Oxidative Stress-related Diseases Research Articles

Liver Fibrosis Amelioration by Macrophage-Biomimetic Polydopamine Nanoparticles via Synergistically Alleviating Inflammation and Scavenging ROS.

The progression of liver fibrosis is determined by the interaction of damaged hepatocytes, active hepatic stellate cells, and macrophages, contributing to the development of oxidative stress and inflammatory environments within the liver. Unfortunately, the current pharmacological treatment for liver fibrosis is limited by its inability to regulate inflammation and oxidative stress concurrently. In this study, we developed a cell membrane biomaterial for the treatment of liver fibrosis, which we designated as PM. PM is a biomimetic nanomaterial constructed by encapsulating polydopamine (PDA) with a macrophage membrane (MM). It is hypothesized that PM nanoparticles (NPs) can successfully target the site of inflammation, simultaneously inhibit inflammation, and scavenge reactive oxygen species (ROS). In vitro experiments demonstrated that PM NPs exhibited strong antioxidant properties and the ability to neutralize pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β). Moreover, the capacity of PM NPs to safeguard cells from oxidative stress and their anti-inflammatory efficacy in an inflammatory model were validated in subsequent cellular experiments. Additionally, PM NPs exhibited a high biocompatibility. In a mouse model of hepatic fibrosis, PM NPs were observed to aggregate efficiently in the fibrotic liver, displaying excellent antioxidant and anti-inflammatory properties. Notably, PM NPs exhibited superior targeting, anti-inflammatory, and ROS scavenging abilities in inflamed tissues compared to MM, PDA, or erythrocyte membrane-encapsulated PDA. Under the synergistic effect of anti-inflammation and antioxidant, PM NPs produced significant therapeutic effects on liver fibrosis in mice. In conclusion, the synergistic alleviation of inflammation and ROS scavenging by this specially designed nanomaterial, PM NPs, provides valuable insights for the treatment of liver fibrosis and other inflammatory- or oxidative stress-related diseases.

The Impact of Clinacanthus nutans (Burm. F.) Leaf Extract on Sperm Quality and Antioxidant Activity in Male Mice Induced with Streptozotocin.

Clinacanthus nutans (C. nutans) is a medicinal herb that most people with diabetes have historically taken. It's a diet high in antioxidants, which are supposed to help people live longer and be healthier. It is the first study to suggest using C. nutans to enhance the quality of sperm in male mice given a streptozotocin (STZ) injection. Sixty mice were divided into two groups at the age of four weeks: group one was fed a regular diet (n=10), while group two was administered a high-fat diet (n=50) for eight weeks to develop obesity. Obese mice were given 100mg/kg of STZ to produce hyperglycemia with a 20% mortality rate. Then, 40 hyperglycemic mice were separated into two groups: STZ (n=10) and sample (n=30). The treatment groups were administered a methanolic extract of C. nutans leaves by gavage at doses of 150, 300, and 500mg/kg of body weight (n=10) for 4 weeks. In contrast to the STZ group, there was a substantial (p=0.001) drop in serum blood glucose and total sperm abnormalities in mice at varying doses. Catalase, glutathione s-transferase (GST), and total antioxidant capacity significantly (p=0.001) increased in the STZ mice group at varying doses, but malondialdehyde was reduced. In comparison to STZ mice, testosterone and luteinizing hormone (LH) levels improved in mice treated with extracts of C. nutans at various doses. For all of the following dependent variables, extraction of the leaf at higher concentrations of 500 milligrams/kilogram has better efficacy than 300 and 150 mg/kg after 4 weeks of treatment. The research and development of new natural agents to combat oxidative stress-related diseases have sparked a lot of interest. As a result, the potential leaf extract of C. nutans contains anti-hyperglycemic compounds and improves the quality of sperm in male mice.

Metabolic dysfunction-associated steatohepatitis treated by poly(ethylene glycol)-block-poly(cysteine) block copolymer-based self-assembling antioxidant nanoparticles

Non-alcoholic steatohepatitis (NASH), now known as metabolic dysfunction-associated steatohepatitis (MASH), involves oxidative stress caused by the overproduction of reactive oxygen species (ROS). Small-molecule antioxidants have not been approved for antioxidant chemotherapy because of severe adverse effects that collapse redox homeostasis, even in healthy tissues. To overcome these disadvantages, we have been developing poly(ethylene glycol)-block-poly(cysteine) (PEG-block-PCys)-based self-assembling polymer nanoparticles (NanoCyses), releasing Cys after in vivo degradation by endogenous enzymes, to obtain antioxidant effects without adverse effects. However, a comprehensive investigation of the effects of polymer design on therapeutic outcomes has not yet been conducted to develop our NanoCys system for antioxidant chemotherapy. In this study, we synthesized different poly(L-cysteine) (PCys) chains whose sulfanyl groups were protected by tert-butyl thiol (StBu) and butyryl (Bu) groups to change the reactivity of the side chains, affording NanoCys(SS) and NanoCys(Bu), respectively. To elucidate the importance of the polymer design, these NanoCyses were orally administered to MASH model mice as a model of oxidative stress-related diseases. Consequently, the acyl-protective NanoCys(Bu) significantly suppressed hepatic lipid accumulation and oxidative stress compared to NanoCys(SS). Furthermore, we substantiated that shorter PCys were much better than longer PCys for therapeutic outcomes and the effects related to the liberation properties of Cys from these nanoparticles. Owing to its antioxidant functions, NanoCyses also significantly attenuated hepatic inflammation and fibrosis in the MASH mouse model.

Roquin-2 promotes oxidative stress-induced cell death by ubiquitination-dependent degradation of TAK1

Reactive oxygen species (ROS) are highly reactive and its accumulation causes oxidative damage to cells. Cells maintain survival upon mild oxidative stress with anti-oxidative systems, such as the kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2) system. On the other hand, upon severe oxidative stress, cells undergo regulated cell death, including apoptosis, for eliminating damaged cells. To execute efficient cell death, cells need to turn off the anti-oxidant systems, while triggering cell death. However, it remains unknown how cells orchestrate these two conflicting systems under excessive oxidative stress.Herein, we show that when cells are exposed to excessive oxidative damage, an E3 ubiquitin ligase Roquin-2 (also known as RC3H2) plays a key role in switching cell fate from survival to death by terminating activation of transforming growth factor-β-activated kinase (TAK1), a positive regulator for Nrf2 activation. Roquin-2 interacted with TAK1 via four cysteine residues in TAK1 (C96, C302, C486, and C500) that are susceptible to oxidative stress and participate in oligomer formation via disulfide bonds, promoting K48-linked polyubiquitination and degradation of TAK1. Nrf2 was inactivated upon lethal oxidative stress in wild-type mouse embryonic fibroblast (MEF) cells, whereas it sustained activation and conferred resistance to Roquin-2 deficient cells, which was reversed by pharmacological or genetic inhibition of TAK1. These data demonstrate that in response to excessive ROS exposure, Roquin-2 promotes ubiquitination and degradation of TAK1 to suppress Nrf2 activation, and thereby contribute to an efficient cell death, providing insight into the pathogenesis of oxidative stress-related diseases, including cancer.

Antioxidant and antimicrobial potentials of biosynthesized Ag-Doped Ni-MOF as a novel hybrid nanocomposite

Metal-organic frameworks (MOFs) are organic–inorganic crystalline compounds that have attracted much attention due to their wide range of applications. Bimetallic MOFs offer more possibilities than MOFs based on single metal. This study focuses on the synthesis and characterization of a Ni-MOF doped with silver nanoparticles (Ag NPs) as potent antioxidant and antimicrobial agent. Red cabbage extract was used as a reducing agent to synthesize Ag NPs. Ag@Ni-MOF nanocomposite exhibited significant growth inhibition of bacteria and fungi, and demonstrated the best antioxidant properties among the synthesized compounds. These results suggest that designed Ag@Ni-MOF nanostructure can be applied in the treatment of oxidative stress-related diseases as well as bacterial/fungal infections.

Unlocking the Therapeutic Potential of a Manila Clam-Derived Antioxidant Peptide: Insights into Mechanisms of Action and Cytoprotective Effects against Oxidative Stress.

Reactive oxygen species (ROS) are implicated in various pathological conditions due to their ability to induce oxidative damage to cellular components. In this study, we investigated the antioxidant properties of a peptide isolated from the hydrolysate of Manila clam (Ruditapes philippinarum) muscle. Purification steps yielded RPTE2-2-4, exhibiting potent scavenging activities against DPPH•, HO•, and O2•-, akin to Vitamin C. Structural analysis showed that the isolated peptide, LFKKNLLTL, exhibited characteristics associated with antioxidant activity, including a short peptide length and the presence of aromatic and hydrophobic amino acid residues. Moreover, our study demonstrated the cytoprotective effects of the peptide against H2O2-induced oxidative stress in HepG2 cells. Pretreatment with the peptide resulted in a dose-dependent reduction in intracellular ROS levels and elevation of glutathione (GSH) levels, indicating its ability to modulate cellular defense mechanisms against oxidative damage. Furthermore, the peptide stimulated the expression of the cytoprotective enzyme heme oxygenase-1 (HO-1), further reinforcing its antioxidant properties. Overall, our findings highlight the potential of the Manila clam-derived peptide as a natural antioxidant agent with therapeutic implications for oxidative stress-related diseases. Further investigation into its mechanisms of action and in vivo efficacy is warranted to validate its therapeutic potential.

Investigating the Potential Effects of CBD in Vitro

Oxidative stress and chronic inflammation play a role in the pathogenesis of many diseases such as cardiovascular disease, diabetes, cancer, and neurodegenerative diseases. Oxidative stress occurs when there is an accumulation of reactive oxygen species (ROS) in cells and tissues and not enough antioxidant elements to eliminate them. In order to protect against oxidative stress, cells activate the nuclear factor erythroid 2-related factor (Nrf2) pathway. Nrf2 is a transcription factor that regulates the expression of antioxidant enzymes, which can protect the cellfrom ROS. Here we focus on the therapeutic potential of cannabidiol (CBD) to mitigate oxidative stress in both microglial and peripheral macrophage cell lines by way of the Nrf2 pathway. We show that CBD can increase Nrf2 protein levels within the cell and thus may be a therapeutic for oxidative stress-related diseases. We also explore the relationship between oxidative stress and inflammation, specifically the NF-kB inflammatory pathway, in the context of Alzheimer’s disease (AD).

Evaluation of In Vitro and In Vivo Antioxidant Potential of the Ethyl Acetate Fraction of Cyperus Pangorei Rhizome

Background and Aim: Antioxidants derived from natural sources, particularly those rich in flavonoids and phenolic compounds, have attracted considerable interest for their potential health benefits in combating oxidative stress-related diseases. This study aimed to evaluate the antioxidant potential of the ethyl acetate (EtAc) fraction obtained from Cyperus pangorei rhizome, focusing on both in vitro and in vivo assessments. Methods: The EtAc fraction was subjected to RP-HPLC analysis to identify and quantify phenolic compounds and flavonoids. Acute toxicity testing was performed to assess the safety profile of the EtAc fraction. In vitro antioxidant activity was determined using DPPH and ABTS+ radical scavenging assays. In vivo evaluation of antioxidant activity was conducted in Triton X-100-induced oxidative stress model in mice, measuring malondialdehyde (MDA) content, glutathione (GSH) levels, and superoxide dismutase (SOD) activity in liver tissues. Results: RP-HPLC analysis confirmed the presence of quercetin, luteolin, and apigenin in the EtAc fraction. The fraction exhibited significant dose-dependent antioxidant activity in both DPPH and ABTS+ assays, with IC50 values indicating potent scavenging effects. In the Triton X-100-induced stress model, administration of the EtAc fraction led to a reduction in MDA levels, restoration of GSH levels, and enhancement of SOD activity in mouse liver tissues. Conclusion: The findings suggest that the EtAc fraction from C. pangorei possesses promising antioxidant properties, as evidenced by its ability to mitigate oxidative stress-related damage both in vitro and in vivo.

SUMO-specific proteases: SENPs in oxidative stress-related signaling and diseases.

Oxidative stress is employed to depict a series of responses detrimental to normal cellular functions resulting from an imbalance between intracellular oxidants, mainly reactive oxygen species and antioxidant defenses. Oxidative stress often contributes to the development of various diseases, including cancer, cardiovascular diseases, and neurodegenerative diseases. In this process, the relationship between small ubiquitin-like modifier (SUMO) and oxidative stress has garnered significant attention, with its posttranslational modification (PTM) frequently serving as a marker of oxidative stress status. Sentrin/SUMO-specific proteases (SENPs), affected by alternative splicing, PTMs such as phosphorylation and ubiquitination, and various protein interactions, are crucial molecules in the SUMO process. The human SENP family has six members (SENP1-3, SENP5-7), which are classified into two categories based on sequence similarity, substrate specificity, and subcellular location. They have two core functions in the human body: first, by cleaving the precursor SUMO and exposing the C-terminal glycine, they initiate the SUMO process; second, they can specifically recognize and dissociate SUMO proteins bound to substrates, a process known as deSUMOylation. However, the connection between deSUMOylation and oxidative stress remains a relatively unexplored area despite their strong association with oxidative diseases such as cancer and cardiovascular disease. This article aims to illustrate the significant contribution of SENPs to the oxidative stress pathway through deSUMOylation by reviewing their structure and classification, their roles in oxidative stress, and the changes in their expression and activity in several typical oxidative stress-related diseases.

Smoking Primes the Metabolomic Response in Trauma.

Smoking is a public health threat due to its well described link to increased oxidative stress-related diseases including peripheral vascular disease and coronary artery disease. Tobacco use has been linked to risk of inpatient trauma morbidity including acute respiratory distress syndrome, however its mechanistic effect on comprehensive metabolic heterogeneity has yet to be examined. Plasma was obtained on arrival from injured patients at a Level 1 Trauma Center and analyzed with modern mass spectrometry-based metabolomics. Patients were stratified by non-smoker, passive smoker and active smoker by lower, inter-quartile and upper quartile ranges of cotinine intensity peaks. Patients were sub-stratified by High Injury/High Shock (Injury Severity Score ≥ 15, Base Excess<-6) and compared to healthy controls. P-value <0.05 following FDR correction of t-test was considered significant. 48 patients with High Injury/High Shock (7 (15%) non-smokers, 25 (52%) passive smokers and 16 (33%) active smokers) and 95 healthy patients who served as controls (30 (32%) non-smokers, 43 (45%) passive smokers and 22 (23%) active smokers) were included. Elevated metabolites in our controls who were active smokers include enrichment in chronic inflammatory and oxidative processes. Elevated metabolites in active smokers in high injury/high shock include enrichment in the malate-aspartate shuttle, tyrosine metabolism, carnitine synthesis, and oxidation of very long-chain fatty acids. Smoking promotes a state of oxidative stress leading to mitochondrial dysfunction which is additive to the inflammatory milieu of trauma. Smoking is associated with impaired mitochondrial substrate utilization of long-chain fatty acids, aspartate and tyrosine all of which accentuate oxidative stress following injury. This altered expression represents an ideal target for therapies to reduce oxidative damage toward the goal of personalized treatment of trauma patients. Level III, Prognostic/Epidemiological.

Prediction of prognosis in patients with ischemic stroke combined with type 2 diabetes mellitus based on serum total bilirubin levels.

Serum bilirubin levels may have therapeutic benefits in oxidative stress-related diseases, but their role in stroke remains unclear. This study aimed to investigate the relationship between serum bilirubin levels on admission and clinical outcomes in ischemic stroke patients. We prospectively collected data from consecutive ischemic stroke admissions. Serum total bilirubin (TBIL) and direct bilirubin levels on admission were measured. Stroke severity at admission was assessed using the National Institutes of Health Stroke Scale, and functional status at discharge was evaluated using the modified Rankin scale. Among 180 patients, lower TBIL levels were observed in all 3 groups, with the mild group (7.89 ± 2.12 μmol/L) having lower levels than the moderate group (8.01 ± 2.12 μmol/L) and the severe group (9.12 ± 2.12 μmol/L). Although TBIL levels were initially associated with stroke severity, this relationship did not hold after adjusting for confounding factors. Serum bilirubin levels appear to be related to stroke severity but not independently associated with outcomes in ischemic stroke patients. Further research is needed to understand the underlying mechanisms of this relationship. There is a strong correlation between serum bilirubin levels and the severity and prognosis of ischemic stroke in patients with type 2 diabetes. Therefore, early control of serum TBIL and direct bilirubin is crucial for the treatment and prognosis of ischemic stroke in patients with type 2 diabetes.

Protective Effects and Mechanisms of Esculetin against H2O2-Induced Oxidative Stress, Apoptosis, and Pyroptosis in Human Hepatoma HepG2 Cells.

Oxidative stress plays a crucial role in the pathogenesis of many diseases. Esculetin is a natural coumarin compound with good antioxidant and anti-inflammatory properties. However, whether esculetin can protect HepG2 cells through inhibiting H2O2-induced apoptosis and pyroptosis is still ambiguous. Therefore, this study aimed to investigate the protective effects and mechanisms of esculetin against oxidative stress-induced cell damage in HepG2 cells. The results of this study demonstrate that pretreatment with esculetin could significantly improve the decrease in cell viability induced by H2O2 and reduce intracellular ROS levels. Esculetin not only apparently reduced the apoptotic rates and prevented MMP loss, but also markedly decreased cleaved-Caspase-3, cleaved-PARP, pro-apoptotic protein (Bax), and MMP-related protein (Cyt-c) expression, and increased anti-apoptotic protein (Bcl-2) expression in H2O2-induced HepG2 cells. Meanwhile, esculetin also remarkably reduced the level of LDH and decreased the expression of the pyroptosis-related proteins NLRP3, cleaved-Caspase-1, Il-1β, and GSDMD-N. Furthermore, esculetin pretreatment evidently downregulated the protein expression of p-JNK, p-c-Fos, and p-c-Jun. Additionally, anisomycin, a specific activator of JNK, blocked the protection of esculetin against H2O2-induced HepG2 cells apoptosis and pyroptosis. In conclusion, esculetin can protect HepG2 cells against H2O2-induced oxidative stress, apoptosis, and pyroptosis via inhibiting the JNK signaling pathway. These findings indicate that esculetin has the potential to be used as an antioxidant that improves oxidative stress-related diseases.

Development of New Resolvin D1 Analogues for Osteoarthritis Therapy: Acellular and Computational Approaches to Study Their Antioxidant Activities.

In osteoarthritis (OA), oxidative stress plays a crucial role in maintaining and sustaining cartilage degradation. Current OA management requires a combination of pharmaceutical and non-pharmacological strategies, including intraarticular injections of hyaluronic acid (HA). However, several lines of evidence reported that HA oxidation by reactive oxygen species (ROS) is linked with HA cleavage and fragmentation, resulting in reduced HA viscosity. Resolvin D1 (RvD1) is a lipid mediator that is biosynthesized from omega-3 polyunsaturated fatty acids and is a good candidate with the potential to regulate a panoply of biological processes, including tissue repair, inflammation, oxidative stress, and cell death in OA. Herein, newly designed and synthesized imidazole-derived RvD1 analogues were introduced to compare their potential antioxidant properties with commercially available RvD1. Their antioxidant capacities were investigated by several in vitro chemical assays including oxygen radical absorbance capacity, 2,2-diphenyl-1-picrylhydrazyl radical scavenging, ferric ion reducing antioxidant power, hydroxyl radical scavenging, and HA fragmentation assay. All results proved that imidazole-derived RvD1 analogues showed excellent antioxidant performance compared to RvD1 due to their structural modifications. Interestingly, they scavenged the formed reactive oxygen species (ROS) and protected HA from degradation, as verified by agarose gel electrophoresis and gel permission chromatography. A computational study using Gaussian 09 with DFT calculations and a B3LYP/6-31 G (d, p) basis set was also employed to study the relationship between the antioxidant properties and chemical structures as well as calculation of the molecular structures, frontier orbital energy, molecular electrostatic potential, and bond length. The results showed that the antioxidant activity of our analogues was higher than that of RvD1. In conclusion, the findings suggest that imidazole-derived RvD1 analogues can be good candidates as antioxidant molecules for the treatment of oxidative stress-related diseases like OA. Therefore, they can prolong the longevity of HA in the knee and thus may improve the mobility of the articulation.

Electrochemical biosensing platform based on AuNWs/rGO-CMC-PEDOT:PSS composite for the detection of superoxide anion released from living cells

Detection of superoxide anion (O2·-) levels holds significant importance for the diagnosis and even clinical treatments of oxidative stress-related diseases. Herein, we prepared a composite electrode material to encapsulate copper-zinc superoxide dismutase (SOD1) for biosensing of O2·-. The sensing material consists of gold nanowires (AuNWs), reduced graphene oxide (rGO), carboxymethyl cellulose (CMC) and PEDOT:PSS. CMC provides abundant -COOH to bind SOD1, with a high adsorption coverage of 1.499 × 10−9 mol cm−2 on the sensor surface. rGO and PEDOT endow the composite with significant conductivity, whereas PSS has antifouling capability. Moreover, AuNWs exhibit excellent electrical conductivity and a high aspect ratio, which promotes electron transfer, and ultimately enhances the catalytic performance of the enzyme. Meanwhile, SOD1(Cu2+) catalyzes the dismutation of O2·- to O2 and H2O2, and H2O2 is then electrochemically oxidized to generate amperometric signals for determination of O2·-. The sensor demonstrates outstanding detection performance for O2·- with a low detection limit of 2.52 nM, and two dynamic ranges (14.30 nM–1.34 μM and 1.34 μM–42.97 μM) with corresponding sensitivity of 0.479 and 0.052 μA μM−1cm−2, respectively. Additionally, the calculated apparent Michaelis constant (Kmapp) of 1.804 μM for SOD1 demonstrates the outstanding catalytic activity and the surface-immobilized enzyme's substrate affinity. Furthermore, the sensor shows the capability to dynamically detect the level of O2·- released from living HepG2 cells. This study provides an inovative design to obtain a biocompatible electrochemical sensing platform with plenty of immobilization sites for biomolecules, large surface area, high conductivity and flexibility.

Rosmarinic Acid-Rich Perilla frutescens Extract-Derived Silver Nanoparticles: A Green Synthesis Approach for Multifunctional Biomedical Applications including Antibacterial, Antioxidant, and Anticancer Activities.

This study describes a simple, cost-effective, and eco-friendly method for synthesizing silver nanoparticles using a rosmarinic acid extract from Perilla frutescens (PFRAE) as the bioreduction agent. The resulting nanoparticles, called PFRAE-AgNPs, were characterized using various analytical techniques. The UV-Vis spectrum confirmed the formation of PFRAE-AgNPs, and the FTIR spectrum indicated the participation of rosmarinic acid in their synthesis and stabilization. The XRD pattern revealed the crystal structure of PFRAE-AgNPs, and the TEM analysis showed their spherical morphology with sizes ranging between 20 and 80 nm. The DLS analysis indicated that PFRAE-AgNPs were monodispersed with an average diameter of 44.0 ± 3.2 nm, and the high negative zeta potential (-19.65 mV) indicated their high stability. In the antibacterial assays, the PFRAE-AgNPs showed potent activity against both Gram-positive (Bacillus subtilis and Staphylococcus aureus) and Gram-negative (Escherichia coli and Pseudomonas aeruginosa) bacterial pathogens, suggesting that they could be used as a potential antibacterial agent in the clinical setting. Moreover, the antioxidant activity of PFRAE-AgNPs against DPPH and ABTS radical scavengers highlights their potential in the treatment of various oxidative stress-related diseases. PFRAE-AgNPs also demonstrated significant anticancer activity against a range of cell lines including human colon cancer (COLO205), human prostate carcinoma (PC-3), human lung adenocarcinoma (A549), and human ovarian cancer (SKOV3) cell lines suggesting their potential in cancer therapy. The nanoparticles may also have potential in drug delivery, as their small size and high stability could enable them to cross biological barriers and deliver drugs to specific target sites. In addition to the aforementioned properties, PFRAE-AgNPs were found to be biocompatible towards normal (CHO) cells, which is a crucial characteristic for their application in cancer therapy and drug delivery systems. Their antibacterial, antioxidant, and anticancer properties make them promising candidates for the development of new therapeutic agents. Furthermore, their small size, high stability, and biocompatibility could enable them to be used in drug delivery systems to enhance drug efficacy and reduce side effects.

Preparation, Characterization, Antioxidant Activities, and Determination of Anti-Alzheimer Effects of PLGA-Based DDSs Containing Ferulic Acid.

Nanoparticle (NP) systems have attracted the attention of researchers in recent years due to their advantages, such as modified release features, increased therapeutic efficacy, and reduced side effects. Ferulic acid (FA) has therapeutic effects such as anti-inflammatory, anti-Alzheimer's, antioxidant, antimicrobial, anticancer, antihyperlipidemic, and antidiabetic. In this study, FA-loaded PLGA-based NPs were prepared by a nanoprecipitation method and the effect of varying concentrations of Poloxamer 188 and Span 60 on NP properties was investigated. FA-loaded A-FA coded formulation was chosen as optimum. High encapsulation efficiency has been achieved due to the low affinity of FA to the water phase and, therefore, its lipophilic nature, which tends to migrate to the organic phase. It was determined that the release of FA from the A-FA was slower than pure FA and prolonged release in 24 h. Antioxidant and anti-Alzheimer's effects of A-FA coded NP formulation were investigated by biological activity studies. A-FA coded NP formulation showed strong DPPH free radical scavenging, ABTS cation decolorizing, and reducing antioxidant activity. Since it has both AChE inhibitor and antioxidant properties according to the results of its anti-Alzheimer activity, it was concluded that the formulation prepared in this study shows promise in the treatment of both oxidative stress-related diseases and Alzheimer's.

Relative quantitation of chiral thiol compounds labeled based on isotope novel mass spectrometry probes: Monitoring of the dynamic changes of chiral thiol compounds in human urine during normal, exercise, and rest recovery states

Monitoring changes in the content of chiral thiol compounds in the human body is crucial for the early diagnosis of oxidative stress-related diseases and the exploration of their pathogenesis. To address this, we synthesized a novel isotope mass spectrometry (MS) probe, denoted as (R)-(5-(3-isothiocyanato (13C) pyrrolidin-1-yl)-5-oxopentyl) triphenylphosphonium (N13CS-OTPP), with triphenylphosphine as its parent structure. In this study, we established a new ultra-high-performance liquid chromatography high-resolution mass spectrometry (UHPLCHRMS) relative quantitative method to monitor chiral thiol compounds in human urine under varying oxidative stress conditions. This method relies on the ratio of 12C/13C isotope-labeled peak areas. To assess the chiral separation efficiency of N13CS-OTPP, we employed three types of thiol compounds (D/L-GSH, D/L-Cys, and D/L-Hcy) and observed separation degrees (Rs) ranging from 1.82 to 1.89. We further validated the accuracy and feasibility of our relative quantitative methods using D/L-Cys-as a model compound. N12C/13CS-OTPP-Cys-exhibited excellent linearity (R2 = 0.9993–0.9994) across different molar ratios (D/L-Cys = 10:1, 4:1, 2:1, 1:1, 1:2, 1:4, 1:10) and achieved a low limit of detection (LOD) of 2.5 fmol. Additionally, we monitored the dynamic changes in urine D/L-Cys-and D/L-Hcy ratios in 12 healthy volunteers (six males and six females) under various oxidative stress states. We generated fitting curves and investigated the trends in chiral thiol compounds in vivo. This study introduces a novel method for the relative quantitative monitoring of chiral thiol compounds in different oxidative stress states within the human body. It also presents a new strategy for understanding the pathogenesis of related diseases resulting from the abnormal metabolism of thiol compounds.

Unraveling the Red Sea soft coral Sarcophyton convolutum potentials against oxidative and inflammatory stresses in zebrafish

The Red Sea is one of the world's hotspots for biodiversity, and for marine natural products (MNPs) as well. These MNPs attract special interest for their capabilities to combat inflammatory and oxidative stress-related diseases, being some of the most serious health problems worldwide nowadays. The current study aimed to identify the bioactive ingredients of the Red Sea soft coral Sarcophyton convolutum, and to assess its protective potentials against oxidative and inflammatory stresses. Coral extract (CE) was analyzed using GC-MS and HPLC. In a protection trial, adult zebrafish were intraperitoneally injected with two doses of crab extract, i.e. 50 and 500 μg/fish in 1 % DMSO as a vehicle, then challenged with 30 μg L−1 of CuSO4 for 48 h. All groups, but the negative control one, were challenged with 30 μg L−1 of CuSO4. Total antioxidant activity, as well as mRNA levels of proinflammatory markers and antioxidant enzyme genes were measured. The results showed richness of S. convolutum extract with various bioactive ingredients, including phenolic compounds, flavonoids, alkanes, fatty acids, sesquiterpenes, and pheromone-like substances. CuSO4 significantly induced the expected signals of inflammatory and oxidative stress, reducing both the antioxidant activity and increasing proinflammatory marker genes. However, CE, especially the low dose, showed significant capability to reduce proinflammatory markers and elevating the total antioxidant activity. Therefore, we concluded that S. convolutum can be a promising source for future efforts of drug discovery and a wide spectrum of pharmaceutical products.

Assessment of the mechanistic role of an Indian traditionally used ayurvedic herb Bacopa monnieri (L.)Wettst. for ameliorating oxidative stress in neuronal cells

Ethnopharmacological relevanceThis study has important ethnopharmacological implications since it systematically investigated the therapeutic potential of Bacopa monnieri(L.) Wettst. (Brahmi) in treating neurological disorders characterized by oxidative stress—a growing issue in the aging population. Bacopa monnieri, which is strongly rooted in Ayurveda, has long been recognized for its neuroprotective and cognitive advantages. The study goes beyond conventional wisdom by delving into the molecular complexities of Bacopa monnieri, particularly its active ingredient, Bacoside-A, in countering oxidative stress. The study adds to the ethnopharmacological foundation for using this herbal remedy in the context of neurodegenerative disorders by unravelling the scientific underpinnings of Bacopa monnieri's effectiveness, particularly at the molecular level, against brain damage and related conditions influenced by oxidative stress. This dual approach, which bridges traditional wisdom and modern investigation, highlights Bacopa monnieri's potential as a helpful natural remedy for oxidative stress-related neurological diseases. Aim of the studyThe aim of this study is to investigate the detailed molecular mechanism of action (in vitro, in silico and in vivo) of Bacopa monnieri (L.) Wettst. methanolic extract and its active compound, Bacoside-A, against oxidative stress in neurodegenerative disorders. Materials and methodsROS generation activity, mitochondrial membrane potential, calcium deposition and apoptosis were studied through DCFDA, Rhodamine-123, FURA-2 AM and AO/EtBr staining respectively. In silico study to check the effect of Bacoside-A on the Nrf-2 and Keap1 axis was performed through molecular docking study and validated experimentally through immunofluorescence co-localization study. In vivo antioxidant activity of Bacopa monnieri extract was assessed by screening the oxidative stress markers and stress-inducing hormone levels as well as through histopathological analysis of tissues. ResultsThe key outcome of this study is that the methanolic extract of Bacopa monnieri (BME) and its active component, Bacoside-A, protect against oxidative stress in neurodegenerative diseases. At 100 and 20 μg/ml, BME and Bacoside-A respectively quenched ROS, preserved mitochondrial membrane potential, decreased calcium deposition, and inhibited HT-22 mouse hippocampus cell death. BME and Bacoside-A regulated the Keap1 and Nrf-2 axis and their downstream antioxidant enzyme-specific genes to modify cellular antioxidant machinery. In vivo experiments utilizing rats subjected to restrained stress indicated that pre-treatment with BME (50 mg/kg) downregulated oxidative stress markers and stress-inducing hormones, and histological staining demonstrated that BME protected the neuronal cells of the Cornu Ammonis (CA1) area in the hippocampus. ConclusionsOverall, the study suggests that Bacopa monnieri(L.) Wettst. has significant potential as a natural remedy for neurodegenerative disorders, and its active compounds could be developed as new drugs for the prevention and treatment of oxidative stress-related diseases.

Potent antioxidant activity of black grass jelly (Mesona palustris BL) leaf extract and fractions

Black grass jelly (Mesona palustris BL) is an Indonesian traditional food that is rich in antioxidants and believed to have potential for treating various diseases such as diabetes, hypertension, and cancer. The present study aimed to determine the antioxidant activity of black grass jelly leaf extract as well as fractions using ABTS, DPPH and FRAP methods. Following ethanol extraction and subsequent fractionations, total flavonoid level was determined, followed by antioxidant activity tests using the ABTS, DPPH and FRAP with vitamin C as references. The tests revealed the following order of antioxidant activities, ethyl acetate fraction&amp;gt;extract&amp;gt;water fraction&amp;gt;n-hexane fraction. All test substances had IC50 of &amp;lt;50 ppm, which categorized them as having very high antioxidant activities. In line with this data, on the basis of reducing power, ethyl acetate extract was shown to be the most potent antioxidant, having a value of 20.24 mgAAE/g sample. Overall, results of the present study suggest the potential use of black grass jelly as a part of the therapeutic armamentarium for oxidative stress-related diseases.