Malondialdehyde Generation Research Articles

Cirsilineol improves anesthesia/surgery-induced postoperative cognitive dysfunction through attenuating oxidative stress and modulating microglia M1/M2 polarization.

Cirsilineol is a trimethoxy and dihydroxy flavonoid isolated from plant species such as Artemisia vestita and has a variety of pharmacological properties. This study analyzed whether cirsilineol could prevent postoperative cognitive dysfunction (POCD). A POCD mouse model induced by anesthesia/surgery induction and a cell model established with hydrogen peroxide (H2O2)-induced microglia BV-2 were employed to explore the efficacy of cirsilineol on POCD. The cognition function of the mice were assessed by carrying out behavioral tests (Morris water maze test and Y-maze test). We assessed the activation and polarization status of microglia using immunofluorescence analysis and detected the expression levels of CD86 and CD206 using the quantitative PCR (qPCR). Subsequently, cell viability was determined by CCK-8 assay and apoptosis was assessed using Calcein-AM/PI staining. Meanwhile, superoxide dismutase (SOD) and malondialdehyde (MDA) levels in plasma and cell culture medium were detected using chemiluminescence. Finally, the phosphorylation levels of JAK/STAT signaling pathway-related proteins were analyzed by Western blot. Cirsilineol reduced the escape latency and times of crossing island and increased spontaneous alternation (SA) rate, restoring the cognitive dysfunctions of POCD-modeled mice. Meanwhile, POCD elevated CD86 expression and malondialdehyde content and lowered the level of SOD; however, cirsilineol promoted CD206 expression and generation of SOD and inhibited malondialdehyde production. In H2O2-induced microglia BV-2, cirsilineol treatment increased SOD content and suppressed the generation of reactive oxygen species (ROS) and malondialdehyde, modulating microglia M1/M2 polarization and JAK/STAT pathway. Cirsilineol prevented against POCD by attenuating oxidative stress and modulating microglia M1/M2 polarization, providing novel insights for the management of POCD.

Comparison of the Effect of Adding Different Levels of Zinc Chloride, Curcumin, Zinc Oxide Nanoparticles (Zano-NPs), Curcumin Loaded on Zano-NPs on Post-Thawing Quality of Ram Semen.

This study looked at how different concentrations of curcumin (Curc), zinc chloride (ZnCl2), zinc oxide nanoparticles (ZnO-NPs) and Curc loaded on ZnO-NPs (Curc-co-ZnO-NPs) in cryopreservation dilution affected the quality of ram sperm after thawing. ZnO-NPs were synthesised using Berberis vulgaris leaf aqueous extract. Then, Curc was loaded on the ZnO-NPs that had been synthesised. We used analytical methods to look at the composition, morphology and size of green synthesised ZnO-NPs and Curc-co-ZnO-NPs, including UV-Vis, zeta potential, EDX, DLS, FE-SEM and FT-IR. Using a Tris-base extender containing various concentrations of Curc, ZnCl2, ZnO-NPs and Curc-co-ZnO-NPs (0, 1, 10 and 100µg/mL), semen samples from four rams were combined. Sperm motility, viability, DNA and plasma membrane integrity, total abnormalities and malondialdehyde (MDA) generation were all evaluated in treatment groups after thawing. The results showed that adding 1µg/mL of ZnO-NPs and Curc-co-ZnO-NPs significantly reduced the level of MDA and total abnormalities (p<0.05). Additionally, following the freeze-thawing procedure, the presence of 1µg/mL of Curc-co-ZnO-NPs in the diluent of ram sperm significantly increased the percentage of sperm viability and motility in comparison to the control and other treatment groups (p<0.05). Furthermore, as compared to the control group and other treatments, treatments containing 1µg/mL of Curc-co-ZnO-NPs significantly improved membrane and DNA integrity (p<0.05). It appears that following freeze-thawing, the Curc-co-ZnO-NPs (1µg/mL) enhanced sperm parameters.

The effects of microplastics exposure on quail's hypothalamus: Neurotransmission disturbance, cytokine imbalance and ROS/TGF-β/Akt/FoxO3a signaling disruption

Microplastics (MPs) have become a major focus of environmental toxicology, raising concerns about their potential adverse effects on animal organs and body systems. As these tiny particles infiltrate ecosystems, they may pose risks to the health of organisms across diverse species. In this study, we attempted to examine the neurotoxic effects of MPs exposure on avian hypothalamus by using an animal model-Japanese quail (Coturnix japonica). The quails of 7-day-old were exposed to 0.02 mg/kg, 0.4 mg/kg and 8 mg/kg polystyrene microplastic (PS-MPs) of environmental relevance for 35 days. The results showed PS-MPs exposure did damages to hypothalamic structure characterized by neuron malformation, irregular arrangement and cellular vacuolation after 5-week exposure. PS-MPs exposure also induced Nissl body reduction and dissolution in the hypothalamus. Moreover, the decrease of acetylcholinesterase (AchE) activity and increasing acetylcholine (Ach) indicated that PS-MPs exposure caused hypothalamic neurotransmission disturbance. PS-MPs exposure also led to neuroinflammation by disrupting the balance between proinflammatory and anti-inflammatory cytokines. Moreover, increasing reactive oxygen species (ROS) and malondialdehyde (MDA) generation with reducing antioxidants indicated PS-MPs led to hypothalamic oxidative stress. Additionally, RNA-Seq analysis found that both transforming growth factor-β (TGF-β) signaling and forkhead box O (FoxO) signaling were disturbed in the hypothalamus by PS-MPs exposure. Especially, the increasing ROS led to TGF-β activation and then induced hypothalamic inflammation by nuclear factor κB (NF-κB) activation. The present study concluded that oxidative stress might be an important mechanistic signaling involved in MPs neurotoxicology.

Higher Sensitivity of Rat Testes to Nano Nickel than Micro Nickel Particles: A Toxicological Evaluation.

Present investigations were undertaken to record the vulnerability of testis to nickel oxide nano and microparticles in Wistar rat with special reference to their preferred bioaccumulation, consequent generation of reactive species, reciprocal influence on testosterone synthesis, DNA damage in spermatids and histopathological changes. Suitable numbers of rats were gavaged NiONPs or NiOMPs (5mg/kg b.w.each) for 15 and 30days. Testes en bloc were removed and processed for the estimation of selected parameters. Results showed that rat testes could accumulate nickel in an exposure time dependent manner. Generation of malondialdehyde, a denominator of ROS, increased significantly in the testes of NiONPs treated rats. Moreover, serum testosterone values also increased in NiONPs treated rats. Higher DNA damage in sperms was also recorded. Nano and microparticles of nickel, both could induce specific dose and time dependent lesions in the testis of rat. Histopathological results revealed degeneration of germinal epithelium and spermatocytes; hypertrophy of seminiferous tubules and necrosis. SEM results also indicated specific morphological changes in cellular components of tubules. This study suggests that testis is also vulnerable to the adverse effects of NiONPs alike liver and kidney. Both micro and nanoparticles of nickel elicited differential effects in a dose and exposure time dependent manner. However, NiONPs induced greater overall toxicity than NiOMPs. The results are expected to be helpful in determining the human reproductive health risks, associated with environmental/ occupational exposure to nanoparticles of nickel.

Xinglou Chengqi Decoction Protects against Cerebral Ischemia/Reperfusion Injury by Inhibiting Ferroptosis via SLC7A11/GPX4 Signaling.

Xinglou Chengqi decoction (XLCQD) is a Chinese formula that offers benefits in ischemic stroke. However, the underlying mechanism of the effects of XLCQD-mediated anti-ischemic stroke effects remains obscure. This study investigates the ferroptosis mechanism of XLCQD against cerebral ischemia/reperfusion (I/R) injury using rat models of middle cerebral artery occlusion/reperfusion (MCAO/R). Ferroptosis differs from traditional cell death pathways and is linked to oxidative stress-induced lipid peroxidation and glutathione (GSH) depletion, which is essential to the development of ischemic stroke. In this study, it is shown that XLCQD improves brain infarction, neurological dysfunction, and histopathological changes caused by MCAO/R exposure, and improving I/R-induced oxidative damage through inhibition of ferroptosis via (Solute Carrier Family 7 Member 11) SLC7A11/ (glutathione peroxidase 4) GPX4 pathway. Interestingly, it is found that XLCQD-mediated protection in I/Ris reversed by the silence of SLC7A11. XLCQD intervention significantly promotes GSH content and suppresses Reactive Oxygen Species(ROS), iron accumulation, as well as Malondialdehyde (MDA) generation, are markedly abrogated when SLC7A11 is knockdown by SLC7A11-shRNA transfection, indicating that SLC7A11 is the main target of XLCQD to further trigger intracellular events. In conclusion, XLCQD attenuates in vivo cerebral I/R injury by reducing ferroptosis via the SLC7A11/GPX4 pathway.

Mangiferin activates the nuclear factor erythroid 2-related factor pathway to protect SOD1-G93A induced NSC-34 motor neurons from oxidative stress and apoptosis.

One of the main factors in the pathophysiology of amyotrophic lateral sclerosis is oxidative stress. Mangiferin (MF), a natural plant polyphenol, has anti-inflammatory and antioxidant effects. The aim of our study was to investigate the protective effects and mechanisms of MF in the hSOD1-G93A ALS cell model. Our result revealed that MF treatment reduced the generation of reactive oxygen species (ROS) and malondialdehyde (MDA), decreased oxidative damage, and reduced apoptosis. Additionally, it was observed that MF significantly increased the synthesis of the antioxidant genes hemeoxygenase-1 and NAD(P)H: quinone oxidoreductase 1, which are downstream of the Nrf2 signaling pathway, and increased the expression and activation of nuclear factor erythroid 2-related factor 2 (Nrf2). Nrf2 knockdown greatly promoted apoptosis, which was reversed by MF treatment. To summarize, MF promoted the Nrf2 pathway and scavenged MDA and ROS to protect the ALS cell model.

Acute exposure to environmentally relevant concentrations of pharmaceutical pollutants induces neurobehavioral toxicity in zebrafish (Danio rerio)

Pharmaceutical waste from point and non-point sources enters, persists, or disseminates in the environment and is known as environmentally persistent pharmaceutical pollutants. Understanding the impacts of pharmaceutical pollutants on the environment and health is essential. This study investigates the behavioral impacts of pharmaceutical pollutants on aquatic organisms and delineates the possible nexus of oxidative stress. The male zebrafish were exposed to four major representative pharmaceutical pollutants, viz., acetaminophen, carbamazepine, metformin, and trimethoprim at environmentally relevant concentrations individually as well as in a mixture for seven days. Substantial alterations in social interaction, aggressive nature, novel tank exploration, and light and dark zone preferences were recorded and the degree varied to different pharmaceutical pollutants. The activity of oxidative stress markers, superoxide dismutase, glutathione-S-transferase, and catalase, was found to be suppressed to 66–20%, 42–25%, and 59–20% respectively with the elevated malondialdehyde generation (180–260%) compared to control. The activity level of acetylcholine esterase was found to be increased to 200–500% across all treatment groups. Despite the synergistic impacts of pharmaceutical pollutants on the whole system that could not be ascertained, this comprehensive study highlights their toxicity nature to induce neurobehavioral toxicity in zebrafish through oxidative stress mechanisms and altered cholinergic systems.

Hepatoprotective Effects of Aqueous Extract of Perilla fructescens against Alcohol-Induced Liver Injury in Mice

Excessive alcohol intake leads to significant physiological complications, particularly alcoholic liver diseases (ALD). The extent of liver damage caused by ethanol correlates with increased oxidative stress and accumulation of lipids in the hepatic tissue. In this study, we investigated the defense properties of the aqueous extract of Perilla frutescens Briton Var. acuta Kudo (PF) on hepatic injury in chronically ethanol-treated mice. The mice were orally administered the water extract from PF for 4 weeks with ethanol treatment (3 g/kg. P.O.). The level of malondialdehyde (MDA) in the liver tissues was determined. A substantial increase in MDA generation was detected in the livers of mice subjected to ethanol exposure, whereas the administration of PF markedly reduced MDA levels in hepatic tissues. Additionally, histological analysis of the liver tissue was performed. Histopathological investigation revealed a significant reduction in hepatocellular necrosis in the PF-treated group. This study demonstrated that the aqueous extract of Perilla frutescens Briton Var. acuta Kudo (PF) attenuated chronic ethanol-induced liver injury by augmenting the antioxidant capacity of mice. These results can be utilized for the development of high-value-added products using PF.

Various investigations of ameliorative role of Ashwagandha seeds (Withania somnifera) against amoxicillin toxicity.

Several studies showed the adverse effects of amoxicillin on various body organs. So, this research has been designed to evaluate the modulatory role of Ashwagandha seed extract (ASE) against amoxicillin (AM) toxicity. Rats treated with AM (90mg/kg), protected by ASE doses (100, 200 and 300mg/kg), and treated by ASE at the same three doses. At the end of the experimental period, DNA comet assay, cytogenetic examinations, sperm-shape analysis, evaluation of the malondialdehyde (MDA) percentages, histopathological examinations, and biophysical tests (modulus, relaxation time, permittivity, entropy, and internal energy change of brain) were documented. The results confirmed that AM treatment induced significant elevation of DNA damage, cytogenetic aberrations, and MDA content in brain, liver, and testis tissues and sperm-shape anomalies. ASE treatment significantly minimized the genetic changes, sperm-shape anomalies, and MDA generation. These enhancements were more pronounced by protective ASE and increased by increasing the dose level. In histopathological examinations, AM treatment caused neurotoxicity in brain tissue. ASE treatment, partially, minimized these damages and the positive effects of therapeutic ASE were more noticeable. Biophysical parameters showed that therapeutic ASE was better for relaxation time, permittivity, and free energy change. Protective and therapeutic ASE were able to recover entropy and internal energy changes in variant degrees.

Neuroprotective properties of UV-C treated Bacopa floribunda leaves: in vitro and in vivo studies

This study investigated the effect of UV-C irradiation on antioxidant, cholinergic and neuroprotective properties of Bacopa floribunda leaves in scopolamine-induced rats. In vitro study was done by the determination of phenolics, flavonoid, total antioxidant capacity, 2, 2-diphenyl-1-picrylhydrazyl scavenging activity, inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. Loss of memory was induced in Wistar rats pre-treated with extracts of Bacopa floribunda using scopolamine (2 mg/kg) administered intraperitoneally. Behavioural studies using elevated plus maze (EPM) and biochemical analysis on the were carried out. Exposure to UV-C radiation increased the phenolics, flavonoid, antioxidant and inhibitory properties against AChE and BChE of the Bacopa floribunda leaves. The administration of scopolamine caused significant increase in the activities of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes, but decrease in the activities of antioxidant enzymes and enhanced generation of malondialdehyde and nitric oxide in vivo. The loss of memory and Biochemical analysis in scopolamine-induced rats was ameliorated by treatment with UV-C treated Bacopa floribunda (TBF) extracts. Treatment with TBF improved memory retention and ameliorated oxidative damage in hippocampus of scopolamine treated rats.

Comparison of the Antioxidant Potency of Four Triterpenes of Centella asiatica against Oxidative Stress.

We comparatively evaluated the antioxidant properties of key triterpenes from Centella asiatica, including asiatic acid (AA), asiaticoside, madecassic acid, and madecassoside, in several cell types, including skin fibroblasts, macrophages, hepatocytes, and endothelial cells, under conditions promoting oxidative stress. AA conferred the highest viability on Hs68 cells exposed to ultraviolet B (UVB) irradiation. Triterpene pretreatment attenuated the UVB-induced generation of reactive oxygen species (ROS) and malondialdehyde (MDA), as well as the UVB-induced depletion of glutathione (GSH) in skin fibroblasts. AA most potently inhibited UVB-induced MMP generation, resulting in increased intracellular collagen levels. Pretreatment with triterpenes, particularly AA, significantly improved cell viability and attenuated TBHP-induced levels of ROS, alanine aminotransferase, and aspartate aminotransferase in HepG2 cells. Triterpenes attenuated ROS levels and reduced MDA and GSH expression in EA.hy926 cells. In RAW264.7 macrophages, production of nitric oxide, tumor necrosis factor-α, and interleukin-6 (indicators of LPS-induced oxidative damage) was significantly reduced by treatment with any of the triterpenes. Statistical analyses of triterpene biological activities using principal component analysis and hierarchical clustering revealed that AA exerted the greatest overall influence and showed remarkable activity in Hs68 and HepG2 cells.

Preparation and functional properties of rice bran globulin-chitooligosaccharide-quercetin-resveratrol covalent complex.

As the major protein (approximately 36%) in rice bran, globulin exhibits excellent foaming and emulsifying properties, endowing its useful application as a foaming and emulsifying agent in the food industry. However, the low water solubility restricts its commercial potential in industrial applications. The present study aimed to improve this protein's processing and functional properties. A novel covalent complex was fabricated by a combination of the Maillard reaction and alkaline oxidation using rice bran globulin (RBG), chitooligosaccharide (C), quercetin (Que) and resveratrol (Res). The Maillard reaction improved the solubility, emulsifying and foaming properties of RBG. The resultant glycosylated protein was covalently bonded with quercetin and resveratrol to form a (RBG-C)-Que-Res complex. (RBG-C)-Que-Res exhibited higher thermal stability and antioxidant ability than the native protein, binary globulin-chitooligosaccharide or ternary globulin-chitooligosaccharide-polyphenol (only containing quercetin or resveratrol) conjugates. (RBG-C)-Que-Res exerted better cytoprotection against the generation of malondialdehyde and reactive oxygen species in HepG2 cells, which was associated with increased activities of antioxidative enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) through upregulated genes SOD1, CAT, GPX1 (i.e. gene for glutathione peroxidase-1), GCLM (i.e. gene for glutamate cysteine ligase modifier subunit), SLC1A11 (i.e. gene for solute carrier family 7, member 11) and SRXN1 (i.e. gene for sulfiredoxin-1). The anti-apoptotic effect of (RBG-C)-Que-Res was confirmed by the downregulation of caspase-3 and p53 and the upregulation of B-cell lymphoma-2 gene expression. The present study highlights the potential of (RBG-C)-Que-Res conjugates as functional ingredients in healthy foods. © 2024 Society of Chemical Industry.

Insights from morpho-physio-biochemical and molecular traits of hot pepper genotypes contrasting for heat tolerance

The present study compared the morpho-physiological, biochemical, and molecular responses of heattolerant (DLS-161-1) and heat-susceptible (DchBL-240) genotypes of hot pepper under high-temperature conditions. The results showed that DLS-161-1 performed significantly better for various morphological parameters such as plant height (60 cm), number of fruits per plant (180.33), average fruit length (8.40 cm) and leaf parameters. While DChBL-240 has significantly higher malformed seeds per fruit (15.06) and average fruit diameter (12.56 cm). The physiological responses also differed significantly between the two genotypes, with the DLS-161-1 exhibiting higher membrane stability index (65.99%), pollen viability (92.10%), photosynthetic rate (20.73 μmol CO2 m²/sec.), stomatal conductance (0.31 mol H2O m²/sec.), and transpiration rate (8.85 mmol H2O m²/sec). Biochemical analysis revealed significantly increased activity of antioxidant enzymes such as guaiacol peroxidase (564.99 U/g F.W) and catalase (711.90 U/g FW), increased protein content (13.38 mg/g F.W) and reduced malondialdehyde generation (13.42 nmol g-1 FW) in DLS-161-1 compared to heat susceptible genotype (DChBL-240). Further, two of the six heat shock protein genes, CaHSP2271 and CaHSP3, were highly upregulated in the DLS 161-1. The observations suggest that DLS-161-1 could adapt to high-temperature conditions by regulating its morphological, physiological, biochemical and molecular mechanisms.

Synergistic effects of biochar and potassium co-application on growth, physiological attributes, and antioxidant defense mechanisms of wheat under water deficit conditions

Global wheat production faces a severe threat from drought stress, necessitating innovative strategies for enhanced crop resilience. This study examined the synergistic impact of biochar and potassium co-application on the growth, physiological attributes, and antioxidant defense system of wheat under water deficit conditions at crown root initiation (CRI), anthesis, and grain development stage. Drought-induced reactive oxygen species (ROS) accumulation, particularly pronounced at the CRI stage, adversely affected all growth stages. At CRI, co-application of biochar and foliar potassium delivered significant improvements in growth parameters, including increased plant height (15.4%), spike length (50%), grain yield (43.0%), photosynthetic performance (chlorophyll content 125.8%), and relative water content (11.2%), compared to untreated drought-exposed counterparts. The combined application of biochar and potassium effectively reduced hydrogen peroxide production, electrolyte leakage, proline accumulation, and malondialdehyde generation, while increasing relative water content and glutathione levels under both well-irrigated and drought stress conditions. Furthermore, the combined biochar and potassium treatment was effective in mitigating oxidative stress and enhancing physiological resilience in wheat, particularly during the anthesis stage of drought stress. Specifically, the combined treatment ameliorated the effects of drought by reducing ROS levels through enhanced antioxidant enzyme activities and elevating osmoprotectants levels. The synergistic modulation of tissue osmotic balance and relative water content holds promise for mitigating drought-induced stress, offering an innovative and practical strategy for resilient wheat production in water-limited environments.

Protective Mechanisms of Juncus effusus and Carbonized Juncus effusus against D-Galactosamine-Induced Acute Liver Injury in Mice.

This study investigated the hepatoprotective effects of Juncus effusus (J. effusus) and Carbonized J. effusus against liver injury caused by D-galactosamine (D-GalN) in mice. J. effusus and Carbonized J. effusus were administered by gavage once daily starting seven days before the D-GalN treatment. The results of the study indicated that J. effusus and Carbonized J. effusus suppressed the D-GalN-induced generation of serum alanine transaminase (ALT), aspartate aminotransferase (AST), hepatic malondialdehyde (MDA) and tumor necrosis factor-alpha (TNF-α) was observed. The values of superoxide dismutase (SOD) exhibited an increase. In addition, J. effusus and Carbonized J. effusus promoted the protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2), NADPH quinone oxidoreductase-1 (NQO-1), heme oxygenase-1 (HO-1) as well as the mRNA expression of Nrf2, HO-1, NQO-1 and Glutamate cysteine ligase catalytic subunit (GCLC). The compressed Carbonized J. effusus demonstrated the optimum impact. These results suggest that J. effusus and Carbonized J. effusus protect against D-GalN-induced acute liver injury through the activation of the Nrf2 pathway.

Nutritional and physicochemical characteristics of Asiatic hard clam powder prepared by different cook-drying processes: a comparative study.

Asiatic hard clam (Meretrix meretrix) is an underutilized bivalve resource. This study discusses dried clam powders prepared from this resource to enhance its utilization and improve nutritional security in protein-deficient populations. Dried clam powder was prepared from Asiatic hard clam and the effects of different pre-cooking methods (boil-dried clam powder, BDCP; steam-dried clam powder, SDCP; and microwave-dried clam powder, MDCP) on nutritional (proximate composition, amino acid profiling, mineral profiling, fatty acid profiling) and physicochemical qualities were investigated. Different pre-cooking methods significantly influenced the characteristics of the clam powder. The MDCP sample showed the highest concentration of amino acids, polyunsaturated fatty acids, Na, K, Ca and Mg content compared to BDCP and SDCP. The boiling process led to a loss of nutritional quality in terms of amino acids and macrominerals. The MDCP displayed the highest solubility in water (30.10%) but its oil and water absorption characteristics were the lowest among all the samples. Boil-cooked clam powder displayed the highest oil binding (2.03 mL g-1 protein) capacity. Boiling and steaming processes resulted in malondialdehyde generation compared to microwaving. Different pre-cooking processes did not influence the colour attributes significantly, but the control sample prepared without pre-cooking (CCP) had a significantly lower L* value (32.34), resulting in a darker product. In vitro digestibility of the clam powder varied in the order MDCP > SDCP > BDCP > CCP. The study demonstrated that nutritionally rich protein powder can be prepared from Asiatic hard clam. Based on the results, microwave pre-cooking is considered the best pre-cooking method to preserve the nutritional qualities of clam powder. © 2024 Society of Chemical Industry.

In Vitro Filaricidal Properties of Aqueous Extracts of Combretum nigricans (Combretaceae) on Onchocerca ochengi (Onchocercidae).

Onchocerciasis is an endemic parasitic disease in sub-Saharan Africa that significantly impacts animal and human health. In Northern Cameroon, medicinal plants from the Combretum genus are used for onchocerciasis traditional treatment although there is no scientific evidence of their antifilarial potential. This study evaluates the in vitro macro- and microfilaricidal properties of water extracts from Combretum nigricans in Onchocerca ochengi. Material and Methods. O. ochengi microfilariae and adult male worms were recovered from cowhide fragments. Oxidative stress indicators and motility tests were used to assess the filaricidal impact. Female albino rats were used to test for acute toxicity. The contents of secondary metabolites were quantified. The bark aqueous extract was more active on macrofilariae at 1 mg/mL for 24 h (100%) than the leaf (63.9%) and root (75%) extracts at the same concentration. Likewise, a stronger microfilaricidal effect was found with this extract at 0.5 mg/mL for 1 h (100%) compared to root and leaf extracts. The dose-response effect with the bark extract gave an inhibitory concentration 50 (IC50) of 351 μg/mL vs. 113 μg/mL for flubendazole after 24 h incubation, while the microfilaricidal efficacy revealed an IC50 of 158.7 μg/mL vs. 54.09 μg/mL for ivermectin after one-hour incubation. Examining stress indicators on parasite homogenates showed that macrofilaricidal activity is associated with a significant increase in nitric oxide, glutathione, and malondialdehyde generation and a decrease in catalase activity. At 2000 mg/kg, rats showed no harm. The phytochemical investigation revealed that the barks contained more phenolic acids, condensed tannins, flavonoids, and saponins than the leaves (p < 0.001). These findings support C. nigricans' antifilarial activity and identify oxidative stress indicators as prospective treatment targets in O. ochengi. It would be interesting to conduct in vivo studies to understand their antifilarial activity better.

Rosavin extends lifespan via the insulin/IGF-1 signaling pathway in Caenorhabditis elegans.

Rosavin, a phenylpropanoid glycoside, is the specific index component and one of the main active components of Rhodiola rosea. Currently, there are few studies describing the antiaging effect of rosavin, and most of them are mainly based on in vitro antioxidant research. Our study aimed to investigate the antiaging activities and mechanisms of rosavin in Caenorhabditis elegans. Using Caenorhabditis elegans as the model, the lifespan of Caenorhabditis elegans under various stressors (heat and juglone) and normal conditions was studied, and the antioxidant activities of rosavin were discussed. To discover the underlying mechanisms, we analyzed daf-16 nuclear localization, the expression of the sod-3p::GFP fusion protein, mRNA levels, and loss-of-function mutants of IIS-associated genes. The results showed that rosavin significantly improved the lifespan of Caenorhabditis elegans under stress and normal conditions. Rosavin can increase the expression and activity of antioxidant enzymes and suppress the generation of malondialdehyde and ROS in nematodes. Additionally, it promotes the nuclear localization of daf-16 and improves the expression of the sod-3 gene in Caenorhabditis elegans. The data revealed that rosavin activated the insulin/IGF-1 signaling pathway by downregulating the upstream components daf-2 and age-1. In summary, these results verify that rosavin could increase the lifespan of Caenorhabditis elegans through the insulin/IGF-1 signaling pathway.

Arsenic trioxide induces ferroptosis in neuroblastoma by mediating GPX4 transcriptional inhibition.

Neuroblastoma (NB), the most common extracranial solid tumor in childhood, significantly contributes to cancer-related mortality, presenting a dearth of efficacious treatment strategies. Previously, our studies have substantiated the potent cytotoxicity of arsenic trioxide (ATO) against NB cells, however, the specific underlying mechanism remains elusive. Here, we first identified ATO as a novel GPX4 inhibitor, which could trigger the ferroptosis in NB cells. Invitro, ATO significantly inhibited the proliferation and migration ability of NB cells SK-N-AS and SH-SY5Y, and induced ferroptosis. Furthermore, the iron chelator deferoxamine reversed ATO-mediated intracellular reactive oxygen species accumulation and hindered the generation of the lipid peroxidation product malondialdehyde. Conversely, ferric ammonium citrate notably intensified its cytotoxic effects, especially on retinoic acid (RA)-resistant SK-N-AS cells. Subsequently, the quantitative real-time polymerase chain reaction results showed ATO significantly inhibited the transcription of GPX4 in NB cells. Remarkably, immunoblotting analysis revealed that MG132 exhibited a notable effect on elevating GPX4 levels in NB cells. Nevertheless, pretreatment with MG132 failed to reverse the ATO-mediated decrease in GPX4 levels. These findings suggested that ATO reduced the GPX4 expression level in NB cells by mediating GPX4 transcriptional repression rather than facilitating ubiquitinated degradation. In conclusion, our research has successfully indicated that ATO could induce ferroptosis and initiate lipid peroxidation by regulating the transcriptional repression of GPX4, and ATO holds promise as a potential anti-tumor agent in NB, specifically for patients with RA-resistant HR-NB.

VDR Activation Attenuates Renal Tubular Epithelial Cell Ferroptosis by Regulating Nrf2/HO-1 Signaling Pathway in Diabetic Nephropathy.

Diabetic nephropathy (DN) is a serious microvascular complication of diabetes. Ferroptosis, a new form of cell death, plays a crucial role in the pathogenesis of DN. Renal tubular injury triggered by ferroptosis might be essential in this process. Numerous studies demonstratethat the vitamin D receptor (VDR) exerts beneficial effects by suppressing ferroptosis. However, the underlying mechanism has not been fully elucidated. Thus, they verified the nephroprotective effect of VDR activation and explored the mechanism by which VDR activation suppressed ferroptosis in db/db mice and high glucose-cultured proximal tubular epithelial cells (PTECs). Paricalcitol (PAR) is a VDR agonist that can mitigate kidney injury and prevent renal dysfunction. PAR treatment could inhibit ferroptosis of PTECs through decreasing iron content, increasing glutathione (GSH) levels, reducing malondialdehyde (MDA) generation, decreasing the expression of positive ferroptosis mediator transferrin receptor 1 (TFR-1), and enhancing the expression of negative ferroptosis mediators including ferritin heavy chain (FTH-1), glutathione peroxidase 4 (GPX4), and cystine/glutamate antiporter solute carrier family 7 member 11(SLC7A11). Mechanistically, VDR activation upregulated the NFE2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) signaling pathway to suppress ferroptosis in PTECs. These findings suggested that VDR activation inhibited ferroptosis of PTECs in DN via modulating the Nrf2/HO-1 signaling pathway.