Decreased Malondialdehyde Levels Research Articles

Biophysical and biochemical study exploring resveratrol protective potential against gamma irradiation effects

BackgroundGamma irradiation causes oxidative stress and disturbs the physiological balance in organisms. Natural antioxidants, like resveratrol (Res), can buffer these effects. The study's goal is to find out whether Res can help reverse changes caused by gamma irradiation in male Wistar rats' total antioxidant capacity (TAC), antioxidant enzyme activity, electrolyte levels, and hemoglobin structure.MethodsTwenty-four rats were divided into four groups: control, Res-treated, irradiated, and Res + irradiated. Blood and tissue samples were collected on the day 16th of the experiment. The levels of antioxidants, catalase (CAT) activity, glutathione (GSH), and glutathione peroxidase (GPx) were estimated along with electrolyte level measurements. UV–FTIR and dielectric spectroscopy were used to assess conformational changes in hemoglobin.ResultsGamma irradiation decreased antioxidant levels and increased markers of oxidative stress. Resveratrol treatment increased the antioxidant capacity and levels of nitric oxide and decreased malondialdehyde levels. Further, Res protected the structure of hemoglobin and decreased the radiation-induced damage.ConclusionResveratrol shows potential as a protective agent against gamma irradiation-induced oxidative stress by enhancing antioxidant defenses and restoring hemoglobin structure.

Protective effect of epidermal growth factor on cryopreservation of dromedary camel epididymal spermatozoa: Evidence from in vitro and in silico studies

Epidermal growth factor (EGF) plays a crucial role in maintaining male reproductive capacity in mammals, however, its protective effects on cryopreserved dromedary camel epididymal spermatozoa have not been thoroughly investigated. This study aims to investigate the potential protective role of EGF on cryopreserved camel epididymal spermatozoa, supported by evidence from a molecular docking study. We assessed sperm motility, kinematics parameters, oxidative stress, ultrastructural changes, apoptosis, and molecular docking markers in camel epididymal spermatozoa following cryopreservation. Camel epididymal spermatozoa (n=30 pairs of testes) were collected from local slaughterhouses. The epididymal spermatozoa were diluted with a freezing medium (SHOTOR extender) supplemented with different concentrations of EGF; 0 (EGF0), 50 (EGF50), 100 (EGF100), 200 (EGF200), and 400 (EGF400) ng/mL in SHOTOR extender and cryopreserved using a standard protocol. All EGF groups showed significant improvements in sperm progressive motility, viability, and sperm membrane function after equilibration at 5 °C for 24hours. Regarding frozen-thawed samples, sperm progressive motility and some kinematic parameters (DAP, VSL, VCL and AHL) were significantly higher in the EFG400 group compared to the other groups (P < 0.01). A significant increase in the percentage of live/acrosome-intact sperm was observed, accompanied by a significant decrease in malondialdehyde levels in all EGF groups (P < 0.05). Both the EGF200 and EGF400 groups showed significantly higher sperm viability and significantly lower percentages of apoptotic and necrotic sperm compared to the other groups (P < 0.05). EGF supplementation preserved the ultrastructural integrity and cryotolerance of epididymal camel spermatozoa. The docking analysis indicated that EGF exhibited higher binding affinity with apoptosis sperm markers, including caspase-3 and bcl-2-associated X (Bax) proteins, with binding energies of -502.0 and -621.0kcal/mol, respectively. In conclusion, the addition of EGF to SHOTOR extender was found to have beneficial effects on sperm motility, kinematics parameters, sperm viability, acrosome integrity, sperm ultrastructural features, and reduced oxidative stress and apoptosis-like changes in cryopreserved epididymal camel sperm.

Gastrodin ameliorates diabetic nephropathy by activating the AMPK/Nrf2 pathway.

Diabetic nephropathy (DN) is a leading cause of end-stage kidney failure, contributing to elevated morbidity and mortality rates in individuals with diabetes. Despite its potential renoprotective effects, the molecular mechanism by which gastrodin (GSTD) impacts DN remains unclear. To investigate this, mice were initially induced with DN via intraperitoneal streptozotocin (STZ) injection (50mg/kg) and subsequently treated with varying doses of GSTD (5, 10, 20mg/kg). Furthermore, the potential molecular mechanism of GSTD in mitigating DN was explored in vivo in conjunction with compound C, an inhibitor of 5'-AMP-activated protein kinase (AMPK). Subsequently, the blood weight, fasting blood glucose levels, and renal injury markers of DN-afflicted mice were assessed. Additionally, renal tissues were subjected to quantitative reverse-transcriptase-polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) to evaluate inflammatory factor levels, colorimetric assays to measure renal malondialdehyde (MDA) levels, and immunoblotting analysis to examine AMPK/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. The results demonstrated that a 6-week GSTD regimen effectively improved metabolic manifestations associated with DN, including reductions in fasting blood glucose levels, 24-hour urine output, renal indices, amelioration of glomerular histopathological abnormalities, diminished glycogen accumulation, and fibrosis. Furthermore, DN-afflicted renal tissues exhibited decreased MDA levels and elevated expression of AMPK/Nrf2 pathway-associated proteins. The beneficial effects of GSTD on DN and its protein modulation were reversed upon co-intervention with compound C. Together, our findings imply that GSTD improves DN by activating the AMPK/Nrf2 pathway, thereby mitigating STZ-induced renal damage, inflammatory responses, and oxidative stress.

Inhibiting Ferroptosis Prevents the Progression of Steatotic Liver Disease in Obese Mice.

Ferroptosis, a form of regulated cell death characterized by lipid peroxidation and iron accumulation, has been implicated in the progression of metabolic-dysfunction-associated steatohepatitis (MASH) in obesity. This study investigated the role of ferroptosis in the development of hepatic steatosis and MASH in obese mice and assessed the therapeutic potential of ferrostatin-1, a ferroptosis inhibitor. C57BL/6J wild-type (n = 8) and ob/ob mice (n = 16) were maintained on a standard chow diet. Mice were divided into three groups that included C57BL/6 (n = 8), ob/ob (n = 8), and ob/ob + ferrostatin-1 (FER) (n = 8), with the latter group receiving an intraperitoneal injection of 5 μM/kg ferrostatin three times per week for eight weeks. Following treatment, serum and tissue samples were collected for analysis. Significant hepatic steatosis and increased lipogenesis markers were observed in ob/ob mice, which were restored to baseline levels in the ob/ob + FER group treated with ferrostatin-1. Elevated oxidative stress was indicated by increased reactive oxygen species (ROS) and malondialdehyde (MDA) levels in the ob/ob group, while glutathione peroxidase 4 (GPX4) activity was significantly reduced. Ferrostatin-1 treatment decreases MDA levels and restores GPX4 activity. Additionally, ferrostatin mitigates iron overload and promotes macrophage polarization from M1 to M2, thereby reducing liver inflammation and fibrosis. Ferrostatin treatment reversed mitochondrial dysfunction in ob/ob mice. Our findings revealed that ferroptosis plays a significant role in the progression of obesity to hepatic steatosis and MASH. Inhibiting ferroptosis using ferrostatin-1 effectively improves liver histology, reduces oxidative stress, normalizes lipogenesis, and modulates macrophage polarization. This study highlights the potential of targeting ferroptosis as a therapeutic strategy for obesity-related liver diseases, warranting further investigation in clinical settings.

Green synthesis of silver nanoparticles containing Cichorium intybus to treat the sepsis-induced DNA damage in the liver of Wistar albino rats

Abstract Sepsis is a severe reaction of the body to an infection, presenting a critical medical crisis. It represents an imbalance between the body’s anti- and pro-inflammatory reactions. The occurrence of sepsis, which leads to multiple-organ failure and increased mortality, is marked by dysfunction in the lungs, heart, kidneys, and liver. The involvement of reactive oxygen species is believed to contribute to the progression of sepsis. Data suggest potential advantages of phenolic compounds derived from plants in combating sepsis. Plant polyphenols can be antioxidants by scavenging free radicals, chelating metals, and binding to proteins. In this research, silver nanoparticles (AgNPs) were produced by the aqueous extract of Cichorium intybus leaf for the purpose of treating sepsis-induced DNA harm. The recent study focused on the biological aspect including the cytotoxicity properties on normal (HUVEC) cell line. The AgNPs were analyzed by transmission electron microscopy (TEM), scanning electron microscopy (SEM), fourier-transform infrared spectroscopy, X-ray powder diffraction, and UV-Vis. The TEM and SEM images of AgNPs exhibited the average size of 35.29 nm with spherical morphology. In the in vivo study, the animals were categorized into four groups: sepsis-induced, sham, AgNPs-20, and AgNPs-100. AgNPs treatment resulted in a significant decrease in tissues damage (p &lt; 0.01). The sepsis-induced group showed a significantly elevated malondialdehyde (MDA) level in comparison to the sham group (p &lt; 0.01). Nevertheless, the groups that received AgNPs experienced a decrease in MDA levels and an increase in glutathione and superoxide dismutases levels (p &lt; 0.01). Additionally, the rats treated with AgNPs exhibited a reduction in the IL-1β mRNA expression levels (p &lt; 0.01).

Mitigating effects of agmatine on myocardial infarction in rats subjected to isoproterenol.

Isoproterenol (ISO) usage is limited by its potential for cardiotoxicity. We sought to investigate the potential of agmatine in mitigating ISO-induced cardiotoxicity. Agmatine (100mg/kg/day) was intraperitoneally administered to Wistar rats for 7days in the presence or absence of cardiotoxicity induced by subcutaneous injection of ISO (85mg/kg) on the sixth and seventh days. ECG parameters, lactate dehydrogenase (LDH), malondialdehyde (MDA), and creatinine phosphokinase (CPK) were investigated. Changes in cardiac tissue were also investigated using H&E staining. The heart weight/body weight ratio increased in ISO-treated rats. In the agmatine + ISO group, the increased heart rate observed in ISO-treated rats was reversed (317.2 ± 10.5 vs 452.2 ± 10.61, P < 0.001). Agmatine ameliorated the change in PR, RR, and ST intervals and the QRS complex, which was reduced by ISO. Treatment with saline, ISO, and agmatine had no significant effect on papillary muscle stimulation (P > 0.05). The administration of agmatine to ISO-receiving group could mitigate several parameters when compared to ISO-receiving group including increasing papillary muscle contraction (0.83 vs 0.71 N/M2 respectively, P < 0.01), decreasing LDH levels (660ng/ml vs 1080ng/ml, respectively, P < 0.05), decreasing CPK levels (377 U/l vs 642 U/l, respectively, P < 0.05) and decreasing MDA levels (20.32µM/l vs 46.83µM/l, P < 0.001). Coadministration of agmatine and ISO is capable of ameliorating ISO cardiotoxicity by antioxidant effects and controlling the hemostasis of calcium in myocytes.

Potential protection of resveratrol-tempeh against nephrotoxic and hepatotoxic histological damage in mice induced by aluminum

Aluminum is a widely distributed metal that, while generally safe at low levels, can become toxic when accumulated in the body. Its exposure is daily through various sources, including food, water, and medications. High levels of aluminum have been shown to adversely affect the kidneys and liver, leading to significant organ damage. Resveratrol-tempeh is a safe protective agent against organ damage caused by aluminum. Here, we investigated the impact of resveratrol on liver and kidney toxicity and Al-induced levels of catalase and malondialdehyde. The mice group was the control group, Al-group, Al+REST5-group, and Al+REST10-group. Aluminum and resveratrol were administered intraperitoneally to mice for four weeks, but resveratrol was administered one hour after exposure to aluminum. Mice were killed by cervical dislocation; the liver and kidney were isolated for slide, and the level of an antioxidant enzyme of catalase and oxidant of malondialdehyde was measured. The results showed that administration of aluminum at a dose of 200 mg/kg body weight caused glomerular shrinkage and proximal tubule degeneration in the kidneys. In addition, it also caused liver tissue damage, with hepatocytes undergoing degeneration, sinusoids dilating, and decreased body weight in the mice. Administration of resveratrol-tempeh tended to decrease malondialdehyde levels and increase catalase activity, although the changes were not significant. It seems that resveratrol-tempeh can repair liver and kidney damage and restore them to normal conditions. Conclusion: Aluminum at 200 mg/kg is toxic to mice. Resveratrol-tempeh can be considered a potential candidate to protect kidney and liver damage caused by aluminum chloride toxicity.

Application of Fluorescent Composite Materials as a Sustained Release System in Treatment of Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is a multifactorial disease characterized by oxidative stress and follicular dysfunction, leading to menstrual irregularities, hyperandrogenism, and infertility. Traditional drug delivery methods often result in drug loss and side effects on normal tissues. To address these issues, we synthesized two novel Co(II)-containing coordination polymers (CPs), {[Co(L)(H2O)2]·2H2O}n (1) and {[Co(L)(H2O)2]·1.5H2O}n (2), through the reaction of the T-shaped ligand (4 - 3'-pyridyl-,6 - 4'-carboxylphenyl)picolinic acid (H2L) with Co(NO3)2·6H2O via a solvothermal process. Fluorescence spectroscopy revealed that the fluorescence emission of the CPs originates from the ligand, indicating their potential application as blue fluorescence materials. Subsequently, we encapsulated these CPs with hyaluronic acid (HA) and carboxymethyl chitosan (CMCS) hydrogels to create two types of metal gel particles carrying spironolactone (HA/CMCS-CPs@spironolactone). SEM and TEM analyses showed that the material consists of tightly stacked sheet-like structures with an average size of approximately 100nm. Thermogravimetric analysis (TGA) indicated that the material begins to decompose at around 115°C, demonstrating good thermal stability. We assessed the inhibitory effects of these materials on oxidative stress induced by PCOS. The results showed that both types of spironolactone-loaded metal gel particles significantly reduced malondialdehyde (MDA) levels, particularly the particles constructed with CP2. HA/CMCS-CP1@spironolactone reduced MDA levels by approximately 17% and 46% at low and high concentrations, respectively, while HA/CMCS-CP2@spironolactone decreased MDA levels by about 55% and 39% at high and low concentrations, respectively. Therefore, the novel drug delivery system reported in this study has the potential to become a safe and effective option for the localized treatment of PCOS.

Anti irradiation nanoparticles shelter immune organ from radio-damage via preventing the IKK/IκB/NF-κB activation

BackgroundNormal tissue and immune organ protection are critical parts of the tumor radiation therapy process. Radiation-induced immune organ damage (RIOD) causes several side reactions by increasing oxidative stress and inflammatory responses, resulting in unsatisfactory curability in tumor radiation therapy. The aim of this study was to develop a novel and efficient anti irradiation nanoparticle and explore its mechanism of protecting splenic tissue from radiation in mice.MethodsNanoparticles of triphenylphosphine cation NIT radicals (NPs-TPP-NIT) were prepared and used to protect the spleens of mice irradiated with X-rays. Splenic tissue histopathology and hematological parameters were investigated to evaluate the protective effect of NPs-TPP-NIT against X-ray radiation. Proteomics was used to identify differentially expressed proteins related to inflammatory factor regulation. In addition, in vitro and in vivo experiments were performed to assess the impact of NPs-TPP-NIT on radiation therapy.ResultsNPs-TPP-NIT increased superoxide dismutase, catalase, and glutathione peroxidase activity and decreased malondialdehyde levels and reactive oxygen species generation in the spleens of mice after exposure to 6.0 Gy X-ray radiation. Moreover, NPs-TPP-NIT inhibited cell apoptosis, blocked the activation of cleaved cysteine aspartic acid–specific protease/proteinase, upregulated the expression of Bcl-2, and downregulated that of Bax. We confirmed that NPs-TPP-NIT prevented the IKK/IκB/NF-κB activation induced by ionizing radiation, thereby alleviating radiation-induced splenic inflammatory damage. In addition, when used during radiotherapy for tumors in mice, NPs-TPP-NIT exhibited no significant toxicity and conferred no significant tumor protective effects.ConclusionsNPs-TPP-NIT prevented activation of IKK/IκB/NF-κB signaling, reduced secretion of pro-inflammatory factors, and promoted production of anti-inflammatory factors in the spleen, which exhibited radiation-induced damage repair capability without diminishing the therapeutic effect of radiation therapy. It suggests that NPs-TPP-NIT serve as a potential radioprotective drug to shelter immune organs from radiation-induced damage.

Pueraria lobata extract ameliorates D-GalN/LPS-induced liver injury through targeting TLR4/NF-κB signalling pathway and regulating gut microbiota

AbstractKudzu root (Pueraria lobata), known for its dual role as a medicinal herb and food ingredient, has proven anti-inflammatory and antioxidant properties. This study explored the effects of P. lobata extract (PLE) on D-galactose/lipopolysaccharide (D-GalN/LPS)-induced liver inflammation and oxidative stress in mice, along with its impact on gut microbiota. The in vivo studies indicated that PLE significantly reduced hepatic levels of pro-inflammatory cytokines (tumour necrosis factor-α, interleukin-1β, and interleukin-6) and increased the anti-inflammatory cytokine interleukin-10. It also lowered serum aspartate aminotransferase and alanine aminotransferase activities, indicating reduced liver damage, and mitigated oxidative stress by decreasing malondialdehyde levels while restoring superoxide dismutase activity. Western blot analysis revealed that PLE inhibited the phosphorylation of NF-κB pathway proteins (p65 and IκB) and suppressed TLR4 expression, highlighting its role in this inflammatory pathway. Additionally, PLE ameliorated D-GalN/LPS-induced gut microbiota dysbiosis, reducing Proteobacteria abundance and promoting beneficial genera such as Lactobacillus, Bifidobacterium, and Akkermansia. These findings suggest that PLE protects against liver inflammation and oxidative stress, while improving gut microbiota composition, offering potential therapeutic strategies for liver-related diseases.

Extraction, Characterization, and Antioxidant Activity of Eucommia ulmoides Polysaccharides.

Herein, the ultrasound-assisted extraction conditions affecting the yield of EUPS (Eucommia ulmoides polysaccharide) were analyzed using a Box-Behnken response surface design. The alleviation effect of EUPS on diquat-induced oxidative stress in mice was also studied. A maximum EUPS yield of 2.60% was obtained under the following optimized conditions: an extraction temperature of 63 °C, extraction time of 1 h, and ratio of liquid to raw materials of 22:1. EUPS exhibited strong 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radical-scavenging ability (87.05%), 2'-Azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS) radical-scavenging ability (101.17%), and hydroxyl radical-scavenging ability (62.92%). The administration of EUPS increased the activities of superoxide dismutase, catalase, and glutathione peroxidase and decreased malondialdehyde levels in the livers of mice exposed to diquat. EUPS may inhibit the downregulation of NAD(P)H:quinoneoxidoreductase 1 and heme oxygenase 1 mRNA expression in the livers of diquat-administered mice through the Nrf2-Keap1 signaling pathway. Moreover, the abundance of Firmicutes and Ligilactobacillus was enhanced, whereas that of Helicobacter decreased in the gut of the remaining groups of mice compared with that of the diquat-treated mice. Therefore, EUPS exhibited an antioxidant effect and improved oxidative stress and intestinal flora abundance in mice.

Comparison of Dietary Supplementation with Krill Oil, Fish Oil, and Astaxanthin on an Experimental Ethanol-Induced Gastric Ulcer Model: A Biochemical and Histological Study

Background/Objectives: Despite advances in ulcer treatment research, the search for new, safe, and effective strategies for preventing and treating ulcer diseases persists. Methods: In this study, the protective effects of dietary supplementation with krill oil (KO), fish oil (FO), and astaxanthin (ASX) on an ethanol-induced gastric ulcer model were compared during biochemical and histological observations. Sprague–Dawley (n = 64) rats randomly divided into four groups—normal control (vehicle), KO, FO, and ASX groups—received the supplements via the orogastric route at a rate of 2.5% (v/w) of their daily feed consumption for 4 weeks. Then, ulcer induction was performed with ethanol. Results: The ulcer group showed increased levels of malondialdehyde (MDA), chemiluminescence (CL), and myeloperoxidase (MPO) activity and decreased levels of glutathione in the gastric tissues. While KO, FO, and ASX supplementation decreased chemiluminescence levels in the ulcer group, only ASX supplementation decreased MDA levels and MPO activity. Conclusions: In conclusion, supplementation with KO or FO has a similar protective effect against ethanol-induced ulcer damage, as it inhibits ROS formation and reduces lipid peroxidation. However, ASX supplementation has a higher protective effect than KO or FO supplementations against experimental ethanol-induced gastric lesions in rats, as it inhibits ROS formation and reduces neutrophil infiltration and lipid peroxidation.

Physicochemical, structural, and biological properties of novel water-soluble polysaccharide derived from the Tunisian Hammada scoparia plant and its application on beef meat preservation

This work aims to characterize a novel water-soluble polysaccharide from Hammada scoparia leaves named PSP. The Infrared (FT-IR) and nuclear magnetic resonance (NMR) spectra confirmed the presence of different polysaccharide functional bands. The High-Performance Liquid Chromatography (HPLC) analysis identified a heteropolysaccharide composed of two monosaccharides. A semi-crystalline structure of PSP was proved using the X-ray diffraction (XRD) and Scanning Electron Microscopy (SEM) analysis. The evaluation of the antioxidant activity revealed an interesting potential to prevent oxidative stress.Additionally, PSP showed interesting functional propreties such as good oil and water retention abilities, higher foaming stability, and higher emulsifying capacity and stability. However, the effect of PSP on the oxidation of lipids in the ground beef meat was established during nine days at 4 °C. Obtained data revealed a significant decrease in malondialdehyde levels, inhibition of metmyoglobin (MetMb) accumulation, and significant inhibition of microbial growth compared with the control sample during storage. Moreover, incorporating PSP in minced meat proved color pH and moisture stability. Overall, the findings in the present study confirmed that PSP could be considered a natural bioactive polymer for food applications.

Evaluation of Antioxidant Effects of Coenzyme Q10 against Hyperglycemia-Mediated Oxidative Stress by Focusing on Nrf2/Keap1/HO-1 Signaling Pathway in the Liver of Diabetic Rats.

Hyperglycemia-induced oxidative stress can damage the liver and lead to diabetes complications. Coenzyme Q10 (CoQ-10) reduces diabetes-related oxidative stress. However, its molecular mechanisms are still unclear. This study aimed to examine CoQ-10's antioxidant capabilities against hyperglycemia-induced oxidative stress in the livers of diabetic rats, specifically targeting the Nrf2/Keap1/ARE signaling pathway. This study was conducted between 2020-2021 at Arak University of Medical Sciences. A total of 30 male adult Wistar rats (8 weeks old) weighing 220-250 g were randomly assigned to five groups (n=6 in each group): control healthy, sesame oil (CoQ-10 solvent), CoQ-10 (10 mg/Kg), diabetic, and diabetic+CoQ-10. Liver oxidative stress indicators, including malondialdehyde, catalase, glutathione peroxidase, and glutathione, were estimated using the spectrophotometry method. Nrf2, Keap1, HO-1, and NQO1 gene expressions were measured using real-time PCR tests in the liver tissue. All treatments were conducted for 6 weeks. Statistical analysis was performed using SPSS software. One-way ANOVA followed by LSD's or Tukey's post hoc tests were used to compare the results of different groups. P<0.05 was considered statistically significant. The findings showed that induction of diabetes significantly increased Keap1 expression (2.1±0.9 folds, P=0.01), and significantly inhibited the mRNA expression of Nrf2 (0.38±0.2 folds, P=0.009), HO-1 (0.27±0.1 folds, P=0.02), and NQO1 (0.26±0.1 folds P=0.01), compared with the healthy group. In the diabetic group, the activity of glutathione peroxidase, catalase enzymes, and glutathione levels was decreased with an increase in malondialdehyde level. CoQ-10 supplementation significantly up-regulated the expressions of Nrf2 (0.85±0.3, P=0.04), HO-1 (0.94±0.2, P=0.04), NQO1 (0.88±0.5, P=0.03) genes, and inhibited Keap1 expression (1.1±0.6, P=0.02). Furthermore, as compared to control diabetic rats, CoQ-10 ameliorated oxidative stress by decreasing malondialdehyde levels and increasing catalase, glutathione peroxidase activities, and glutathione levels in the liver tissues of the treated rats in the treatment group. The findings of this study revealed that CoQ-10 could increase the antioxidant capacity of the liver tissue in diabetic rats by modulating the Nrf2/Keap1/HO-1/NQO1 signaling pathway.

Diosgenin ameliorating non-alcoholic fatty liver disease via Nrf2-mediated regulation of oxidative stress and ferroptosis.

This study aimed to investigate the mechanisms through which diosgenin inhibits the pathogenesis of non-alcoholic fatty liver disease, focusing particularly on ferroptosis-related pathways and its reliance on nuclear factor erythroid 2-related factor 2. Using a rat model, we showed diosgenin's efficacy in reducing lipid deposition throughout the body and examined its impact on ferroptosis-related gene expression in vivo. Moreover, in vitro experiments using human hepatocellular liver carcinoma cell line cells were conducted to assess oxidative stress and ferroptosis levels. Diosgenin decreased lipid accumulation and steatosis; lowered serum levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol, glutamic pyruvic transaminase and glutamic oxaloacetic transaminase; reduced interleukin-1β and tumour necrosis factor-α; diosgenin decreased malondialdehyde levels; and increased serum superoxide dismutase levels in a rat model of high-fat diet-induced non-alcoholic fatty liver disease. Diosgenin upregulated the expression of nuclear factor erythroid 2-related factor 2 and its downstream ferroptosis-related genes to inhibit ferroptosis in the livers of rats with non-alcoholic fatty liver disease. Diosgenin decreased reactive oxygen species levels and enhanced the expression of ferroptosis-related genes in human hepatocellular liver carcinoma cells induced by free fatty acids, with its effects being dependent on nuclear factor erythroid 2-related factor 2. This study highlights the potential of diosgenin from Dioscoreaceae plants in mitigating oxidative stress and ferroptosis levels through nuclear factor erythroid 2-related factor 2 regulation, offering novel insights into the treatment of non-alcoholic fatty liver disease and other metabolic disorders through traditional Chinese medicine.

Effect of Incorporating Soursop (Annona muricata) Leaves Powder on Reproductive Performance of Japanese Quail (Coturnix coturnix japonica)

Introduction: Soursop leaves are rich in various molecules, including total phenols, terpenes, and steroids, which possess a range of pharmacological properties that can be utilized in animal production to enhance both growth and reproduction of animals. The present study aimed to evaluate the effect of incorporating soursop (Annona muricata; A. muricata) leaves powder into feed on the reproductive performance of Japanese quail. Materials and methods: A total of 80 Japanese quails (64 females and 16 males) aged two weeks were randomly divided into four experimental groups, labeled T0, T1, T2, and T3, and received feed additives with 0 mg/kg body weight (bw), 250 mg/kg bw, 500 mg/kg bw, and 750 mg/kg bw of powdered soursop leaves, respectively. Additionally, water was provided ad libitum, and the quails' weights were measured every 7 days for a period of 75 days. At the end of the period, 12 female quails from each group were sacrificed after 24 hours fasting period. Blood was collected for hematological (Leukocyte, Erythrocyte, and Platelet indices) and serum biochemical (total serum cholesterol, total proteins, albumin, and globulin, Aspartate aminotransferase, Alanine aminotransferase, Urea, and Creatinine) analysis. The males were also sacrificed to evaluate the spermatozoa characteristics (mobility, concentration, and viability). Results: No statistical significant changes in growth characteristics or hematological parameters were observed. However, biochemical parameters increased significantly with the inclusion of Soursop (A. muricate) in quail feed, including increased total cholesterol, total protein, and globulin levels, and decreased malondialdehyde levels. This effect was most significant at dosage of 500 mg/kg bw. Serum levels of urea, Alanine aminotransferase, and Aspartate aminotransferase were not significantly affected by A. muricata whatever the concentration considered. A significant increase in fast progressive spermatozoa, along with a decrease in immotile spermatozoa, was observed with A. muricate at dosage of 500 mg/kg bw compared to the control. Sperm viability also increased significantly, particularly in live at dosage of 500 mg/kg bw. Significant increase was observed in fertility parameters, including increased fertility rate, hatchability rate of fertile eggs, total hatchability rate, and chick weight, along with decreased embryonic mortality at 500 mg/kg bw treatment compared to the control. Conclusion: In conclusion, the findings indicated that incorporating A. muricata leaf powder at 500 mg/kg bw into quail feed positively influences reproductive cells and boosts fertility growth promoters.

Mitigation of lipopolysaccharide-induced intestinal injury in rats by Chimonanthus nitens Oliv. essential oil via suppression of mitochondrial fusion protein mitofusin 2 (MFN2)-mediated mitochondrial-associated endoplasmic reticulum membranes (MAMs) formation

Ethnopharmacological relevanceChimonanthus nitens Oliv. is a traditional Chinese medicine with anti-inflammatory and antioxidant properties that has commonly been used for colds, fevers, and other diseases. However, its role and specific mechanism in sepsis-associated intestinal injury have not been reported. Aim of the studyC. nitens Oliv. essential oil (CEO), an organic active compound extracted from the traditional Chinese medicine C. nitens Oliv. exhibits notable anti-inflammatory and antioxidant properties. Nevertheless, the therapeutic potential of CEO for septic intestinal injury remains undocumented. This study thus aims to elucidate the anti-inflammatory and antioxidant effects of CEO in the context of acute intestinal injury and to investigate its mechanisms of action in septic rats. Materials and methodsCell and animal models were established using LPS to investigate the impact of CEO on LPS-induced intestinal pathological injury and the secretion of inflammatory factor IL-1β. The effects of CEO on the expression of NLRP3, caspase-1, and MFN2, p-p65 protein were also examined, as well as its influence on oxidative stress injury and mitochondrial-associated endoplasmic reticulum membrane (MAM) formation. Generation of an MFN2 knockout IEC-6 cell line allowed comprehensive investigation of the protective mechanism of CEO. ResultsIn rat models, CEO reduced IL-1β secretion, inhibited caspase-1, ZO-1 expression and NF-κB p65 phosphorylation, while also decreasing malondialdehyde levels and enhancing superoxide dismutase activity in intestinal tissues. Cellular experiments demonstrated its ability to decrease IL-1β secretion; NLRP3, caspase-1, and MFN2 expression; NF-κB p65 phosphorylation; reactive oxygen species (ROS) production, and mitochondrial dysfunction. MFN2 knockdown enhanced these effects synergistically with CEO, indicating potential therapeutic synergy. Further, MFN2 knockdown significantly mitigated LPS-induced NLRP3 and caspase-1 expression, IL-1β secretion, ROS production, NF-κB p65 phosphorylation and MMP reduction in IEC-6 cells, while inhibiting MAM formation and NLRP3 localization on MAMs. Importantly, MFN2 downregulation and CEO synergistically reduced LPS-induced IL-1β secretion and ROS production while inhibiting MAM formation in IEC-6 cells, thus inhibiting NLRP3 inflammasome activation. ConclusionCEO mitigates inflammation and oxidative stress by inhibiting MAM formation and is thus a promising intervention for septic intestinal injury.

Phloretin inhibits the growth of Arabidopsis shoots by inducing chloroplast damage and programmed cell death

Phloretin is a key secondary metabolite produced by apple trees. Known for its strong antioxidant properties, this dihydrochalcone has been extensively studied in animals but less so in plants. Recently, we identified phloretin as a phytotoxic allelochemical that inhibits growth in the model plant Arabidopsis by disrupting auxin metabolism and distribution in the roots. In this study, we found that phloretin significantly hinders the growth of Arabidopsis seedlings' aerial parts after a short-term treatment (10 days) and causes their decay after long-term exposure (28 days). These effects result from ultrastructural damage in the mesophyll cells of the leaves, including chloroplast displacement and swelling, lesions, and alterations in thylakoid and cell wall organization. Interestingly, phloretin-treated plants showed a decrease in malondialdehyde levels and antioxidant enzyme activities, while hydrogen peroxide and proline levels remained unchanged. This suggests that phloretin-induced chlorosis and seedling decay are not due to oxidative stress but rather to severe chloroplast structural damage, leading to inefficient photosynthesis, starch degradation, starvation, and activation of micro- and macroautophagic processes for self-preservation. Ultimately, these processes result in programmed cell death. These new insights into the phytotoxic effects of phloretin on Arabidopsis shoots could pave the way for future research into phloretin as a potential multitarget bioherbicide and enhance our understanding of autoallelopathy in apple trees.

Liposome-based Freezing Medium Improves the Outcome of Mouse Prepubertal Testicular Tissue Cryopreservation

AbstractCryopreservation of testicular tissue holds an important role in the field of fertility preservation, particularly for prepubertal boys diagnosed with cancer. However, prepubertal testicular tissue cryopreservation is still considered to be in the experimental stage necessitating the refinement of cryopreservation protocol. Considering the fact that loss of membrane lipids is the primary cause of freeze–thaw-induced loss of testicular cell functions, in this study, we explored the beneficial properties of exogenous supplementation of membrane lipids in the form of liposomes in enhancing the cryosurvival of prepubertal testicular tissue. The freezing medium supplemented with liposomes (prepared from soy lecithin, phosphatidylethanolamine, phosphatidylserine, and cholesterol) was used for the experiments. Prepubertal testicular tissues from Swiss albino mice were cryopreserved in a liposome-containing freezing medium (LFM) composed of 0.25 mg/mL liposomes, 5% DMSO, and 30% FCS in the DMEM/F12 medium using a slow freezing protocol. The tissues were thawed and assessed for various testicular cell functions. Freezing in LFM mitigated the loss of viability, decreased malondialdehyde level (p &lt; 0.05), and reduced apoptosis (p &lt; 0.05) in the testicular cells compared to the testicular tissue cryopreserved in the control freezing medium (CFM). Further, DMSO (5%) appears to be the ideal penetrating cryoprotectant for prepubertal testicular tissue cryopreservation with liposome-based freezing medium. Similar enhancement in cryosurvival of cells was observed in adult human testicular tissue frozen with LFM. These findings highlight the translational value of liposome-based freezing medium in the cryopreservation of testicular tissue of prepubertal boys undergoing chemotherapy.

New Utilization of Fraxinus mandshurica Leaves: As a Safe and Promising Natural Antioxidant.

In this paper, an in-depth study on Fraxinus mandshurica (FM) was conducted, focusing on the chemical constituents, in vitro and in vivo antioxidant activities of flavonoids, acute oral toxicity testing, network pharmacology, and molecular docking in the leaves of FM. The in vitro antioxidant results revealed that the total flavonoid extract (TFE), kaempferol, quercetin, and rutin exhibited similar antioxidant activities, with TFE demonstrating significantly better scavenging ability against hydroxyl radical compared to the other flavonoids. Moreover, in vivo antioxidant findings indicated that TFE led to a significant increase in glutathione peroxidase and superoxide dismutase activities along with a decrease in malondialdehyde levels in the liver tissues of mice in an ethanol-induced oxidative stress model, outperforming quercetin. The acute oral toxicity test established 5000 mg/kg of bw as the LD50 for TFE in rats. Through network pharmacological analysis, it was observed that all seven flavonoids in FM exhibited spontaneous binding to their respective key targets, reinforcing their potential antioxidant properties. Consequently, based on the experimental outcomes, TFE appears to be a safe and promising antioxidant source, indicating its potential as a new natural antioxidant resource.