b-axis by maximizing the exposure of these channel openings on the a-c crystal surface with the recoverability advantage of micrometer-scale crystals. In this study, micron-sized plate-like TS-1 was successfully synthesized by introducing sodium persulfate (Na₂S₂O₈) as an inorganic morphology-regulating additive. Through comparative experiments with ammonium persulfate, potassium persulfate, sodium carbonate, and sodium sulfate, the regulatory role of persulfate anion (S₂O₈²⁻), rather than the sodium cation, was identified. By varying the Na₂S₂O₈/SiO₂ molar ratio from 0.03 to 0.07, plate-like crystals with a- and c-axis dimensions in the micrometer range and b-axis thickness of 400–1100 nm were obtained. This morphology-regulation strategy was shown to be universal in both steam-assisted crystallization (SAC) and hydrothermal synthesis methods. Furthermore, post-treatment with tetrapropylammonium hydroxide (TPAOH) was applied to introduce additional textural porosity and construct a hierarchical pore structure. The optimized sample (TS-1-0.06SP-HT-P) achieved a total surface area of 444 m² g⁻¹ and a pore volume of 0.28 cm³ g⁻¹. The catalytic performance of the hierarchically porous samples was evaluated using 1-hexene epoxidation and phenol hydroxylation as model reactions. Catalytic stability tests using phenol hydroxylation (cat. 300 mg, phenol 36 mmol, n(phenol):n(H₂O₂) = 2, H₂O 4 mL, 353 K, 1 h) showed that TS-1-0.06SP-HT-P maintained stable performance over five consecutive cycles, with phenol conversion remaining at 20.8–22.3% and hydroquinone plus catechol selectivity at 73.0–78.1%. This work provides a feasible approach for the plate-like morphology regulation and performance optimization of TS-1 zeolites. Full article

Chlorophenols (CPs), such as 4-chlorophenol (4-CP) and 2,4-dichlorophenol (2,4-DCP), are persistent and toxic organic pollutants commonly found in industrial effluents. This study investigates their photocatalytic degradation using a TiO₂-based heterogeneous catalyst under UV irradiation, in the presence of hydrogen peroxide. The degradation kinetics were analyzed using both pseudo-first order and nonlinear Langmuir–Hinshelwood (L–H) models, accounting for competitive adsorption and successive oxidation of intermediates. Gas chromatography–mass spectrometry (GC–MS) identified key intermediates, including hydroquinone, catechol, chlorocatechols, and benzoquinone. Nonlinear kinetic modeling of coupled differential equations accurately reproduced the temporal profiles of both the parent compounds and their intermediates, providing mechanistic insights into multi-step hydroxylation, dechlorination, and oxidation processes. The results demonstrate that photocatalytic oxidation effectively mineralizes chlorophenols within 500–600 min, and the developed kinetic model offers a predictive tool for optimizing photocatalytic remediation strategies for chlorinated aromatic pollutants. The novelty of this study lies in the development of a nonlinear Langmuir–Hinshelwood kinetic model integrating experimentally identified degradation intermediates, competitive adsorption phenomena, and parallel photocatalytic reaction pathways for both 4-chlorophenol and 2,4-dichlorophenol oxidation systems. Full article

Atherosclerosis is a chronic inflammatory arterial disease and the primary underlying cause of cardiovascular morbidity and mortality worldwide. Its development and progression are driven by a mechanistically interconnected triad of endothelial dysfunction, oxidative stress, and vascular inflammation. Current pharmacotherapy, primarily focused on low-density lipoprotein cholesterol (LDL-C) reduction through statin-based and adjunctive therapies, does not fully address the residual inflammatory and calcific components of atherosclerotic risk. Menaquinone-7 (MK-7), a long-chain isoform of vitamin K2 with superior bioavailability and extrahepatic tissue distribution, has emerged as a multi-target modulator of atherogenic processes. Its classical function is to serve as a cofactor for the gamma-carboxylation of vitamin K-dependent proteins (VKDPs), principally matrix Gla protein (MGP), the primary endogenous inhibitor of vascular calcification. Beyond this established pathway, a growing body of experimental evidence indicates that MK-7 may modulate endothelial nitric oxide (NO) production through carboxylation-dependent activation of Growth Arrest-Specific Protein 6 (Gas6) and suppress lipid peroxidation and ferroptosis via Ferroptosis Suppressor Protein 1 (FSP1)-mediated reduction of vitamin K hydroquinone (VKH₂). In addition, it may attenuate nuclear factor kappa-B (NF-κB)-driven inflammatory gene transcription in vascular cells. Previous reviews mainly focused on how vitamin K2 influences vascular calcification and cardiovascular outcomes. However, emerging mechanistic evidence linking MK-7 to endothelial dysfunction, oxidative stress, ferroptosis, and vascular inflammation has not been comprehensively integrated. This review summarizes the current knowledge of in vitro, animal, observational, and randomized controlled trial evidence for MK-7 in the context of atherosclerosis. It particularly emphasises mechanistic pathways, the strength of evidence, and translational limitations, highlighting the lack of direct human vascular evidence in several areas. Full article

Molybdenum blue dispersions were synthesized via an ion-exchange approach using hydroquinone and glucose as reducing agents to clarify the influence of reductant chemistry on redox evolution and colloidal stability. Electrolyte-free conditions enabled controlled self-assembly of reduced polyoxomolybdate clusters. UV–Vis spectroscopy revealed characteristic absorption bands at ~750 and ~1100 nm associated with intervalence charge transfer in mixed-valence Mo⁵⁺/Mo⁶⁺ clusters, with hydroquinone stabilizing more deeply reduced clusters, while glucose-derived systems demonstrated a higher degree of reduction with a higher ratio of reducing agent to metal. Time dependence of oxidation–reduction potential and optical density measurements demonstrated prolonged redox equilibration and gradual self-organization over several weeks. Dynamic light scattering confirmed the formation of nanoclusters with comparable hydrodynamic diameters of approximately 3.5 nm for both reducing agents. Raman and FT-IR spectroscopy indicated structurally similar polyoxomolybdate frameworks. In contrast, electrokinetic measurements revealed pronounced differences in surface chemistry and stability: hydroquinone-derived dispersions exhibited robust, pH-independent electrostatic stabilization, whereas glucose-derived systems showed weaker, pH-dependent stabilization and rapid electrolyte-induced aggregation. These results demonstrate that the nature of the reducing agent has an impact on the synthesis and colloidal behavior of molybdenum blue dispersions synthesized by the ion-exchange route. Full article

Nitrogen-doped carbon dots (CDs) were fabricated via a one-pot hydrothermal route using hydroquinone and o-phenylenediamine as dual precursors. The as-prepared CDs were then anchored onto iron-cobalt oxide nanosheets (FeCo-ONSs) to construct a composite nanozyme, denoted as CDs/FeCo-ONSs. Although FeCo-ONSs possess intrinsic peroxidase-like (POD-like) activity, the integration of CDs with FeCo-ONSs resulted in a remarkable enhancement of catalytic performance. Specifically, in the presence of hydrogen peroxide (H₂O₂), the CDs/FeCo-ONS composite promoted the efficient oxidative transformation of 3,3′,5,5′-tetramethylbenzidine (TMB), leading to the formation of a blue-colored oxidized product. Based upon the enhanced POD-like activity of CDs/FeCo-ONSs, a highly sensitive colorimetric sensor was developed for the detection of ascorbic acid (AA). This method exhibited a wide linear detection range of 0.1 to 50 µM with a low limit of detection (LOD) of 0.018 µM. Furthermore, the developed method was successfully applied to the determination of AA in commercial beverages and fresh fruits, verifying its potential feasibility for practical applications in food quality control. Full article