Antioxidant Drug Research Articles

Nrf2 Pathway and Oxidative Stress as a Common Target for Treatment of Diabetes and Its Comorbidities.

Diabetes is a chronic disease that induces many comorbidities, including cardiovascular disease, nephropathy, and liver damage. Many mechanisms have been suggested as to how diabetes leads to these comorbidities, of which increased oxidative stress in diabetic patients has been strongly implicated. Limited knowledge of antioxidative antidiabetic drugs and substances that can address diabetic comorbidities through the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway calls for detailed investigation. This review will describe how diabetes increases oxidative stress, the general impact of that oxidative stress, and how oxidative stress primarily contributes to diabetic comorbidities. It will also address how treatments for diabetes, especially focusing on their effects on the Nrf2 antioxidative pathway, have been shown to similarly affect the Nrf2 pathway of the heart, kidney, and liver systems. This review demonstrates that the Nrf2 pathway is a common pathogenic component of diabetes and its associated comorbidities, potentially identifying this pathway as a target to guide future treatments.

The effect of antioxidants on the productivity and enzymatic activity of the gastrointestinal tract of quails while reducing the risk of T-2 toxicosis

Purpose: to study the effect of antioxidants santoquine and vitamin E, included in the composition of wheat-sorghum-rapeseed type feed with a tolerant level of T-2 toxin, on the productivity and digestive processes of meat quail.Materials and methods. The experiment was carried out on meat quails of the Pharaoh breed. At one day of age, according to the principle of analogous groups, 4 groups of 40 animals each were formed. Raised for meat until 42 days of age. Quails were individually weighed weekly to determine live weight gain and calculate feed costs per unit of production. After control slaughter at the age of 42 days, the activity of digestive enzymes: proteinases, amylases and cellulases was studied in the contents of the muscular stomach and duodenum of 5 animals from each group.Results. In the course of the studies, new experimentally substantiated data were obtained on the effectiveness of reducing the risk of T-2 toxicosis in the body of meat quails due to the rational joint use of santoquin antioxidant drugs in the composition of mixed feeds of the wheat-sorghum-rapeseed type with a tolerant level of T-2 toxin at a dose of 150 g/ t and vitamin E at a dose of 25 thousand IU/t. Thanks to this, in the quails of the 3rd experimental group, there was an increase in the survival rate of the livestock by 7.8 %, and an increase in live weight by 13.19 % (P<0.05). The meat poultry of the 3rd experimental group had the best pay for feed in terms of live weight gain, having spent 12.01 % less feed to obtain 1 kg of gain compared to the quails of the control group. Combined additions of the tested antioxidants contributed to a significant (P<0.05) increase in the activity of proteinases, cellulases and amylases in the contents of the muscular stomach by 24.15, 33.30 and 18.18 % and in the duodenum - by 13, compared to the analogues of the control group. 58, 13.93 and 15.02%, respectively.

Drug repurposing: insights into the antimicrobial effects of AKBA against MRSA

Staphylococcus aureus is a major threat in infectious diseases due to its varied infection types and increased resistance. S. aureus could form persister cells under certain condition and could also attach on medical apparatus to form biofilms, which exhibited extremely high resistance to antibiotics. 3-Acetyl-11-keto-beta-boswellic acid (AKBA) is a well-studied anti-tumor and antioxidant drug. This study is aimed to determine the antimicrobial effects of AKBA against S. aureus and its persister cells and biofilms. The in vitro antimicrobial susceptibility of AKBA was assessed by micro-dilution assay, disc diffusion assay and time-killing assay. Drug combination between AKBA and conventional antibiotics was detected by checkerboard assay. And the antibiofilm effects of AKBA against S. aureus were explored by crystal violet staining combined with SYTO/PI probes staining. Next, RBC lysis activity and CCK-8 kit were used to determine the cytotoxicity of AKBA. In addition, murine subcutaneous abscess model was used to assess the antimicrobial effects of AKBA in vivo. Our results revealed that AKBA was found to show effective antimicrobial activity against methicillin-resistant S. aureus (MRSA) with the minimal inhibitory concentration of 4–8 µg/mL with undetectable cytotoxicity. And no resistant mutation was induced by AKBA after 20 days of consecutive passage. Further, we found that AKBA could be synergy with gentamycin or amikacin against S. aureus and its clinical isolates. By crystal violet and SYTO9/PI staining, AKBA exhibited strong biofilm inhibitory and eradication effects at the concentration of 1 ~ 4 µg/mL. In addition, the effective antimicrobial effect was verified in vivo in a mouse model. And no detectable in vivo toxicity was found. These results indicated that AKBA has great potential to development as an alternative treatment for the refractory S. aureus infections.

Identification of new antioxidant drugs in a human in vitro model of ageing‐associated cataract

Aims/Purpose: Cataracts are a significant cause of global blindness, impacting millions (10.8 million patients), and their prevalence is expected to increase over the coming decades as our populations age. Oxidative stress disrupts ROS (reactive oxygen species) balance in lens fibre cells, leading to lens protein degradation and accumulation, developing age‐related cataracts. The lens has protective mechanisms, including high GSH levels and antioxidant enzymes like catalase, safeguarding lens health. While surgery is currently the only effective treatment, non‐invasive drug‐based approaches show potential by reducing risks and complications. With its potent antioxidant activity, resveratrol may protect lens cells and slow cataract development. However, the limited ability of resveratrol to penetrate lens tissue restricts its direct effects. Therefore, designing new molecules to improve ADME (absorption, distribution, metabolism and excretion) properties is required.Methods: In this study, we used an in vitro model of cataracts by inducing oxidative stress and cell death by adding hydrogen peroxide (H2O2) and luperox to lens epithelial cells to evaluate the protective effects of new molecules against oxidative stress and compared them with resveratrol. Our study assessed the cell viability, intracellular ROS level, mitochondrial function, catalase activity and GSH/GSSH level.Results: These compounds preserved cell viability, reduced ROS levels, maintained mitochondrial function and enhanced catalase activity and GSH levels in lens epithelial cells exposed to H2O2. The novel drugs, CAB‐C1 and CAB‐C2, demonstrated beneficial effects on cellular health.Conclusions: Developing drugs for cataract treatment enables early intervention, particularly for individuals with mild or moderate cataracts who may not require surgery yet. Such advancements might improve patients' quality of life and have implications for ocular science and age‐related eye diseases.

Optimization of pyridine based Schiff bases: Design, synthesis and determination of anti-inflammatory, antioxidant and antimicrobial activity

The present paper proposed the tri-potassium phosphate catalyzed synthesis of some novel series of Schiff bases (3a to 3l) derived from 2-aminopyridine using microwave technique. All synthesized Schiff bases were confirmed by different spectroscopic methods. Further all synthesized imines have been evaluated to screen for antimicrobial, antioxidant and anti-inflammatory activity. The compound 3c displays potent anti-inflammatory activity with 42.307%±1.322 inhibition of inflammation. The antioxidant activity data revealed that all synthesized Schiff bases exhibit potency to scavenge DPPH and nitric oxide radicals. Antimicrobial properties of these compounds showed moderate to excellent growth of inhibitory activity against various tested pathogens. Our observations and examination for pharmacological study towards the presence of active pharmacological functional groups present in the main structural nucleus of synthesized imines. Therefore, present study may lead to the development of a new class of anti-inflammatory and antioxidant drugs with structural modification.

Diosmin protects the testicles from doxorubicin-induced damage by increasing steroidogenesis and suppressing oxido-inflammation and apoptotic mediators.

Cancer chemotherapy with doxorubicin (DOX) has been linked to serious testicular damage and spermatotoxicity due to the induction of oxidative stress, inflammation, and apoptosis. Thus, the current study was carried out to assess the potential ameliorative impact of diosmin, an antioxidant drug, against DOX-mediated spermatoxicity and testicular injury in rats. In the experimental protocol, rats were grouped into 4: Group 1 received vehicle and saline for 8 weeks while group 2 received diosmin and saline concomitantly for 8 weeks. Group 3 was given 3 mg/kg intraperitoneal DOX once every 7 days for 8 weeks. Group 4 was given 40 mg/kg of diosmin orally for 56 days followed by DOX diosmin administration after one hour. After 56 days of treatment, sperm quality, hormonal testing, biochemical parameters, and histological alterations in the testes were evaluated. DOX-induced reduce spermatogenic function, testicular 3- and 17β-Hydroxysteroid dehydrogenases, and serum follicle stimulating hormone, luteinizing hormone, and testosterone. It also enhanced inflammation, testicular oxidative damage, and apoptosis. The histopathologic examinations corroborated the biochemical results obtained. Significantly, diosmin treatment reduced DOX-induced injury, as evidenced by restored testicular architecture, increased steroidogenesis, preservation of spermatogenesis, suppression of oxide-inflammatory response, and apoptosis. It was found that through diosmin antioxidant, anti-apoptotic, and anti-oxido-inflammatory it presents a possible therapeutic alternative for protecting testicular tissue against DOX's harmful effects.

Phytochemical, Antioxidant and Antimicrobial Properties of Mirabilis jalapa

Background and Aim: The phytochemical screening for the detection of plant secondary metabolites as well as the antimicrobial and antioxidant properties of the plant were evaluated in this study using standard chemical and instrumental methods. This study aims to determine the chemical constituents, antioxidant, and antimicrobial properties of Mirabilis jalapa plant. Experimental Procedure: The phytochemical screening for the detection of plant secondary metabolites as well as the antimicrobial and antioxidant properties of the plant were evaluated using standard chemical and instrumental methods. Results: A total of twenty-four (24) chemical compounds were identified in GC-MS analysis, among these the highest percentage composition was 9-octadecenamide (46.89%) followed by cholest-5-ene-3,16, 22, 26-tetrol (8.49%), octadecanoic acid (8.39%), hexadecanamide (7.14%), 8,11-octadecadienoic acid, methyl ester (6.41%) and hexadecanoic acid (6.40%). The antimicrobial activity of the various extracts on six selected microorganisms showed that the methanolic root extracts inhibited E. coli (18.5 mm) and S. aureus (18 mm) at higher inhibition zones which is more than the standard drugs. The total antioxidant capacity and strength of the plant extract revealed that the leaves is a powerful antioxidant. Conclusion: The results of the study support folklore claims in treating infection and inflammation. It also revealed the immense potential of the plant for further research that aims at identifying the bioactive components responsible for the anti-oxidant and antimicrobial activity. The phytomedicinal attributes of the M. jalapa plant can be used for the formulation of antimicrobial and antioxidant drugs.

Multifunctional liposomes Co-encapsulating epigallocatechin-3-gallate (EGCG) and miRNA for atherosclerosis lesion elimination.

Atherosclerosis (AS) is a chronic inflammatory disease, characterized by a lipid accumulated plaque. Anti-oxidative and anti-inflammation and lipid metabolism promoting therapeutic strategies have been applied for atherosclerosis treatment. However, the therapeutic effect of a single therapeutic method is limited. It is suggested that a combination of these two strategies could help prevent lipid accumulation caused by inflammation and oxidative stress, and also promote lipid efflux from atherosclerotic plaque, to normalize arteries to the maximum extent. Hence, a strategy involving a multifunctional liposome co-encapsulating an antioxidant and anti-inflammatory drug epigallocatechin-3-gallate (EGCG) and a lipid-efflux-promoting gene miR-223 was established. The system (lip@EGCG/miR-223) could encapsulate miR-223 in core areas of the liposomes to provide a protective effect for gene drugs. Moreover, lip@EGCG/miR-223 was smaller in size (91.28 ± 2.28 nm characterized by DLS), making it easier to target AS lesions, which have smaller vascular endothelial spaces. After being efficiently internalized into the cells, lip@EGCG/miR-223 exhibited excellent antioxidant and anti-inflammatory effects in vitro by eliminating overproduced ROS and decreasing the level of inflammatory cytokines (TNF-α, IL-1β, and MCP-1), which was due to the effect of EGCG. Besides, the lipid-efflux-promoting protein ABCA1 was upregulated when treated with lip@EGCG/miR-223. Through the two therapies mentioned, lip@EGCG/miR-223 could effectively inhibit the formation of foam cells, which are a main component of atherosclerotic plaques. In AS model mice, after intravenous (i.v.) administration, lip@EGCG/miR-223 was effectively accumulated in atherosclerotic plaques, and the distribution of drugs in the heart and aorta compared to that in the kidney was significantly increased when compared with free drugs (the ratio was 6.27% for the free miR-223-treated group, which increased to 66.10% for the lip@EGCG/miR-223-treated group). By decreasing the inflammation level and lipid accumulation, the arterial vessels in AS were normalized, with less macrophages and micro-angiogenesis, when treated with lip@EGCG/miR-223. Overall, this study demonstrated that lip@EGCG/miR-223 could be developed as a potential system for atherosclerosis treatment by a combined treatment of antioxidant, anti-inflammatory, and lipid-efflux-promoting effects, which provides a novel strategy for the safe and efficient management of atherosclerosis.

Magnesium Ion-Doped Mesoporous Bioactive Glasses Loaded with Gallic Acid Against Myocardial Ischemia/Reperfusion Injury by Affecting the Biological Functions of Multiple Cells.

Excessive generation of reactive oxygen species (ROS) following myocardial ischemia-reperfusion (I/R) can result in additional death of myocardial cells. The rapid clearance of ROS after reperfusion injury and intervention during subsequent cardiac repair stages are crucial for the ultimate recovery of cardiac function. Magnesium-doped mesoporous bioactive glasses were prepared and loaded with the antioxidant drug gallic acid into MgNPs by sol-gel method. The antioxidant effects of MgNPs/GA were tested for their pro-angiogenic and anti-inflammatory effects based on the release characteristics of GA and Mg2+ from MgNPs/GA. Later, we confirmed in our in vivo tests through immunofluorescence staining of tissue sections at various time points that MgNPs/GA exhibited initial antioxidant effects and had both pro-angiogenic and anti-inflammatory effects during the cardiac repair phase. Finally, we evaluated the cardiac function in mice treated with MgNPs/GA. We provide evidence that GA released by MgNPs/GA can effectively eliminate ROS in the early stage, decreasing myocardial cell apoptosis. During the subsequent cardiac repair phase, the gradual release of Mg2+ from MgNPs/GA stimulated angiogenesis and promoted M2 macrophage polarization, thereby reducing the release of inflammatory factors. MgNPs/GA acting on multiple cell types is an integrated solution for comprehensive attenuation of myocardial ischaemia-reperfusion injury and cardiac function protection.

Sulfated polysaccharides from Caulerpa lentillifera: Optimizing the process of extraction, structural characteristics, antioxidant capabilities, and anti-glycation properties

The polysaccharides found in Caulerpa lentillifera (sea grape algae) are potentially an important bioactive resource. This study makes use of RSM (response surface methodology) to determine the optimal conditions for the extraction of valuable SGP (sea grape polysaccharides). The findings indicated that a water/raw material ratio of 10:1 mL/g, temperature of 90 °C, and extraction time of 45 min would maximize the yield, with experimentation achieving a yield of 21.576 %. After undergoing purification through DEAE-52 cellulose and Sephacryl S-100 column chromatography, three distinct fractions were obtained, namely SGP11, SGP21, and SGP31, each possessing average molecular weights of 38.24 kDa, 30.13 kDa, and 30.65 kDa, respectively. Following characterization, the fractions were shown to comprise glucose, galacturonic acid, xylose, and mannose, while the sulfate content was in the range of 12.2–21.8 %. Using Fourier transform infrared spectroscopy (FT-IR) it was possible to confirm with absolute certainty the sulfate polysaccharide attributes of SGP11, SGP21, and SGP31. NMR (nuclear magnetic resonance) findings made it clear that SGP11 exhibited α-glycosidic configurations, while the configurations of SGP21 and SGP31 were instead β-glycosidic. The in vitro antioxidant assays which were conducted revealed that each of the fractions was able to demonstrate detectable scavenging activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals and 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical cations. All fractions were also found to exhibit the capacity to scavenge NO radicals in a dose-dependent manner. SGP11, SGP21, and SGP31 were also able to display cellular antioxidant activity (CAA) against the human adenocarcinoma colon (Caco-2) cell line when oxidative damage was induced. The concentration levels were found to govern the extent of such activity. Moreover, purified SGP were found to exert strong inhibitory effects upon glycation, with the responses dependent upon dosage, thus confirming the potential for SGP to find a role as a natural resource for the production of polysaccharide-based antioxidant drugs, or products to promote improved health.

Optimization of boronic ester-based amphiphilic copolymers for ROS-responsive drug delivery.

This study introduces boronic ester-based ROS-responsive amphiphilic copolymers for antioxidant drug delivery. Tuning the hydrophobic/hydrophilic balance optimized the size, curcumin encapsulation, ROS-triggered release, cellular uptake, and intracellular ROS scavenging. The lead P1b formulation self-assembled into stable 10 nm micelles enabling rapid ROS-triggered curcumin release and preferential cellular internalization. P1b eliminated over 90% of pathogenic intracellular ROS within 10 minutes, demonstrating a rapid antioxidant therapy.

Nanomedicines as Guardians of the Heart: Unleashing the Power of Antioxidants to Alleviate Myocardial Ischemic Injury.

Ischemic heart disease (IHD) is increasingly recognized as a significant cardiovascular disease with a growing global incidence. Interventions targeting the oxidative microenvironment have long been pivotal in therapeutic strategies. However, many antioxidant drugs face limitations due to pharmacokinetic and delivery challenges, such as short half-life, poor stability, low bioavailability, and significant side effects. Fortunately, nanotherapies exhibit considerable potential in addressing IHD. Nanomedicines offer advantages such as passive/active targeting, prolonged circulation time, enhanced bioavailability, and diverse carrier options. This comprehensive review explores the advancements in nanomedicines for mitigating IHD through oxidative stress regulation, providing an extensive overview for researchers in the field of antioxidant nanomedicines. By inspiring further research, this study aims to accelerate the development of novel therapies for myocardial injury.

Role of Etanercept Against Renal Damage Induced by Cecal Ligation and Puncture in Male Rats

Cecal ligation and puncture (CLP) is one of the most widely utilized models for rat experimental polymicrobial sepsis. In this work, we examine how the anti-oxidant and anti-inflammatory drug Etanercept (ENT), which has been FDA-approved, might lessen the damaging effects of sepsis on renal tissues. In this study, rats were divided into four groups: the control group, which received just CLP; the solvent group, which received DMSO intravenously before CLP; and the treatment group, which received ENT intraperitoneally before CLP, might possibly reduce the risk of sepsis-induced renal tissue damage. According to our results, ENT reduced NF-kB, TNF-\(\alpha\), and TLR levels compared to the solvent alone group or control group. A positive tissue integrity was found in the ENT-pretreated group as compared to the solvent-only group or control group during a histopathological evaluation of the renal tissues. The findings indicate that ENT could potentially lower the risk of renal tissue damage due to CLP.

Molecular docking of antioxidant activity of bougainvillea spectabilis wild bractea ethanol fraction with aryl hydro carbon inhibitors and vitamin C comparator

Antioxidant compounds are increasingly being used in the health sector. In the health sector, antioxidant compounds also have a very important role. Antioxidant compounds have been scientifically proven to reduce the risk of chronic diseases, such as cancer, coronary heart disease, disorders such as redness, hyperpigmentation, wrinkles and premature aging. Antioxidant compound found in many plants, both bracteas, leaves and fruit, one of which is bracteas Bougainvillea spectabilis Willd. The ethanol fraction of bracteas Bougainvillea spectabillis Willd include: butil hydroxytoluene;ρ-Trimethylsilyloxyphenyl (tri.methylsilyloxy) trimethylsilylacrylate; 2,5 pyrrolidinedione, 1-methyl; Dimethylsulfoxonium formylmethylide; Formamide, N,N-dimethyl; Dimethyl sulfone and Cyclotetrasiloxane, octamethyl. Identified by the Liquid Chromatography - Mass Spectrometry method, then docked with Molegro Virtual Docker. Butyl hydroxytoluene has the same Root Mean Square Deviation value as vitamin C and smaller than the standard ligand BHF_401 (A), which can be seen from Rerank scores are - 76,0629, -76,1096, -105,0070. Hydrogen and electrostratic bonds in the ethanol fraction: Butyl hydroxytoluene with 3 amino acid residues including Tyr 334, Leu 292 and Leu 281, in the control Vitamin C with 9 amino acid residues Tyr 336, Leu 307, Val 308, As 306, Tyr 305, Gly 304, Gly 303, Phe 279 and His 275 with standard ligand BHF_401 (A) with 4 amino acid residues Val 316, Tyr 305, His 275 and Tyr 334. Butyl hydroxytoluenemore harmonious and stable and as a candidate for antioxidant drugs that have the same activity as vitamin C as a positive control

A Review: Pharmacological Effect of Natural Compounds in Diospyros kaki Leaves from the Perspective of Oxidative Stress.

Oxidative stress is caused by an imbalance between reactive oxygen species and antioxidant levels. Current research suggests that oxidative stress is one of the key factors in the development of many chronic diseases, and it has been a concern for many years. Many natural compounds have been studied for their special free-radical-scavenging properties. The major chemical constituents of the leaves of Diospyros kaki are flavonoids and triterpenoids, both of which are potential antioxidants that can prevent damage caused by reactive oxygen species or reactive nitrogen species and ameliorate diseases associated with oxidative stress. In addition to the major constituents such as flavonoids and triterpenoids, the leaves of Diospyros kaki include compounds such as phenylpropanoids, alkaloids, phenolic acids, and terpenes. Studies have shown these compounds have certain antioxidant and neuroprotective activities. Experiments have shown that flavonoids or the extracts from the leaves of Diospyros kaki have a variety of good pharmacological activities, which could activate oxidative stress and mitochondrial apoptosis, inhibit the proliferation of human prostate cancer cells and induce apoptosis. It also could achieve the effect of anti-cancer cell proliferation and induce apoptosis by regulating oxidative stress. The main chemical substance of the leaves of Diospyros kaki regulating oxidative stress may be these multi-hydroxyl structure compounds. These natural products exhibit significant antioxidant activity and are an important basis for the leaves of Diospyros kaki to treat human diseases by regulating oxidative stress. This review summarizes the structural types of natural products in the leaves of Diospyros kaki and elaborates the mechanism of the leaves of Diospyros kaki in neuroprotection, anti-diabetes, renal protection, retinal degenerative diseases, and anti-cancer from a new perspective of oxidative stress, including how it supplements other pharmacological effects. The chemical constituents and pharmacological effects of the leaves of Diospyros kaki are summarized in this paper. The relationship between the chemical components in the leaves of Diospyros kaki and their pharmacological effects is summarized from the perspective of oxidative stress. This review provides a reference for the study of natural anti-oxidative stress drugs.

A Microenvironment-responsive small-molecule probe and application in quick acute myocardial infarction imaging

Acute myocardial infarction (AMI) patients are at an elevated risk for life-threatening myocardial ischemia/reperfusion injury. Early-stage nonradioactive and noninvasive diagnosis of AMI is imperative for the subsequent disease treatment, yet it presents substantial challenges. After AMI, the myocardium typically exhibits elevated levels of peroxynitrite (ONOO−), constituting a distinct microenvironmental feature. In this context, the near-infrared imaging probe (BBEB) is employed to precisely delineate the boundaries of AMI lesions with a high level of sensitivity and specificity by monitoring endogenous ONOO−. This probe allows for the early detection of myocardial damage at cellular and animal levels, providing exceptional temporal and spatial resolution. Notably, BBEB enables visualization of ONOO− level alterations during AMI treatment incorporating antioxidant drugs. Overall, BBEB can rapidly and accurately visualize myocardial injury, particularly in the early stages, and can further facilitate antioxidant drug screening.

Natural ursolic acid based self-therapeutic polymer as nanocarrier to deliver natural resveratrol for natural therapy of acute kidney injury

Acute kidney injury (AKI) is a common kidney disease associated with excessive reactive oxygen species (ROS). Unfortunately, due to the low kidney targeting and undesired side effects, the existing antioxidant and anti-inflammatory drugs are unavailable for AKI management in clinic. Therefore, it’s essential to develop effective nanodrugs with high renal targeting and biocompatibility for AKI treatment. Herein, we reported a novel nanodrug for AKI treatment, utilizing poly(ursolic acid) (PUA) as a bioactive nanocarrier and resveratrol (RES) as a model drug. The PUA polymer was synthesized form ursolic acid with intrinsic antioxidant and anti-inflammatory activities, and successfully encapsulated RES through a nanoprecipitation method. Subsequently, we systemically investigated the therapeutic potential of RES-loaded PUA nanoparticles (PUA NPs@RES) against AKI. In vitro results demonstrated that PUA NPs@RES effectively scavenged ROS and provided substantial protection against H2O2-induced cellular damage. In vivo studies revealed that PUA NPs significantly improved drug accumulation in the kidneys and exhibited favorable biocompatibility. Furthermore, PUA NPs alone exhibited additional anti-inflammatory and antioxidant effect, synergistically enhancing therapeutic efficacy in AKI mouse models when combined with RES. Overall, our study successfully developed an effective nanodrug using self-therapeutic nanocarriers, presenting a promising option for the treatment of AKI.Graphical abstract

Development of Dual-Responsive Fluorescent Probe for Drug Screening of Diabetes Cardiomyopathy.

For specific drug research and development, a drug-screening strategy (DSS) plays an indispensable role in the biomedical field. Unfortunately, traditional strategies are complicated and insufficiently accurate due to the widely used single-target screening method. Herein, a simple dual-target-based drug-screening strategy (dt-DSS) is proposed to screen highly effective drugs by fluorescence imaging. As a proof of concept, we utilized a dual-responsive fluorescence probe to screen drugs for diabetic cardiomyopathy (DCM). We first developed and took advantage of a dual-response probe HDB to detect reactive oxygen species (ROS) and mitophagy levels in cellular starvation and high glucose models. Based on this, HDB was utilized to study the effects of different drugs in the mitophagy process caused by the high-glucose cell model for DCM. Combined with Western blotting assays, we found that Drp-1 inhibitors could fundamentally reduce mitophagy caused by the high-glucose cells model. Compared with commercial single-target antioxidant drugs, the drugs with simultaneous antioxidant capacity and Drp-1 inhibition screened by dt-DSS, such as resveratrol and icariin, could treat DCM better. Therefore, HDB as an effective tool could accurately and quickly screen high-potency drugs for DCM. We believe that this work provides an attractive strategy to explore the pathogenesis of diabetic cardiomyopathy and precisely screen for highly effective drugs.

Turmeric Powder Counteracts Oxidative Stress and Reduces AFB1 Content in the Liver of Broilers Exposed to the EU Maximum Levels of the Mycotoxin.

The most frequent adverse effects of AFB1 in chicken are low performance, the depression of the immune system, and a reduced quality of both eggs and meat, leading to economic losses. Since oxidative stress plays a major role in AFB1 toxicity, natural products are increasingly being used as an alternative to mineral binders to tackle AFB1 toxicosis in farm animals. In this study, an in vivo trial was performed by exposing broilers for 10 days to AFB1 at dietary concentrations approaching the maximum limits set by the EU (0.02 mg/kg feed) in the presence or absence of turmeric powder (TP) (included in the feed at 400 mg/kg). The aims were to evaluate (i) the effects of AFB1 on lipid peroxidation, antioxidant parameters, histology, and the expression of drug transporters and biotransformation enzymes in the liver; (ii) the hepatic accumulation of AFB1 and its main metabolites (assessed using an in-house-validated HPLC-FLD method); (iii) the possible modulation of the above parameters elicited by TP. Broilers exposed to AFB1 alone displayed a significant increase in lipid peroxidation in the liver, which was completely reverted by the concomitant administration of TP. Although no changes in glutathione levels and antioxidant enzyme activities were detected in any treatment group, AFB1 significantly upregulated and downregulated the mRNA expression of CYP2A6 and Nrf2, respectively. TP counteracted such negative effects and increased the hepatic gene expression of selected antioxidant enzymes (i.e., CAT and SOD2) and drug transporters (i.e., ABCG2), which were further enhanced in combination with AFB1. Moreover, both AFB1 and TP increased the mRNA levels of ABCC2 and ABCG2 in the duodenum. The latter changes might be implicated in the decrease in hepatic AFB1 to undetectable levels (<LOD) in the TP supplemented group. Overall, our findings further support the use of TP as an effective feeding strategy to prevent AFB1-related adverse effects in broilers.

Structural Elucidation, In vitro and In silico Biological Evaluations of New Fluorinated Chalcone Derivatives for Potential Antioxidant Activity

Abstract: The newly synthesized fluorinated chalcone derivatives are observed to possess antioxidant potential. Two new fluorinated chalcone compounds were effectively synthesized using the Claisen- Schmidt condensation reaction and were recrystallized using the slow evaporation method. The single crystal structure of the compounds was determined and refined through the X-ray single crystal diffraction method. All compounds were subjected to computational structural characterization and Hirshfeld surface analysis. The compounds were then further characterized through the Ultravioletvisible (UV-Vis) spectroscopic study. The chalcone derivatives were further analysed with biological experimentation and simulation such as in vitro antioxidant (DPPH) assay, molecular docking and in silico ADMET study. The crystal packing revealed that the molecules in the compounds were linked together through the intermolecular C—H···O and C—H···π interactions. Hirshfeld surface analysis validated the presence of intermolecular interactions in crystal packing. The UV-Vis spectroscopic study revealed that the absorption wavelength of the compounds that range from 421.79 to 428.98 nm was within the visible region with the energy gap value of 2.58 to 2.62 eV. The DPPH assay disclosed weak antioxidant activity of both compounds (-31 to 20 %, 10000 μg/mL) compared to the standard ascorbic acid (94.5 %, 50 μg/mL). The binding energy of the docked complex inside the target protein, 2CAG was within the range of -7.3 to -7.5 kcal/mol. In the silico model, SwissADME predicted that the two compounds have overall good drug-like properties. Different substituents, more planar configuration and high intramolecular interactions in the crystal packing played their role in increasing the antioxidant activities, binding energy and drug likeliness of the synthesized compounds.