Effectiveness of different antioxidants in suppressing the evolution of thermally induced peroxidation products in hemp seed oil.

Several scientific studies have warned that the ingestion of dietary lipid oxidation products (LOPs) may initiate or exacerbate the development of several chronic non-communicable diseases in humans. Indeed, the constantly increasing consumption of culinary oils by larger global populations indicates the need for scientific techniques to suppress the evolution of LOPs in thermo-oxidised oils. This study employed a 600.13 MHz frequency NMR spectrometer in evaluating the effect of 10, 50, and 100 ppm concentrations of chemical compounds reported to have antioxidant properties in continuously-stirred and thermally stressed polyunsaturated fatty acid (PUFA)-rich hemp seed oil at a frying temperature of 180℃ for 180 min. Research data acquired showed that the antioxidants α- and γ-tocopherol, γ-oryzanol, ß-carotene, eugenol, resveratrol, ascorbyl palmitate, gentisic acid, and L-ascorbic acid all played a vital role in suppressing the evolution of secondary aldehydic lipid oxidation products in hemp seed oil. However, the most ineffective LOP-suppressing agent was L-lysine, an observation which may be accountable by its poor oil solubility. Nonetheless, trends deduced for compounds acting as antioxidants were mainly unique for each class of agent tested. Conversely, the antioxidant capacity of resveratrol was consistently higher, and this effect was found to be independent of its added amounts. This report provides a direct approach in developing scientific methods for the suppression of LOPs in thermo-oxidatively susceptible PUFA-rich cooking oils.

The mechanism of resveratrol stabilization and degradation by synergistic interactions between constituent proteins of whey protein.

Whey protein isolate (WPI) is mainly composed of ß-lactoglobulin (ß-LG), α-lactalbumin (α-LA) and bovine serum albumin (BSA). The aim of this study was to compare and analyze the influence of WPI and its three main constituent proteins, as well as proportionally reconstituted WPI (R-WPI) on resveratrol. It was found that the storage stability of resveratrol was protected by WPI, not affected by R-WPI, but reduced by individual whey proteins at 45°C for 30 days. The rank of accelerated degradation of resveratrol by individual whey proteins was BSA > α-LA > ß-LG. The antioxidant activity, localization of resveratrol and oxidation of carrier proteins were determined by ABTS, H2O2 assay, synchronous fluorescence, carbonyl and circular dichroism. The non-covalent interactions and disulfide bonds between constituent proteins improved the antioxidant activity of the R-WPI-resveratrol complex, the oxidation stability of the carrier and the solvent shielding effect on resveratrol, which synergistically inhibited the degradation of resveratrol in R-WPI system. The results gave insight into elucidating the interaction mechanism of resveratrol with protein carriers.

Theoretical Study of Cyanidin-Resveratrol Copigmentation by the Functional Density Theory.

Anthocyanins are colored water-soluble plant pigments. Upon consumption, anthocyanins are quickly absorbed and can penetrate the blood-brain barrier (BBB). Research based on population studies suggests that including anthocyanin-rich sources in the diet lowers the risk of neurodegenerative diseases. The copigmentation caused by copigments is considered an effective way to stabilize anthocyanins against adverse environmental conditions. This is attributed to the covalent and noncovalent interactions between colored forms of anthocyanins (flavylium ions and quinoidal bases) and colorless or pale-yellow organic molecules (copigments). The present work carried out a theoretical study of the copigmentation process between cyanidin and resveratrol (CINRES). We used three levels of density functional theory: M06-2x/6-31g+(d,p) (d3bj); ωB97X-D/6-31+(d,p); APFD/6-31+(d,p), implemented in the Gaussian16W package. In a vacuum, the CINRES was found at a copigmentation distance of 3.54 Å between cyanidin and resveratrol. In water, a binding free energy ∆G was calculated, rendering -3.31, -1.68, and -6.91 kcal/mol, at M06-2x/6-31g+(d,p) (d3bj), ωB97X-D/6-31+(d,p), and APFD/6-31+(d,p) levels of theory, respectively. A time-dependent density functional theory (TD-DFT) was used to calculate the UV spectra of the complexes and then compared to its parent molecules, resulting in a lower energy gap at forming complexes. Excited states' properties were analyzed with the ωB97X-D functional. Finally, Shannon aromaticity indices were calculated and isosurfaces of non-covalent interactions were evaluated.

Development of Recombinant High-Density Lipoprotein Platform with Innate Adipose Tissue-Targeting Abilities for Regional Fat Reduction.

As an escalating public health issue, obesity and overweight conditions are predispositions to various diseases and are exacerbated by concurrent chronic inflammation. Nonetheless, extant antiobesity pharmaceuticals (quercetin, capsaicin, catecholamine, etc.) manifest constrained efficacy alongside systemic toxic effects. Effective therapeutic approaches that selectively target adipose tissue, thereby enhancing local energy expenditure, surmounting the limitations of prevailing antiobesity modalities are highly expected. In this context, we developed a temperature-sensitive hydrogel loaded with recombinant high-density lipoprotein (rHDL) to achieve targeted delivery of resveratrol, an adipose browning activator, to adipose tissue. rHDL exhibits self-regulation on fat cell metabolism and demonstrates natural targeting toward scavenger receptor class B type I (SR-BI), which is highly expressed by fat cells, thereby achieving a synergistic effect for the treatment of obesity. Additionally, the dispersion of rHDL@Res in temperature-sensitive hydrogels, coupled with the regulation of their degradation and drug release rate, facilitated sustainable drug release at local adipose tissues over an extended period. Following 24 days' treatment regimen, obese mice exhibited improved metabolic status, resulting in a reduction of 68.2% of their inguinal white adipose tissue (ingWAT). Specifically, rHDL@Res/gel facilitated the conversion of fatty acids to phospholipids (PA, PC), expediting fat mobilization, mitigating triglyceride accumulation, and therefore facilitating adipose tissue reduction. Furthermore, rHDL@Res/gel demonstrated efficacy in attenuating obesity-induced inflammation and fostering angiogenesis in ingWAT. Collectively, this engineered local fat reduction platform demonstrated heightened effectiveness and safety through simultaneously targeting adipocytes, promoting WAT browning, regulating lipid metabolism, and controlling inflammation, showing promise for adipose-targeted therapy.

Preparation of Eudragit S100-pullulan/hydroxypropyl-ß-cyclodextrin complex-Eudragit S100 multilayer nanofiber film for resveratrol colon delivery.

Cyclodextrin-based electrospun nanofibers are promising for encapsulating and preserving unstable compounds, but quick dissolution of certain nanofibers hinders their delivery application. In this study, hydroxypropyl-ß-cyclodextrin (HPßCD) was used as an effective carrier of resveratrol (RSV) to obtain the RSV/HPßCD inclusion complex (HPIC), which was then incorporated into pullulan nanofibers. For enhancement of RSV release toward colon target, multilayer structure with a pullulan/HPIC film sandwiched between two layers of hydrophobic Eudragit S100 (ES100) nanofibers was employed. The relationship between the superiority of the ES100-pullulan/HPIC-ES100 film and its multilayer structure was verified. The intimate interactions of hydrogen bonds between two adjacent layers enhanced thermal stability, and the hydrophobic outer layers improved water contact resistance. According to release results, multilayer films also showed excellent colon-targeted delivery property and approximately 78.58 % of RSV was observed to release in colon stage. In terms of release mechanism, complex mechanism best described RSV colonic release. Additionally, ES100-pullulan/HPIC-ES100 multilayer films performed higher encapsulation efficiency when compared to the structures without HPIC, which further increased the antioxidant activity and total release amount of RSV. These results suggest a promising strategy for designing safe colonic delivery systems based on multilayer and HPIC structures with superior preservation for RSV.

Glycerophospholipid polyunsaturation modulates resveratrol action on biomimetic membranes.

The phytoalexin resveratrol has received increasing attention for its potential to prevent oxidative damages in human organism. To shed further light on molecular mechanisms of its interaction with lipid membranes we study resveratrol influence on the organisation and mechanical properties of biomimetic lipid systems composed of synthetic phosphatidylcholines with mixed aliphatic chains and different degree of unsaturation at sn-2 position (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, POPC, and 1-palmitoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine, PDPC). High-sensitivity isothermal titration calorimetric measurements reveal stronger spontaneous resveratrol association to polyunsaturated phosphatidylcholine bilayers compared to the monounsaturated ones resulting from hydrophobic interactions, conformational changes of the interacting species and desolvation of molecular surfaces. The latter is supported by the results from Laurdan spectroscopy of large unilamellar vesicles providing data on hydration at the glycerol backbones of glycerophospholipides. Higher degree of lipid order is reported for POPC membranes compared to PDPC. While resveratrol mostly enhances the hydration of PDPC membranes, increasing POPC dehydration is reported upon treatment with the polyphenol. Dehydration of the polyunsaturated lipid bilayers is measured only at the highest phytoalexin content studied (resveratrol/lipid 0.5 mol/mol) and is less pronounced than the effect reported for POPC membranes. The polyphenol effect on membrane mechanics is probed by thermal shape fluctuation analysis of quasispherical giant unilamellar vesicles. Markedly different trend of the bending elasticity with increasing resveratrol concentration is reported for the two types of phospholipid bilayers studied. POPC membranes become more rigid in the presence of resveratrol, whereas PDPC-containing bilayers exhibit softening at lower concentrations of the polyphenol followed by a slight growth without bilayer stiffening even at the highest resveratrol content explored. The new data on the structural organization and membrane properties of resveratrol-treated phosphatidylcholine membranes may underpin the development of future liposomal applications of the polyphenol in medicinal chemistry.

Fabrication and characterization of novel prolamin nanoparticle-filled starch gels incorporating resveratrol.

This study aimed to improve the mechanical properties of wheat starch gels (WSG) and the stability and bioaccessibility of resveratrol (Res) in prolamin nanoparticles. Res-loaded gliadin (Gli), zein, deamidated gliadin (DG) and deamidated zein (DZ) nanoparticles were filled in WSG. The hardness, G' and G'' of WSG were notably increased. It can be attributed to the more ordered and stable structure induced by the interaction of prolamin nanoparticles and starch. The Res retention of nanoparticles and nanoparticle-filled starch gels was at least 24.6 % and 36.0 % higher than free Res upon heating. When exposed to ultraviolet, the Res retention was enhanced by over 6.1 % and 37.5 %. The in-vitro digestion demonstrated that the Res releasing percentage for nanoparticle-filled starch gels was 25.8 %-38.7 % lower than nanoparticles in the simulated stomach, and more Res was released in the simulated intestine. This resulted in a higher bioaccessibility of 82.1 %-93.2 %. The bioaccessibility of Res in Gli/Res/WSG and DG/Res/WSG was greater than that of Zein/Res/WSG and DZ/Res/WSG. More hydrophobic interactions occurred between Res and Gli, DG. The interactions between Res and zein, DZ were mainly hydrogen bonding. The microstructure showed that nanoparticles exhibited dense spherical structures and were uniformly embedded in the pores of starch gels.

Construction of resveratrol and quercetin nanoparticles based on folic acid targeted Maillard products between Jiuzao glutelin isolate and carboxymethyl chitosan: Improved stability and function.

Advanced targeted nanoparticles (NPs) were designed to enhance the targeted delivery of resveratrol (RES) and quercetin (QUE) by utilizing carboxymethyl chitosan (CTS) and Jiuzao glutelin isolate (JGI) conjugates. Briefly, RES and QUE were encapsuled within CTS-JGI-2 (CTS/JGI, m/m, 2:1). The carrier's targeting properties were further improved through the incorporation of folic acid (FA) and polyethylenimine (PEI). Moreover, the stability against digestion was enhanced by incorporating baker yeast cell walls (BYCWs) to construct RES-QUE/FA-PEI/CTS-JGI-2/MAT/BYCW NPs. The results demonstrated that FA-PEI/CTS-JGI-2/MAT/BYCW NPs could improve cellular uptake and targeting property of RES and QUE through endocytosis of folic acid receptors (FOLRs). Additionally, RES-QUE successfully alleviated LPS- and DSS-induced inflammation by regulating NF-κB/IkBa/AP-1 and AMPK/SIRT1signaling pathways and reducing the secretion of inflammatory mediators and factors. These findings indicate FA-PEI/CTS-JGI-2/MAT/BYCW NPs hold promise as an oral drug delivery system with targeted delivery capacities for functional substances prone to instability in dietary supplements.

Stilbenes: a journey from folklore to pharmaceutical innovation.

In modern times, medicine is predominantly based on evidence-based practices, whereas in ancient times, indigenous people relied on plant-based medicines with factual evidence documented in ancient books or folklore that demonstrated their effectiveness against specific infections. Plants and microbes account for 70% of drugs approved by the USFDA (U.S. Food and Drug Administration). Stilbenes, polyphenolic compounds synthesized by plants under stress conditions, have garnered significant attention for their therapeutic potential, bridging ancient wisdom with modern healthcare. Resveratrol, the most studied stilbene, initially discovered in grapes, red wine, peanuts, and blueberries, exhibits diverse pharmacological properties, including cardiovascular protection, antioxidant effects, anticancer activity, and neuroprotection. Traditional remedies, documented in ancient texts like the Ayurvedic Charak Samhita, foreshadowed the medicinal properties of stilbenes long before their modern scientific validation. Today, stilbenes are integral to the booming wellness and health supplement market, with resveratrol alone projected to reach a market value of 90 million US$ by 2025. However, challenges in stilbene production persist due to limited natural sources and costly extraction methods. Bioprospecting efforts reveal promising candidates for stilbene production, particularly endophytic fungi, which demonstrate high-yield capabilities and genetic modifiability. However, the identification of optimal strains and fermentation processes remains a critical consideration. The current review emphasizes the knowledge of the medicinal properties of Stilbenes (i.e., cardiovascular, antioxidant, anticancer, anti-inflammatory, etc.) isolated from plant and microbial sources, while also discussing strategies for their commercial production and future research directions. This also includes examples of novel stilbenes compounds reported from plant and endophytic fungi.

Enhanced in vitro bioavailability of resveratrol-loaded emulsion stabilized by ß-lactoglobulin-catechin with excellent antioxidant activity.

The study aimed to fabricate ß-Lactoglobulin-catechin (ß-La-Ca) conjugates as a natural designed antioxidant emulsifier to improve the physicochemical stability of resveratrol emulsion delivery system. Fourier transform infrared (FT-IR) and fluorescence spectroscopy analysis confirmed the formation of conjugates using free radical grafting. The antioxidant ability of emulsion was evaluated by DPPH scavenging activities and ORAC experiments. The emulsion stabilized by ß-La-Ca conjugates exhibited strong antioxidant activity with ORAC value of 2541.39 ± 29.58 µmol TE/g, which was significantly higher than that by ß-Lactoglobulin alone with 387.96 ± 23.45 µmol TE/g or their mixture with 948.23 ± 32.77 µmol TE/g. During the whole simulated gastrointestinal digestion, emulsion stabilized by ß-La-Ca conjugates exhibited excellent oxidative stability that the lipid was mainly digested in the small intestine. This behavior attributed to the greater stability of resveratrol to chemical transformation leading to a higher overall bioavailability in vivo. These results suggested that the ß-La-Ca conjugates could be used to fabricate the emulsion-based delivery system to improve the oxidative stability and bioavailability of chemically labile hydrophobic bioactive compounds.

Effect of gold-conjugated resveratrol nanoparticles on glioma cells and its underlying mechanism.

BACKGROUND:  Glioblastoma is the most aggressive brain tumor with poor prognosis. Although Resveratrol (Rsv) is known to have therapeutic effects on glioma, the effects of gold-conjugated resveratrol nanoparticles (Rsv-AuNPs) on glioma cells are rarely reported. OBJECTIVE: We aimed to investigate the effects of Rsv-AuNPs on glioma cells and its underlying mechanism. METHOD: Human glioma cell line U87 was treated with different concentrations of Rsv-AuNPs. CCK-8, transwell, and wound healing assay were performed to measure the effects of Rsv-AuNPs on cell proliferation, invasion, and migration ability, respectively. Flow cytometry assay was used to detect the effects of Rsv-AuNPs on apoptosis. Changes of protein expressions related to proliferation, invasion, migration, and apoptosis were measured by Western blot assay. In addition, the inhibitory role of Rsv-AuNPs in the PI3K/AKT/mTOR signaling pathway was verified by using PI3K inhibitor LY294002. RESULTS: Rsv-AuNPs treatment significantly suppressed proliferation, migration, and invasion of U87 cells (all P < 0.05) and increased the apoptosis rate (P < 0.05). The changes of proteins related to proliferation, migration, invasion and apoptosis were consistent (all P < 0.05). Moreover, Rsv-AuNPs treatment significantly inhibited the phosphorylation of PI3K, AKT and mTOR proteins in U87 cells (P < 0.05). CONCLUSION: The present study found that Rsv-AuNPs inhibited the proliferation, migration, and invasion of U87 cells and induced apoptosis by inhibiting the activation of PI3K/AKT/mTOR signaling pathway. In the future, Rsv-AuNPs might be applied to the clinical treatment of glioma through more in-depth animal and clinical research.

Novel resveratrol smart lipids; design, formulation, and biological evaluation of anticancer activity.

PURPOSE: Although resveratrol (RES) is an efficacious molecule, its therapeutic activity is impeded by significant limitations, such as rapid oral absorption, poor oral bioavailability, and low water solubility. Therefore, the preparation of RES in different pharmaceutical carriers represents an important tool to enhance its therapeutic applications. This study aims to potentiate the anti-cancer activity of RES by formulating it into a novel nanocarrier called Smart Lipid. METHODS: RES-loaded Smart Lipids were prepared by high-shear hot homogenization method utilizing a 21 × 32 factorial design with three factors at different levels: the total lipid concentration, the concentration of surfactant, and the type of surfactant. The responses were evaluated based on entrapment efficiency percentages and particle size. RESULTS: Our novel optimized RES-loaded Smart Lipid formula showed small particle size (288.63 ± 5.55 nm), good zeta potential (-16.44 ± 0.99 mV), and an entrapment efficiency of 86.346 ± 3.61% with spherical, clearly distinct, and no signs of fusion by transmission electron microscopy. Further characterization was done using differential scanning calorimetry, which showed no interaction between the drug and other components as the optimum lyophilized formula showed a peak at 54.75°C, which represents the lipid mixture, with an undetectable characteristic peak of the drug, which indicates entrapment of the drug, and the structure of the compounds was confirmed by Fourier transform-infrared spectroscopy, in which the majority of the drug's characteristic peaks disappeared when loaded into Smart Lipid, which may indicate Smart Lipid's ability to reduce the stretching and bending between bonds in RES. In addition, the optimized formula showed a sustained release pattern compared to RES suspension. Finally, the cytotoxic activity of the optimized RES-loaded Smart Lipid on different cell lines (human breast adenocarcinoma (MCF7), human hepatocellular carcinoma (HepG2), and human colon cancer cells (HT29)) was assessed through MTT assay (7-fold reduction in the IC50, from 3.7 ± 0.5 µM for free RES to 0.5 ± 0.033 µM for Smart Lipid loaded formula against MCF7, 3-fold reduction in the IC50 against HepG2 cells, from 10.01 ± 0.35 to 3.16 ± 0.21 µMm, and a more than 10-fold reduction in the IC50 from more than 100 to 10 ± 0.57 µM against HT-29 cells) and its effect on cell cycle progression and apoptosis induction were assessed using flow cytometry and annexin V kit, respectively. Our results showed that RES-loaded Smart Lipid significantly reduced cell viability, induced cell cycle arrest at G0/G1 phase, and apoptosis compared to free formula and free RES suspension. CONCLUSION: Loading RES into this novel kind of nanocarrier enhanced RES absorption, cellular accumulation, and improved its anticancer properties.

Integrating network pharmacology and renal metabonomics to reveal the protective mechanism of resveratrol on gouty nephropathy.

Resveratrol (Res) has been demonstrated to have beneficial effects on gouty nephropathy (GN). However, the mechanisms of Res on GN remain unclear. This study aimed to investigate the mechanisms of Res on GN. In this study, network pharmacology technology was used to predict the Res targets in the prevention and treatment of GN. Renal metabonomics was used to identify differential metabolites in kidney tissue of GN model rats. Finally, molecular docking technology was used to verify the binding ability of Res to key targets. Metabonomics analysis showed that 24 potentially important metabolites were involved in the prevention and treatment of GN with Res. After exposure to Res, metabolite levels normalized. The network pharmacology analysis showed that 24 key targets were involved in the prevention and treatment of GN disease. According to the metabolite-gene network diagram, we identified two core genes, PTGS1 and PTGS2, and found that both were involved in the arachidonic acid metabolism pathway. Molecular docking further verified the affinity of Res binding to PTGS1 and PTGS2. In conclusion, the mechanism of Res against GN may be the regulation of arachidonic acid metabolism through the regulation of PTGS 1 and PTGS 2.

Resveratrol and its metabolites elicit neuroprotection via high-affinity binding to the laminin receptor at low nanomolar concentrations.

Resveratrol prevents various neurodegenerative diseases in animal models despite reaching only low nanomolar concentrations in the brain after oral administration. In this study, based on the quenching of intrinsic tryptophan fluorescence and molecular docking, we found that trans-resveratrol, its conjugates (glucuronide and sulfate), and dihydro-resveratrol (intestinal microbial metabolite) bind with high affinities (Kd, 0.2-2 nm) to the peptide G palindromic sequence (near glycosaminoglycan-binding motif) of the 67-kDa laminin receptor (67LR). Preconditioning with low concentrations (0.01-10 nm) of these polyphenols, especially resveratrol-glucuronide, protected neuronal cells from death induced by serum withdrawal via activation of cAMP-mediated signaling pathways. This protection was prevented by a 67LR-blocking antibody, suggesting a role for this cell-surface receptor in neuroprotection by resveratrol metabolites.

Prediction of resveratrol target proteins: a bioinformatics analysis.

Resveratrol is a natural compound with a wide range of biological functions that generate health benefits under normal conditions and in multiple diseases. This has attracted the attention of the scientific community, which has revealed that this compound exerts these effects through its action on different proteins. Despite the great efforts made, due to the challenges involved, not all the proteins with which resveratrol interacts have yet been identified. In this work, using protein target prediction bioinformatics systems, RNA sequencing analysis and protein-protein interaction networks, 16 proteins were identified as potential targets of resveratrol. Due to its biological relevance, the interaction of resveratrol with the predicted target CDK5 was further investigated. A docking analysis found that resveratrol can interact with CDK5 and be positioned in its ATP-binding pocket. Resveratrol forms hydrogen bonds between its three hydroxyl groups (-OH) and CDK5 residues C83, D86, K89 and D144. Molecular dynamics analysis showed that these bonds allow resveratrol to remain in the pocket and suggest inhibition of CDK5 activity. All this allows us to better understand how resveratrol acts and to consider CDK5 inhibition within its biological actions, mainly in neurodegenerative diseases where this protein has been shown to be relevant.Communicated by Ramaswamy H. Sarma.

Nanoparticles prepared by polysaccharides extracted from Biyang floral mushroom loaded with resveratrol: Characterization, bioactivity and release behavior under in vitro digestion.

Resveratrol (RES) is a common active factor in the functional food field, but poor water solubility and low bioavailability have limited its application. In the present study, the novel nanoparticles (RES-CBFMP NPs) using floral mushroom polysaccharide as the wall material have been developed for delivering RES, aiming to overcome its application shortcomings. After ratio optimization, RES-CBFMP NPs (RES-CBFMP,1:8 w/w), which combined through the hydrogen bonds between RES and CBFMP, showed the best overall performance, with the encapsulation efficiency (EE) of 49.74 ± 0.16%, loading efficiency (LE) of 5.53 ± 0.02%, particle size of 158.56 ± 1.97 nm and zeta-potential of -17.56 ± 0.24 mV. In addition, RES-CBFMP NPs exhibited good physicochemical stabilities, sustained gastrointestinal digestive release property, as well as improved in vitro antioxidant and anticancer activities. This study may contribute to the development of RES oral delivery systems and the application of hydrophobic active molecules in the functional food field.

In Vitro Anti-Inflammatory and Antioxidant Activities of pH-Responsive Resveratrol-Urocanic Acid Nano-Assemblies.

Inflammatory environments provide vital biochemical stimuli (i.e., oxidative stress, pH, and enzymes) for triggered drug delivery in a controlled manner. Inflammation alters the local pH within the affected tissues. As a result, pH-sensitive nanomaterials can be used to effectively target drugs to the site of inflammation. Herein, we designed pH-sensitive nanoparticles in which resveratrol (an anti-inflammatory and antioxidant compound (RES)) and urocanic acid (UA) were complexed with a pH-sensitive moiety using an emulsion method. These RES-UA NPs were characterized by transmission electron microscopy, dynamic light scattering, zeta potential, and FT-IR spectroscopy. The anti-inflammatory and antioxidant activities of the RES-UA NPs were assessed in RAW 264.7 macrophages. The NPs were circular in shape and ranged in size from 106 to 180 nm. The RES-UA NPs suppressed the mRNA expression of the pro-inflammatory molecules inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-1ß (IL-1ß), and tumor necrosis factor-α (TNF-α) in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages in a concentration-dependent manner. Incubation of LPS-stimulated macrophages with RES-UA NPs reduced the generation of reactive oxygen species (ROS) in a concentration-dependent manner. These results suggest that pH-responsive RES-UA NPs can be used to decrease ROS generation and inflammation.

UPLC-MS/MS Method Development for Simultaneous Estimation of Diclofenac and Resveratrol-Loaded Liposomal Gel Formulation in Mice Skin Model: Application to Dermatokinetic Study.

The current research work describes the development of a simple, fast, sensitive and efficient bioanalytical UPLC/MS-MS method for the simultaneous estimation of diclofenac and resveratrol in mice skin samples. Quetiapine was used as an internal standard (IS). Analytical separation was performed on ACQUITY UPLC C18 Column (2.1 × 100 mm; 1.7 µm) using ammonium acetate (5 mM) in water and methanol (B) with isocratic elution at ratio of (50, 50 v/v) and flow rate of 0.4 mL/min. The duration of separation was maintained for 3 min. Electrospray ionization mass spectrometry in a positive and negative ionization mode was used for detection. Selective ion mode monitoring was used for the quantification of m/z 296.025> 249.93 for diclofenac, m/z 229.09 > 143.03 for resveratrol and MRM/ES+ve mode applied in m/z 384.25> 253.189 for IS transitions from parent to daughter ion. The lower detection and quantification limits were accomplished, and precision (repeatability and intermediate precision) with a coefficient of variation below 10% produced satisfactory results. The developed bioanalytical method was found to be useful for its suitability for the dermatokinetic evaluation of treatments through rat skin. Improvement in AUC (1.58-fold for diclofenac and 1.60-fold for resveratrol) and t1/2 in the dermis (2.13 for diclofenac and 2.21-fold for resveratrol) followed by epidermis was observed for diclofenac and resveratrol-loaded liposomal gel formulation over the conventional gel. Overall, the developed method for the dermatokinetic studies of the above-mentioned dual drugs-loaded liposome gel was found to be reproducible and effective for bioanalytical.

Sirtuin 1-Activating Compounds: Discovery of a Class of Thiazole-Based Derivatives.

Sirtuin 1 (SIRT1) is a NAD+-dependent deacetylase implicated in various biological and pathological processes, including cancer, diabetes, and cardiovascular diseases. In recent years, SIRT1-activating compounds have been demonstrated to exert cardioprotective effects. Therefore, this enzyme has become a feasible target to treat cardiovascular diseases, and many SIRT1 activators, of a natural or synthetic origin, have been identified. In the present work, we developed thiazole-based SIRT1 activators, which showed remarkably higher SIRT1 activation potencies compared with those of the reference compound resveratrol when tested in enzymatic assays. Thiazole 8, a representative compound of this series, was also subjected to further pharmacological investigations, where it was proven to reduce myocardial damage induced by an in vivo occlusion/reperfusion event, thus confirming its cardioprotective properties. In addition, the cardioprotective effect of compound 8 was significantly higher than that of resveratrol. Molecular modeling studies suggest the binding mode of these derivatives within SIRT1 in the presence of the p53-AMC peptide. These promising results could pave the way to further expand and optimize this chemical class of new and potent SIRT1 activators as potential cardioprotective agents.

Oxidized Chitin Nanocrystals Greatly Strengthen the Stability of Resveratrol-Loaded Gliadin Nanoparticles.

Resveratrol (RES) is a natural polyphenol with a variety of health beneficial properties, but its application is greatly limited due to low aqueous solubility and poor bioavailability. This study aims to address these issues via gliadin nanoparticles stabilized with oxidized chitin nanocrystals (O-ChNCs) as a delivery system for RES. RES-loaded gliadin nanoparticles (GRNPs) were fabricated by an antisolvent method, and their formation mechanism was elucidated using zeta-potential, FTIR, XRD, and TEM. Furthermore, the effect of O-ChNCs on the colloidal stability and bioactiveness of GRNPs was discussed. The results demonstrate that O-ChNCs are adsorbed onto the surface of GRNPs through hydrogen bonding and electrostatic interactions, leading to the enhanced absolute potential and the improved hydrophobicity of the particles, which in turn facilitates the stability of the GRNPs. Furthermore, the changes in the release profile and antioxidant activity of RES in the simulated gastric and intestinal tracts indicate that the adsorption of O-ChNCs not only delays the release of RES but also has a protective effect on the antioxidant capacity of RES. This study provides significant implications for developing stable gliadin nanoparticles as delivery vehicles for bioactive substances.