CAT Activity Research Articles

Antioxidant and Immunological Properties of Dracocephalum moldavica Extract in Penaeus vannamei

Objectives: The effects of different concentrations of Dracocephalum moldavica extract (DME) supplement on growth, survival, antioxidants, some biochemical parameters and innate immunity of White leg shrimp (Penaeus vannamei) juveniles investigated. Methods: For 56 days, shrimp (4.5-5 g) received diets that were enhanced with 0 (control), 50, 100, 200 mg DME/kg feed to attain apparent satiety. Results: The results revealed that feeding shrimp with DME significantly improved Feed efficiency and Feed conversion ratio with an optimum level of 200 mg/kg diet. Dietary DME supplementation had no significant effects on their carcass composition. Total albumin and protein higher (P > 0.05) in DME-fed particularly at 200 mg/kg treatment On the other hand, shrimp fed 200 mg DME/kg feed experienced significant decreases in aspartate and alanine aminotransferase levels. As dietary extract levels increased, there was a significant (P < 0.05) increase in SOD and CAT activities, as well as LYZ and PO levels, so that treatments with 100 and 200 mg DME/kg feed had the highest values, and Significant (P < 0.05) reductions in MDA and NO levels were observed at high dietary extract levels of 100 and 200 mg DME/kg. Conclusion: P. vannamei's growth, antioxidant capacity and innate immunity were boosted by diets that contained 200 mg DME/kg feed.

Unpredictable chronic mild stress induced anxio-depressive disorders and enterobacteria dysbiosis: Potential protective effects of Detariummicrocarpum

Ethnopharmacological relevanceDetarium microcarpum Guill. & Perr. is used traditionally in Far North Cameroun to treat stomach aches, anxiety, epilepsy, and other mental disorders. Aim of the studyEvaluate the anxiolytic and antidepressant-like effects of D. microcarpum (DM) in unpredictable chronic mild stress (UCMS) model of depression in male rats and its impact on fecal enterobacteria of stressed rats. Materials and methodsRats were handled daily (control) or subjected to the UCMS procedure for 42 days. Anxiety-like behaviors were assessed using the light and dark box test (LBD) and the open field test (OFT). Depressive-like behaviors were assessed using the forced swimming test (FST), the sucrose preference test (SPT), and the novelty suppressed feeding test (NSFT). Feces were then collected, followed by blood, brain, and duodenum sections after sacrifice. Monoamine levels, pro-inflammatory cytokines, oxidative stress factors, and nitrosative stress were assessed. Feces were introduced into Hectoen enteric agar for the identification of enterobacteria. An in vitro growth test was performed. ResultsThe DM ethanolic extract has significantly increased the time spent in the light box, in the LBD, and in the center area of the OFT. Moreover, the extract has significantly reduced the preference for sucrose in the SPT, the time of immobility in the FST, and the latency period to consume the pet in the NSFT. DM extract has significantly reduced serum cortisol levels. It also significantly decreased the pro-inflammatory cytokines TNF-α and Il-1β in both brain and duodenum homogenate. DM has increased the brain's serotonin, GABA, and dopamine levels. The DM extract also decreased the MDA and nitrite levels. It also increased the SOD and CAT activities in both brain and duodenal homogenate. Histologically, the DM extract restored the cell's density in hippocampi sections and prevented gut inflammation and peroxidation characterizing leaky gut syndrome. DM extract has no effect on the growth of enterobacteria species isolated in vitro. ConclusionThe ethanolic extract of DM would have anxiolytic and antidepressant effects via the modulation of the HPA axis, brain antioxidant enzyme activities, inflammation, and nitrosative stress. Moreover, it could act by preventing leaky gut syndrome.

Cognitive-Enhancing Effect of Marine Brown Algae-Derived Phenolics through S100B Inhibition and Antioxidant Activity in the Rat Model of Ischemic Stroke.

Cognitive impairments are frequently reported after ischemic strokes. Novel and effective treatments are required. This study aimed to develop a functional ingredient obtained from marine algae and to determine the effect of the extract on antioxidative stress, as well as neuroprotective effects, in a rat model of MCAO-induced ischemic stroke. Among the selected marine algal extracts, Sargassum polycystum displayed the highest total phenolic content and antioxidative potential, and was subsequently used to evaluate cognitive function in rat models of ischemic stroke. The S. polycystum extract, administered at doses of 100, 300, and 500 mg/kg BW, significantly improved cognitive function by enhancing cognitive performance in the Morris water maze and novel object recognition tests. Biochemical changes revealed that providing S. polycystum increased the activities of SOD, CAT, and GSH-Px by 52.48%, 50.77%, and 66.20%, respectively, and decreased the concentrations of MDA by 51.58% and S100B by 36.64% compared to the vehicle group. These findings suggest that S. polycystum extract may mitigate cognitive impairment in ischemic stroke by reducing oxidative stress and inhibiting S100B expression, thus highlighting its potential as a functional ingredient for drugs and nutraceuticals aimed at neuroprotection.

Reno-protective potential of poncirin against polyethylene microplastics instigated kidney damage in rats via regulating Nrf-2/Keap-1 pathway

Polyethylene microplastics (PEMPs) are noxious environmental pollutants that are documented to cause organ damage including the kidneys. Poncirin (PON) is a naturally occurring flavonoid which demonstrates a wide range of pharmacological properties. This experiment was conducted to evaluate the palliative potential of PON against PEMPs by examining a range of biochemical and physiological parameters. Twenty-four male albino rats were randomly apportioned into four distinct groups including the control, PEMPs (1.5 mgkg−1), PEMPs (1.5 mgkg−1) + PON (20 mgkg−1) & only PON (20 mgkg−1). Our results displayed that PEMPs intoxication escalated the levels of urea, KIM-1, creatinine & NGAL while demising the creatinine clearance level. Besides reduction in the activities of GPx, GST, HO-1, CAT, GSR & upsurge in the levels of MDA and ROS were detected in PEMPs group. Conversely, the levels of inflammatory markers including COX-2, IL-1β, NF-kB and TNF-α were augmented following the PEMPs intoxication. Besides, the results of current research demonstrated that levels of Bax & caspase-3 were more than normal whereas the Bcl-2 expression was lowered from its standard value due to PEMPs provision. However, PON treatment significantly restored the PEMPs-induced biochemical impairments. Therefore, PON could be used as a therapeutic compound to ameliorate PEMPs-induced kidney impairments in rats, possibly due to its tremendous pharmacotherapeutic potential.

PAT exposure caused human hepatocytes apoptosis and induced mice subacute liver injury by activating oxidative stress and the ERS-associated PERK pathway

With the widespread use of antimony compounds in synthetic materials and processing, the occupational exposure and environmental pollution caused by antimony have attracted the attention of researchers. Studies have shown that antimony compounds can cause liver damage, but the mechanism has not yet been elucidated. In this study, we used the trivalent potassium antimony tartrate (PAT) to infect L02 hepatocytes and Kunming (KM) mice to establish an antimony-induced apoptosis model of L02 cells and a subacute liver injury model of KM mice. We found that PAT exposure caused hepatocyte apoptosis and was accompanied by oxidative stress and endoplasmic reticulum stress (ERS), and the ERS-associated PERK pathway was activated. Further experimental results showed that N-acetyl-l-cysteine (NAC) pretreatment or silencing of the PERK gene in L02 cells reduced PAT-induced apoptosis. The activity of SOD and CAT in treated L02 cells was increased, the malondialdehyde content in L02 cells and liver tissues was decreased, and the content of ERS-related proteins GRP78 and CHOP, as well as the content of PERK-pathway-related proteins p-PERK/PERK, p-eif2α/eif2α and ATF4 protein were significantly reduced. Overall, PAT exposure triggered hepatocyte apoptosis and liver injury by inducing oxidative stress and activating the ERS-associated PERK pathway; however, this effect could be alleviated by NAC intervention or silencing of PERK in hepatocytes.

The effects of Selenium phytotoxicity on two wheat (Triticum aestivum) cultivars differing in Se tolerance and the role of antioxidant enzymes in the tolerance mechanism

Abstract Wheat seedlings were hydroponically grown in Hoagland solution containing various levels of Se. Tolerance response to Se toxicity was investigated by determining the level of thiobarbituric acid reactive substance (TBARS), proline and chlorophyll content, the growth parameters, and the activity of antioxidant enzymes. The toxic level of Se treatment significantly retarded the seedling growth. A substantial amount of proline accumulation was also observed in response to toxic Se concentration, but it was more pronounced in putative-sensitive cultivars. Chlorophyll content significantly decreased in Se-intoxicated seedlings and increased at the lowest Se dose in both cultivars. Severe and mild chlorosis was observed in putative-sensitive and tolerant cultivars at the highest Se level. Alterations in the activities of glutathione reductase (GR, 1.6.4.2), glutathione S transferase (GST, 2.5.1.18), guaiacol peroxidase (GPX, 1.11.1.7), catalase (CAT, 1.11.1.6), and ascorbate peroxidase (APX, 1.11.1.11) and superoxide dismutase (SOD, EC 1.15.1.1) were determined. TBAR level did not significantly increase in putative tolerant cultivars as an indicator of membrane lipid peroxidation. However, a significant increase was observed in putative-sensitive cultivars in response to higher selenium concentrations. In higher Se treatment groups, CAT and GST activities significantly increased in putative Se tolerant cultivars. However, excluding SOD, the activity of all the studied enzymes was increased considerably in putative-sensitive cultivars in a dose-dependent manner. Higher antioxidant enzyme activities and a substantial amount of proline accumulation did not significantly contribute to overcoming Se phytotoxicity in wheat seedlings grown in media supplemented with toxic selenium levels.

Chromium uptake and its impact on antioxidant level, photosynthetic machinery, and related gene expression in Brassica napus cultivars.

The development of heavy metals, particularly chromium (Cr)-tolerant crop cultivars, is hampered due to lack of understanding of the mechanisms behind Cr stress tolerance. In this study, two Brassica napus cultivars, ZS758 and ZD622, were compared for Cr stress resistance by using the chlorophyll a fluorescence technique and biochemical characteristics. In both cultivars, Cr stress dramatically decreased PSII and PSI efficiency, biomass accumulation, and antioxidant enzyme levels. Although, cultivar ZS758 showed reduction in oxidative stress by decreasing the production of reactive oxygen species (ROS) in terms of reduced H2O2 and MDA content and increased enzymatic activities of key antioxidants enzymes including SOD, APX, CAT, and POD activities that play a crucial role in the regulation of numerous transcriptional pathways involved in oxidative stress responses. Higher non-photochemical quenching (NPQ) and QY were found in tolerant ZS758 cultivar under Cr stress, indicating that tolerant cultivar had a greater capacity to preserve PSII activity under Cr stress by enhancing heat dissipation as a photo-protective component of NPQ. Lower PSI activity and electron transfer from PSII were confirmed by lower PSI efficiency and higher donor end limitation of PSI in both rapeseed cultivars. The Cr concentration was greater in the ZD622 as compared to ZS758, which affected the mineral nutrients profile and damaged the cellular ultrastructure and related gene expression levels. However, current study suggest that cultivar ZS758 is more resistant to Cr stress than ZD622 due to improved metabolism and structural integrity and Cr stress tolerance that is linked with the increased PSII activity, NPQ, and antioxidant potential; these physiological characteristics can be exploited to select cultivars for Cr stress tolerance.

The transcription factor ZmNAC84 increases maize salt tolerance by regulating ZmCAT1 expression

Salt stress severely affects plant growth and yield. The transcription factor NAC plays a variety of important roles in plant abiotic stress, but we know relatively little about the specific molecular mechanisms of NAC in antioxidant defense. Here, our genetic studies reveal the positive regulation of salt tolerance in maize by the transcription factor ZmNAC84. Under salt stress, overexpression of ZmNAC84 in maize increased the expression of ZmCAT1, enhanced CAT activity, and consequently reduced H2O2 accumulation, thereby improving salt stress tolerance in maize. Whereas RNA interference-mediated knockdown of ZmNAC84 produced the opposite effect. Subsequently, we found that ZmNAC84 directly binds to and regulates the expression of the ZmCAT1 promoter, and the hybridized material also demonstrated that ZmCAT1 is a downstream target gene of ZmNAC84. In addition, phenotypic and biochemical analyses indicated that ZmCAT1 positively regulated salt tolerance by regulating H2O2 accumulation under salt stress. Taken together, these results reveal the function of ZmNAC84 in regulating ZmCAT1-mediated antioxidant defense in response to salt stress in plants.

Protective Effect of Chlorogenic Acid Against Testicular Damage Induced By Glyphosate Isopropilamine in Rats

The aim of this subchronic toxicity study was to determine the prophylactic effect of chlorogenic acid (CGA) on the histopathologic-histologic changes and oxidative stress induced by Glyphosate isopropylamine (GLF-ISO) in testicular tissues. A sum of 42 male Wistar rats were divided into six equal groups, each containing 7 rats. For pretreatment, rats were given CGA at doses of 12.5, 25 and 50 mg/kg (po) and GLF-ISO at 787.85 mg/kg (po) for 7 weeks. GLF-ISO significantly increased malondialdehyde levels while decreasing SOD and CAT activities and GSH levels in testicular tissues. On the contrary, these parameters were improved in CGA-treated groups. Furthermore, CGA ameliorated the histopathological and histological changes in testicular tissues induced by GLF-ISO in a dose-dependent manner. The results indicate that testicular damage caused by GLF-ISO can potentially be prevented or managed by CGA.

Effect of Synthetic Wastewater on Antioxidant Defence System in Dreissena polymorpha

The effects of the synthetic wastewater on antioxidant defence system in Dreissena polymorpha evaluated. For this purpose, SOD, CAT, GPX activities and TBARS and GSH levels in tissues were determined by using commercial kits. The activities of SOD and CAT were in sythtetic group were determined lower than the control group in D. polymorpha during 24 and 96 h (p

Adaptive strategies in architecture and allocation for the asymmetric growth of camphor tree (Cinnamomum camphora L.)

The stability-related asymmetry in roots, trunk, and crown is always found as a typical effect of biomechanical design under heterogeneous stimulus environment. However, it appears to be a conflict between the biomechanical principle and the source-sink distance of nutrient allocation strategies when the orientational asymmetry occurs. Adaptive growth strategies associated with biomass and nutrient allocation remain to be explored. This study used both the minirhizotron and harvest methods to test the effect of trunk inclination of camphor trees (Cinnamomum camphora) and found that the asymmetry coefficient of root biomass was − 0.29, showing more root biomass distributed on the other side of trunk inclination. This side had larger surface area and volume of fine roots, the smaller in diameter and the larger in length of the first level roots, higher leaf total nitrogen (TN) and slightly higher root TN content, higher activities of antioxidant enzymes SOD, POD, and CAT in leaves, and lower soluble sugar and protein. The biomass, morphological and physiological characteristics suggest that trees may follow both the biomechanical design and source-sink distance of nutrient allocation strategies. The research results expand the connotation of root-shoot balance in the orientational allocation of biomass and physiological responses.

Artemisia Argyi essential oil ameliorates acetaminophen-induced hepatotoxicity via CYP2E1 and γ-glutamyl cycle reprogramming

BackgroundThe hepatotoxicity induced by acetaminophen (APAP), a commonly used antipyretic, analgesic and anti-inflammatory drug in clinical practice, has received accumulated attention. Artemisia argyi essential oil (AAEO), a volatile oil component extracted from traditional Chinese medicine Artemisia argyi H.Lév. & Vaniot, has great hepatoprotective effects. However, the potential role of AAEO in APAP-induced hepatotoxicity has not been characterized. The present study aimed to investigate the effects of AAEO on hepatic metabolic changes in mice exposed to APAP. MethodsIn this study, 300.00 mg/kg acetaminophen was used to establish liver injury model in C57BL/6 J mice. Hepatoprotective effect of AAEO on APAP-induced hepatotoxicity in mice was investigated by detecting liver function enzymes and histopathological examination. Secondly, UPLC-MS/MS was used to analyze the to analyze the small molecule metabolites and metabolic pathways induced by AAEO treatment; In addition, the effect of AAEO on APAP-induced oxidative stress and inflammation were evaluated by detecting the levels of glutathione peroxidase 4, malondialdehyde, reactive oxygen species and inflammatory factors. Finally, the active components of AAEO were preliminarily screened by cellular assays. The hepatoprotective effect of AAEO against APAP-induced hepatotoxicity was examined through the Western blotting, after the CYP2E1 gene was knocked down in AML12 cells by siRNA transfection. ResultsCompared with the APAP group, AAEO could reduce the abnormal increase in the levels of liver function enzymes caused by APAP. AAEO could enhance the antioxidant capacity by down-regulating the biosynthesis pathway of unsaturated fatty acids and promoting the activity of antioxidant enzymes SOD and CAT in liver tissue induced by APAP. Our study revealed that AAEO promoted GSH synthesis and covalently combined to form APAP-GSH conjugates to reduce the accumulation of APAP in liver tissue. In addition, the chemical constituents in AAEO were analyzed by GC–MS/MS, and it was determined to identify that dihydro-beta-ionone and (-)-verbenone in AAEO might have a significant protective effect on hepatocyte survival after APAP exposure. Further studies on the hepatoprotective mechanism of AAEO indicated that it might reduce the production of toxic metabolites by regulating CYP2E1 levels. ConclusionAAEO exerted hepatoprotective effects on acetaminophen-induced hepatotoxicity in mice via regulating the activity of CYP2E1 and regulating the γ-glutamyl cycle pathway.

Effects of Selenium, Iron, and Zinc Enrichment on Cultured Sea Cucumber (Apostichopus Japonicus).

Selenium, iron, and zinc (Se, Fe, Zn) are essential trace elements crucial for animal growth, development, and immune protection, but they can be detrimental in excess. This study evaluates the impacts of Se, Fe and Zn on Apostichopus japonicus over a period of nine days, utilizing concentrations ranging from low to high: Se (0.20 µmol/L and 0.82 µmol/L), Fe (4.74 µmol/L and 18.96 µmol/L), Zn (1.88 µmol/L and 7.51 µmol/L). Concentrations of these trace elements in sea cucumbers increased with exposure time. Activities of CAT, SOD, and GSH-PX enzymes were enhanced. Transcriptomic analyses of sea cucumber body wall revealed significant gene expression changes, with differentially expressed genes (DEGs) numbering 294 at high and 945 at low Se concentrations, 906 at high and 210 at low Fe concentrations, and 423 at high and 123 at low Zn concentrations. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses highlighted DEGs enrichment in critical metabolic and immune-related pathways, including DNA replication, arachidonic acid metabolism, and oxidative phosphorylation. These results suggest that energy metabolism and immune regulation are pivotal in managing these elements, potentially enhancing sea cucumber immunity. This study enhances our comprehension of the physiological responses of sea cucumbers to trace elements and provides a theoretical basis for their use in aquaculture.

Herbicide paraquat dichloride augments the expression of the c-abl-noxa-apoptotic pathway, instigating ovarian atresia in edible fish, Channa punctatus.

Ovarian cells of animals undergo atresia to regulate egg numbers and their release. However, unrestrained atretic activity decreases the chances of oocyte maturity and further process, ultimately resulting in a reduced population. Edible fishes are a critical source of nutrition and it is required to regulate their population. The application of herbicides at fish production sites is a threat to their population by altering female reproductive activity. In concern to this, here, this 60-day study investigates herbicide paraquat dichloride (PD)-induced atresia in ovarian cells of Channa punctatus (C. punctatus). Further, 96-h LC50 of PD for C. punctatus was calculated as 58.40mg/L. At the end of each exposure period, an increase in intracellular ROS in blood cells and activities of SOD and CAT in ovary tissue were observed in PD-treated fish with increasing concentration. The frequency of micronuclei in blood cells subsequently increased with the highest PD concentration. A significant (p < 0.05) increase in the relative expression of target genes was observed at the 30th and 60th day of the sampling periods in the fish treated with the highest concentration of PD. The histological study confirmed the occurrence of atretic ovary cells in PD-exposed fish. From the results it can be concluded that PD enhances the uncontrolled death of ovarian cells and has consequences of impairing the ovary health and reproductive potential of fish, hence reducing the fish population.

Metabolomic Changes Associated with AGXT2 Genotype Variants and Stone Formation in a Colony of Cats.

The objective of this study was to assess serum chemistries and metabolomic parameters in cats with genetic variants of the alanine-glyoxylate aminotransferase 2 (AGXT2) gene to determine abnormalities associated with urolith formation and better understand effective approaches for the treatment of cats with uroliths. AGXT2 genotypes of 445 cats in the colony at Hill's Pet Nutrition, Inc. (Topeka, KS, USA) were assessed in a genome-wide association study. Additionally, the serum chemistries and metabolic profiles of each cat were determined, along with their lifetime history of stone incidence. Factor analysis was used as a data-reduction method for metabolites in order to perform statistical hypothesis testing and to select significant metabolites from the more than 600 serum metabolites identified. Of the 82 cats forming stones in the colony (18.4%), the majority were calcium oxalate. Results showed that approximately one third of the cats with the AA variant of the AGXT2 gene have stones, that chronic kidney disease (CKD) is more common in cats with stones, and that having stones results in a shorter lifespan. A discriminant variable selection process was performed to determine the complete blood count, serum biochemistries, and serum metabolomic factors that best discriminated among the three genotypes (AA, AG, GG) and between cats forming stones and non-stone formers. Several of the highly ranked discriminating factors included metabolites related to decreased aminotransferase activity in cats with the AA variant of the AGXT2 gene. Another factor that ranked highly for discriminating between stone formers and non-stone formers contained lipid metabolites, consisting of multiple sphingomyelin species and cholesterol. These findings support the results of feeding studies in cats, whereby CKD cats fed food supplemented with betaine and prebiotics have experienced an increase in total body mass, reduced uremic toxins, and altered sphingomyelin concentrations.

Overexpression of TdNACB improves the drought resistance of rice

Drought stress greatly affects disrupts the productivity, ecological structure, physiological and biochemical activities of wheat at different growth stages. However, drought stress tolerance is a complex quantitative trait and involves multiple metabolic pathways. We found that a wild emmer introgression line BAd7-209 had stronger drought resistance compared with drought resistant wheat Zhongmai 175. The transcriptome analysis found 14,284, 22,383 and 21,451 genes had expression corresponding responsed to drought stress at 24h, 48h, 120h, respectively and significantly enriched in ‘Arginine and proline metabolism’ and ‘Peroxisome’ in BAd7-209. 1666 transcription factors (TFs) related responsed to drought stress in which TdNACB showed high expression at 24h, 48h and 120h and had the closest relationship with TaNAC48 and OsNAC6 in phylogenetic analysis. Overexpression of TdNACB significantly enhanced drought resistance in rice and overexpression lines had significantly higher CAT, POD and SOD activity, Pro content and lower MDA content than those of the WT under drought stress. The result demonstrated that TdNACB positively regulates drought resistance through increasing proline content and enhancing activity of enzyme related to ROS scavenging. The results of this study provides candidate genes for improving wheat drought resistance and guide as reference for studying the molecular mechanisms of wheat drought resistance.

Foliar application of silicon and selenium reduce the toxicity of cadmium to soybeans

Silicon (Si) and selenium (Se), two environmental protection materials, which are beneficial to plant growth and stress resistance, can also alleviate crop stress induced by heavy metals. However, the effects of Si, Se and their interactions in reducing cadmium (Cd) toxicity and the related mechanisms require further elucidation. Hence, this study implemented a foliar application of Si and Se on soybean (Glycine max L.) that subjected to Cd-induced stress with four treatments (sole/combined application of Si, Se, no fertilizer treatment). The results demonstrated that Si and Se showed effective mitigation of Cd toxicity on soybeans mainly by promoting growth, enhancing photosynthesis, maintaining root vigor, improving antioxidant capacity, alleviating oxidative damage, altering the storage form, subcellular distribution of Cd in soybeans, and was more noticeable when combined overall (Si + Se＞Se＞Si). Si + Se increased root activity by 28% and CAT activity in leaves by 130.65%. Overall, the combined application of Si and Se exhibited a pronounced synergistic effect in enhancing the healthy growth of soybean plants under Cd pollution, with a more prominent impact observed following the second fertilization.

Thymoquinone Abrogates Acrylamide-Induced Cerebellar Toxicity via Modulation of Nuclear Factor Erythroid 2-Related Factor 2/Nuclear Factor Kappa B Signaling, Oxidative Neuroinflammation, and Neuroapoptosis in Rats.

Acrylamide (ACR) is an obligate human neurotoxicant ubiquitously produced and found in foods processed at high temperature. There is an increasing public health concern regarding its probable carcinogenic potential. Its prevailing toxicity mechanism is oxidative inflammation and apoptosis. Herein, we explored whether thymoquinone (TQ), a bioactive quinone in Nigella sativa seed, could mitigate ACR-induced cerebellar toxicity in rats. Our study design featured four rat groups: control, TQ (5 mg/kg bw), ACR (50 mg/kg bw), and TQ + ACR (5 mg/kg + 50 mg/kg). After 14 days of respective treatments, cerebellar homogenate was used to estimate acetylcholinesterase activity (AchE) activity, antioxidant enzymes (catalase [CAT], superoxide dismutase [SOD], and glutathione peroxidase [GPx]), malondialdehyde (MDA), inflammatory cytokines (interleukin [IL]-6, tumor necrosis factor [TNF]-α, IL-4, and IL-10), nuclear factor kappa B (NF-κB), nuclear factor erythroid 2-related factor 2 (Nrf2), caspase-3, and caspase-9. The level of DNA damage by fragmentation and histopathological lesions was also determined in the cerebellum. The rat exposure to ACR caused significant decreases in the cerebellar activities of AchE, CAT, SOD, and GPx, IL-4, IL-10, and expression of Nrf2, whereas the levels of MDA, IL-6, TNF-α, caspase-3, and caspase-9 were prominently increased compared with the control. ACR induced significant DNA fragments and cerebellar lesions when compared with the control. Contrarily, TQ treatment inhibited the depression of CAT, SOD, and GPx activities and reversed the MDA level and expression of Nrf2/NF-κB, cytokines, and caspases. These effects were confirmed by reduced DNA damage and cerebellar histopathological lesions in comparison with the ACR. TQ afforded neuroprotection via its antioxidant, anti-inflammatory, and antiapoptotic mechanisms in rats.

Rho4 interacts with BbGDI and is essential for the biocontrol potential of Beauveria bassiana by maintaining intracellular redox homeostasis

Rho4 is a member of the Rho-family small GTPases. In this study, we revealed the function of Rho4 and explored its mechanism involved in intracellular redox homeostasis in Beauveria bassiana, one of the most widely utilized filamentous entomopathogenic fungi. The disruption of Rho4 in B. bassiana resulted in significant phenotypic changes, such as fungal virulence, growth rate on different media, thermotolerance, germination, and conidiation. Integrated analysis of proteomic and transcriptomic data unveiled differential expression patterns of various redox-related genes and proteins in Δrho4, including the down-regulation of GST shown in proteomic and transcriptomic data, and the down-regulated gene expression levels of NOX, SOD, CAT, and GR in the transcriptome. Based on the bi-omics analysis, we focused on the impact of Rho4 in maintaining intracellular redox homeostasis. A decreased ROS content observed in Δrho4 might be attributed to the reduced NOX activity, which subsequently affects the GSH-producing/consuming metabolisms, with the attenuated activities of GR and GST. The imbalanced redox homeostasis also resulted in the reduced enzyme activities of SOD and CAT. Exogenous oxides could partially complement the ROS level and rescue the growth defect in Δrho4 to a certain extent. Besides, BbGDI was initially identified as an interacting protein of Rho4 in entomopathogenic fungi. Our results provide a comprehensive understanding of the function and regulating mechanism of Rho4 in B. bassiana.

Ellagitannin Component Punicalin Ameliorates Cognitive Dysfunction, Oxidative Stress, and Neuroinflammation via the Inhibition of cGAS-STING Signaling in the Brain of an Aging Mouse Model.

Despite remarkable breakthroughs in pharmacotherapy, many potential therapies for aging remain unexplored. Punicalin (PUN), an ellagitannin component, exerts anti-inflammatory, antioxidant, and anti-apoptotic effects. This study investigated the beneficial effects of PUN against age-related brain damage in mice and explored the underlying mechanisms. We validated the protective effects of PUN against D-galactose (D-gal)-induced neuroinflammation and subsequent neuronal damage in BV2 microglia and N2a cells, respectively, in vitro. In vivo experiments were conducted on mice that were administered an 8-week regimen of intraperitoneal injections of D-gal at a dosage of 150 mg/kg/day, concurrently with oral gavage of PUN at the same dose. PUN inhibited the production of D-gal-induced inflammatory cytokines (iNOS, COX2, TNF-α, IL-6, IL-2, and IL-1β) in BV2 cells and conferred protection to N2a cells against synaptic damage mediated by BV2 microglia-induced neuroinflammation. The in vivo findings revealed that PUN considerably improved memory and learning deficits, reduced MDA levels, enhanced GSH-Px, CAT, and SOD activities, and modulated the expression of inflammatory proteins such as iNOS, COX-2, IL-1β, IL-2, IL-6, and TNF-α. Furthermore, PUN inhibited the secretion of SASP factors (ICAM-1, PAI-1, MMP-3, and MMP-9), decreased microglial activation, and reduced astrocytosis. Additionally, PUN suppressed the expression of cGAS, p-STING, p-TBK1, p-p65, and p-IRF3 in aging mouse brains and cultured BV2 microglia. In conclusion, PUN improved cognitive dysfunction in aging mice through antioxidant and anti-inflammatory mechanisms via inhibition of the cGAS-STING pathway, suggesting that it can be a promising therapeutic agent for brain aging and aging-related diseases.