PM2.5 exacerbates brain injury in diarrhea-predominant irritable bowel syndrome mice via the disruption of the microbiota-gut-brain axis and the restoring effect of resveratrol.

Self-disintegrating electrospun short fibers as intra-articular drug depots for gouty arthritis.

Resveratrol ameliorates sepsis-induced immune dysfunction by targeting GADD45A to maintain hematopoietic stem cell homeostasis: A predictive study integrating ensemble machine learning, single-cell transcriptomics, and molecular dynamics simulation.

Background/Objectives: Endophytic fungi represent an alternative source for resveratrol (RES) production. The present study aims to utilize mycoendophytic-derived resveratrol as a reducing agent for the synthesis of silver nanoparticles (AgNPs), in addition to further assay the cytotoxic activity of a RES-conjugated nanocarrier system toward human epidermoid carcinoma A-431 cells. Methods: Alternaria alternata AUMC 16209 was isolated from the stem of grapevine Vitis vinifera L. cultivar prime. Strain identification was achieved through morphological and molecular characterization using ITS sequencing. A. alternata AUMC 16209 exhibited RES production capability upon cultivation on PDB medium for seven days with a total of 8.25 mg/L as determined by HPLC. The crude RES was purified using flash chromatography followed by structure elucidation through 1H and 13C NMR analyses. The purified RES was used for green synthesis of nanoparticles, acting as a reducing agent for silver ions. Results: Stable RES-AgNPs were fabricated at particle sizes ranging from 25 to 47 nm. RES-AgNPs observed a plasmon resonance absorption band at 415 nm with a negative zeta potential value of −38.5 mV. The crystalline structure of RES-AgNPs was addressed through X-ray diffraction analysis. FT-IR spectroscopy confirms the involvement of the functional –OH group and the aromatic C=C bond in the reduction and stabilization process. RES-AgNPs was more efficient to inhibit the cellular proliferation of human epidermoid carcinoma A-431 cells compared to RES alone. Conclusions: This report introduces for the first time an endophytic A. alternata as a sustainable source for RES production and emphasizes its potential for green synthesis of stable AgNPs with promising cytotoxic activity.

ABSTRACT The objective of this work was to generate and characterize complexes of quinoa proteins (QP) with either resveratrol (RSV) or tocopherol (TOC) whose dimensions fell into the nanoscale. The QP‐based nanocomplexes characterization was carried out jointly with encapsulation efficiency determination. Fourier‐Transform Infrared Spectroscopy (FTIR) showed no covalent bond formation and indicated that the protein's secondary structure was modified. Transmission Electron Microscopy (TEM) images and Dynamic Light Scattering (DLS) measurements confirmed that the addition of bioactive compounds did not substantially alter the protein's original size. A consistent particle diameter of 100 nm was observed in both types of nanocomplexes with and without RSV and TOC. The antioxidant capacity of nanocomplexes was analyzed after an in vitro simulated digestion process, showing an increase in this property postdigestion. These nanocomplexes hold great potential as functional ingredients.

A covalent resveratrol-nitroxide conjugate protects against oxidative stress-induced cellular senescence.

To develop cosmetic film-forming agents that combine sustainability with functionality, this study synthesized a series of bio-based polyols using epoxidized soybean oil (ESO) as raw material through acid-catalyzed ring-opening reactions. These polyols partially replaced petroleum-based polyols and reacted with isophorone diisocyanate (IPDI). By incorporating β-cyclodextrin (β-CD), a water-based polyurethane (CPS-ESO) was successfully developed that combines degradability with active ingredient delivery capability. Experiments demonstrated that the resulting CPS-M film exhibits excellent water repellency (contact angle 66.7°), mechanical properties (tensile strength 14.21 MPa, elongation at break 229.42%), adhesion (Level 0), and breathability, while displaying controllable degradation behavior under both enzymatic and alkaline hydrolysis conditions. Due to the cavity structure of β-cyclodextrin, this material efficiently loaded resveratrol (RES) at a loading rate of 0.16%. Formulated into a setting spray (F1), the product demonstrated outstanding makeup longevity (lowest ΔE value after water/sweat immersion), anti-friction performance (ΔE value after friction only one-third of the control group), and antioxidant activity (DPPH scavenging rate of 86.25%), with RES remaining stable under high-temperature storage conditions. This study provides new insights for designing green multifunctional cosmetic film-forming agents.

Skeletal muscle differentiation is tightly regulated by membrane potential dynamics and voltage-dependent ion channel activity. Potassium (K+) and calcium (Ca2+) currents cooperate to orchestrate the transition of myoblasts into fusion-competent myotubes, and alterations in this process are associated with dystrophic phenotypes. Here, we investigated the electrophysiological remodeling accompanying C2C12 myogenesis and the modulatory effects of the polyphenol resveratrol (RES) on calcium voltage-gated channel subunit alpha 1 S (CACNA1S, Cav1.1, L-type) currents. Whole-cell patch-clamp recordings were performed in proliferating and differentiating C2C12 cells to characterize the temporal expression of K+ currents and voltage-dependent Ca2+ channels (VDCCs). During differentiation, three electrophysiological subpopulations were identified according to K+ current profiles: SK4+/EAG-/Kir-, SK4-/EAG+/Kir-, and SK4-/EAG+/Kir+. This sequence paralleled a progressive membrane hyperpolarization from -20 mV to -70 mV, consistent with the physiological maturation of myogenic cells. In C2C12 myocytes, nimodipine-sensitive L-type currents were the only Ca2+ conductance observed. Their activation threshold (~-30 mV) and half-activation voltage (V/2 ≈ -12 mV) indicated the co-expression of embryonic and adult Cav1.1 isoforms. Exposure to RES (30 µM, 48 h) produced a depolarizing shift in activation (ΔV/2 ≈ +9 mV) and a reduction in current amplitude across all voltages, consistent with a transition toward the adult splice variant of Cav1.1. These findings suggest that RES promotes electrophysiological maturation of skeletal muscle cells by modulating calcium channel expression and gating behavior. Given its known ability to correct splicing abnormalities in CACNA1S and related genes, resveratrol emerges as a promising pharmacological agent for restoring calcium homeostasis in neuromuscular disorders such as myotonic dystrophy type 1 (DM1).

Diabetic bacterial infected wounds are severe complications in diabetic patients, posing significant challenges to clinical management. The wound site is prone to bacterial colonization and biofilm formation, triggering a persistent inflammatory response and forming a vicious cycle of "hyperglycemia-infection-inflammation". Therefore, the development of antibacterial materials that are efficient, safe, and less likely to induce drug resistance is of great significance for improving wound repair. In this study, a thermosensitive composite hydrogel based on chitosan (CS) and poloxamer (P407/P188), named CPP, was developed for the codelivery of berberine (BBR) and resveratrol (RES). This system undergoes a phase transition at physiological temperature to form a porous network structure, enabling controllable and sustained drug release. In vivo experiments using a diabetic mouse model with infected wounds showed that the CPP@BBR@RES hydrogel effectively inhibited bacterial colonization, alleviated the inflammatory response, and significantly promoted collagen deposition, angiogenesis, and wound closure. This study innovatively combines the thermogelling and sustained-release properties of the material with the synergistic antibacterial, anti-inflammatory, and repair-promoting functions of the dual drugs, providing a multifunctional integrated therapeutic strategy for diabetic infected wounds.

The role of histone acetylation in mediating the anticancer effects of polyphenols: Insights from genistein, resveratrol, quercetin, curcumin, and epigallocatechin-3-gallate.

ABSTRACTOsteosarcoma (OS) is an aggressive primary bone tumour with high metastatic potential. Current treatments including surgery and chemotherapy are limited by side effects and chemoresistance, underscoring the need for novel therapies. This study aimed to investigate the antitumor potential of resveratrol (RSV), a natural polyphenol, as a novel treatment for OS. The effects of RSV were evaluated in two osteosarcoma cell lines (SAOS‐2 and U2‐OS). A viability assay established 100 μM as the effective concentration, and hyperspectral imaging confirmed cellular uptake. Apoptosis was measured via caspase‐3/7 activity and Annexin V/PI staining, while qRT‐PCR assessed pro‐apoptotic gene expression. Flow cytometry evaluated cell‐cycle progression, and a wound‐healing assay measured migration. Gene expression analyses (qRT‐PCR) examined markers of cell adhesion, tumour progression and epithelial–mesenchymal transition. Finally, RSV's impact on the Wnt/β‐catenin pathway was determined by quantifying nuclear β‐catenin accumulation and the expression of its downstream oncogenic targets. RSV inhibited cell proliferation and induced apoptosis, increasing caspase‐3/7 activity and modulating apoptotic gene expression. RSV also caused cell cycle arrest in S‐phase. It reduced the cells' migration and altered the expression of cell adhesion and tumour progression genes, promoting a less invasive phenotype. Notably, RSV decreased nuclear β‐catenin accumulation, downregulated oncogenic targets like c‐Myc and MMPs, and upregulated E‐cadherin while reducing vimentin levels, suggesting a reversal of epithelial–mesenchymal transition. These results suggest that RSV may offer a promising therapeutic approach for osteosarcoma, modulating key pathways involved in tumour progression, metastasis and chemoresistance. Further studies are required to assess its clinical applicability.

Microwave time tunes broccoli-stem pectin fine structure and calcium gelation for sustained resveratrol release.

Structural properties, rheological characteristics, and drug delivery efficiency of resveratrol-loaded soybean protein isolate and hemp protein isolate emulsion gels: Synergistic effects of carboxymethyl cellulose incorporation and ultrasound treatment.

Resveratrol (RES) has been shown to exhibit therapeutic efficacy against fatty liver disease. Yet, the molecular mechanisms by which RES ameliorates liver injury remain unclear. The aim of this study was to investigate the therapeutic effect and mechanism of resveratrol in fatty liver disease. It was found that dairy cows with fatty liver exhibit characteristic hepatic pathologies, including ballooning degeneration, lipid accumulation and elevated serum AST and ALT levels. Parallel to these changes, we observed significant upregulation of the NLRP3 inflammasome alongside suppression of mitophagy in the liver. Additionally, it was demonstrated in vitro that resveratrol pretreatment effectively alleviated PA-triggered NLRP3 inflammasome activation and mitochondrial dysfunction. Furthermore, RES's mitigating effects against NLRP3 inflammation and mitochondrial injury were reversed by suppressing PINK1-medicated mitophagy. In vivo experiments further demonstrated that resveratrol administration attenuated HFD-induced liver injury and lipid accumulation in a mouse model, concurrent with suppressed NLRP3 activation and an increase in mitophagy, further confirming the mechanism identified in vitro. Our findings reveal that RES ameliorates fatty liver injury primarily by inhibiting the NLRP3 inflammasome through PINK1-mediated mitophagy, which provides a potential novel therapeutic strategy for mitigating fatty liver disease.

NASA intends to return humans to the Moon, where partial gravity will put them at risk of musculoskeletal deconditioning. Resveratrol (RSV) is a promising nutritional countermeasure that may protect muscle health during disuse; however, its efficacy and mechanism in simulated lunar gravity are unknown. Forty adult male Wistar rats underwent 14 days of normal loading or partial weight-bearing at 20% of normal loading (PWB20). Unloaded animals received daily RSV supplementation with or without an ERα antagonist to test whether ERα was required to mediate RSV benefits. Muscle function was longitudinally assessed, and a Western blot was used to quantify key signaling proteins in the soleus muscle. PWB20 led to a significant reduction in grip strength (-14.2%) associated with marked changes in electrophysiological muscle properties. RSV-supplemented animals performed better throughout the study, but not when Erα was inhibited. RSV supplementation resulted in a greater ERα phosphorylation ratio compared to PWB20 alone (3.5 vs. 1.91). These results suggest that RSV can mitigate muscle deconditioning in a lunar gravity analog and that ERα signaling is required.

Hypoxic-ischemic encephalopathy (HIE) is a major cause of neurological injury in neonates, with pathological cascades such as neuroinflammation and ferroptosis driving disease progression. Current therapeutic strategies for HIE are largely limited to supportive care and therapeutic hypothermia, which fail to effectively target these mechanisms. To address this challenge, we developed a microglia-derived exosome-liposome hybrid membrane systems (HMS) (R+si@LPs-TK/TAT+Exo, abbreviated as Rs@LP-T/T-E) for the co-delivery of resveratrol (RES) and acyl-CoA synthetase long-chain family member 4 (ACSL4) siRNA. The nanosystem exhibited favorable stability, reactive oxygen species (ROS)-responsive drug release, and efficient blood-brain barrier (BBB) penetration, enabling targeted accumulation within ischemic brain regions. In experimental models, Rs@LP-T/T-E significantly attenuated neuroinflammation and ferroptosis, promoted microglial polarization toward the anti-inflammatory M2 microglial phenotype, and restored mitochondrial function, thereby reducing cerebral infarct volume and improving cerebral perfusion. In conclusion, this study presents an efficient, targeted, and biocompatible nanodelivery strategy that holds strong translational potential for HIE therapy.

Objective: To investigate the neuroprotective effects of resveratrol (RSV) against ferroptosis in a rat model of cerebral ischaemia. Methods: Photochemical embolisation was used to generate focal cerebral ischemic injury in Sprague-Dawley rats. The modified neurological severity score system and adhesive removal experiment were used to evaluate neurological deficits) in model rats. Cerebral infarction volume was determined using TTC staining. Commercially available glutathione (GSH), iron ion, reactive oxygen species (ROS), and malondialdehyde (MDA) kits were used to detect ferroptosis. Western blot was used to detect the expression of the ferroptosis-related proteins Sirt1 and Gpx4. Results: We found in a rat model of focal cerebral ischaemia that RSV treatment could significantly alleviate the neurological deficit score, reduce the adhesive removal time, reduce cerebral infarct area, reduce brain water content, and alleviate the neurological damage caused by cerebral ischaemia. Meanwhile, RSV treatment can significantly restore GSH and iron ion levels, reduce ROS and MDA levels, and activate the expression of the ferroptosis-related proteins Sirt1 and Gpx4. Conclusion: RSV improved neurological deficits, reduced the area of cerebral infarction, and alleviated neuronal damage. This protective effect may be achieved by upregulation of Sirt1 and Gpx4 protein expression to alleviate damage caused by ferroptosis.

Resveratrol (RSV), a dietary polyphenol widely present in traditional medicinal plants and foods, exhibits antioxidant and anti-inflammatory properties that are relevant to ethnopharmacological strategies for protecting against environmental neurotoxicants. Given increasing real-world co-exposure to lead (Pb) and cadmium (Cd), elucidating RSV's capacity to preserve gut-brain axis (GBA) homeostasis has direct translational relevance for populations relying on phytochemical interventions. Sprague-Dawley rats were randomized into control, Pb-Cd model, and RSV treatment groups (10, 20, or 40 mg/kg). For 4 weeks, rats received Pb (300 mg/L) and Cd (50 mg/L) in drinking water with daily RSV. Cognitive function was assessed by Morris water maze; barrier integrity by Evans blue assay, histology, and Western blot for ZO-1/Occludin; synaptic ultrastructure by TEM; microbiota composition by 16S rRNA sequencing; and short-chain fatty acids (SCFAs) by GC-MS. Neurotransmitters (5-HT, GABA, SP, VIP) and cytokines (IL-6, IL-1β, TNF-α) were measured by ELISA. RSV improved spatial learning, reduced EB extravasation, preserved synaptic ultrastructure and proteins (BDNF, SYN, PSD-95), and restored intestinal architecture with increased ZO-1/Occludin. RSV attenuated cytokine release, normalized goblet cells, reversed dysbiosis by restoring Lactobacillaceae/Prevotellaceae, and increased acetate, propionate, and butyrate. It reinstated 5-HT and GABA while reducing SP and restoring VIP across serum, colon, and hippocampus. RSV attenuated Pb-Cd-associated neurotoxicity and was accompanied by improved intestinal and BBB-related readouts, partial normalization of gut microbiota features and SCFA levels, and preservation of synaptic and neurotransmitter-related markers, consistent with a link to gut-brain axis function. This study is among the first to test RSV in a Pb-Cd co-exposure model using a multi-dose regimen with integrated behavioral, barrier, microbial, and neurochemical endpoints.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with limited therapeutic options and a poor prognosis. Resveratrol (RES), a natural polyphenolic compound, has demonstrated antitumor activity in multiple cancer types; however, its underlying mechanisms in pancreatic cancer remain incompletely understood. In this study, we investigated the effects of RES on pancreatic cancer cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), with a particular focus on the role of inhibitor of growth family member 5 (ING5). Pancreatic cancer cell lines PANC1 and SW1990 were treated with RES, and cell viability, clonogenic growth, migration, and invasion were assessed using CCK-8, colony formation, wound-healing, and Transwell assays, respectively. ING5 expression and localization were evaluated by immunofluorescence, RT-qPCR, and Western blotting, and its functional significance was further examined using siRNA-mediated knockdown. RES treatment significantly suppressed pancreatic cancer cell proliferation, migration, invasion, and EMT in vitro, accompanied by upregulation of ING5 expression and increased E-cadherin levels with concomitant reduction of N-cadherin expression. Silencing ING5 enhanced malignant cellular behaviors and partially reversed the inhibitory effects of RES on EMT-associated phenotypes and cell growth. These findings indicate that ING5 contributes to the antitumor effects of RES and functions as an important mediator in the suppression of pancreatic cancer progression. Collectively, our results suggest that RES restrains pancreatic cancer cell aggressiveness at least in part through upregulation of ING5, highlighting the RES-ING5 axis as a potential therapeutic target for pancreatic cancer intervention.

Brain vascular aging is increasingly recognized as a critical therapeutic target for age-related cognitive decline. Oxidative stress, bioenergetic dysfunction, and molecular damage play central roles in the progression of vascular aging, contributing to cerebrovascular dysfunction and impaired cognitive function. While naturally occurring polyphenols such as resveratrol (RSV) have demonstrated potential in mitigating aging-related pathologies, their poor bioavailability and limited brain targeting efficiency significantly constrain their therapeutic impact. As a result, high doses or advanced drug delivery strategies are necessary to achieve meaningful physiological effects. We introduce a novel nanocarrier system designed to enhance RSV delivery to the cerebral endothelium by leveraging the natural formation of an apolipoprotein E (ApoE)-enriched protein corona around fusogenic liposomes (FL) in vivo . These nanoparticles directly fuse with cytoplasmic cell membranes and thus evade endocytosis. We found that once in the circulation FL spontaneously acquire a protein corona, which is highly enriched in ApoE, a key ligand for brain endothelial low-density lipoprotein receptors (LDLR). Based on this observation, we engineered an ApoE-functionalized protein corona around FL (ApoE-FL) to systematically evaluate whether this mechanism could be exploited for targeted brain delivery. Following optimization and physicochemical characterization, the RSV-loaded liposomes were evaluated in vitro using human cerebral microvascular endothelial cells and in vivo C57BL/6 aged mice to assess their therapeutic potential. Both FL and engineered ApoE-FL liposomal delivery systems exhibited a strong affinity for endothelial cell membranes in vitro . The knockdown of the ApoE receptor, low-density lipoprotein receptor-related protein 1 (LRP1), significantly reduced liposomal docking. Microscopy analysis revealed that both ApoE-FL and non-functionalized FL directly fused with endothelial plasma membranes, thus bypassing intracellular organelles and minimizing lysosomal degradation. This suggests that the naturally formed ApoE corona in vivo may contribute to efficient cerebrovascular targeting, a property successfully replicated by the engineered ApoE corona strategy. In vivo biodistribution and kinetic studies demonstrated that especially ApoE-FL achieved enhanced brain-targeting efficiency, prolonged cerebrovascular retention, and extended targeting distance along the arteriovenous axis. This emphasizes that fusogenic liposomes effectively engage almost the entire microvascular network, including capillaries and post-capillary venules. Functionally, fusogenic liposome-delivered RSV improved blood-brain barrier (BBB) integrity, enhanced neurovascular coupling (NVC) responses, and promoted brain vascularization in aged mice. Single-cell RNA sequencing (scRNA-seq) revealed enhanced endothelial angiogenesis and barrier protective transcriptional profiles in cerebrovascular cells treated with ApoE-FL/RSV, suggesting a molecular basis for the observed vascular benefits. Liposomal RSV delivery achieved near-complete cerebrovascular and cognitive rejuvenation in aged mice applying a 2000-fold lower RSV dose than oral administration used as control sample. Thus, ApoE-FL liposomes exhibited exceptionally high delivery efficiency in deeper brain regions, further expanding their therapeutic potential. These findings underscore the importance of targeted drug delivery in optimizing therapeutic outcomes and establish ApoE-functionalized fusogenic liposomes as a promising strategy for mitigating brain vascular aging and cognitive decline.