Inherent Antioxidant Research Articles

Bench to Any Side—The Pharmacology and Applications of Natural and Synthetic Alkylated Hydroxy Cinnamates and Cinnamides

Natural alkylated hydroxy cinnamates (AHCs) isolated from medicinal plants and the thereby designed and synthesized cinnamides are derivatives of hydroxy cinnamic acids such as p-coumaric, sinapic, ferulic, and caffeic acids, which are naturally derived from human dietary sources. The pharmacological properties displayed by AHCs based on their inherent structure range include antioxidant, antimicrobial, antiplasmodial, anti-tyrosinase, Alzheimer’s and Parkinson’s disease therapy, anticancer therapy, metabolic disease therapy, and biopesticides, which have not been reviewed together. Based on their inherent antioxidant, antimicrobial, and UV absorption and their structure–activity relationships, these cinnamyl esters and amides can be used for food preservation in emulsions and oils, as sun-protective components of skin care formulations, and in many other multifunctional applications. In conclusion, the fine-tuning of the structural features such as the type of hydroxy cinnamic acid used, the length of alkyl chains for variable lipophilicity, conversion from cinnamic to propanoic for antioxidants, the increase in methoxy or the change to amino groups to increase the molar absorption coefficient and loss of absorption values, the substitution by halides or amino groups for potent biopesticides, and conversion from esters to amide bonds leads to different AHCs for biomedical, cosmetic, and agriculture applications as an emerging field of investigation that can overall provide natural, safe, biodegradable, and sustainable molecules.

Self-Exfoliated Guanidinium Covalent Organic Nanosheets as High-Capacity Curcumin Carrier.

Drug administration is commonly used to treat chronic wounds but faces challenges such as poor bioavailability, instability, and uncontrollable release. Existing drug delivery platforms are limited by chemical instability, poor functionality, complex synthesis, and toxic by-products. Presently, research efforts are focused on developing novel drug carriers to enhance drug efficacy. Guanidinium Covalent Organic Nanosheets (gCONs) offer promising alternatives due to their high porosity, surface area, loading capacity, and ability to provide controlled, sustained, and target-specific drug delivery. Herein, we successfully synthesized self-exfoliated gCONs using a Schiff base condensation reaction and embedded curcumin (CUR), a polyphenolic pleiotropic drug with antioxidant and anti-inflammatory properties, via the wet impregnation method. The BET porosimeter exhibited the filling of gCON pores with CUR. Morphological investigations revealed the formation of sheet-like structures in gCON. Culturing human dermal fibroblasts (hDFs) on gCON demonstrated cytocompatibility even at a concentration as high as 1000 µg/mL. Drug release studies demonstrated a controlled and sustained release of CUR over an extended period of 5 days, facilitated by the high loading capacity of gCON. Furthermore, the inherent antioxidant and anti-inflammatory properties of CUR were preserved after loading into the gCON, underscoring the potential of CUR-loaded gCON formulation for effective therapeutic applications. Conclusively, this study provides fundamental information relevant to the performance of gCONs as a drug delivery system and the synergistic effect of CUR and CONs addressing issues like drug bioavailability and instability.

Prolonging the oxidative stability of walnut oil by endogenous antioxidants: Phytosterol compounding for improved antioxidant capacity

Walnut oil, loaded with unsaturated fatty acids, offers significant health advantages yet is greatly vulnerable to oxidative spoilage.The investigation explored the impact of four oil extraction techniques on the inherent antioxidants, fatty acid profiles, antioxidant efficacy, and oxidation stability index (OSI) of walnut oil. The investigation utilized variance analysis coefficients and partial least squares regression analyses were conducted. It identified β-sitosterol and stigmasterol as crucial inherent antioxidant compounds. The maximal concentrations achieved through hot pressing were 943.16 mg/kg for β-sitosterol and 121.54 mg/kg for stigmasterol. Stigmasterol contribution to the DPPH radical scavenging activity was found to be 0.8224 in PLS1 (R2>0.95). Consequently, the combined effect of these antioxidants on the OSI was tested., revealing that a 2:1 ratio of these substances, under conditions of 45 ℃ ultrasound temperature and 27 minutes ultrasound duration(p<0.05), improved the OSI from 2 to 6.42.

Yellow Mustard Protein a Immunoreactivity Reduction Through Seed Germination, Lactic Acid Fermentation, and Cooking.

Food allergens are becoming increasingly threatening and are disrupting the health and social structure of a significantly large population worldwide. Proteins from mustard are among the well-recognized food allergens which affect many sensitive individuals. Many processing methods are continually being explored to reduce allergen immunoreactivity and for developing hypoallergenic foods. Cooking, germination, and fermentation have been evaluated to attenuate the immunoreactivity of food allergens. The objective of this study is to evaluate the effect of seed germination, lactic acid fermentation, and/or cooking on yellow mustard seed protein immunoreactivity (IR) (protein A) using ELISA techniques. Samples from five-day germination at 35-40 °C and three-day fermentation between 25 °C and 35 °C were evaluated. The germination and fermentation processes yielded varying reductions in the IRs of mustard proteins, with a combined yield of about 90% reduction. When complemented with further stovetop cooking, protein IR reduction was extended up to 98%, while cooking alone resulted only in about a 70% reduction. FTIR results confirmed that changes in mustard protein conformation maybe due to the unfolding and/or denaturation of mustard proteins. These processing methods are beneficial as they not only help reduce the native mustard protein IR, but also increased inherent antioxidant activities in germinated and fermented mustard seeds.

VEGF-loaded ROS-responsive nanodots improve the structure and function of sciatic nerve lesions in type II diabetic peripheral neuropathy

Diabetic peripheral neuropathy (DPN) is a prevalent complication of diabetes mellitus (DM), significantly contributing to the risk of amputation and mortality. Reactive oxygen species (ROS) can induce both neurological and structural harm through direct impact and pyroptosis, underscoring the critical role of ROS regulation in mitigating DPN. In this research endeavor, we propose harnessing the inherent antioxidant properties of sulfhydryl groups by grafting them onto gold nanodots through an amidation reaction, resulting in the creation of ROS-responsive AuNDs. Additionally, we aim to synthesize AuNDs-VEGF, wherein VEGF is attached to AuNDs via electrostatic interactions, as a therapeutic strategy for addressing DPN in rat models. The results of in vivo experiments showed that AuNDs and AuNDs-VEGF nanoparticles could increase the nerve conduction velocity, shorten the latency of nerve conduction in the sciatic nerve, promote the regeneration of nerve trophectodermal vessels, improve the structure and function of the sciatic nerve, reduce the apoptosis of neural cells, and alleviate the atrophy of the gastrocnemius muscle. Thus, VEGF-loaded ROS-responsive nanodots present a promising avenue for ameliorating diabetic peripheral neuropathy. This innovative approach not only extends the application possibilities of nanodots but also introduces a novel avenue for the treatment of diabetic neuropathy.

Multimodal Photodynamic Therapy by Inhibiting the Nrf2/ARE Signaling Pathway in Tumors.

Photodynamic therapy (PDT) has been widely used in the clinical therapy of various tumors, especially superficial tumors. However, the tumor microenvironment presents hypoxia, as well as the inherent antioxidant system (e.g., Nrf2) of tumor cells limits the therapeutic outcomes. Herein, a cascade-responsive "oxidative stress amplifier" (named EZ@TD) is designed by encapsulating manganese-doped carbon dots acting as a photosensitizer and catalase (CAT)-like nanozyme within pH-sensitive ZIF-8 and Zn2+-activated DNAzyme for relieving hypoxia and efficient Nrf2 gene disruption to enhance PDT. It is demonstrated that EZ@TD synergistically inhibited tumor growth and activated the antitumor immune response by inhibiting the Nrf2/ARE signaling pathway in tumors. We provide a new paradigm for amplifying intracellular oxidative stress by interfering with various signaling pathways.

Isolation and Structural Characterization of Natural Deep Eutectic Solvent Lignin from Brewer's Spent Grains.

Brewer's spent grains (BSG) offer valuable opportunities for valorization beyond its conventional use as animal feed. Among its components, lignin-a natural polymer with inherent antioxidant properties-holds significant industrial potential. This work investigates the use of microwave-assisted extraction combined with acidic natural deep eutectic solvents (NaDESs) for efficient lignin recovery, evaluating three different NaDES formulations. The results indicate that choline chloride-lactic acid (ChCl-LA), a NaDES with superior thermal stability as confirmed via thermogravimetric analysis (TGA), is an ideal solvent for lignin extraction at 150 °C and 15 min, achieving a balance of high yield and quality. ChCl-LA also demonstrated good solubility and cell disruption capabilities, while microwaves significantly reduced processing time and severity. Under optimal conditions, i.e., 150 °C, 15 min, in the presence of ChCl-LA NaDES, the extracted lignin achieved a purity of up to 79% and demonstrated an IC50 (inhibitory concentration 50%) of approximately 0.022 mg/L, indicating a relatively strong antioxidant activity. Fourier transform infrared (FTIR) and 2D-HSQC NMR (heteronuclear single quantum coherence nuclear magnetic resonance) spectroscopy confirmed the successful isolation and preservation of its structural integrity. This study highlights the potential of BSG as a valuable lignocellulosic resource and underscores the effectiveness of acidic NaDESs combined with microwave extraction for lignin recovery.

Stretchable, Self-Healing, and Bioactive Hydrogel with High-Functionality N,N'-bis(acryloyl)cystamine Dynamically Bonded Ag@polydopamine Crosslinkers for Wearable Sensors.

Hydrogels present attractive opportunities as flexible sensors due to their soft nature and tunable physicochemical properties. Despite significant advances, practical application of hydrogel-based sensor is limited by the lack of general routes to fabricate materials with combination of mechanical, conductive, and biological properties. Here, a multi-functional hydrogel sensor is reported by in situ polymerizing of acrylamide (AM) with N,N'-bis(acryloyl)cystamine (BA) dynamic crosslinked silver-modified polydopamine (PDA) nanoparticles, namely PAM/BA-Ag@PDA. Compared with traditional polyacrylamide (PAM) hydrogel, the BA-Ag@PDA nanoparticles provide both high-functionality crosslinks and multiple interactions within PAM networks, thereby endowing the optimized PAM/BA-Ag@PDA hydrogel with significantly enhanced tensile/compressive strength (349.80kPa at 383.57% tensile strain, 263.08kPa at 90% compressive strain), lower hysteresis (5.2%), improved conductivity (2.51 S m-1) and excellent near-infrared (NIR) light-triggered self-healing ability. As a strain sensor, the PAM/BA-Ag@PDAhydrogel shows a good sensitivity (gauge factor of 1.86), rapid response time (138ms), and high stability. Owing to abundant reactive groups in PDA, the PAM/BA-Ag@PDA hydrogel exhibits inherent tissue adhesiveness and antioxidant, along with a synergistic antibacterial effect by PDA and Ag. Toward practical applications, the PAM/BA-Ag@PDA hydrogel can conformally adhere to skin and monitor subtle activities and large-scale movements with excellent reliability, demonstrating its promising applications as wearable sensors for healthcare.

Physicochemical and bioactive characterization of pink guava pulp microcapsules prepared by freeze-drying using coffee mucilage as a wall material

This study investigated the potential of coffee mucilage (CM), a readily available coffee industry byproduct, as a wall material for the microencapsulation of pink guava pulp via freeze-drying (FD). Microcapsules with varying wall compositions incorporating powdered coffee mucilage, maltodextrin (MD), or a combination of both (FD-CM/MD) were developed and characterized using techniques such as FT-IR spectroscopy, SEM, TGA/DSC, and zeta potential analysis. The retention of bioactive compounds was assessed using total phenolic content, antioxidant capacity and carotenoid analyses. Results revealed that the incorporation of powdered coffee mucilage significantly influenced the physicochemical properties of the microcapsules, resulting in larger particle sizes and less rough surface morphologies compared with maltodextrin-based formulations. Notably, FD-CM microcapsules exhibited a thermal stability (Tg ≈ 50 °C) and retention total polyphenols of 30.19 ± 5.26 mg GAE/g dry weight (DW) and carotenoids of 5.50 ± 0.29 mg β-carotene/100 g DW, which can be attributed to the protective effects and inherent antioxidant capacity of 91.85 ± 9.93 μmol Trolox Equivalents/g DW in the coffee mucilage matrix. While influencing the color attributes, all microcapsule formulations retained a commercially appealing (hab = 79.80 ± 0.06) red-yellow hue. This study demonstrated the potential of powdered coffee mucilage as a sustainable and effective encapsulating wall material for enhancing the stability and bioavailability of bioactive compounds in food products.

Protective effect of curcumin against microplastic and nanoplastics toxicity.

Microplastics and nanoplastics (MNPs) are present in urban dust and the aquatic environments of industrialized cities. MNPs in the human body accumulate in the lymphoid follicles, Peyer's patches of the gastrointestinal tract, and pulmonary vascular endothelial cells, which slowly result in toxicity. Since previous studies introduced curcumin as a natural protective agent against environmental toxins, we reviewed preclinical studies that had used curcumin to protect organs or cells from toxicity secondary to exposure to MNPs. It was found that exposure to MNPs resulted in osteolysis, immunotoxicity, thyroid disturbances, nephrotoxicity, neurotoxicity, hepatotoxicity, pulmonary toxicity, gastrointestinal toxicity, cardiovascular toxicity, and especially endocrine, and reproductive toxicity. Nevertheless, except for one study reviewed, curcumin restored all oxidative and histopathological damages induced by MNPs to normal due to curcumin's inherent antioxidant, antiapoptotic, anti-inflammatory, and anti-proliferative properties.

Biodegradable capsules as a sustainable and accessible container for vitrification of gonadal tissue using the zebrafish animal model

Cryopreservation of fish gonadal tissue is an important technique for preserving genetic variability. However, this technique involves the use of cryotubes, plastic containers with low degradability that are expensive and difficult to obtain in certain parts of the world. Therefore, this study aimed to evaluate the efficiency of gelatin and hypromellose hard capsules as a sustainable and accessible alternative container to the cryotube for vitrification of zebrafish (Danio rerio) gonadal tissue. The gonadal tissues (testicular or ovarian) were vitrified in cryotubes, hard-gelatin, and hard-hypromellose capsules. Gelatin capsules exhibited comparable efficacy to cryotubes in preserving spermatogonia viability (33.03 ± 10.03 % and 37.96 ± 8.35 %, respectively), whereas hypromellose capsules showed decreased viability (18.38 ± 2.09 %). Immature oocyte viability remained unaffected by the capsule materials, with no difference compared to cryotubes at all oocyte stages (Primary Growth: p < 0.0001; Cortical Alveolar: p < 0.0001; Vitellogenic: p < 0.0001). Mitochondrial activity and lipid peroxidation demonstrated no difference among cryotubes and capsules for both gonadal tissues. However, antioxidant activity was notably higher in gelatin capsules (Testes: 147.2 ± 32.32 μg; Ovary: 87.98 ± 10.91 μg) than in cryotubes (Testes: 81.04 ± 26.05 μg; Ovary: 54.35 ± 11.23 μg) and hypromellose capsules (Testes: 62.36 ± 17.10 μg; Ovary: 63.96 ± 7.51 μg), likely due to the inherent antioxidant properties of gelatin. The results obtained in this study demonstrate that the cryotube can be replaced by gelatin capsules for vitrification of both gonadal tissues of zebrafish, being a sustainable and accessible alternative as it is a low-cost and environmentally friendly container.

The cytoprotective effect of Gymnema inodorum leaf extract against hypoxia-induced cardiomyocytes injury

Ischemic heart disease stands out as a major global contributor to mortality, with the initiation of hypoxia, marked by reduced oxygen availability, disrupting the balance of reactive oxygen species (ROS), leading to cellular injury. Exploring antioxidants derived from medicinal plants is becoming more interesting as a potential alternative treatment, especially for mitigating myocardial injury. Thus, this study aimed to assess the cytoprotective efficacy of Gymnema inodorum leaf extract (GIE) in a rat cardiac myoblast, H9c2, subjected to an in vitro hypoxia. The cell viability, intracellular ROS production and the expression of inflammatory cytokines were quantified, and hypoxia-induced cell morphology changes were observed using confocal fluorescence microscopy. The results showed that GIE notably enhanced cell viability, preserving membrane integrity, when compared with the hypoxic group. Remarkably, GIE significantly reduced hypoxia-induced intracellular ROS production, attributable to its inherent antioxidant properties. Furthermore, GIE significantly reduced interleukin (IL)-1β, interleukin (IL)-6 mRNA expression level and tended to reduce tumor necrosis factor-α (TNF-α) mRNA expression. In conclusion, these findings underscore the potential of GIE in mitigating hypoxia-induced myocardial injury, highlighting its robust antioxidant and anti-inflammatory attributes.

Protective properties of melanin from lichen Lobaria pulmonaria (L.) HOFFM. In models of oxidative stress in skeletal muscle

Melanin is a dark pigment from the group of phenolic or indole polymers with inherent biocompatibility and antioxidant capacity. In extremophilic lichen Lobaria pulmonaria, melanin is responsible for protective properties against hostile environments. Herein, the ability of melanin extracted from L. pulmonaria to counteract oxidative stress and related damages was studied in the mouse diaphragm, the main respiratory muscle. Initial in vitro experiments demonstrated ultraviolet (UV)-absorbing, antioxidant and metal chelating activities of melanin. This melanin can form nanoparticles and stabile colloidal system at concentration of 5 μg/ml. Pretreatment of the muscle with melanin (5 μg/ml) markedly reduced UV-induced increase in intracellular and extracellular reactive oxygen species (ROS) as well as antimycin A-mediated enhancement in mitochondrial ROS production accompanied by lipid peroxidation and membrane asymmetry loss. In addition, melanin attenuated suppression of neuromuscular transmission and alterations of contractile responses provoked by hydrogen peroxide. Thus, this study shed the light on the perspectives of the application of a lichen melanin as a protective component for treatment of skeletal muscle disorders, which are accompanied with an increased ROS production.

P-088 Bleomycin, etoposide and cisplatin (BEP) chemotherapy-induced testicular toxicity: ameliorative effect of sodium alginate by inhibiting oxidative stress, apoptosis and inflammation

Abstract Study question Is there a potential for sodium alginate (NaAL) to alleviate the damage induced by BEP chemotherapy in testicular cells and the spermatogenesis process? Summary answer Administering NaAL at doses of 25 and 50 mg/kg demonstrates protective effects against BEP-evoked toxicity damage through the modulation of nitro-oxidative stress, inflammation, and apoptosis. What is known already Testicular tumours are a prevalent malignancy affecting young males aged 20 to 35 years. The globally accepted chemotherapy for testicular cancer involves administering the bleomycin, etoposide, and cisplatin (BEP) regimen in three to four cycles. Unfortunately, the BEP regimen poses a substantial risk of reproductive system toxicity, presenting a significant concern and one of the most challenging long-term complications for young cancer survivors. Sodium alginate (NaAL), an anionic polysaccharide abundant in nature, offers potential solutions with its inherent antioxidant, anti-inflammatory, anti-apoptotic, and anti-proliferative properties. Study design, size, duration Sixty adult male Wistar rats were randomly assigned to six groups (n = 10/group). Groups 1, 3, and 4 received a vehicle, 25 mg/kg, and 50 mg/kg of NaAL, respectively. The remaining groups underwent a three-week cycle of bleomycin, etoposide, and cisplatin (BEP) with or without NaAL. NaAL administration began one week before BEP initiation, continued on days 2, 9, and 16, and extended for one week post the BEP cycle. Participants/materials, setting, methods At the end of the study (day 42), various parameters, including body and testes weight, sperm parameters (count, motility, viability, and morphology), testosterone hormone levels, testicular histopathology, stereological parameters of the testes, and levels of malondialdehyde (MDA), nitric oxide (NO), and total antioxidant capacity (TAC), were assessed. Additionally, the expression of Bcl-2, Bax, caspase-3, p53, and TNF-α was evaluated using real-time PCR and immunohistochemistry. Main results and the role of chance NaAL treatment resulted in a significant improvement in both body weight and testis weight in animals injected with BEP compared to the BEP group (P &amp;lt; 0.05). Stereological procedures, QRT-PCR examination, and immunohistochemical (IHC) staining for quantitative testis analysis indicated that NaAL reversed the impaired spermatogenesis induced by BEP (P &amp;lt; 0.05). Additionally, NaAL restored the disturbance caused by BEP in sperm count, motility, viability, and morphology. The testosterone level significantly decreased in the BEP-treated group compared to the control group (P &amp;lt; 0.05). However, co-administration of 50 mg/kg of NaAL significantly increased the serum testosterone level (P &amp;lt; 0.05). Furthermore, NaAL improved the antioxidant status of the testis by increasing TAC and ameliorating MDA and NO levels. Notably, QRT-PCR examination revealed that NaAL treatment suppressed BEP-induced apoptosis and inflammation by modulating genes such as Bcl-2, Bax, Caspase-3, and p53 in the testis (P &amp;lt; 0.05). Co-administration of 25 and 50 mg/kg of NaAL with the BEP regimen significantly reduced the number of p53 and TNF-α-positive cells compared to the BEP group. Further, NaAL at low and high doses increased the expression of Bcl-2 protein in spermatogenic cells compared to the BEP-treated group. Limitations, reasons for caution Due to limitations in our laboratory resources, we were unable to pursue further studies to validate the mechanism of sodium alginate on specific targets using more advanced techniques such as transfection and transgenic methodologies. Wider implications of the findings These findings illuminate the potential clinical applications of sodium alginate, suggesting its promising role as a beneficial supplement in medical contexts, particularly in addressing fertility issues. Additionally, this antioxidant could accelerate the fertility recovery period in young patients undergoing the BEP chemotherapy regimen, ultimately enhancing their overall quality of life. Trial registration number N/A

Mitochondria‐Targeted Polyphenol‐Cysteine Nanoparticles Regulating AMPK‐Mediated Mitochondrial Homeostasis for Enhanced Bone Regeneration

AbstractMitochondria are the energy source for basal cell functions as well as for tissue repair and regeneration. Excessive accumulation of reactive oxygen species (ROS) generated by bone tissue injury can cause cell oxidative stress and mitochondrial damage, negatively affecting osteogenic differentiation and tissue repair. However, efficient scavenging of mitochondrial ROS (mtROS) and restoration of mitochondrial homeostasis remain challenging. In this study, mitochondria‐targeted polyphenol/amino acid assembled nanoparticles (denoted as EC NPs) are constructed, which can achieve efficient intracellular ROS scavenging, especially for mtROS, recover the mitochondrial membrane potential, and enhance the inherent antioxidant system by increasing the antioxidase activity and GSH levels, following the re‐establishment of redox homeostasis. The EC NPs promoted AMPK‐mediated mitochondrial biogenesis, thereby providing more energy for osteogenic differentiation. Furthermore, the EC NPs not only recovered the osteogenic potential of the stem cells under oxidative stress but also demonstrated the ability to directly promote osteogenic differentiation by activating the cGMP‐PKG signaling pathway. In vivo experiments showed that the EC NPs significantly enhanced mitochondrial biogenesis and facilitated bone regeneration with a higher bone mass and bone mineral density. Thus, this multifunctional mitochondria‐targeted nanosystem represents a promising therapeutic strategy for bone regeneration based on mitochondrial homeostasis regulation.

Fabrication of soy protein-polyphenol covalent complex nanoparticles with improved wettability to stabilize high-oil-phase curcumin emulsions.

Recent studies have shown that the wettability of protein-based emulsifiers is critical for emulsion stability. However, few studies have been conducted to investigate the effects of varying epigallocatechin gallate (EGCG) concentrations on the wettability of protein-based emulsifiers. Additionally, limited studies have examined the effectiveness of soy protein-EGCG covalent complex nanoparticles with improved wettability as emulsifiers for stabilizing high-oil-phase (≥ 30%) curcumin emulsions. Soy protein isolate (SPI)-EGCG complex nanoparticles (SPIEn) with improved wettability were fabricated to stabilize high-oil-phase curcumin emulsions. The results showed that EGCG forms covalent bonds with SPI, which changes its secondary structure, enhances its surface charge, and improves its wettability. Moreover, SPIEn with 2.0 g L -1 EGCG (SPIEn-2.0) exhibited a better three-phase contact angle (56.8 ± 0.3o) and zeta potential (-27 mV) than SPI. SPIEn-2.0 also facilitated the development of curcumin emulsion gels at an oil volume fraction of 0.5. Specifically, the enhanced network between droplets as a result of the packing effects and SPIEn-2.0 with inherent antioxidant function was more effective at inhibiting curcumin degradation during long-term storage and ultraviolet light exposure. The results of the present study indicate that SPIEn with 2.0 g L -1 EGCG (SPIEn-2.0) comprises the optimum conditions for fabricating emulsifiers with improved wettability. Additionally, SPIEn-0.2 can improve the physicochemical stability of high-oil-phase curcumin emulsions, suggesting a novel strategy to design and fabricate high-oil-phase emulsion for encapsulating bioactive compounds. © 2024 Society of Chemical Industry.

Design and investigation of celastrol‐peptide nanoassemblies and their binding interactions with superoxide dismutase 1 and its mutants

AbstractThe misfolding and aggregation of superoxide dismutase 1 (SOD1) and its mutants has been implicated in amyotrophic lateral sclerosis (ALS). In this study, we have created three peptide conjugates with the antioxidant pentacyclic terpene celastrol and examined their interactions with SOD1 and its mutants A4V and G93A. The peptides YYIVS, MPDAHL, and GSGGL are derived from natural sources and are known for their inherent antioxidant properties. Docking studies revealed that most conjugates showed strong binding with the metal binding and electrostatic loops as well as the β1, β5, and β6 hydrophobic core of SOD1. The conjugates were synthesized and self‐assembled into nanoassemblies. Surface plasmon resonance studies further confirmed the binding interactions of the nanoassemblies with the SOD1 proteins. The nanoassemblies were found to internalize into HEK293T cells. The HEK 293T cells were then transfected with GFP fused WT (Wild Type), A4V and G93A SOD1 mutants. Flow cytometry revealed that treatment with celastrol‐peptide nanoassemblies, affected the fluorescence of the SOD1 protein, implying their role in modulating SOD1, particularly for the mutants. N–Acetyl–Leu–Leu–Norleucinal (ALLN) induced SOD1 aggregation was also affected upon treatment with the nanoassemblies. These results suggest that the nanoassemblies may potentially modulate the activity and structure of SOD1.

Engineered‐Doping Strategy for Self‐Sufficient Reactive Oxygen Species Blossom to Amplify Ferroptosis/Cuproptosis Sensibilization in Hepatocellular Carcinoma Treatment

AbstractFerroptosis and cuproptosis are emerging modes of programmed cell death and have been increasingly used to eliminate tumor cells. However, converting ferroptosis/cuproptosis into effective treatments is challenging because of the inherent antioxidant and plasma membrane repair systems and inefficient copper ion delivery. Herein, an engineered doping method is developed to encapsulate ZnO2 with Cu2+‐doped ZIF‐8 and modify the surface by transferrin (Tf). In the resulting ZnO2@Cu/ZIF‐8‐Tf nanosystem, Tf specifically binds to transferrin receptors for targeting and aggregation. In the tumor microenvironment, Cu2+/Fe3+ is released from the nanosystem and reacted with glutathione (GSH) to produce Cu+/Fe2+. Excessive accumulation of Cu+ interfered with the tricarboxylic acid cycle and induced coproptosis. Furthermore, the additional Fe2+ caused iron overload and enhanced ferroptosis. ZnO2 supplied hydrogen peroxide to mediate the overproduction of reactive oxygen species (ROS). Moreover, the depletion of GSH deactivated glutathione peroxidase 4 (GPX4) and inhibited the system Xc−‐GSH‐GPX4 pathway, and the amplified ROS triggered lipid peroxidation and reprogrammed lipid metabolism, causing malfunctioning of both antioxidant and membrane repair systems. In summary, the ferroptosis/cuproptosis pathways are activated at multiple levels in the ZnO2@Cu/ZIF‐8‐Tf nanosystem, which ensures its outstanding antitumor effect.

Stability of antioxidant activity of aloe vera powder during storage

Aloe vera powder is known to offer health benefits and possesses inherent antioxidant properties. However, the powder shows hygroscopic characteristics and causes a decrease in antioxidant activity. Implementing appropriate packaging measures to safeguard the integrity of the antioxidant activity is essential. In order to assess the antioxidant properties of aloe vera powder’s shelf life and stability throughout storage until it reaches critical conditions, this research was conducted.. A non-factorial, completely randomized design was used with open and closed storage using 0.80 mm polypropylene plastic packaging. Aloe vera powder was stored at 25°C and relative humidity (RH) of 75-80% until the critical conditions were reached at a moisture content of 12.00%. The analysis was carried out periodically for water, phenol, and antioxidant activity to scavenge free radicals DPPH (2,2-diphenyl-1-picrylhydrazyl). The results showed a significant increase in the moisture content during storage and decreased phenol and antioxidant activity. The unpacked powder reached its critical condition after 120 hours, whereas the powder enclosed in 0.80 mm polypropylene plastic packaging required a significantly longer duration of 44 weeks. Therefore, storage without packaging experienced a decrease in phenol and antioxidant activity levels by 88.69% and 91.45% in critical conditions. In the polypropylene packaging, there was a decline in phenol and antioxidant activity levels by 30.49% and 27.94%, respectively.

Hydroxytyrosol Linoleoyl Ether Ameliorates Metabolic-Associated Fatty Liver Disease Symptoms in Obese Zucker Rats.

A main hepatic consequence of obesity is metabolic-associated fatty liver disease (MAFLD), currently treated by improving eating habits and administrating fibrates yet often yielding suboptimal outcomes. Searching for a new therapeutic approach, we aimed to evaluate the efficacy of hydroxytyrosol linoleoyl ether (HTLE), a dual Ppar-α agonist/Cb1 antagonist with inherent antioxidant properties, as an antisteatotic agent. Using lean and obese Zucker rats, they were administrated daily doses of HTLE (3 mg/kg) over a 15-day period, evaluating its safety profile, pharmacokinetics, impact on body weight, hepatic fat content, expression of key enzymes involved in lipogenesis/fatty acid oxidation, and antioxidant capacity. HTLE decreased the body weight and food intake in both rat genotypes. Biochemical analysis demonstrated a favorable safety profile for HTLE along with decreased concentrations of urea, total cholesterol, and aspartate aminotransferase AST transaminases in plasma. Notably, HTLE exhibited potent antisteatotic effects in obese rats, evidenced by a decrease in liver fat content and downregulation of lipogenesis-related enzymes, alongside increased expression of proteins controlling lipid oxidation. Moreover, HTLE successfully counteracted the redox imbalance associated with MAFLD in obese rats, attenuating lipid peroxidation and replenishing both glutathione levels and the overall antioxidant. Our findings highlight the effectiveness of triple-action strategies in managing MAFLD effectively. Based on our results in the Zucker rat model, HTLE emerges as a promising candidate with triple functionality as an anorexigenic, antisteatotic, and antioxidant agent, offering potential relief from MAFLD symptoms associated with obesity while exhibiting minimal side effects. In conclusion, our study positions HTLE as a highly promising compound for therapeutic intervention in MAFLD treatment, warranting further exploration in clinical trials.