RESUMEN
Sensorineural hearing loss (SNHL) represents a significant clinical challenge, predominantly attributed to oxidative stress-related mechanisms. In this work, we report an innovative antioxidant strategy for mitigating SNHL, utilizing synthetically engineered allomelanin nanoparticles (AMNPs). Empirical evidence elucidates AMNPs' profound capability in free radical neutralization, substantiated by a significant decrement in reactive oxygen species (ROS) levels within HEI-OC1 auditory cells exposure to cisplatin or hydrogen peroxide (H2O2). Comparative analyses reveal that AMNPs afford protection against cisplatin-induced and noise-induced auditory impairments, mirroring the effect of dexamethasone (DEX), a standard pharmacological treatment for acute SNHL. AMNPs exhibit notable cytoprotective properties for auditory hair cells (HCs), effectively preventing ototoxicity from cisplatin or H2O2 exposure, as confirmed by both in vitro assays and cultured organ of Corti studies. Further in vivo research corroborates AMNPs' ability to reverse auditory brainstem response (ABR) threshold shifts resulting from acoustic injury, concurrently reducing HCs loss, ribbon synapse depletion, and spiral ganglion neuron degeneration. The therapeutic benefits of AMNPs are attributed to mitigating oxidative stress and inflammation within the cochlea, with transcriptome analysis indicating downregulated gene expression related to these processes post-AMNPs treatment. The pronounced antioxidative and anti-inflammatory effects of AMNPs position them as a promising alternative to DEX for SNHL treatment.
RESUMEN
Cadmium (Cd) is a toxic heavy metal that poses risks to crop production and food safety worldwide. This study evaluated whether manganese (Mn) addition could mitigate Cd toxicity and reduce Cd accumulation in barley seedlings. Hydroponically grown seedlings of Cd-tolerant (WSBZ) and Cd-sensitive (Dong17) barley cultivars were treated with 0.1 µM and 1 µM Cd as well as 0.2 mM Mn alone and in a combination with 0.1 or 1.0 µM Cd for 21 days. Cd exposure caused the dramatic alteration of growth and physiological parameters by disrupting chloroplast, and increased Cd accumulation in both genotypes. However, Mn addition markedly alleviated the negative impacts of all examined parameters caused by Cd stress. Cd addition enhanced expression of anti-oxidative enzyme related genes, including HvSOD, HvCAT, HvAPX, HvPOD in the two barley genotypes exposed to Cd stress. The expression analysis showed nearly all HvNRAMPs genes are dramatically up regulated by both Mn and Cd, with WSBZ having higher expression than Dong 17. Notably, HvNRAMP1 showed the highest expression due to Mn addition, highlighting its crucial role in Mn uptake and transportation in barley. Moreover, Cd stress and Mn addition increased and suppressed the expression of HvYSL5, HvHMA2 and HvHMA3, respectively. Conversely, the expression of HvYSL2, HvIRT1 and HvMTP8 was upregulated by both Mn and Cd treatments, with a further increase observed in the combined Cd and Mn treatments. It may be concluded that sufficient Mn supply is quite important for reducing Cd uptake and accumulation in plants.
RESUMEN
Acetaminophen (APAP) overdose is a prevalent cause of clinical pharmacological liver injury worldwide. Artemether (ART), a first-line antimalarial drug, has demonstrated hepatoprotective activity. However, its effect on APAP-induced acute liver injury (AILI) remains unclear. In this study, we investigated whether ART can protect against AILI and examined its underlying mechanisms. In vivo, ART mitigated APAP-induced liver histological changes, including mitochondrial damage, hepatocyte necrosis, hepatocyte apoptosis, and inflammatory infiltration. Additionally, ART reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in APAP-induced mice. ART also activated the Nrf2-HO-1/GPX4 signaling pathway, exerting antioxidant effects in both in vitro and in vivo models of AILI. To confirm Nrf2 as a target of ART in vivo, we pretreated C57BL/6 mice with the Nrf2 inhibitor, ML385. The results indicated that inhibiting Nrf2 diminishes the protective effect of ART against AILI. Overall, our findings suggest that ART's protective effect against AILI is mediated through the Nrf2-related antioxidant pathway.
RESUMEN
Background: Inhibiting ROS overproduction is considered a very effective strategy for the treatment of peripheral nerve injuries, and Se has a remarkable antioxidant effect; however, since the difference between the effective concentration of Se and the toxic dose is not large, we synthesized a nanomaterial that can release Se slowly so that it can be used more effectively. Methods: Se@SiO2 NPs were synthesized using a mixture of Cu2-x Se nanocrystals, and the mechanism of action of Se@SiO2 NPs was initially explored by performing sequencing, immunofluorescence staining and Western blotting of cellular experiments. The mechanism of action of Se@SiO2 NPs was further determined by performing behavioral assays after animal experiments and by sampling the material for histological staining, immunofluorescence staining, and ELISA. The effects, mechanisms and biocompatibility of Se@SiO2 NPs for peripheral nerve regeneration were determined. Results: Porous Se@SiO2 was successfully synthesized, had good particle properties, and could release Se slowly. CCK-8 experiments revealed that the optimal experimental doses were 100 µM H2O2 and 200 µg/mL Se@SiO2, and RNA-seq revealed that porous Se@SiO2 was associated with cell proliferation, apoptosis, and the PI3K/AKT pathway. WB showed that porous Se@SiO2 could increase the expression of cell proliferation antigens (PCNA and S100) and antiapoptotic proteins (Bcl-2), decrease the expression of proapoptotic proteins (Bax), and increase the expression of antioxidative stress proteins (Nrf2, HO-1, and SOD2). EdU cell proliferation and ROS fluorescence assays showed that porous Se@SiO2 promoted cell proliferation and reduced ROS levels. The therapeutic effect of LY294002 (a PI3K/AKT pathway inhibitor) was decreased significantly and its effect was lost when it was added simultaneously with porous Se@SiO2. Animal experiments revealed that the regenerated nerve fiber density, myelin thickness, axon area, gastrocnemius muscle wet-to-weight ratio, myofiber area, sciatic nerve function index (SFI), CMAP, apoptotic cell ratio, and levels of antioxidative stress proteins and anti-inflammatory factors were increased following the administration of porous Se@SiO2. The levels of oxidative stress proteins and anti-inflammatory factors were significantly greater in the Se@SiO2 group than in the PNI group, and the effect of LY294002 was decreased significantly and was lost when it was added simultaneously with porous Se@SiO2. Conclusion: Se@SiO2 NPs are promising, economical and effective Se-releasing nanomaterials that can effectively reduce ROS production, inhibit apoptosis and promote cell proliferation after nerve injury via the PI3K/AKT pathway, ultimately accelerating nerve regeneration. These findings could be used to design new, promising drugs for the treatment of peripheral nerve injury.
Asunto(s)
Proliferación Celular , Regeneración Nerviosa , Traumatismos de los Nervios Periféricos , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Selenio , Transducción de Señal , Dióxido de Silicio , Animales , Selenio/química , Selenio/farmacología , Dióxido de Silicio/química , Dióxido de Silicio/farmacología , Traumatismos de los Nervios Periféricos/tratamiento farmacológico , Fosfatidilinositol 3-Quinasas/metabolismo , Transducción de Señal/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Regeneración Nerviosa/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Ratas , Apoptosis/efectos de los fármacos , Antioxidantes/farmacología , Antioxidantes/química , Nanopartículas/química , Masculino , Preparaciones de Acción Retardada/farmacología , Preparaciones de Acción Retardada/química , Ratas Sprague-Dawley , Estrés Oxidativo/efectos de los fármacos , Nervio Ciático/efectos de los fármacos , Nervio Ciático/lesiones , Células de Schwann/efectos de los fármacos , Células de Schwann/metabolismoRESUMEN
The adsorption characteristics of ß-glucooligosaccharides on activated carbon and the purification were systematically investigated. The maximum adsorption capacity of activated carbon reached 0.419 g/g in the optimal conditions. The adsorption behavior was described to be monolayer, spontaneous, and exothermic based on several models' fitting results. Five fractions with different degrees of polymerization (DPs) and structures of ß-glucooligosaccharides were obtained by gradient ethanol elution. 10E mainly contained disaccharides with dp2a (G1â6G) and dp2b (G1â3G). 20E possessed trisaccharides with dp3a (G1â6G1â3G) and dp3b (G1â3G1â3G). 30E mainly consisted of dp3a and dp4a (G1â3G1â3(G1â6)G), dp4b (G1â6G1â3G1â3G), and dp4c (G1â3G1â3G1â3G). In addition to tetrasaccharides, 40E and 50E also contained pentasaccharides and hexasaccharides with ß-(1â3)-linked or ß-(1â6)-linked glucose residues. All fractions could inhibit the accumulation of intracellular reactive oxygen species (ROS) in H2O2-induced Caco-2 cells, and they could improve oxidative stress damage by increasing the activity of superoxide dismutase (SOD) and reduced glutathione (GSH), which were related to their DPs and structures. 50E with high DPs showed better anti-oxidative stress activity.
RESUMEN
Aging is often accompanied by irreversible decline in body function, which causes a large number of age-related diseases and brings a huge economic burden to society and families. Many traditional Chinese medicines have been known to extend lifespan, but it has still been a challenge to isolate a single active molecule from them and verify the mechanism of anti-aging action. Drugs that inhibit senescence-associated secretory phenotypes (SASPs) are called "senomorphics". In this study, arctigenin (ATG), a senomorphic, was screened from the Chinese medicine Fructus arctii using K6001 yeast replicative lifespan. Autophagy, oxidative stress, and telomerase activity are key mechanisms related to aging. We found that ATG may act through multiple mechanisms to become an effective anti-aging molecule. In exploring the effect of ATG on autophagy, it was clearly observed that ATG significantly enhanced autophagy in yeast. We further verified that ATG can enhance autophagy by targeting protein phosphatase 2A (PP2A), leading to an increased lifespan. Meanwhile, we evaluated the antioxidant capacity of ATG and found that ATG increased the activities of the antioxidant enzymes, thereby reducing reactive oxygen species (ROS) and malondialdehyde (MDA) levels to improve the survival of yeast under oxidative stress. In addition, ATG was able to increase telomerase activity by enhancing the expression of EST1, EST2, and EST3 genes in yeast. In conclusion, ATG exerts anti-aging effects through induction of autophagy, antioxidative stress, and enhancement of telomerase activity in yeast, which is recognized as a potential molecule with promising anti-aging effects, deserving in-depth research in the future.
RESUMEN
We used a replicative lifespan (RLS) experiment of K6001 yeast to screen for anti-aging compounds within lavender extract (Lavandula angustifolia Mill.), leading to the discovery of ß-cyclocitral (CYC) as a potential anti-aging compound. Concurrently, the chronological lifespan (CLS) of YOM36 yeast and mammalian cells confirmed the anti-aging effect of CYC. This molecule extended the yeast lifespan and inhibited etoposide (ETO)-induced cell senescence. To understand the mechanism of CYC, we analyzed its effects on telomeres, oxidative stress, and autophagy. CYC administration resulted in notable increases in the telomerase content, telomere length, and the expression of the telomeric shelterin protein components telomeric-repeat binding factor 2 (TRF2) and repressor activator protein 1 (RAP1). More interestingly, CYC reversed H2O2-induced telomere damage and exhibited strong antioxidant capacity. Moreover, CYC improved the survival rate of BY4741 yeast under oxidative stress induced by 6.2 mM H2O2, increasing the antioxidant enzyme activity while reducing the reactive oxygen species (ROS), reactive nitrogen species (RNS), and malondialdehyde (MDA) levels. Additionally, CYC enhanced autophagic flux and free green fluorescent protein (GFP) expression in the YOM38-GFP-ATG8 yeast strain. However, CYC did not extend the RLS of K6001 yeast mutants, such as Δsod1, Δsod2, Δcat, Δgpx, Δatg2, and Δatg32, which lack antioxidant enzymes or autophagy-related genes. These findings reveal that CYC acts as an anti-aging agent by modifying telomeres, oxidative stress, and autophagy. It is a promising compound with potential anti-aging effects and warrants further study.
RESUMEN
Hepatocellular carcinoma (HCC), the fifth most prevalent cancer worldwide, is influenced by a myriad of clinic-pathological factors, including viral infections and genetic abnormalities. This study delineates the synthesis, characterization, and the biological efficacy of iron oxide nanoparticles (Fe3O4) and chitosan-coated iron oxide nanoparticles (Fe3O4-CS) against HCC. Analytical methods confirmed the successful synthesis of both nanoparticles, with Fe3O4-CS demonstrating a smaller, uniform spherical morphology and distinct surface and magnetic properties attributable to its chitosan coating. The prepared materials were analyzed using various techniques, and their potential cytotoxic effects on HepG2 cancer cells line for HCC were investigated. In biological evaluations against HepG2 cells, a notable distinction in cytotoxicity was observed. Fe3O4 showed modest anticancer activity with an IC50 of 383.71 ± 23.9 µg/mL, whereas Fe3O4 exhibited a significantly enhanced cytotoxic effect, with a much lower IC50 of 39.15 ± 39.2 µg/mL. The Comet assay further evidenced Fe3O4-CS potent DNA damaging effect, showcasing its superior ability to induce apoptosis through extensive DNA fragmentation. Biochemical analyses integrated into our results reveal that Fe3O4-CS not only induces significant DNA damage but also markedly alters oxidative stress markers. Compared to control and Fe3O4-treated cells, Fe3O4-CS exposure significantly elevated levels of oxidative stress markers: superoxide dismutase (SOD) increased to 192.07 U/ml, catalase (CAT) decreased to 0.03 U/L, glutathione peroxidase (GPx) rose dramatically to 18.76 U/gT, and malondialdehyde (MDA) levels heightened to 30.33 nmol/gT. These results underscore the potential of Fe3O4-CS nanoparticles not only in inducing significant DNA damage conducive to cancer cell apoptosis but also in altering enzymatic activities and oxidative stress markers, suggesting a dual mechanism of action that may underpin their therapeutic advantage in cancer treatment. Our findings advocate for the further exploration of Fe3O4-CS nanoparticles in the development of anticancer drugs, emphasizing their capability to trigger oxidative stress and enhance antioxidant defense mechanisms.
Asunto(s)
Apoptosis , Carcinoma Hepatocelular , Quitosano , Daño del ADN , Neoplasias Hepáticas , Nanopartículas Magnéticas de Óxido de Hierro , Estrés Oxidativo , Humanos , Quitosano/química , Quitosano/farmacología , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Nanopartículas Magnéticas de Óxido de Hierro/química , Nanopartículas Magnéticas de Óxido de Hierro/toxicidad , Células Hep G2 , Daño del ADN/efectos de los fármacos , Apoptosis/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Antineoplásicos/farmacología , Antineoplásicos/química , Superóxido Dismutasa/metabolismo , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Glutatión Peroxidasa/metabolismo , Catalasa/metabolismo , Ensayo CometaRESUMEN
The development of antiepileptic drugs is still a long process. In this study, heparin-modified superparamagnetic iron oxide nanoparticles (UFH-SPIONs) were prepared, and their antiepileptic effect and underlying mechanism were investigated. UFH-SPIONs are stable, homogeneous nanosystems with antioxidant enzyme activity that are able to cross the blood-brain barrier (BBB) and enriched in hippocampal epileptogenic foci. The pretreatment with UFH-SPIONs effectively prolonged the onset of seizures and reduced seizure severity after lithium/pilocarpine (LP)-induced seizures in rats. The pretreatment with UFH-SPIONs significantly decreased the expression of inflammatory factors in hippocampal tissues, including IL-6, IL-1ß, and TNF-α. LP-induced oxidative stress in hippocampal tissues was in turn reduced upon pretreatment with UFH-SPIONs, as evidenced by an increase in the levels of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) and a decrease in the level of lipid peroxidation (MDA). Moreover, the LP-induced upregulation of apoptotic cells was decreased upon pretreatment with UFH-SPIONs. Together, these observations suggest that the pretreatment with UFH-SPIONs ameliorates LP-induced seizures and downregulates the inflammatory response and oxidative stress, which exerts neuronal protection during epilepsy.
Asunto(s)
Epilepsia del Lóbulo Temporal , Heparina , Inflamación , Cloruro de Litio , Nanopartículas Magnéticas de Óxido de Hierro , Estrés Oxidativo , Pilocarpina , Animales , Estrés Oxidativo/efectos de los fármacos , Ratas , Masculino , Epilepsia del Lóbulo Temporal/inducido químicamente , Epilepsia del Lóbulo Temporal/metabolismo , Epilepsia del Lóbulo Temporal/tratamiento farmacológico , Cloruro de Litio/farmacología , Heparina/farmacología , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Inflamación/inducido químicamente , Ratas Sprague-Dawley , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Anticonvulsivantes/farmacologíaRESUMEN
Glutathione (GSH) has long been recognised for its antioxidant and detoxifying effects on the liver. The hepatoprotective effect of GSH involves the activation of antioxidative systems such as NRF2; however, details of the mechanisms remain limited. A comparative analysis of the biological events regulated by GSH under physiological and oxidative stress conditions has also not been reported. In this study, DNA microarray analysis was performed with four experiment arms including Control, GSH, hydrogen peroxide (HP), and GSH + HP treatment groups. The GSH-treated group exhibited a significant upregulation of genes clustered in cell proliferation, growth, and differentiation, particularly those related to MAPK, when compared with the Control group. Additionally, liver functions such as alcohol and cholesterol metabolic processes were significantly upregulated. On the other hand, in the HP-induced oxidative stress condition, GSH (GSH + HP group) demonstrated a significant activation of cell proliferation, cell cycle, and various signalling pathways (including TGFß, MAPK, PI3K/AKT, and HIF-1) in comparison to the HP group. Furthermore, several disease-related pathways, such as chemical carcinogenesis-reactive oxygen species and fibrosis, were significantly downregulated in the GSH + HP group compared to the HP group. Collectively, our study provides a comprehensive analysis of the effects of GSH under both physiological and oxidative stress conditions. Our study provides essential insights to direct the utilisation of GSH as a supplement in the management of conditions associated with oxidative stress.
Asunto(s)
Antioxidantes , Fosfatidilinositol 3-Quinasas , Humanos , Antioxidantes/farmacología , Células Hep G2 , Fosfatidilinositol 3-Quinasas/metabolismo , Glutatión/metabolismo , Estrés Oxidativo , Especies Reactivas de Oxígeno/metabolismo , Perfilación de la Expresión Génica , Peróxido de Hidrógeno/farmacología , Factor 2 Relacionado con NF-E2/metabolismoRESUMEN
Surgical bleeding and cumulative oxidative stress are significant factors in the development of postoperative adhesions, which are always associated with adverse patient outcomes. However, effective strategies for adhesion prevention are currently lacking in clinical practice. In this study, we propose a solution using polydopamine-decorated manganese dioxide nanoparticles (MnO2@PDA) with rapid hemostasis and remarkable antioxidant properties to prevent postsurgical adhesion. The PDA modification provides MnO2@PDA with enhanced tissue adhesiveness and hemocompatibility with negligible hemolysis. Furthermore, MnO2@PDA exhibits impressive antioxidant and free radical scavenging properties, protecting cells from the negative effects of oxidative stress. The hemostatic activity of MnO2@PDA is evaluated in a mouse truncated tail model and a liver injury model, with results demonstrating reduced bleeding time and volume. The in vivo test on a mouse cecal abrasion model shows that MnO2@PDA exhibits excellent antiadhesion properties coupled with alleviated inflammation around the damaged tissue. Therefore, MnO2@PDA, which exhibits high biosafety, rapid hemostasis, and beneficial antioxidant capacity, displays exceptional antiadhesion performance, holding great potential for clinical applications to prevent postoperative adhesion.
Asunto(s)
Antioxidantes , Indoles , Nanopartículas , Polímeros , Humanos , Ratones , Animales , Antioxidantes/farmacología , Compuestos de Manganeso/farmacología , Contención de Riesgos Biológicos , Óxidos/farmacología , HemostasisRESUMEN
GM1 is a major brain ganglioside that exerts neurotrophic, neuroprotective and antineuroinflammatory effects. The aim of this study was to obtain insights into the antineuroinflammatory mechanisms of exogenous GM1 in lipopolysaccharide (LPS)-stimulated MG6 mouse transformed microglial cell line. First, we found that GM1 prevented the LPS-induced transformation of microglia into an amoeboid-like shape. GM1 treatment inhibited LPS-induced expression of inducible nitric oxide synthase, cyclooxygenase-2 (COX-2), and proinflammatory cytokines such as TNF-α, IL-1ß and IL-6 in MG6 cells. In LPS-treated mice, GM1 also reduced striatal microglia activation and attenuated COX-2 expression. Subsequent mechanistic studies showed that GM1 suppressed LPS-induced nuclear translocation of nuclear factor κB (NF-κB) and activator protein-1 (AP-1), two critical transcription factors responsible for the production of proinflammatory mediators. GM1 exhibited antineuroinflammatory properties by suppressing Akt/NF-κB signaling and the activation of mitogen-activated protein kinases (MAPKs), including p38 MAPK, extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK). Furthermore, GM1 suppressed LPS-induced activation of transforming growth factor-ß-activated kinase 1 (TAK1) and NADPH oxidase 2 (NOX2), upstream regulators of the IκBα/NF-κB and MAPK/AP-1 signaling pathways. GM1 also inhibited NOX-mediated reactive oxygen species (ROS) production and protected against LPS-induced MG6 cell death, suggesting an antioxidant role of GM1. In conclusion, GM1 exerts both antineuroinflammatory and antioxidative effects by inhibiting Akt, TAK1 and NOX2 activation.
Asunto(s)
Microglía , FN-kappa B , Ratones , Animales , FN-kappa B/metabolismo , Microglía/metabolismo , Gangliósido G(M1)/metabolismo , Lipopolisacáridos/toxicidad , Lipopolisacáridos/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , NADPH Oxidasas/metabolismo , NADPH Oxidasas/farmacología , Factor de Transcripción AP-1/metabolismo , Factor de Transcripción AP-1/farmacología , Ciclooxigenasa 2/metabolismo , Ciclooxigenasa 2/farmacología , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/metabolismo , Fosforilación , Estrés OxidativoRESUMEN
Research on the toxicity effects of nano-plastics on submerged macrophytes has been increasing over the past several years. However, how the endophytic bacteria of submerged macrophytes respond to nano-plastics remains unknown, although they have been widely shown to help terrestrial plants cope with various environmental stressors. Here, a microcosm experiment was performed to unravel the effects of high concentration of nano-plastics (20 mg/L) on three submerged macrophyte (Vallisneria natans, Potamogeton maackianus, Myriophyllum spicatum) and their endophytic bacterial communities. Results indicated that nano-plastics induced antioxidative stress in plants, but significantly reduction in relative growth rate (RGR) only occurred in V. natans (from 0.0034 to -0.0029 day-1), accompanied by change in the stem/leaves endophyte community composition. Further analysis suggested nano-plastics caused a reduction in environmental nutrient availability and the proportion of positive interactions between endophyte communities (43%), resulting in the lowest RGR of V. natans. In contrast, endophytes may help P. maackianus and M. spicatum cope with nano-plastic stress by increasing the proportion of positive correlations among communities (70% and 75%), leaving their RGR unaffected. Collectively, our study elucidates the species-specific response strategies of submerged macrophyte-endophyte to nano-plastics, which helps to reveal the different phytoremediation potential of submerged macrophytes against nano-plastic pollution.
Asunto(s)
Hydrocharitaceae , Potamogetonaceae , Saxifragales , Endófitos , Microplásticos/farmacología , BacteriasRESUMEN
The nephroprotective potential of the Brassica nigra sprout (BNS) hydroalcoholic extract against carbon tetrachloride (CCl4)-induced renal toxicity in rats was the object of this study. B. nigra sprouts were prepared in the lab to monitor the bio-changes in bioactive compounds during the sprouting for up to 7 days at 17 ± 1 °C and 90% relative humidity. Subsequently, 6-day sprouts of B. nigra were selected according to their phenolics and antioxidant activity, extracted, and examined for their nephroprotective and antioxidative stress potential at 250 and 500 mg sprout extracts kg-1 bw, in vivo. Weight gain, organ weight, lipid profile, atherogenic index, kidney functions, and oxidative stress biomarkers were assessed. The results indicated that the most proficient treatment for weight gain improvement was BNS extract at 500 mg kg-1. BNS at 250 mg kg-1 was remarked as the lowest weight gain enhancer compared to the NR group. A significant increase in TG, TC, LDL-c, and VLDL-c levels in the rats with CCl4-induced renal toxicity, and a significant decrease in HDL level, was noted. The administration of the BNS extract at 250 and 500 mg kg-1 considerably attenuated TG, TC, LDL-c, and VLDL-c levels, compared to the NR group. The most efficient treatment for improving the lipid profile was the BNS extract at 500 mg kg-1, even better than 250 mg kg-1. Administrating the BNS extract substantially attenuated the alterations in the creatinine, urea, and BUN caused by the CCl4 injection. The most efficient improvement was markedly recorded with the BNS extract at 500 mg kg-1, compared to the NR group. The rats treated with the BNS extract showed significant enhancement in GSH, CAT, and SOD activities and a considerable reduction in MDA levels. Administering the BNS extract at 250 and 500 mg kg-1 can efficiently reverse CCl4 inhibition of antioxidant enzyme activities, significantly increase GSH, CAT, and SOD, and decrease the MDA levels dose-dependently. The BNS extract at 250 and 500 mg kg-1 exhibits nephroprotection and antioxidative stress in a dose-dependent matter. The total nephroprotection % was recorded at 65.18% and 99.21% for rats treated with 250 and 500 mg kg-1, respectively. These findings could prove and potentiate the nephroprotective activities of the BNS extract in the range of the given doses. Further clinical studies are highly recommended for confirming the nephroprotection efficiency of the B. nigra sprout.
RESUMEN
BACKGROUND: With the development of an aging sociality, aging-related diseases, such as Alzheimer's disease, cardiovascular disease, and diabetes, are dramatically increasing. To find small molecules from natural products that can prevent the aging of human beings and the occurrence of these diseases, we used the lifespan assay of yeast as a bioassay system to screen an antiaging substance. Isoquercitrin (IQ), an antiaging substance, was isolated from Apocynum venetum L., an herbal tea commonly consumed in Xinjiang, China. AIM OF THE STUDY: In the present study, we utilized molecular-biology technology to clarify the mechanism of action of IQ. METHODS: The replicative lifespans of K6001 yeasts and the chronological lifespans of YOM36 yeasts were used to screen and confirm the antiaging effect of IQ. Furthermore, the reactive oxygen species (ROS) and malondialdehyde (MDA) assay, the survival assay of yeast under stresses, real-time polymerase chain reaction (RT-PCR) and Western blotting analyses, the replicative-lifespan assay of mutants, such as Δsod1, Δsod2, Δgpx, Δcat, Δskn7, Δuth1, Δatg32, Δatg2, and Δrim15 of K6001, autophagy flux analysis, and a lifespan assay of K6001 yeast after giving a mitophagy inhibitor and activator were performed. RESULTS: IQ extended the replicative lifespans of the K6001 yeasts and the chronological lifespans of the YOM36 yeasts. Furthermore, the reactive nitrogen species (RNS) showed no change during the growth phase but significantly decreased in the stationary phase after treatment with IQ. The survival rates of the yeasts under oxidative- and thermal-stress conditions improved upon IQ treatment, and thermal stress was alleviated by the increasing superoxide dismutase (Sod) activity. Additionally, IQ decreased the ROS and MDA of the yeast while increasing the activity of antioxidant enzymes. However, it could not prolong the replicative lifespans of Δsod1, Δsod2, Δgpx, Δcat, Δskn7, and Δuth1 of K6001. IQ significantly increased autophagy and mitophagy induction, the presence of free green fluorescent protein (GFP) in the cytoplasm, and ubiquitination in the mitochondria of the YOM38 yeasts at the protein level. IQ did not prolong the replicative lifespans of Δatg2 and Δatg32 of K6001. Moreover, IQ treatment led to a decrease in Sch9 at the protein level and an increase in the nuclear translocation of Rim15 and Msn2. CONCLUSIONS: These results indicated that the Sch9/Rim15/Msn signaling pathway, as well as antioxidative stress, anti-thermal stress, and autophagy, were involved in the antiaging effects of IQ in the yeasts.
RESUMEN
The aim of this study was to conduct a screening of potential therapeutic compounds found in the Atractylodes macrocephala rhizoma essential oil (AO) and explore its mechanism of action in the treatment of ulcerative colitis (UC). An inflammation cell model was employed in conjunction with phospho-antibody array technology to explore potential therapeutic compounds of AO and their anti-inflammatory and antioxidant effects. Furthermore, we assessed their efficacy and mechanisms of action in treating dextran sulfate sodium (DSS)-induced colitis in mice. Via the screening process, we identified atractylone (ATR) as the primary active compound in AO. It has been demonstrated that ATR can both decrease the levels of tumor necrosis factor (TNF)-α and reactive oxygen species (ROS) and increase the expression of adhesion proteins such as claudin, ZO-1, and occludin in vitro. Moreover, ATR has been shown to improve UC symptoms in vivo. Via a non-targeted metabolomics analysis of colon tissue, we identified 57 distinct metabolites that responded to ATR treatment. Subsequent analysis of the metabolic pathways revealed that the action of ATR was primarily focused on the amino acid metabolism pathway. In summary, ATR may alleviate the symptoms of UC by regulating multiple signaling pathways. Additionally, ATR has a comprehensive function in anti-inflammation, antioxidative stress, and intestinal injury reduction.
Asunto(s)
Atractylodes , Colitis Ulcerosa , Colitis , Aceites Volátiles , Animales , Ratones , Atractylodes/química , Aceites Volátiles/uso terapéutico , Antiinflamatorios/uso terapéutico , Colitis Ulcerosa/tratamiento farmacológico , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Colitis/metabolismo , Colon/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Sulfato de Dextran/efectos adversos , Modelos Animales de Enfermedad , Ratones Endogámicos C57BLRESUMEN
The increasing incidence of metabolic diseases, including obesity and diabetes, is a serious social public problem. Therefore, there is an urgent need to find effective prevention and treatment measures for these diseases. DsbA-L is a protein that is widely expressed in many tissues and is closely related to metabolism. Emerging evidence shows that DsbA-L plays an important role in antioxidative stress, promoting the synthesis and secretion of adiponectin and maintaining mitochondrial homeostasis, and the abnormalities of these functions are also closely related to the occurrence and development of metabolic diseases. Here, we reviewed the tissue expression patterns and regulatory factors of DsbA-L, summarized its biological functions and the current research progress of DsbA-L in metabolic diseases, and found that DsbA-L may be a promising target for metabolic diseases.
RESUMEN
High body mass index (high BMI, obesity) is a serious public health problem, and "obesity-induced oxidative stress, inflammation, and cancer" have become modern epidemic diseases. We carried out this study to explore a functional beverage that may protect against obesity-induced diseases. The Engleromyces goetzei Henn herbal tea is such a candidate. For this study, we carried out LC-MS analysis of E. goetzei Henn aqueous extract (EgH-AE); then used the Caco-2 cell line for the model cells and treated the cells with t-BHP to form an oxidative stress system. An MTT assay was used for testing the biocompatibility and cytoprotective effects; reactive oxygen species and malondialdehyde determination was used for evaluating the antioxidative stress effect; TNF-α and IL-1ß were used for observing the anti-inflammatory effect, and 8-OHdG for monitoring anticancer activity. The results of this study demonstrate that the EgH-AE has very good biocompatibility with the Caco-2 cell line and has good cytoprotective, antioxidant, anti-inflammatory, and anticancer properties. It is clear that EgH-AE, a kind of ancient herbal tea, may be used to develop a functional beverage that can be given to people with a high BMI to protect against obesity-induced diseases.
RESUMEN
Deoxynivalenol (DON), one of the most common mycotoxins contaminating food and feed, has been shown to induce hepatotoxicity. Lactoferrin (LF) enriched in human milk is a critical functional food component and performs the hepatoprotection function. Here, we aimed to explore whether dietary LF supplementation can protect from DON-induced hepatotoxicity and uncover the underlying mechanism in mice and alpha mouse liver 12 (AML12) hepatocytes. In vivo results revealed that LF alleviated DON-induced liver injury, reflected by repairing the hepatic histomorphology and decreasing the plasma alanine aminotransferase (ALT) level and the number of blood white blood cells (WBC) and neutrophils (Neu). Moreover, LF decreased the hepatic reactive oxygen species (ROS) and malondialdehyde (MDA) accumulation and enhanced the hepatic GSH-px activity and protein expression of Nrf2 and GPX4 to reverse the DON-induced hepatic oxidative stress. Furthermore, LF downregulated the pro-inflammatory-response-related gene expressions (IL1ß, TNFα, and Tlr4) and the phosphorylation levels of IKK, IκBα, and p38 in the liver of DON-exposed mice. Additionally, in vitro studies confirmed that LF ameliorated the DON-induced oxidation-reduction imbalance, inflammatory responses, and associated core modulators of the Nrf2 and MAPK pathways in DON-induced hepatotoxicity. In conclusion, LF performs hepatic antioxidative and anti-inflammatory functions by regulating the Nrf2/MAPK signaling pathways, thus reducing DON-induced hepatotoxicity.
Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas , Factor 2 Relacionado con NF-E2 , Humanos , Ratones , Animales , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Lactoferrina/genética , Lactoferrina/metabolismo , Estrés Oxidativo , Hígado/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Enfermedad Hepática Inducida por Sustancias y Drogas/genética , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismoRESUMEN
Copper (Cu) was recently demonstrated to play a critical role in cellular physiological and biochemical processes, including energy production and maintenance, antioxidation and enzymatic activity, and signal transduction. Antioxidant 1 (ATOX1), a chaperone of Cu previously named human ATX1 homologue (HAH1), has been found to play an indispensable role in maintaining cellular Cu homeostasis, antioxidative stress, and transcriptional regulation. In the past decade, it has also been found to be involved in a variety of diseases, including numerous neurodegenerative diseases, cancers, and metabolic diseases. Recently, increasing evidence has revealed that ATOX1 is involved in the regulation of cell migration, proliferation, autophagy, DNA damage repair (DDR), and death, as well as in organism development and reproduction. This review summarizes recent advances in the research on the diverse physiological and cytological functions of ATOX1 and the underlying mechanisms of its action in human health and diseases. The potential of ATOX1 as a therapeutic target is also discussed. This review aims to pose unanswered questions related to ATOX1 biology and explore the potential use of ATOX1 as a therapeutic target.