From ROS scavenging to boosted osseointegration: cerium-containing mesoporous bioactive glass nanoparticles functionalized implants in diabetes.

Excessive production of reactive oxygen species (ROS) around titanium implants under diabetic conditions causes persistent inflammation, leading to poor osseointegration and even implant failure. Surface modification is an effective way to promote ROS clearance, alleviate inflammation, and stimulate bone formation. In this study, a multifunctional coating is fabricated by introducing cerium (Ce)-containing mesoporous bioactive glass nanoparticles (Ce-MBGNs) onto the titanium surface via an electrophoretic deposition method. The incorporation of Ce-MBGNs remarkably improves surface hydrophilicity by increasing the surface areas. The bioactive ions are appropriately released, thereby promoting mesenchymal stem cell proliferation and differentiation under diabetic conditions. The conversion between Ce(III) and Ce(IV) endows Ce-MBGNs coating with antioxidative nanoenzymes properties to scavenge diabetes-induced ROS, resulting in macrophage polarization towards the anti-inflammatory phenotype. The therapeutic effect of Ce-MBGNs-modified titanium implants is also verified in diabetic rats by inhibiting inflammatory responses and accelerating early osseointegration. Taken together, the findings reveal that the ROS-scavenging and immunomodulation activity of the Ce-MBGNs coating contributes to enhanced osseointegration, and provides a novel implant surface for diabetic patients.

Peroxynitrite scavenger FeTPPS binds with hCT to effectively inhibit its amyloid aggregation.

Human calcitonin (hCT) is an endogenous polypeptide commonly employed in treating bone resorption-related illnesses, but its clinical application is limited due to its high aggregation tendency. Metalloporphyrins are effective in suppressing amyloid fibrillation, positioning them as potential drug candidates for amyloidogenic disorders like Alzheimer's and type 2 diabetes. In this work, we investigated the effects of Fe(III) meso-tetra(4-sulfonatophenyl)porphine chloride (FeTPPS), a highly efficient ONOO- decomposition catalyst, on hCT aggregation. Our findings reveal that FeTPPS effectively precludes hCT fibrillation by stabilizing the monomers and delaying the structural transition from α-helix bundles to ß-sheet-rich aggregates. The macrocyclic ring of FeTPPS plays a significant role in disrupting hCT self-associations. Among various porphyrin analogs, those with an iron center and negatively charged peripheral substituents exhibit a stronger inhibitory effect on hCT aggregation. Spectroscopic analyses and computational simulations indicate that FeTPPS binds to hCT's core aggregation region via complexation with His20 in a 1 : 1 molar ratio. Hydrophobic interaction, hydrogen bonding, and π-π stacking with the residues involving Tyr12, Phe19, and Ala26 also contribute to the interactions. Collectively, our study provides a promising approach for developing novel hCT drug formulations and offers theoretical guidance for designing metalloporphyrin-based inhibitors for various amyloidosis conditions.

Oral antioxidant edaravone protects against cognitive deficits induced by chronic hypobaric hypoxia at high altitudes.

Chronic hypobaric hypoxia at high altitudes can impair cognitive functions, especially causing deficits in learning and memory, which require therapeutic intervention. Here, we showed that mice subjected to hypobaric hypoxia (simulating an altitude of 5000 m) for one month experienced significant cognitive impairment, accompanied by increased biomarker levels of oxidative stress in the brain and blood. Oral administration of a novel formulation of edaravone, a free radical scavenger approved for the treatment of ischaemic stroke and amyotrophic lateral sclerosis, significantly alleviated oxidative stress and cognitive impairments caused by chronic hypobaric hypoxia. Furthermore, oral edaravone treatment also mitigated neuroinflammation and restored hippocampal neural stem cell exhaustion. Additionally, periostin (Postn) is vital in the cognitive deficits caused by chronic hypobaric hypoxia and may be a molecular target of edaravone. In conclusion, our results suggest that oxidative stress plays a crucial role in the cognitive deficits caused by chronic hypobaric hypoxia and that oral edaravone is a potential medicine for protecting against cognitive deficits caused by chronic hypobaric hypoxia in high-altitude areas.

In vitro 5-LOX inhibitory and antioxidant potential of isoxazole derivatives.

5-Lipoxygenase (5-LOX) is a key enzyme involved in the biosynthesis of pro-inflammatory leukotrienes, leading to asthma. Developing potent 5-LOX inhibitors are highly attractive. In this research the previously synthesized isoxazole derivatives has been investigated against 5-LOX inhibitory and antioxidant in vitro assay. The compound 3 caused concentration dependent inhibition of 5-LOX with overall IC50 value of 8.47 µM. The investigated compounds C5 also exhibited good 5-LOX inhibitory effect. The IC50 demonstrated for C5 was 10.48. Among the 10 synthesized compounds, the potential 5-LOX inhibitory effect was reported for C6. The most potent compound which showed excellent free radical scavenging effect was C3 having IC50 value of 10.96 µM. The next most potent antioxidant activity was reported for C5 which non-significantly showed free radical scavenging effect. The IC50 value observed for C5 was 13.12 µM. Compound C6 also showed potent dose dependent antioxidant effect with IC50 value of 18.87 µM having percent inhibition of 91.63±0.55, 88.45±0.49, 83.53±0.45, 78.42±0.66 and 73.72±0.64 at concentration 1000-62.5 µg/mL respectively. Among the tested compounds, C6 was found most potent which showed significant 5-LOX percent inhibition assay and also reported the minimum IC50 value comparable to the reference drug. The in vitro 5-LOX enzymes inhibition assays of C5 and C3 also showed excellent percent inhibition and good potency next to C6. We concluded that amongst the investigated designed molecules the C3 was found best potent and showed significant dose dependent antioxidant activity against DPPH screening. The IC50 value reported for C3 was found good as compared to standard drug. Moreover, C5 and C6 also showed excellent free radical scavenging effect against DPPH assay. Computational methods have also been employed to explore the probable interaction model of inhibitors and enzyme active sites, and also to correlate the results of in silico and in vitro studies.

Functional Properties and Components of Koenigia alpina Extract.

BACKGROUND: Koenigia alpina (All.) T.M.Schust. & Reveal (alpine knotweed) is a perennial herb belonging to the Polygonaceae family. Several studies have examined Polygonaceae species' potential applications as cosmeceutical materials; however, the potential of K. alpina as a cosmeceutical has not yet been studied. MATERIALS AND METHODS: Hydrogen peroxide (H2O2) and lipopolysaccharide were used to induce an inflammatory response in RAW 264.7 cells. 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radicals and H2O2 were used to evaluate the free-radical scavenging activity of K. alpina extract and its protective effect against reactive oxygen species (ROS)-induced cell damage. The whitening, antiaging, and cell proliferation/migration effects of the extracts were evaluated via tyrosinase inhibition, collagenase/elastase inhibition, and wound healing assays, respectively. The anti-inflammatory effect was confirmed by evaluating nitric oxide (NO) production in RAW 264.7 cells. High-performance liquid chromatography (HPLC), UV, and MS/MS were used to determine the main components of the extract and fractions. RESULTS: The ethyl acetate (EA) fraction and its aglycone fraction showed very high free-radical scavenging activities (47.5 and 47.1 µg/mL, respectively). The extract/fractions also showed significant tyrosinase inhibition (IC50 = 0.38 mg/mL in EA fraction), collagenase inhibition (IC50 = 0.21 mg/mL in EA fraction), and elastase inhibition (IC50 = 0.57 mg/mL in aglycone fraction). NO production in lipopolysaccharide-induced RAW 264.7 cells was inhibited by the extract/fractions. The extract also promoted the closure of scratch wounds in HaCaT cells. The K. alpina extract/fractions contained cardamonin, quercetin, and quercitrin. CONCLUSION: K. alpina extracts/fractions showed antioxidant, antiaging, whitening, and anti-inflammatory activities, suggesting they may have potential as antiaging cosmeceuticals.

Cholesteryl Phenolipids as Potential Biomembrane Antioxidants.

The lipophilization of polyphenols (phenolipids) may increase their affinity for membranes, leading to better antioxidant protection. Cholesteryl esters of caffeic, dihydrocaffeic, homoprotocatechuic and protocatechuic acids were synthetized in a one-step procedure with good to excellent yields of ~50-95%. After evaluation of their radical scavenging capacity by the DPPH method and establishing the anodic peak potential by cyclic voltammetry, their antioxidant capacity against AAPH-induced oxidative stress in soybean PC liposomes was determined. Their interaction with the liposomal membrane was studied with the aid of three fluorescence probes located at different depths in the membrane. The cholesteryl esters showed a better or similar radical scavenging capacity to that of α-tocopherol and a lower anodic peak potential than the corresponding parental phenolic acids. Cholesteryl esters were able to protect liposomes to a similar or greater extent than α-tocopherol. However, despite their antiradical capacity and being able to penetrate and orientate in the membrane in a parallel position to phospholipids, the antioxidant efficiency of cholesteryl esters was deeply dependent on the phenolipid polyphenolic moiety structure. When incorporated during liposome preparation, cholesteryl protocatechuate and caffeate showed more than double the activity of α-tocopherol. Thus, cholesteryl phenolipids may protect biomembranes against oxidative stress to a greater extent than α-tocopherol.

Streptomyces sp. from desert soil as a biofactory for antioxidants with radical scavenging and iron chelating potential.

Iron homeostasis is vital for normal physiology, but in the majority of circumstances, like iron overload, this equilibrium is upset leading to free iron in the plasma. This condition with excess iron is known as hemochromatosis, which has been linked to many side effects, including cancer and liver cirrhosis. The current research aimed to investigate active molecules from Streptomyces sp. isolated from the extreme environment of Bahawalpur deserts. The strain was characterized using 16 S rRNA sequencing. Chemical analysis of the ethyl acetate cure extract revealed the presence of phenols, flavonoids, alkaloids, and tannins. Multiple ultraviolet (UV) active metabolites that were essential for the stated pharmacological activities were also demonstrated by thin layer chromatography (TLC) and high-performance liquid chromatography (HPLC). Additionally, Gas chromatography/mass spectrometry (GC-MS) analysis revealed the primary constituents of the extract to compose of phenol and ester compounds. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay was used to assess the extract's antioxidant capacity, and the results showed a good half-maximal inhibitory concentration (IC50) value of 0.034 µg/mL in comparison to the positive control ascorbic acid's 0.12 µg/mL. In addition, iron chelation activity of extract showed significant chelation potential at 250 and 125 µg/mL, while 62.5 µg/mL showed only mild chelation of the ferrous ion using ethylene diamine tetra acetic acid (EDTA) as a positive control. Likewise, the extract's cytotoxicity was analyzed through 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay using varying concentrations of the extract and showed 51% cytotoxicity at 350 µg/mL and 65% inhibition of cell growth at 700 µg/mL, respectively. The bioactive compounds from Streptomyces sp. demonstrated strong antioxidant and iron chelating potentials and can prolong the cell survival in extreme environment.

The inhibitory potential of 4,7-dihydroxycoumarin derivatives on ROS-producing enzymes and direct HOO•/o2• - radical scavenging activity - a comprehensive kinetic DFT study.

This study examined the antiradical activity of three synthesized coumarin derivatives: (E)-3-(1-((2-hydroxyphenyl)amino)ethylidene)-2,4-dioxochroman-7-yl acetate (A1-OH), (E)-3-(1-((3-hydroxyphenyl)amino)ethylidene)-2,4-dioxochroman-7-yl acetate (A2-OH), and (E)-3-(1-((4-hydroxyphenyl)amino)ethylidene)-2,4-dioxochroman-7-yl acetate (A3-OH) against HOO•/O2•- radical species. The investigation included electron spin resonance (ESR) measurements and a DFT kinetic study. Thermodynamic and kinetic parameters of antiradical mechanisms-Formal Hydrogen Atom Transfer (f-HAT), Radical Adduct Formation (RAF), Sequential Proton Loss followed by Electron Transfer (SPLET), and Single-Electron Transfer followed by Proton Transfer (SET-PT)-were evaluated using the Quantum Mechanics-based test for Overall Free Radical Scavenging Activity (QM-ORSA) under physiological conditions. ESR results indicated antiradical activity decreased in the sequence A1-OH (58.7%) > A2-OH (57.5%) > A3-OH (53.1%). Kinetic analysis revealed the f-HAT mechanism dominated HOO• inactivation. A newly formulated Sequential Proton Loss followed by Radical Adduct Formation (SPL-RAF) mechanism described interactions with O2•-. The activity toward O2•- was A2-OH (1.26 × 106 M-1s-1) > A3-OH (7.71 × 105 M-1s-1) > A1-OH (4.22 × 105 M-1s-1). Molecular docking and dynamics studies tested inhibitory capability against enzymes producing reactive species: Lipoxygenase (LOX), Myeloperoxidase (MPO), NAD(P)H oxidase (NOX), and Xanthine Oxidase (XOD). Affinity to enzymes decreased in the order: XOD > LOX > NOX > MPO.

Exopolysaccharide from Leuconostoc mesenteroides XR1: Yield optimization, partial characterization and properties.

The production conditions of exopolysaccharide (EPS) from Leuconostoc mesenteroides XR1 were optimized by response surface methodology (RSM). Maximum EPS yield was 56.59 ± 0.51 g/L under fermentation conditions with 2.6 g/L ammonium citrate, initial pH 6.5 and temperature 23 °C, which was 6.21-fold greater than the EPS yield before optimization. Characterization of the chain conformation using Congo red test and circular dichroism (CD) showed that EPS exhibited a random coil structure in aqueous solution. The CD results revealed that the EPS concentration altered its hydrogen-bond interactions and chirality, but did not change its chain conformation. The average polydispersity index (PDI) of the EPS solution was only 27.16 %, indicating that it was uniformly distributed in the aqueous solution with high stability. The degradation temperature of EPS was 253.11 °C, indicating high thermal stability. EPS possessed the ability to scavenge activities of free radicals and was protective against oxidative stress-induced plasmid DNA damage. In addition, stable hydrogels could be formed at EPS concentrations above 5 % (w/v). These results collectively showed that EPS can be used commercially as an antioxidant and drug delivery carrier.

pH-Dependent Extraction of Antioxidant Peptides from Red Seaweed Palmaria palmata: A Sequential Approach.

This study employed a diverse approach to extract antioxidant peptides from red seaweed Palmaria palmata, recognized for its comparatively high protein content. Initially, an aqueous extraction of the entire seaweed was performed, followed by enzymatic hydrolysis of the solid residues prepared from the first step. The effects of three different pH levels (3, 6, and 9) during the aqueous extraction were also examined. Results indicated that the solid fraction from the sequential extraction process contained significantly higher levels of proteins and amino acids than other fractions (p < 0.05). Furthermore, the solid fractions (IC50 ranging from 2.29 to 8.15 mg.mL-1) demonstrated significantly greater free radical scavengers than the liquid fractions (IC50 ranging from 9.03 to 10.41 mg.mL-1 or not obtained at the highest concentration tested) at both stages of extraction (p < 0.05). Among the solid fractions, those produced fractions under alkaline conditions were less effective in radical scavenging than the produced fractions under acidic or neutral conditions. The fractions with most effective metal ion chelating activity were the solid fractions from the enzymatic stage, particularly at pH 3 (IC50 = 0.63 ± 0.04 mg.mL-1) and pH 6 (IC50 = 0.89 ± 0.07 mg.mL-1), which were significantly more effective than those from the initial extraction stage (p < 0.05). Despite no significant difference in the total phenolic content between these solid fractions and their corresponding liquid fractions (3.79 ± 0.05 vs. 3.48 ± 0.02 mg.mL-1 at pH 3 and 2.43 ± 0.22 vs. 2.51 ± 0.00 mg.mL-1 at pH 6) (p > 0.05), the observed antioxidant properties may be attributed to bioactive amino acids such as histidine, glutamic acid, aspartic acid, tyrosine, and methionine, either as free amino acids or within proteins and peptides.

Effect of UV Radiation and Temperature on Radical Scavenging Activity of Hippophaë rhamnoides L. and Vaccinium oxycoccos L. Fruit Extracts.

New active ingredients, including those of plant origin, which could protect the skin against various harmful factors, such as UV radiation and free radicals responsible for skin ageing, are still being sought. The present study was focused on the antioxidant activity of Hippophaë rhamnoides L. and Vaccinium oxycoccos L. fruit glycolic extracts. Investigations were also carried out to evaluate the effect of UVA radiation and the storage of the sea buckthorn and European cranberry extracts at an elevated temperature of 50 °C on their interactions with free radicals. The kinetics of the interactions of the extracts with DPPH were assessed using electron paramagnetic resonance (EPR) spectroscopy. The sea buckthorn and European cranberry extracts quench the EPR signal of DPPH free radicals, which indicates their antioxidant potential. The EPR method further showed that a mixture of sea buckthorn and cranberry extracts in a volume ratio of 2:1 was more potent in quenching free radicals compared to a mixture of these extracts in a ratio of 1:2. Our findings demonstrate that long-term UVA radiation exposure reduces the ability of sea buckthorn and cranberry extracts to interact with free radicals. Moreover, storage at elevated temperatures does not affect the interaction of sea buckthorn extract with free radicals, while it alters the ability of cranberry extract to interact with free radicals. This study has demonstrated that an important factor in maintaining the ability to scavenge radicals is the storage of raw materials under appropriate conditions. H. rhamnoides and V. oxycoccos extracts can be used as valuable raw materials with antioxidant properties in the pharmaceutical and cosmetic industries.

The Enhancement Origin of Antioxidant Property of Carboxylated Lignin Isolated from Herbaceous Biomass Using the Maleic Acid Hydrotropic Fractionation.

Lignin is endowed with antioxidant activity due to its diverse chemical structure. It is necessary to explore the relationship between antioxidant activity and the chemical structure of the lignin to develop its high-value utilization. Herein, we employed maleic acid (MA) as a hydrotropic agent to preferably isolate the lignin from distinct herbaceous sources (wheat straw and switchgrass) under atmospheric pressure conditions. The resultant acid hydrotropic lignin (AHL) isolated from wheat straw exhibited high radical scavenging rates, up to 98% toward DPPH and 94% toward ABTS. Further investigations indicated that during the MA hydrotropic fractionation (MAHF) process, lignin was carboxylated by MA at γ-OH of the side-chain, providing additional antioxidant activity from the carboxy group. It was also found that the radical scavenging rate of AHL has a positive correlation with carboxyl, phenolic hydroxyl contents, and the S-G (syringyl-guaiacyl) ratio, which could be realized by increasing the MAHF severity. Overall, this work underlies the enhancement origin of the antioxidant property of lignin, which will facilitate its application in biological fields as an efficient, cheap, and renewable antioxidant additive.

Extraction of polysaccharide fraction from cadamba (Neolamarckia cadamba) fruits and evaluation of its in vitro and in vivo antioxidant activities.

In this study, polysaccharide fraction (PFFNC) derived from Neolamarckia cadamba fruits showed remarkable antioxidant activity. The PFFNC was successfully extracted from the fruits by the hot water extraction process, followed by decolorization, defatting, and deproteinization. The chemical composition of PFFNC was effectively characterized by the use of UV-Vis, FT-IR, CHN, GC-MS, and 13C NMR spectroscopy. The findings indicated that PFFNC had an average molecular weight of 292 kDa and was predominantly composed of carbohydrates (76 %), with notable contributions from uronic acids (37.22 %) and proteins (12.35 %). The primary components of the sugar content were glucose (19.24 %), galactose (10.19 %), mannose (4.09 %), and glucuronic acid (2.8 %). The tertiary structural study verified the existence of a triple-helical structure. PFFNC exhibited a strong reducing power in vitro as determined by ABTS (IC50: 121 ± 0.12 µg/mL), DPPH (IC50: 146.065 ± 0.54 µg/mL), FRAP (677.788 ± 24.189 mM Fe (II)/g), hydroxyl radical scavenging (IC50: 78.736 ± 0.32 µg/mL), and phosphomolybdate assay (90.7 ± 0.43 mg AAE/g). In addition, the PFFNC furthermore showed significant in vivo antioxidant capacity, as determined using the brine shrimp (Bsmp) (Artemia salina Leach) model. The PFFNC exhibits significant antioxidant potential, suggesting broad spectrum applications in pharmaceuticals, nutraceuticals, and oxidative stress-related disorders.

Hybrid nanoparticle-mediated simultaneous ROS scavenging and STING activation improve the antitumor immunity of in situ vaccines.

In situ vaccine (ISV) is a versatile and personalized local immunotherapeutic strategy. However, the compromised viability and function of dendritic cells (DCs) in a tumor microenvironment (TME) largely limit the therapeutic efficacy. We designed a hybrid nanoparticle-based ISV, which accomplished superior cancer immunotherapy via simultaneously scavenging reactive oxygen species (ROS) and activating the stimulator of interferon genes (STING) pathway in DCs. This ISV was constructed by encapsulating a chemodrug, SN38, into diselenide bond-bridged organosilica nanoparticles, followed by coating with a Mn2+-based metal phenolic network. We show that this ISV can activate the STING pathway through Mn2+ and SN38 comediated signaling and simultaneously scavenge preexisting H2O2 in the TME and Mn2+-catalyzed •OH by leveraging the antioxidant property of diselenide and polyphenol. This ISV effectively activated DCs and protected them from oxidative damage, leading to remarkable downstream T cell activation and systemic antitumor immunity. This work highlights a nanoparticle design that manipulates DCs in the TME for improving the ISV.

Investigation of the Structural Properties and Antioxidant Potency of Pectic Polysaccharides Derived from Rohdea japonica (Thunb.) Roth.

This study investigated the structural composition and antioxidant properties of pectic polysaccharides extracted from Rohdea japonica (Thunb.) Roth. Pectins, which belong to a complex category of acidic polysaccharides, possess a wide range of biological effects stemming from their distinctive structural domains. The polysaccharides were extracted using water, and were subsequently purified through ion exchange and gel permeation chromatography. In order to elucidate their structural features, Fourier Transform Infrared Spectroscopy and Nuclear Magnetic Resonance techniques were applied. Two specific polysaccharides, WRJP-A2a and WRJP-A3b, with molecular weights of 42.7 kDa and 64.1 kDa, respectively, were identified to contain varying proportions of homogalacturonan, rhamnogalacturonan I, and rhamnogalacturonan II domains. Regarding antioxidant capacity, WRJP-A3b exhibited superior scavenging capabilities against DPPH, ABTS, and hydroxyl radicals, potentially attributed to its higher galacturonic acid content and abundance of homogalacturonan domains. These results enhance our comprehension of the structure-activity interplay of pectic polysaccharides sourced from Rohdea japonica (Thunb.) Roth and their potential utility in the healthcare and functional food sectors.

Amphetamine-like Deferiprone and Clioquinol Derivatives as Iron Chelating Agents.

The accumulation of iron in dopaminergic neurons can cause oxidative stress and dopaminergic neuron degeneration. Iron chelation therapy may reduce dopaminergic neurodegeneration, but chelators should be targeted towards dopaminergic cells. In this work, two series of compounds based on 8-hydroxyquinoline and deferiprone, iron chelators that have amphetamine-like structures, have been designed, synthesized and characterized. Each of these compounds chelated iron ions in aqueous solution. The hydroxyquinoline-based compounds exhibited stronger iron-binding constants than those of the deferiprone derivatives. The hydroxyquinoline-based compounds also exhibited greater free radical scavenging activities compared to the deferiprone derivatives. Molecular dynamics simulations showed that the hydroxyquinoline-based compounds generally bound well within human dopamine transporter cavities. Thus, these compounds are excellent candidates for future exploration as drugs against diseases that are affected by iron-induced dopaminergic neuron damage, such as Parkinson's disease.

A low-swelling alginate hydrogel with antibacterial hemostatic and radical scavenging properties for open wound healing.

Development of a low-cost and biocompatible hydrogel dressing with antimicrobial, antioxidant, and low swelling properties is important for accelerating wound healing. Here, a multifunctional alginate hydrogel dressing was fabricated using the D-(+)-gluconic acidδ-lactone/CaCO3system. The addition of hyaluronic acid and tannic acid (TA) provides the alginate hydrogel with anti-reactive oxygen species (ROS), hemostatic, and pro-wound healing properties. Notably, soaking the alginate hydrogel in a poly-ϵ-lysine (EPL) aqueous solution enables the alginate hydrogel to be di-crosslinked with EPL through electrostatic interactions, forming a dense network resembling 'armor' on the surface. This simple one-step soaking strategy provides the alginate hydrogel with antibacterial and anti-swelling properties. Swelling tests demonstrated that the cross-sectional area of the fully swollen multifunctional alginate hydrogel was only 1.3 times its initial size, thus preventing excessive wound expansion caused by excessive swelling. After 5 h ofin vitrorelease, only 7% of TA was cumulatively released, indicating a distinctly slow-release behavior. Furthermore, as evidenced by the removal of 2,2-diphenyl-1-picrylhydrazyl free radicals, this integrated alginate hydrogel systems demonstrate a notable capacity to eliminate ROS. Full-thickness skin wound repair experiment and histological analysis of the healing site in mice demonstrate that the developed multifunctional alginate hydrogels have a prominent effect on extracellular matrix formation and promotion of wound closure. Overall, this study introduces a cost-effective and convenient multifunctional hydrogel dressing with high potential for clinical application in treating open wounds.

Synthesis, Antioxidant Activity, and Molecular Docking of Novel Paeoniflorin Derivatives.

Paeoniflorin (PF) is one of the active constituents of the traditional Chinese medicine Paeoniae Radix Rubra and has been actively explored in the pharmaceutical area due to its numerous pharmacological effects. However, severe difficulties such as limited bioavailability and low permeability limit its utilization. Therefore, this study developed and synthesized 25 derivatives of PF, characterized them by 1H NMR, 13C NMR, and HR-MS, and evaluated their antioxidant activity. Firstly, the antioxidant capacity of PF derivatives was investigated through DPPH radical scavenging experiment, ABTS radical scavenging experiment, reducing ability experiment, and O2 .- radical scavenging experiment. PC12 cells are routinely used to evaluate the antioxidant activity of medicines, therefore we utilize it to establish a cellular model of oxidative stress. Among all derivatives, compound 22 demonstrates high DPPH radical scavenging capacity, ABTS radical scavenging ability, reduction ability, and O2 .- radical scavenging ability. The results of cell tests reveal that compound 22 has a non-toxic effect on PC12 cells and a protective effect on H2O2-induced oxidative stress models. This might be due to the introduction of 2, 5-difluorobenzene sulfonate group in PF, which helps in scavenging free radicals under oxidative stress. Western blot and molecular docking indicated that compound 22 may exert antioxidant activity by activating Nrf2 protein expression. As noted in the study, compound 22 has the potential to be a novel antioxidant.

Thiol-containing hyperbranched polysiloxane for scavenging reactive oxygen species.

Unconventional luminescent polymers have attracted considerable attention in the biological field due to their intrinsic fluorescence properties and excellent biocompatibility. However, exploring the luminescent properties of thiol-containing polymers and the mechanism of their scavenging of ROS remains unclear. In this work, we synthesised three kinds of hyperbranched polysiloxanes (HE, HP, and HB) with terminal thiol groups containing different chain lengths by the polycondensation reaction. Surprisingly, HP exhibits longer-wavelength emission at 480 nm with a quantum yield of 12.23% compared to HE and HB. Experiments and density functional theory (DFT) calculations have revealed that the rigidity of the conformation is enhanced by substantial hydrogen bonds and through-space O⋯O interactions in the polymer structure. These interactions, combined with the rigid carbon chains, balance the flexibility of the Si-O-C chain segments, which emerges as a critical factor contributing to the superior fluorescence performance of HP. In addition, HP exhibits excellent biocompatibility and ROS scavenging ability with a scavenging capacity of up to 35.095%. This work provides a new fluorescent polymer for scavenging ROS for the treatment of ROS-related diseases.

Polyphenolic metacyclophane as a radical scavenger for therapeutic activation: a computational study.

Modeling antioxidants for improved human health is a prime area of research. Inclusion complexes exhibit antioxidant activity. Supramolecular scaffolds like calixtyrosol are anticipated to have considerable antioxidant and therapeutic activity. In this study, we have designed 30 polyphenolic metacyclophanes and investigated their antioxidant properties. Exceptional O─H bond dissociation energy of 44 kcal/mol is reported for a metacyclophane with acyl urea linkage. This may be explained through a cooperative effect of localization of spin density distribution and an intramolecular hydrogen bonding of the corresponding radical. Further, the pharmacokinetics and toxicity analysis screened eight drug-like candidates. The interaction of the eight screened molecules with the Lysozyme transport protein and SOD protein has been studied using the molecular docking approach. Lastly, the MD simulations are performed to analyze the conformational changes of the transport protein after complexation with the proposed molecules. Comprehensive analyses including density functional studies of physiological parameters, favorable pharmacokinetics, toxicity, molecular docking, and MD simulations affirmed polyphenolic metacyclophane XXI as a radical scavenging and drug-like candidate.