Enhanced Superoxide Dismutase Research Articles

Comparative Analysis of Phytochemicals and Gene Expression in Soybean (Glycine max) Under Acute Moderated and Severe Elevated Ozone: Unravelling the Role of Antioxidant Defence

ABSTRACTThe increasing concentrations of ground‐level ozone (O3) resulting from industrialisation and anthropogenic activities present a substantial environmental threat to agricultural productivity, particularly affecting O3‐sensitive crops such as soybeans. The effects of acute O3 exposure on soybean yield attributes and seed quality and whether soybean showed different detoxification mechanisms in response to moderate and severe O3 stress are not extensively explored. In this study, soybean seedlings were exposed to moderate (80 nmol mol−1) and acute severe (200 nmol mol−1) O3 stress, and then growth parameters, yield attributes, reactive oxygen species (ROS) levels, enzymatic and non‐enzymatic antioxidant properties and associated gene expression in the leaves were assessed. The results revealed that moderate O3 exposure enhanced growth parameters but reduced the 100‐grain weight, while acute severe exposure sharply depressed growth parameters, yield attributes and the 100‐grain weight. Moderate O3 fumigation significantly increased hydrogen peroxide (H2O2) levels and catalase (CAT) activity from 4 to 32 h. Acute severe O3 stress induced the overproduction of superoxide anions (O2.−) and H2O2 during nearly the whole experiment period, but only enhanced superoxide dismutase (SOD) activity at 32 h, and showed no stimulatory effects on CAT activity. Additionally, the relative expression levels of the SOD and CAT gene family in soybean leaves exposed to elevated O3 were upregulated, peaking at 8 h. Moderate O3 treatment enhanced reduced glutathione (GSH) and ascorbate (AsA) levels and increased the activities of AsA–GSH cycle‐related enzymes. In contrast, acute severe O3 exposure inhibited GSH and AsA contents and markedly suppressed AsA–GSH cycle‐related enzymes, particularly from 8 to 32 h. Redundancy analysis indicated that CAT and AsA play crucial roles in scavenging O3‐induced ROS under moderate stress, while ascorbate peroxidase (APX) and GSH were more effective under acute severe stress conditions. These findings provide insights into the differential impacts of acute O3 stress on soybeans, emphasising the importance of considering both crop yield and grain quality in assessing O3 risks to crops.

Systems Pharmacology to Explore the Potential Mechanism of Ginseng Against Heart Failure.

The aim of this study is to elucidate the pharmacological mechanism underlying the effects of Ginseng Radix et Rhizoma (ginseng) in heart failure (HF), providing a theoretical foundation for its clinical application. The potential mechanism of ginseng in the context of HF was investigated using systems pharmacology that combined network pharmacology, Gene Expression Omnibus (GEO) analysis, molecular docking, and experimental verification. Network pharmacology was employed to identify drug-disease targets. Core gene targets were subsequently subjected to enrichment analysis by integrating network pharmacology with GEO. Molecular docking was utilized to predict the binding affinities between identified targets and ginseng compounds. Furthermore, the therapeutic efficacy of ginseng was validated in an isoproterenol (ISO)-induced rat model of HF. The modulation of key signaling pathways by ginseng was confirmed through Western blot analysis. A total of 154 potential targets of ginseng in the treatment of HF were identified through network pharmacology analysis. The analysis of GSE71613 revealed that the PI3K-Akt pathway, reactive oxygen species, oxidative phosphorylation, MAPK signaling, and Ras signaling pathways are predominantly associated with patients with HF. By integrating the findings from network pharmacology and GEO analysis, ginsenoside Rg1 and ginsenoside Rb3 were identified as the potential components in ginseng, while FN1 and PRKAA2 were recognized as key targets involved in the PI3K-AKT and AMPK pathways, respectively. Molecular docking analysis revealed a strong affinity between the potential components and the identified core targets. In vivo experiments indicated that the extract of ginseng (EPG) significantly ameliorated ISO-induced cardiac dysfunction by improving cardiac parameters such as cardiac left ventricular internal systolic diameter, left ventricular end-diastolic volume, left ventricular end systolic volume, and left ventricular ejection fraction, while also reducing malondialdehyde production. In addition, EPG was found to enhance superoxide dismutase activity and ATP levels, while concurrently reducing the levels of interleukin (IL)-1β, IL-6, and TNF-α. The extract also reduced myocardial oxygen consumption, inflammatory cell infiltration, and the number of damaged myocardial fibers. Moreover, EPG was observed to upregulate the expression of p-PI3K, p-AKT, p-AMPK, and Bcl-2, while downregulating the expression of p-NFκB, TGF-β, and Bax. The therapeutic effects of ginseng on HF are primarily mediated through the PI3K-Akt and AMPK pathways. Ginsenoside Rg1 and ginsenoside Rb3 have been identified as potential therapeutic agents for HF.

Optimizing chlorine dioxide treatment for enhanced post-harvest storage quality of Toona Sinensis.

This study investigated the impact of chlorine dioxide (ClO2) treatment on the storage quality of Toona sinensis after harvesting. Toona sinensis samples treated with different concentrations (0.2, 0.4, 0.8, 1.6 mg/L) of chlorine dioxide and stored at (4 ± 1) °C, with sampling test every 2nd day. The changes in sensory, nutritional, and chlorine dioxide residues of T. sinensis were checked regularly. Results revealed that moderate (0.4~0.8 mg/L) chlorine dioxide concentrations maintained sensory quality, inhibited T. sinensis weight loss, slowed flavonoid and vitamin C content depletion, reduced nitrite content, and enhanced superoxide dismutase activity. The chlorine dioxide resides in T. sinensis were below the national standards (<2.0 mg/kg; GB 5009.244-2016). Overall, 0.4~0.8 mg/L chlorine dioxide treatment showed optimal effects on T. sinensis, providing a scientific basis for extended storage and preservation of T. sinensis.

Optimizing nutraceutical-loaded trehalosomes in-situ gel for diabetic cataract management: Comprehensive in vitro and in vivo evaluations

This study aimed to develop Baicalin-loaded trehalosomes in situ gel (BA-THs-ISG) for the treatment of cataract, a degenerative eye condition that requires innovative approaches to enhance visual acuity and quality of life. A 33 D-optimal design was implemented for the preparation and statistical optimization of BA-THs. Various in-vitro studies were conducted to evaluate the features of the optimized formula, which was subsequently loaded into an optimum ISG to sustain the release pattern. To assess the therapeutic efficacy of BA-THs-ISG, an in-vivo study was conducted using a streptozotocin (STZ) induced diabetic cataract model. The results demonstrated that the optimized formula of desirability function of 0.878 had a particle size (PS) of 237.9 ± 2.87 nm, a polydispersity index (PDI) of 0.27 ± 0.03, a zeta potential (ZP) of −27.31 ± 1.27 mV, an entrapment efficiency (EE%) of 74.32 ± 1.08 % and sustained drug release over 6 h. After being loaded into ISG, BA-THs-ISG exhibited a gelation temperature of 35.00 ± 0.30 °C and a gelation time of 49 ± 2.63 s, meeting the intended criteria. Moreover, it effectively maintained drug release for a duration of 12 h. Compared to the BA solution in the in-vivo studies, BA-THs-ISG significantly reduced malondialdehyde content and enhanced superoxide dismutase and glutathione peroxidase activities without any irritation potential. Therefore, BA-THs-ISG is inferred to be a highly effective option for improving cataract symptoms.

Selenium Nanoparticles Regulate Antioxidant Enzymes and Flavonoid Compounds in Fagopyrum dibotrys.

Fagopyrum dibotrys is a herbal plant. Selenium (Se) is a beneficial element for plants; selenium nanoparticles (SeNPs) are gaining importance in food and agriculture due to their low toxicity and high activity. This study revealed that foliar application of SeNPs enhanced superoxide dismutase, glutathione peroxidase, and peroxisome activities and significantly enhanced the flavonoid compound content in F. dibotrys. SeNPs with a concentration of 5.0 mg L-1 also promoted the growth of F. dibotrys. The foliar application of SeNPs could be absorbed by pores in leaves of F. dibotrys and mainly transformed to selenomethionine (32.5-43.2%) and selenocysteine (23.4-38.4%) in leaves and tubers of F. dibotrys. Consequently, this study offers a profound understanding of plants' uptake and biotransformation of SeNPs. Furthermore, the findings of this study have suggested that SeNPs can be applied to improve the quantity and quality of the herbal plant of F. dibotrys.

Boosting Stevia's sweetness: Growth regulators mitigate salt stress and enhance steviol glycosides

Stevia rebaudiana Bertoni is a plant species with sweet-tasting leaves that can be used as a natural, low-calorie sweetener with potential health benefits. Salt stress can reduce plant growth and productivity, but the application of growth regulators like salicylic acid (SA), methyl jasmonate (MeJ), and spermidine (Spd) can manage various plant abiotic stresses and improve plant growth and productivity. In this work, we investigated the role of exogenous SA, MeJ, and Spd in conferring salt stress tolerance in Stevia by analyzing plant growth, chlorophyll (Chl), total phenolic, total carotenoid content, antioxidant defense system and steviol glycosides. The aim of a recent study was to assess the effects of these regulators on Stevia plants under both individual and combined salt stress conditions. Foliar application of these regulators improved plant growth under salt stress, with moderate salinity stress increasing glycoside compounds. SA was most effective in increasing rebaudioside A (Reb A), while MeJ + Spd combination was best for increasing stevioside (Stv) content. Individual applications of Spd, MeJ, and SA significantly impacted plant growth and antioxidant content, although their combined use was less effective. Spd application under salt stress yielded the highest increases in total carotenoid and Chl a content, while MeJ and Spd together significantly boosted Chl b content. The study found that SA enhanced superoxide dismutase (SOD) activity and reduced catalase (CAT) activity under salt stress, whereas MeJ alone increased both CAT and SOD activity. The distinct responses to Spd, SA, and MeJ suggest varied mechanisms in oxidative stress-induced antioxidant production. Overall, the use of these growth regulators can improve the growth, yield, and nutritional value of Stevia under salt stress, offering significant implications for agriculture and food security.

Influence of Foliar Application of Nanoparticles on Low Temperature Resistance of Rice Seedlings.

Chilling stress, a common abiotic factor, adversely affects the growth and biomass of rice seedlings during the early stages, ultimately reducing the yield. Effective strategies to mitigate these negative impacts are essential for improving rice productivity. The application of nanotechnology in agriculture, particularly nanoparticles (NPs), has shown a promising effect in alleviating chilling stress in plants. This study evaluates the effects of various nanoparticles, ZnO (0, 50, 100, and 200 mg/L), Fe2O3 (0, 50, 75, and 100 mg/L), TiO2 (0, 50, 75, and 100 mg/L), and CeO2 (0, 50, 75, and 100 mg/L) on the chilling resistance with one control (a water spray) under a normal temperature. Four rice cultivars: LLY-7108 and XZX-6 (Low-temperature-tolerant), and LLY-32 and ZJZ-17 (Low-temperature-susceptible) were tested in this experiment. Rice seedlings were subjected to low temperature conditions (12 h light 14 °C/12 h dark, at 10 °C) for five days, followed by seven days of recovery. The results of this study demonstrate that NPs significantly enhanced seedling height fresh/dry weight and root length compared to untreated controls under chilling stress. NP treatment also reduced the reactive oxygen species (ROS), malondialdehyde (MDA), and proline content, while enhancing superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) activities, thereby mitigating oxidative damage. The four rice varieties exhibited clear signs of rapid growth recovery and positive physiological changes due to NPs' application. Among the tested cultivars, LLY-7108 showed the most substantial recovery and physiological responses, while ZJZ-17 exhibited the least. The findings of this study indicate that the foliar application of ZnO (100 mg/L), Fe2O3 (50 mg/L), TiO2 (50 mg/L), and CeO2 (75 mg/L) NPs effectively mitigates chilling stress in rice seedlings, likely by enhancing the antioxidant enzymatic activity while reducing the oxidative damage. This study highlights the potential of NPs as effective agents in reducing the adverse effects of chilling stress on rice.

SiLOXL2 Inhibits Endothelial Inflammatory Response and EndMT Induced by ox-LDL

Introduction: Our research aimed to investigate the potential role and mechanism of lysyl oxidase (LOX)-like 2 (LOXL2) in atherosclerosis (AS) by using the human umbilical vein endothelial cells (HUVECs) stimulated by oxidized low-density lipoprotein (ox-LDL). Methods: HUVECs were treated with ox-LDL at different concentrations (0, 10, 25, 50, and 100 μg/mL) and incubated for 24 h. The transfection efficacy of siLOXL2 was investigated by Western blot and real-time quantitative polymerase chain reaction (RT-qPCR). Cell migration, intracellular ROS measurement, oxidative stress, enzyme-linked immunosorbent assay, and adhesion assays were carried out to examine the ox-LDL-induced HUVECs injury. RT-qPCR and Western blot were used to determine gene and protein expression levels. Results: LOXL2 protein expression increased in ox-LDL-induced endothelial cells (ECs). ox-LDL + siLOXL2 significantly inhibited the migration ability of HUVECs and reduced the expression of vascular endothelial growth factor A (VEGFA) and matrix metalloproteinase 9 gene expressions (all, p < 0.05). The ox-LDL + siLOXL2 significantly reduced intracellular ROS production and inhibited the expression of Malondialdehyde, whereas it markedly enhanced superoxide dismutase and catalase (all, p < 0.05). Supernatant levels of interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) were significantly attenuated by the ox-LDL + siLOXL2 treatment (all, p < 0.05). ox-LDL + siLOXL2 markedly suppressed the expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 (all, p < 0.05). ox-LDL + siLOXL2 treatment remarkably reduced the expression of α-smooth muscle actin and vimentin, while increased CD31 and von Willebrand factor gene expression (all, p < 0.05). Conclusion: LOXL2 silencing is protected against ox-LDL-induced EC dysfunction, and the mechanism may be related to the inhibition of the EndMT pathway.

Sodium transport and redox regulation in Saccharomyces cerevisiae under osmotic stress depending on oxygen availability

This study explores the molecular mechanisms behind the differential responses of Saccharomyces cerevisiae industrial strains (ATCC 9804 and ATCC 13007) to osmotic stress. We observed that, in contrast to ATCC 9804 strain, sodium flux in ATCC 13,007 is not N, N’-dicyclohexylcarbodiimide (DCCD)-sensitive under osmotic stress, suggesting a distinct ion homeostasis mechanism. Under aerobic conditions, osmotic stress increased reduced SH groups by 45% in ATCC 9804 and 34% in ATCC 13,007. In contrast, under microaerophilic conditions, both strains experienced a 50% reduction in thiol groups. Notably, ATCC 13,007 exhibited a 1.5-fold increase in catalase (CAT) activity under aerobic stress compared to standard conditions, while ATCC 9804 showed enhanced CAT activity due to SH group binding. Additionally, superoxide dismutase (SOD) activity was doubled during aerobic growth in both strains, with ATCC 13,007 showing a 1.5-fold higher SOD activity under osmotic stress. The results demonstrate that S. cerevisiae adapts to osmotic stress differently under aerobic and microaerophilic conditions, with aerobic conditions promoting Pma-Ena-Trk interplay, reduced thiol levels and increased catalase activity, while microaerophilic conditions demonstrate Pma-Nha-Trk interplay and shifts redox balance towards oxidized thiol groups and enhance superoxide dismutase activity. Understanding these mechanisms can aid in developing stress-resistant yeast strains for industrial applications.

Mechanistic studies on the alleviation of lipid accumulation and oxidative stress by Majia pomelo seed oil

In this study, hot-pressed Majia pomelo seed oil (MPSO), which has high oxidative stability and antioxidant capacity, was used to study the effects and potential mechanisms of lipid accumulation and oxidative stress. The results indicated that the low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TG) levels in HepG2 cells were lowest when the MPSO concentration was 0.5 mg/mL. At this concentration, MPSO could alleviate oleic acid (OA)-induced lipid accumulation, reduce intracellular lipid level, and decrease lipid and cholesterol synthesis by increasing AMPK phosphorylation and down-regulating the expression levels of genes and proteins of ACC, SREBP-1c, PPAR-γ, and FAS. Meanwhile, MPSO can reduce reactive oxygen species (ROS) and malondialdehyde (MDA) content and enhance superoxide dismutase (SOD) content in HepG2 cells by down-regulating the expression levels of Nrf2, γ-GCS, and HO-1 genes and proteins, thus acting as an anti-oxidative stress. In addition, molecular docking results indicated that the active ingredients of MPSO could effectively bind AMPK protein and Keap1 protein, which further demonstrated that MPSO could alleviate lipid accumulation and oxidative stress.

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.

Sodium Houttuybonate Promotes the Browning of White Adipose Tissue by Inhibiting Ferroptosis via the AMPK-NRF2-HO1 Pathway.

The rising prevalence of obesity has resulted in an increased demand for innovative and effective treatment strategies. Houttuynia cordata Thunb. (H. cordata) has demonstrated promising potential in preventing obesity. However, the mechanism underlying the anti-obesity effects of H. cordata and its bioactive component, sodium houttuybonate (SH), remains unclear. Our study reveals that SH treatment promotes the browning of inguinal white adipose tissue (iWAT) and prevents the obesity induced by a high-fat diet. SH significantly mitigates ferroptosis by upregulating glutathione peroxidase 4 (Gpx4) and decreasing malondialdehyde (MDA) levels, while also enhancing superoxide dismutase (SOD) levels. Furthermore, SH promotes the phosphorylation of AMP-activated protein kinase (AMPK), which subsequently increases the expression of nuclear factor erythroid 2-related factor 2 (NRF2) and heme oxygenase-1 (HO-1) in the iWAT. However, the effects of SH were attenuated by ML385, an Nrf2 inhibitor. Collectively, our findings suggest that SH induces iWAT browning and prevents diet-induced obesity primarily through the AMPK/NRF2/HO-1 pathway by inhibiting ferroptosis.

A Photoactivated Self-Assembled Nanoreactor for Inducing Cascade-Amplified Oxidative Stress toward Type I Photodynamic Therapy in Hypoxic Tumors.

Type I photodynamic therapy (PDT) generates reactive oxygen species (ROS) through oxygen-independent photoreactions, making it a promising method for treating hypoxic tumors. However, the superoxide anion (O2∙-) generated usually exhibits a low oxidation capacity, restricting the antitumor efficacy of PDT in clinical practice. Herein, a photoactivated self-assembled nanoreactor (1-NBS@CeO2) is designed through integration of type I PDT and cerium oxide (CeO2) nanozymes for inducing cascade-amplified oxidative stress in hypoxic tumors. The nanoreactor is constructed though co-assembly of an amphiphilic peptide (1-NBS) and CeO2, giving well-dispersed spherical nanoparticles with enhanced superoxide dismutase (SOD)-like and peroxidase (POD)-like activities. Following light irradiation, 1-NBS@CeO2 undergoes type I photoreactions to generated O2∙-, which is further catalyzed by the nanoreactors, ultimately forming hypertoxic hydroxyl radical (∙OH) through cascade-amplified reactions. The PDT treatment using 1-NBS@CeO2 results in elevation of intracellular ROS and depletion of GSH content in A375 cells, thereby inducing mitochondrial dysfunction and triggering apoptosis and ferroptosis of tumor cells. Importantly, intravenous administration of 1-NBS@CeO2 alongside light irradiation showcases enhances antitumor efficacy and satisfactory biocompatibility in vivo. Together, the self-assembled nanoreactor facilitates cascade-amplified photoreactions for achieving efficacious type I PDT, which holds great promise in developing therapeutic modules towards hypoxic tumors.

Alleviation of arsenic stress in pakchoi by foliar spraying of engineered nanomaterials.

Addressing heavy metal contamination in leafy vegetables is critically important due to its adverse effects on human health. In this study, we investigated the inhibitory effects of foliar spraying with four nanoparticles (CeO2, ZnO, SiO2, and S NPs) on arsenic (As) stress in pakchoi (Brassica rapa var. Chinensis). The findings reveal that foliar application of ZnO NPs at 1 ~ 2.5 mg plant-1 and CeO2 NPs at 5 mg plant-1 significantly reduces As in shoots by 40.9 ~ 47.3% and 39.4%, respectively. Moreover, 5 mg plant-1 CeO2 NPs increased plant height by 6.06% and chlorophyll a (Chla) content by 30.2% under As stress. Foliar spraying of CeO2 NPs at 0.2-5 mg plant-1 also significantly enhanced superoxide dismutase (SOD) activity in shoots by 9.4 ~ 13.9%, lowered H2O2 content by 42.4 ~ 53.25%, and increased root protein contents by 79 ~ 109.2%. CeO2 NPs regulate the As(III)/As(V) ratio, aiding in As efflux from roots and thereby reducing As toxicity to plants. In vitro digestion experiments reveal that the consumption of CeO2 NPs carries the lowest health risk of As. In addition, foliar spraying of ZnO NPs at 1 ~ 2.5 mg plant-1 can suppress plant As uptake by modulating enzyme activity, reducing leaf damage, and enhancing chlorophyll content. The study demonstrates that high CeO2 NP concentrations and suitable ZnO NP concentrations can alleviate As toxicity in pakchoi, consequently reducing human health risks.

Novel insights into the molecular mechanisms underlying anti-nociceptive effect of myricitrin against reserpine-induced fibromyalgia model in rats: Implication of SIRT1 and miRNAs

Ethnopharmacological relevanceManilkara zapota (L.) P. Royen, also termed sapodilla or chikoo, is a significant plant in ethnomedicine because of its long history of traditional medical applications. In diverse cultures, sapodilla is believed to protect against oxidative stress, inflammation, and some chronic diseases because of its high antioxidant content. The naturally occurring antioxidant myricitrin (MYR) flavonoid is primarily found in the leaves and other plant parts of sapodilla and it is well-known for having therapeutic qualities and possible health advantages. Aim of the studyTo appraise the possible impact of MYR on a rat model of reserpine-induced fibromyalgia (FM) and explore its mechanism of action. Materials and methodsIsolation and identification of MYR with more than 99% purity from Manilkara zapota leaves were primarily done and confirmed through chromatographic and spectrophotometric techniques. To develop FM model, reserpine (RSP) was injected daily (1 mg/kg, s.c.) for three successive days. Then, MYR (10 mg/kg, i.p.) and pregabalin (PGB, 30 mg/kg, p.o.) were given daily for another five days. Behavioral changes were assessed through open field test (OFT), hot plate test, and forced swimming test (FST). Further analyses of different brain parameters and signaling pathways were performed to assess monoamines levels, oxidative stress, inflammatory response, apoptotic changes as well as silent information regulator 1 (SIRT1) and micro RNAs (miRNAs) expressions. ResultsFrom High-Performance Liquid Chromatography (HPLC) analysis, the methanol extract of sapodilla leaves contains 166.17 μg/ml of MYR. Results of behavioral tests showed a significant improvement in RSP-induced nociceptive stimulation, reduced locomotion and exploration and depressive-like behavior by MYR. Biochemical analyses showed that MYR significantly ameliorated the RSP-induced imbalance in brain monoamine neurotransmitters. In addition, MYR significantly attenuated oxidative stress elicited by RSP via up-regulating nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) protein expressions, enhancing superoxide dismutase (SOD) and catalase (CAT) activities, and reducing malondialdehyde (MDA) content in brain. The RSP-provoked inflammatory response was also diminished by MYR treatment as shown by a significant decreased NOD-like receptor protein 3 (NLRP3) inflammasome expression along with reduced levels of interleukin 1 beta (IL-1β) and nuclear factor-κB (NF-κB). Furthermore, the anti-apoptotic activity of MYR was demonstrated by a marked rise in Bcl-2-associated X protein (BAX)/B cell lymphoma-2 (Bcl-2) ratio by lowering Bcl-2 while increasing BAX levels. In addition, MYR treatment significantly boosted the expression of SIRT1 deacetylase in RSP-treated animals. Interestingly, molecular docking showed the ability of MYR to form a stable complex in the binding site of SIRT1. Regarding miRNAs, MYR effectively ameliorated RSP-induced changes in miR-320 and miR-107 gene expressions. ConclusionOur findings afford new insights into the anti-nociceptive profile of MYR in the RSP-induced FM model in rats. The underlying mechanisms involved direct binding and activation of SIRT1 to influence different signaling cascades, including Nrf2 and NF-κB/NLRP3 together with modulation of miRNAs. However, more in-depth studies are needed before proposing MYR as a new clinically relevant drug in the management of FM.

Targeting TRPV1 signaling: Galangin improves ethanol-induced gastric mucosal injury

Galangin, a bioactive compound extracted from Alpinia officinarum Hance (Zingiberaceae), a plant with significant ethnopharmacological importance, has been used for thousands of years as a spice, condiment, and medicinal agent for various conditions, including gastrointestinal disorders. Although there is evidence suggesting its potential to improve gastric ulcers, the molecular mechanisms underlying its anti-ulcer properties are not fully understood. of the Study: This study aimed to investigate the effects of galangin on ethanol-induced acute gastric mucosal injury (AGMI) in mice and elucidate its molecular mechanisms. Sixty BALB/c mice were randomly assigned into two main groups: a normal control group (n=10) and an ethanol-induced group (n=50). After establishing the AGMI model in mice using a combination of 40% ethanol and anhydrous ethanol, the ethanol-induced group was further subdivided into five subgroups (n=10): an omeprazole control group (20mg/kg), an untreated ethanol group, and three treatment groups receiving high-dose (50mg/kg) or low-dose (25mg/kg) galangin or capsazepine (CPZ, 2mg/kg). The protective effects of galangin were evaluated through mucosal injury indices, hematoxylin and eosin staining, and quantification of inflammatory markers (IL-1β, IL-6, IL-8, and TNF-α). Oxidative stress levels and matrix metalloproteinase activity were measured using specific assay kits. Molecular docking was conducted to assess the binding affinity of galangin to key proteins within the transient receptor potential vanilloid 1 (TRPV1) pathway. Real-time fluorescence quantitative PCR (qPCR) was used to determine mRNA expression levels of TRPV1, calmodulin (CaM), substance P (SP), and CGRP in gastric tissues. Protein expression levels of TRPV1, nerve growth factor (NGF), tropomyosin receptor kinase A (TRKA), transforming growth factor beta (TGF-β), cyclooxygenase-2 (COX-2), and nuclear factor kappa B (NF-κB) were assessed through Western blot analysis. In cellular experiments, Culture of Human Gastric Epithelial Cells (GES-1) were treated with various concentrations of galangin after 7% ethanol induction. Cell proliferation, apoptosis, and migration were evaluated using Hoechst 33258 staining and transwell migration assays. TRPV1 protein expression was detected using immunofluorescence, and the expression levels of Bcl-2, BCL2-Associated X (BAX), and Caspase-3 were quantified by qPCR. Additionally, specific probe kits were used to measure intracellular calcium ions (Ca2+) and mitochondrial membrane potential. The findings indicate that galangin significantly improved mucosal pathology by reducing ulcer indices and inflammatory levels, while enhancing superoxide dismutase (SOD) activity and decreasing malondialdehyde (MDA) concentration. Galangin also reduced matrix metalloproteinase-2 (MMP-2), m metalloproteinase-9 (MMP-9) levels, promoting mucosal repair. At the cellular level, galangin decreased intracellular calcium ion concentration and mitigated the decline in mitochondrial membrane potential, enhance the restoration of mucosal cells, increased migration and proliferation, and reduced apoptosis. Molecularly, galangin demonstrated favorable binding to TRPV1, NGF, TRKA, TGF-β, COX-2, and NF-κB, and reversed the elevated expression of these proteins. Additionally, galangin downregulated the mRNA expression of TRPV1, CaM, SP, CGRP, BAX, and Caspase-3 in gastric tissues/cells, while upregulating Bcl-2 mRNA expression. Galangin mitigates AGMI by inhibiting the overactivation of the TRPV1 pathway, thereby blocking aberrant signal transduction. This study suggests that galangin has therapeutic potential against ethanol-induced AGMI and may be a viable alternative for the treatment of alcohol-induced gastric mucosal injuries.

Protium heptaphyllum essential oil from the fruit as a sedative and anesthetic in Rhamdia quelen: influence in cardiac frequency, biochemical, and oxidative parameters.

This study aimed to evaluate the effects of Protium heptaphyllum fruit essential oil (PHEO) on the physiology of silver catfish (Rhamdia quelen) during anesthesia and recovery, through studying echocardiograms, oxidative status, and metabolic parameters. Three experiments were performed: (1) 50 silver catfish juveniles were submitted to anesthesia and recovery tests with 300, 400, 500, 600, and 700mg L-1 of PHEO. (2) Echocardiogram analysis was performed in anesthetized and non-anesthetized fish. (3) Biochemical parameters were evaluated at 0, 30, 60, and 120min of recovery after being anesthetized for 3min with 600mg L-1 PHEO. Times to sedation and deep anesthesia were reduced with PHEO increasing concentrations. The echocardiogram showed a higher cardiac rate in anesthetized fish. Plasma glucose levels increased in control fish through recovery time, but anesthetized fish showed lower levels than controls at 120min of recovery. Metabolic parameters such as plasma and hepatic glucose did not show changes considering the recovery time of up to 120min. Hepatic glycogen, lactate, and triglycerides reduced their levels over recovery times. Fish anesthetized enhanced superoxide dismutase activity and thiobarbituric acid reactive substances levels but decreased reduced glutathione (GSH) levels at 30min compared to controls. After 60min, GSH values were significantly higher in anesthetized fish than in controls. These results suggest that PHEO at 600mg L-1 is an effective anesthetic for the rapid handling of silver catfish, providing stable metabolic parameters and enhanced antioxidant responses during recovery. Echocardiogram analysis confirms the anesthetic effect, supporting PHEO as a viable and efficient option for fish anesthesia in aquaculture. The use of PHEO in aquaculture can enhance fish welfare by reducing stress during handling and transportation, potentially leading to improved growth, health, and survival rates.

A Se Nanoparticle/MgFe-LDH Composite Nanosheet as a Multifunctional Platform for Osteosarcoma Eradication, Antibacterial and Bone Reconstruction.

Despite advances in treating osteosarcoma, postoperative tumor recurrence, periprosthetic infection, and critical bone defects remain critical concerns. Herein, the growth of selenium nanoparticles (SeNPs) onto MgFe-LDH nanosheets (LDH) is reported to develop a multifunctional nanocomposite (LDH/Se) and further modification of the nanocomposite on a bioactive glass scaffold (BGS) to obtain a versatile platform (BGS@LDH/Se) for comprehensive postoperative osteosarcoma management. The uniform dispersion of negatively charged SeNPs on the LDH surface restrains toxicity-inducing aggregation and inactivation, thus enhancing superoxide dismutase (SOD) activation and superoxide anion radical (·O2 -)-H2O2 conversion. Meanwhile, Fe3+ within the LDH nanosheets can be reduced to Fe2+ by depleting glutathione (GSH) in the tumor microenvironments (TME), which can catalyze H2O2 into highly toxic reactive oxygen species. More importantly, incorporating SeNPs significantly promotes the anti-bacterial and osteogenic properties of BGS@LDH/Se. Thus, the developed BGS@LDH/Se platform can simultaneously inhibit tumor recurrence and periprosthetic infection as well as promote bone regeneration, thus holding great potential for postoperative "one-stop-shop" management of patients who need osteosarcoma resection and scaffold implantation.

Purple sweet potato antioxidants for oxidative stress caused by intense physical exercise

Background: Intense exercise increases ROS and reactive nitrogen species, leading to oxidative stress and potential health issues. Balancing free radical production and antioxidant defence is crucial. Endogenous antioxidants help neutralise ROS, but additional supplementation is required to prevent cell damage. Objective: This literature review explores the potential of purple sweet potato (Ipomoea batatas L.) as an antioxidant source to counteract exercise-induced oxidative stress. Method: Scientific articles from various platforms were collected using keywords such as "Physical exercise," "Oxidative stress," "Purple sweet potato," and "Antioxidant”. Result: Purple sweet potato, rich in anthocyanins and vitamin C, exhibits potent free radical scavenging properties. Consumption of purple sweet potato enhances superoxide dismutase (SOD) levels, reduces lipid peroxidation (MDA), inhibits the NF-kB signalling pathway, and prevents increased heat shock protein 72 (HSP72) expression. These findings suggest that purple sweet potato consumption promotes cellular health and mitigates oxidative stress caused by intense physical exercise. Conclusion: In conclusion, incorporating purple sweet potato into the diet shows promise in countering exercise-induced oxidative stress, promoting overall well-being, and preventing chronic diseases. Further research is needed to fully understand the mechanisms and optimal dosage for combating oxidative stress during rigorous physical training.

Repeated Sulforaphane Treatment Reverses Depressive-like Behavior and Exerts Antioxidant Effects in the Olfactory Bulbectomy Model in Mice.

Growing evidence suggests that activators of nuclear factor erythroid-derived 2-like 2 (Nrf2), such as sulforaphane, may represent promising novel pharmacological targets for conditions related to oxidative stress, including depressive disorder. Therefore, we conducted a study to explore the behavioral and biochemical effects of repeated (14 days) sulforaphane (SFN) treatment in the olfactory bulbectomy (OB) animal model of depression. An open field test (OFT), splash test (ST), and spontaneous locomotor activity test (LA) were used to assess changes in depressive-like behavior and the potential antidepressant-like activity of SFN. The OB model induced hyperactivity in mice during the OFT and LA as well as a temporary loss of self-care and motivation in the ST. The repeated administration of SFN (10 mg/kg) effectively reversed these behavioral changes in OB mice across all tests. Additionally, a biochemical analysis revealed that SFN (10 mg/kg) increased the total antioxidant capacity in the frontal cortex and serum of the OB model. Furthermore, SFN (10 mg/kg) significantly enhanced superoxide dismutase activity in the serum of OB mice. Overall, the present study is the first to demonstrate the antidepressant-like effects of repeated SFN (10 mg/kg) treatment in the OB model and indicates that these benefits may be linked to improved oxidative status.