GSH Activity Research Articles

Polysaccharides from Ziziphus jujuba prolong lifespan and attenuate oxidative stress in Caenorhabditis elegans via DAF-16 and SKN-1

Jujube is a commonly consumed traditional Chinese medicine (TCM) food-drug interaction. Recent evidence revealed crude polysaccharides of jujube extract (CPJE) exhibited bioactive properties in vitro; however, its antioxidant capacity in vivo remains unknown. The objectives of this study were to evaluate the effects of CPJE on growth, locomotion, reproduction, lifespan, and antioxidant defense system using Caenorhabditis elegans. Results showed CPJE were not toxic to C. elegans with no effects on bacterial growth. Compared to control, CPJE significantly increased body length and width, head thrashes, body bends, and brood size of nematodes. In addition, CPJE at higher concentrations significantly increased pharyngeal pumping of the nematodes. Moreover, CPJE at 0.25, 0.5, and 1 mg/mL promoted lifespan by 17.9 %, 34.7 % and 46.3 %, respectively. CPJE at higher concentrations reduced level of ROS, increased activities of SOD, CAT, and GSH. CPJE also upregulated the expression of daf-16, skn-1, sod-3, and gcs-1 in N2 nematodes. Meanwhile, results from studies with nematode mutants also suggested that improved stress resistance of CPJE was due to modulation of daf-16 and skn-1. Overall, our results suggest CPJE promote longevity and reduce oxidative stress via DAF-16 and SKN-1. Our findings shed a new light on the utilization of CPJE to attenuate oxidative stress.

Structural characterization and in vitro hepatoprotective activity of an acidic polysaccharide from Dendrobium nobile Lindl. Flower

This study aimed to investigate the structural characterization, conformational properties, and hepatoprotectiveactivity of acidic polysaccharide (DNLPS-3) from Dendrobium nobile flower. DNLPS-3 with molecular weights of 15.65 KDa was composed of Fuc: Rha: Ara: Gal: Glc: Xyl: GalA: GlcA in a molar ratio of 0.26 %: 2.38 %: 4.47 %: 3.55 %: 0.43 %: 17.84 %: 69.80 %: 1.26 %. Structural analysis with methylation indicated that DNLPS-3 mainly contained T-Ara(f), T-Xyl(p), T-Gal(p)A, 3-Gal(p)A, 4-Gal(p)A, 3,4-Gal(p)A, 3,4-Glc(p), 2,4-Gal(p)A, 2,3,4-Gal(p), 4,6-Gal(p), 3,4,6-Gal(p). NMR results show that DNLPS-3 may be a pectin polysaccharide with →4)-α-Gal(p)A-(→main chain. In vitro experiments showed that DNLPS-3 exhibited significant hepatoprotective effects. The effect was achieved by reducing the activities of ALT and AST, suppressing the production of LDH and MDA, and enhancing the anti-oxidant activities of SOD and GSH, and the specific mechanism of its hepatoprotective effect is that DNLPS-3 up-regulates Nrf2/HO-1 pathway protein expression.

Establishment of a cell culture from Daphnia magna as an in vitro model for (eco)toxicology assays: Case study using Bisphenol A as a representative cytotoxic and endocrine disrupting chemical

Bisphenol A (BPA) is a widely used industrial compound found in polycarbonate plastics, epoxy resin, and various polymer materials, leading to its ubiquitous presence in the environment. The toxicity of BPA to aquatic organisms has been well documented following in vivo exposure scenarios, with known cytotoxic and endocrine-disrupting effects. As such, BPA was used in this study as a well-characterized chemical to implement more ethical and resource-efficient scientific practices in toxicity testing through new approach methods (NAMs). Due to the frequent use of Daphnia spp. as a model organism in toxicology, we developed an in vitro cell culture system from Daphnia magna embryos, with optimized medium to support cell longevity. The cultures were maintained for up to two months, demonstrating their stability and suitability for cytotoxicity studies. Using this novel system, lethal concentration 50 (LC50) values were determined at the 24 and 48 h time points following BPA exposure. Subsequently, oxidative stress, endocrine disruption, and DNA damage were assessed through gene expression, activity assays, and a comet assay in BPA-exposed cells. LC50 values of 52 µM and 20 µM BPA were calculated after 24 and 48 h exposures, respectively. BPA cells exposed to 20 and 52 µM had significantly increased GSH, GPx, and GST activity levels. mRNA expression analysis revealed significant upregulations in the mRNA expression of hsp70, hsp90, gst, gpx, vtg1, and cyp4, with downregulations of sod, cat, and ecr following BPA exposure. Furthermore, comet assays showed a significantly higher level of DNA damage induced by BPA compared to controls, with greater comet and tail lengths. This study established a novel in vitro Daphnia model, using BPA as a case study for determining toxic effects, further highlighting the importance and applicability of utilizing alternative methods in ecotoxicological research through reducing animal use.

Neuroprotective role of curcumin on the hippocampus against the oxidative stress and inflammation of streptozotocin-induced diabetes in rats.

In recent years, it has gained importance to determine the effects of diabetes on central nervous system complications. This study aimed to assess the neuroprotective properties of curcumin against neuronal damage in the rat hippocampus caused by diabetes. In accordance with this purpose, we investigated the effects of curcumin on oxidative/antioxidative parameters and pro-inflammatory cytokines in the hippocampal tissue of diabetic Wistar rats. For this purpose, 32 adults, male and healthy Wistar Albino rats were used. Animals were randomly divided into four separate groups: control (C), curcumin(Cu), diabetes (D) and Diabetes + Curcumin (DCu)-treated groups. 60mg/kg STZ i.p. A single dose was administered to D and DCu groups. Cu and DCu groups were given 50mg/kg/day curcumin by gavage. After four weeks of treatment, the animals were decapitated under anesthesia and tissue samples were taken for analyses of the parameters (TNF-α, IL-6, IL-1, IL-10, MDA, SOD, catalase, and GSH activities) in the hippocampal tissue. TNF-α, IL-6, IL-1, and MDA levels were increased significantly (p < 0.05) in rats with diabetes compared to the other three groups. TNF-α, IL-6, IL-1, and MDA levels were lower in DCu group animals compared to the D group. It was determined that IL-10, SOD, Catalase, and GSH levels, which were significantly decreased in the D group, increased in the curcumin-supplemented diabetic group (DCu). The relevant sentence has been changed as follows. In conclusion, our findings from this study prove the protective effect of curcumin against diabetes-induced neuropathy in the hippocampus in rats with STZ-induced diabetes.

Design, synthesis and molecular docking studies of tailored coumarin and chromone derivatives for use as anti-Alzheimer agents

Two new series of coumarin hydrazide and chromone pyrazole derivatives were designed and synthesized to evaluate their in vitro and in vivo anti-Alzheimer activity. All the derivatives were tested for their ability to inhibit cholinesterases. Compound 14 displayed the highest in vitro inhibitory activity against acetylcholinesterase and butyrylcholinesterase with IC50 values of 3.31 µM and 1.60 µM, respectively. The in vivo study revealed the capability of the promising derivative to cause a decline in acetylcholinesterase levels, ameliorate the antioxidative activities of TAC and GSH, decrease the levels of MDA and NO, and down regulate that of MAP-TAU and APP. Moreover, the examination of the AD-brain regions treated with the synthetic compound 14 revealed an improvement of AD histological hallmarks. Molecular modeling of compound 14 demonstrated the interactions of the derivative with the key amino acids in AChE active site. A molecular dynamic simulation and an in silico pharmacokinetic study were conducted as well.

Effect of Matrine on growth performance, gut health, and gut microbiota in chickens infected with avian pathogenic Escherichia coli

Avian pathogenic Escherichia coli (APEC) is a major cause of avian colibacillosis. Matrine, a natural component derived from Sophora flavescens, exhibits various pharmacological effects, including anti-inflammatory and antioxidant activities. However, its role in mitigating APEC-induced intestinal damage in chickens remains insufficiently understood. This study aimed to explore the protective effects and potential mechanisms of matrine against APEC-induced intestinal damage. Chickens were administered matrine (10 or 20 mg/kg) from 6 days old for 5 days, followed by an APEC intraperitoneal injection on day 10. After 72 h of APEC infection, tissues were collected for analysis. Results indicated that pretreatment with matrine alleviated the symptoms of APEC infection in chickens, improving survival rates and promoting weight gain. Additionally, pretreatment with matrine reduced the secretion and gene expression of IL-1β, IL-6, and TNF-α in intestinal tissues, while enhancing serum SOD, GSH, and CAT activity, as well as gene expression levels in the intestine. Pretreatment with matrine reduced the levels of TLR4, MyD88, and NF-κB in intestinal tissues. Moreover, pretreatment with matrine ameliorated intestinal inflammation and pathological damage, restoring the expression of ZO-1, Occludin, and MUC2 in the intestine during APEC infection. Furthermore, pretreatment with matrine alleviated gut microbiota dysbiosis by lowering the abundance of harmful bacteria. In summary, matrine alleviated APEC-induced intestinal inflammation and damage, potentially by inhibiting NF-κB signaling pathway and reshaping the gut microbiota. These findings provide promising insights into the prevention and treatment of avian colibacillosis.

The possible protective effect of luteolin on cardiovascular and hepatic changes in metabolic syndrome rat model.

The metabolic syndrome, or MetS, is currently a global health concern. The anti-inflammatory, anti-proliferative, and antioxidant properties of luteolin are some of its advantageous pharmacological characteristics. This research was designed to establish a MetS rat model and investigate the possible protective effect of luteolin on cardiovascular, hepatic, and metabolic changes in diet-induced metabolic syndrome in rats. Forty adult male albino rats were split into four groups: a negative control group, a group treated with luteolin, a group induced MetS (fed 20% fructose), and a group treated with luteolin (fed 20% fructose and given luteolin). Following the experiment after 8weeks, biochemical, histological (light and electron), and immunohistochemistry analyses were performed on liver and heart tissues. Serum levels of cTnI, CK-MB, and LDH were significantly elevated in response to the cardiovascular effect of MetS. Furthermore, compared to the negative control group, the MetS group showed a marked increase in lipid peroxidation in the cardiac and hepatic tissues, as evidenced by elevated levels of MDA and a decline in the antioxidant defense system, as demonstrated by lower activities of GSH and SOD. The fatty liver-induced group exhibited histological alterations, including disrupted hepatic architecture, dilated and congested central veins, blood sinusoids, and portal veins. In addition to nuclear structural alterations, most hepatocytes displayed varying degrees of cytoplasmic vacuolation, mitochondrial alterations, and endoplasmic reticulum dilatation. These alterations were linked to inflammatory cellular infiltrations, collagen fiber deposition, active hepatic stellate cells, and scattered hypertrophied Kupffer cells, as demonstrated by electron microscopy and validated by immunohistochemical analysis. It is interesting to note that eosinophils were seen between the liver cells and in dilated blood sinusoids. Moreover, the biochemical (hepatic and cardiac) and histological (liver) changes were significantly less severe in luteolin-treated raton a high-fructose diet.These results suggested that luteolin protects against a type of metabolic syndrome that is produced experimentally.

Ascorbic acid regulates in vitro and in vivo toxicogenetic effects of hydroxyurea on eukaryotic cells

Hydroxyurea (HU) exerts unique and diverse biological effects as an anti-leukemic agent, irradiation sensitizer, and HbS inducer in patients with sickle cell anemia. Herein, we assessed the potential toxicogenic and/or oxidant effects of hydroxyurea associated with ascorbic acid by in vivo examinations in Allium cepa and human cancer cells and systemically on mice tissues. Growing A. cepa roots and HCT-116 colorectal tumor cells were examined after HU and HU plus ascorbic acid exposure. DNA damage and antioxidant enzymatic activity were quantified in peripheral blood mononuclear cells (PBMC), bone marrow leukocytes and livers of mice after 7 day-HU treatment (7.5, 15 and 30 mg/kg/day) and Vitamin C 2 μM. Hydroxyurea presented toxic effects on meristematic Allium cepa cells, causing chromosomal abnormalities and reduction of mitotic index, killed HCT-116 colorectal carcinoma cells and induced DNA injuries upon mice cells (hepatocytes, bone marrow leukocytes and PBMC). Simultaneously, hydroxyurea decreased levels of CAT and GSH activities and expand lipid peroxidation. All these biochemical and physiological changes were ameliorated when associated with ascorbic acid, indicating it restored antioxidant enzymes, decreased MDA levels, removed peroxides and, consequently, presented cytoprotection against HU-provoked cellular damage in normal cells. On the other hand, antioxidants compounds may interfere on effectiveness of HU during anticancer chemotherapies.

Bacillus amyloliquefaciens SC06 alleviates LPS-induced intestinal damage by inhibiting endoplasmic reticulum stress and mitochondrial dysfunction in piglets

Endoplasmic reticulum stress (ERS) and mitochondrial dysfunction play an important role in the pathogenesis of intestinal diseases. Our studies investigated the effects of Bacillus amyloliquefaciens SC06 on jejunal mitochondria and ER in piglets under the LPS-induced intestinal injury model. Eighteen piglets (male, 21 days old) were randomly assigned to three treatments: CON (basal diet), LPS (basal diet +100 μg/kg LPS), and SC06 + LPS (basal diet +1 × 108 cfu/kg SC06 + 100 μg/kg LPS). Compared to the LPS group, administration of SC06 improved jejunal morphology and barrier function. In addition, SC06 reduced reactive oxygen species (ROS) and MDA generation in the jejunum by activating the Nrf2/keap1 pathway, which increased the activity of CAT, GSH and SOD in LPS-challenged pigs. In addition, SC06 reduced LPS-induced mitochondrial dysfunction and ERS as evidenced by a decrease in ROS, an improvement in mitochondrial membrane potential and an increase in adenosine triphosphate levels. The results of in vitro IPEC-J2 cell experiments also indicate that SC06 can reduce LPS-induced oxidative stress, mitochondrial dysfunction, ERS, and intestinal barrier function damage by activating the Nrf2/keap1 signaling pathway. Finally, treatment with the Nrf2-specific inhibitor ML-385 inhibited the upregulated effect of SC06 on antioxidant capacity and intestinal barrier function in IPEC-J2 cells. In conclusion, SC06 ameliorated intestinal damage and mitochondrial dysfunction and attenuated endoplasmic reticulum stress via activation of the Nrf2/keap1 signaling pathway in LPS-challenged piglets.

Sulforaphane alleviates acute liver injury induced by diquat in mice by activating Keap1/Nrf2 signaling pathway

To investigate the protective effect and possible mechanism of sulforaphane (SFN) on acute liver injury in mice induced by diquat (DQ) poisoning. Forty-eight male C57BL/6 mice were divided into Control group, DQ model group (DQ group), SFN intervention group (DQ+SFN group), and SFN control group (SFN group) using a random number table method, with 12 mice in each group. Acute liver injury mice model was established by one-time intraperitoneal injection of 1 mL of 40 mg/kg DQ solution at once. SFN group was injected with 1 mL of ddH2O. After 4 hours of molding, 0.5 mL of 5 mg/kg SFN solution was injected into the peritoneal cavity of the DQ+SFN group and SFN group, once daily for 7 consecutive days. DQ group and Control group were injected with an equal amount of ddH2O. Then, the mice were euthanized to collect liver tissue and blood samples, and the levels of plasma biomarkers alanine aminotransferase (ALT) and aspartate aminotransferase (AST), as well as oxidative stress indicators such as superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) in liver tissue were measured. The changes of liver structure were observed under transmission electron microscopy. The apoptosis and reactive oxygen species (ROS) level in liver tissue were observed under fluorescence microscope. Western blotting was used to detect the protein expressions of nuclear factor E2-related factor 2 (Nrf2), hemeoxygenase-1 (HO-1), Kelch-like ECH-associated protein 1 (Keap1), and cleaved caspase-9 in liver tissue. Compared with the Control group, the liver mitochondria in the DQ group showed severe swelling, partial dissolution of the matrix, and cristae rupture and loss; the levels of plasma AST and ALT significantly increased, the MDA content in the liver increased, the activities of SOD and GSH decreased, the level of ROS significantly increased, the number of apoptotic cells in the liver significantly increased, the protein expressions of Nrf2 and HO-1 significantly decreased, and the protein expressions of Keap1 and cleaved caspase-9 significantly increased. Compared with the DQ group, the mitochondrial damage in the DQ+SFN group was reduced, the levels of plasma AST and ALT were significantly reduced [ALT (U/L): 58.22±4.39 vs. 79.94±3.32, AST (U/L): 177.64±8.40 vs. 219.62±11.60, both P < 0.01], the liver MDA content decreased, and the activities of SOD and GSH increased [MDA (μmol/g: 5.63±0.18 vs. 5.96±0.29, SOD (kU/g): 102.05±4.01 vs. 84.34±5.34, GSH (mmol/g): 16.32±1.40 vs. 13.12±1.84, all P < 0.05], the production of ROS in liver tissue was significantly reduced [ROS (fluorescence intensity): 115.90±10.89 vs. 190.70±10.16, P < 0.05], and apoptotic cells were significantly reduced (cell apoptosis index: 4.39±1.00 vs. 10.71±0.56, P < 0.01), the protein expressions of Nrf2 and HO-1 were significantly increased, while the protein expressions of Keap1 and cleaved caspase-9 were significantly decreased (Nrf2/β-actin: 1.15±0.04 vs. 0.93±0.05, HO-1/β-actin: 1.75±0.12 vs. 0.78±0.04, Keap1/β-actin: 1.00±0.14 vs. 1.28±0.13, cleaved caspase-9/β-actin: 1.31±0.12 vs. 1.81±0.09, all P < 0.05). However, there was no statistically significant difference in various indicators between the SFN group and the Control group. SFN can activate the Keap1/Nrf2 signaling pathway to alleviate DQ induced acute liver injury in mice.

Protective Effects of Ascorbic Acid Against Cadmium-Induced Toxicity in the Placenta and Fetus of Rats.

This study aimed to determine the protective role of l-ascorbic acid in a pregnant rat model of cadmium-induced toxicity. Cadmium is a toxic heavy metal that can seriously harm placenta and fetus tissue in pregnant women. Forty-two healthy female Wistar albino rats (250-300 g weight and 14-16 weeks) were randomly distributed into six equal groups (n = 7): control, cadmium 1 mg (CD1), cadmium 5 mg (CD5), ascorbic acid (AA), CD1+AA, CD5+AA. Cadmium was administered to pregnant rats by oral gavage every other day, and/or AA (200 mg) was administered every day. At the end of pregnancy (Day 21), blood, placenta, and fetuses were collected from rats. The results indicated that cadmium-induced oxidative stress by increasing the level of MDA and by decreasing the levels of GSH, SOD, and CAT activity in the serum of maternal. However, AA administration significantly decreased MDA levels and increased GSH levels, SOD, and CAT activity (p < 0.05). Cadmium (5 mg/kg) exposure significantly increased creatinine levels compared to AA and CD1+AA groups (p < 0.05). In addition, AA (200 mg/kg) significantly attenuated cadmium-induced histopathological alteration in the placental and fetal tissues. In conclusion, AA may prevent cadmium toxicity in maternal and fetal tissues, as it regulates oxidative imbalance in pregnant rat tissues and alleviates histopathological changes.

Cardioprotective potential of sakuranetin to counteract polyethylene microplastics induced cardiotoxicity

Polyethylene microplastics (PEMPs) are toxic environmental contaminants which can impair multiple organs including heart. Sakuranetin (SKN) is a potential flavonoid with diverse pharmacological benefits. This research was undertaken to analyze the defensive impact of SKN to avert PEMPs-induced cardiotoxicity. Rats were allocated into 4 separate groups: control, PEMPs (1.5 mg kg−1), PEMPs + SKN (1.5 mg kg−1 + 10 mg kg−1) & only SKN (10 mg kg−1) treated group. After 30 days of treatment, our results revealed that PEMPs exposure reduced Nrf2 & antioxidant genes whereas increased Keap1 expression. Besides PEMPs intoxication escalated the level of cardiac biomarkers (CPK, LDH, Troponin I & CK-MB). Additionally, it lessened the activities of GSH, GST, SOD, HO-1, CAT, GSR, GPx whereas the levels of MDA and OS were increased. Conversely, the levels of inflammatory biomarkers i.e., COX-2 activity IL-1β, TNF-α, NF-kB & IL-6 were augmented. Besides, the expressions of apoptotic biomarkers i.e., Bax & caspase-3 were enhanced while the Bcl-2 expression was decreased. Furthermore, histological analysis indicated substantial cardiac tissue damage. However, SKN treatment significantly restored the PEMPs-induced biochemical as well as histological impairments. Therefore, SKN could be used as a therapeutic compound to ameliorate PEMPs-induced cardiac impairments in rats, possibly due to its tremendous pharmacotherapeutic potential.

Resveratrol improved mitochondrial biogenesis by activating SIRT1/PGC-1α signal pathway in SAP

NLRP3 inflammasomes- pyroptosis axis is activated by microcirculation dysfunction and touched off severe acute pancreatitis (SAP). Activation of PGC-1α can improve microcirculation dysfunction by promoting mitochondrial biogenesis. Resveratrol (RSV), one typical SIRT1 agonist, possesses the ability of alleviating SAP and activing PGC-1α. Therefore, the study was designated to explore whether the protective effect of RSV in SAP was though suppressing NLRP3 inflammasomes- pyroptosis axis via advancing SIRT1/PGC-1α-dependent mitochondrial biogenesis. The models of SAP were induced by treating with sodium taurodeoxycholate in rats and AR42J cells. The pathological injury, water content (dry/wet ratio) and microcirculation function of pancreas, activity of lipase and amylase were used to evaluate pancreatic damage. The expression of inflammatory cytokine was measured by ELISA and RT-PCR. The damage of mitochondrial was evaluated by measuring the changes in Mitochondrial Membrane Potential (ΔΨm), mitochondrial ROS, ATP content and MDA as well as relocation of mtDNA and the activity of SOD and GSH. The expressions of NLRP3 inflammasomes- pyroptosis axis proteins were detected by Western blotting as well as SIRT1/PGC-1α/NRF1/TFAM pathway protein. Moreover, the modification of PGC-1α was measured by co-immunoprecipitation. The results displayed that RSV can significantly improve the damage of pancreas and mitochondrial, decrease the expression of pro-inflammatory factor and the activation of NLRP3 inflammasomes- pyroptosis axis, promote the expression of an-inflammatory factor and the deacetylation of PGC-1α together with facilitating SIRT1/PGC-1α-mediating mitochondrial biogenesis. Therefore, the protective effect of RSV in SAP is though inactivation of NLRP3 inflammasomes- pyroptosis axis via promoting mitochondrial biogenesis in a SIRT1/PGC-1α-dependent manner.

Taxifolin ameliorates the D-galactose-induced aging of mouse hippocampal neurons HT-22 cells through modulating SIRT1/p53 and PI3K/AKT signaling pathways

By establishing an in vitro model of D-Gal-induced brain neuronal cell (HT-22) senescence, it was found that TAX treatment significantly increased the activities of SOD and GSH, while decreasing MDA levels in aging HT-22 cells, indicating that TAX effectively restored the total antioxidant capacity and antioxidant enzyme activity of aging HT-22 cells induced by D-Gal, and attenuated cellular oxidative stress injury. In addition, taxifolin could also protect HT-22 cells from aging by up-regulating SIRT1 while reducing the expression of Ac-p53, indicating that TAX may be an active substance that can effectively delay cell aging.

Synthesis, characterization and MAFLD prevention potential of Ganoderma lucidum spore polysaccharide-stabilized selenium nanoparticles

The unstability of selenium nanoparticles (SeNPs) results in decreased activity which limits its therapeutic potential. In this study, we utilized Ganoderma lucidum spore polysaccharide (GLP, Mw = 983.96 kDa) as a novel stabilizer to synthesize GLP-SeNPs. GLP-SeNPs (Se/GLP = 1/3) with an average diameter of 149 nm were successfully prepared and it was stable for at least 30 days at 4 °C. It exhibited an orange-red color, zero valence state, amorphous structure, selenium uniform distribution, a zeta potential of −29.73 mV, selenium content of 16.04 %. GLP-SeNPs pretreatment decreased lipid accumulation, reduced ROS content and enhanced SOD and CAT activity in HepG2 cells. Fe2+ and MDA contents were decreased, while GPX4 and GSH activities were increased. All these ameliorated effects could be abolished by NRF2 antagonist ML385. The expression of anti-oxidant genes and iron exporter was up-regulated, while that of pro-oxidant and lipid biosynthesis gene was down-regulated. The GPX4 activity could be reduced by ML385 addition. In conclusion, GLP-SeNPs was successfully constructed at the ratio of 1/3 (Se/GLP). It prevents MAFLD by targeting ferroptosis, including lowering iron overload, inhibiting lipid accumulation and attenuating oxidative stress. The improvement was conducted via activating SLC40A1-mediated iron pathway, ACSL4-mediated lipid metabolism and NRF2-mediated GSH-GPX4 pathway. Therefore, GLP-SeNPs can be used as potential selenium nutritional supplements or adjuvants for MAFLD prevention.

Beta vulgaris L. beetroot protects against iron-induced liver injury by restoring antioxidant pathways and regulating cellular functions

Beta vulgaris L. is a root vegetable that is consumed mainly as a food additive. This study aimed to describe the protective effect of B. vulgaris on Fe2+-mediated oxidative liver damage through in vitro, ex vivo, and in silico studies to establish a strong rationale for its protective effect. To induce oxidative damage, we incubated the livers of healthy male rats with 0.1 mM FeSO4 to induce oxidative injury and coincubated them with an aqueous extract of B. vulgaris root (BVFE) (15–240 µg/mL). Induction of liver damage significantly (p < .05) decreased the levels of GSH, SOD, CAT, and ENTPDase activities, with a corresponding increase in MDA and NO levels and Na+/K+ ATPase, G6 Pase, and F-1,6-BPase enzyme activities. BVFE treatment (p < .05) reduced these levels and activities to almost normal levels, with the most prominent effects observed at 240 µg/mL BVFE. An HPLC investigation revealed sixteen compounds in BVFE, with quercetin being the most abundant. Chlorogenic acid and iso-orientation showed the highest binding affinities for G6 Pase and Na+/K + ATPase, respectively. These findings suggest that B. vulgaris can protect against Fe2+-mediated liver damage by suppressing oxidative stress and cholinergic and purinergic activities while regulating gluconeogenesis. Overall, the hepatoprotective activity of this extract might be driven by the synergistic effect of the identified compounds and their probable interactions with target proteins.

Copaiba Oleoresin Improves Weight Gain and IL-10 Concentration, with No Impact on Hepatic Histology, in Liver Cirrhosis.

Copaifera sp. is a native tree in the Amazon region. Copaiba oleoresin has components such as sesquiterpenes, which have anti-inflammatory and antioxidant potential. Liver cirrhosis is the end stage of liver disease with limited therapeutic options. We aimed to evaluate the effect of copaiba oleoresin supplementation on the liver of animals with thioacetamide (TAA)-induced cirrhosis. For the induction of liver cirrhosis, 100 mg/kg of TAA was administered intraperitoneally twice a week for 8 weeks. A total of 200 mg/kg/day of copaiba oleoresin was administered via gavage for the same period. Copaiba oleoresin supplementation improved cirrhosis-associated cachexia by increasing weight gain and body fat. In addition, copaiba oleoresin attenuated systemic inflammation, as shown by the decrease in the circulating C-reactive protein. In the liver, the copaiba oleoresin decreased carbonyl proteins and increased IL-10 compared with TAA-treated rats. TAA groups demonstrated increased SOD, catalase, GST, and GSH activity in the liver. In conclusion, the supplementation of copaiba oleoresin demonstrated a beneficial systemic effect in alleviating cirrhotic cachexia and antioxidant and anti-inflammatory action in the liver. However, it failed to improve the serological and histological markers of liver damage, which could be associated with the advanced stage of the disease.

Exploring the antioxidant and protective effects of Marsdenia thyrsiflora Hook.f. leaf extract against carbon tetrachloride-induced hepatic damage in rat models.

Medicinal plants are vital to healthcare, yet many remain unexplored. Marsdenia thyrsiflora Hook.f., from Bangladesh's Bhawal Forest, lacks research on its medicinal properties, especially its antioxidant capacities and protection against CCl4-induced liver toxicity. This study aims to evaluate the antioxidant properties of M. thyrsiflora leaf extract to determine its protective effects on rodents against CCl4-induced liver injury. After extraction, the total phenol, flavonoid content, and antioxidant capacity of the leaf extract were measured using established protocols. Free radical scavenging abilities were evaluated with 2,2'-diphenyl-1-picrylhydrazyl (DPPH), nitric oxide (NO) assays. Additionally, reducing power was assessed through cupric-reducing and ferric-reducing assays. Based on the OECD 420 recommendation, acute toxicity was tested on Swiss albino mice to establish an effective and safe dosage. For the hepatoprotective study, Sprague-Dawley rats were pre-treated with M. thyrsiflora leaf methanolic extract (MTLM) at 250 and 500mg/kg body weight, and CCl4 was administered to induce liver damage. Serum hepatic enzyme levels (alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT)), lipid profile (total cholesterol, triglycerides), total bilirubin, and markers of lipid peroxidation (Malondialdehyde (MDA)) were measured. The activities of antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) were also evaluated to assess oxidative stress. The results demonstrated that MTLM, rich in phenolic and flavonoid content, exhibits significant antioxidant activities in DPPH and NO radical scavenging assays, as well as in reducing power assays. The acute toxicity study confirmed the safety of MTLM, with no adverse effects observed even at high doses. For the hepatoprotective study, rats were administered CCl4 to induce liver damage, followed by treatment with MTLM. Results showed that MTLM significantly reduces liver damage markers such as elevated serum hepatic enzyme levels, lipid profile, total bilirubin, and lipid peroxidation and improves the activities of GSH and key antioxidant enzymes such as SOD and CAT. Histopathological analysis corroborated these findings, displaying reduced necrosis, inflammation, and edema in liver tissues treated with MTLM. MTLM extract exhibits potent antioxidant and hepatoprotective properties. Its ability to attenuate oxidative stress, enhance antioxidant enzyme activities, and facilitate histopathological changes in the liver highlights its potential as a natural therapeutic agent for liver damage. However, further investigation is required to understand its molecular processes, safety profiles, and active component characterization.

Mulberry galacto-oligosaccharides ameliorates non-alcoholic fatty liver disease in mice induced by a high-fat diet

A type of oligosaccharide named mulberry galacto-oligosaccharides (MGO), was isolated from mulberry with a galactose-only, weighs 987 Da and displays diverse biological properties. The objective of this work was to investigate the protective effects of MGO in non-alcoholic fatty liver disease (NAFLD) mice. The results showed that MGO can reduce the body weight and liver weight of NAFLD mice, and reduce the levels of NEFA, TG, TC and LDL-C in serum and liver as well as the activities of AST and ALT. Increase HDL-C content, SOD, and GSH activity in serum and improve pathological damage. MGO regulates the AMPK lipid metabolism pathway, upregulates the expression of ATGL, downregulates the expression of SREBP-1, inhibits lipogenesis, and promotes lipolysis. MGO alleviates liver function damage in NAFLD mice, improves blood lipids, liver metabolism, and increases the body’s antioxidant capacity, suggesting MGO potential as a dietary supplement and functional food to combat HFD-induced NAFLD.

The integrated effect of roflumilast and selenium nanoparticles on nephrotoxicity generated by cisplatin through the regulation of the antioxidant and apoptotic pathways

AimThe current investigations aimed to investigate the potential synergistic effect of Roflumilast (ROF) and Selenium nanoparticles (SeNPs) administration on Cisplatin (Cis) -induced nephrotoxicity. Materials and methodsFifty male rats were divided into five groups; Control group: animals were administered 0.9 % saline solution. Cis group: animals were injected with a single dose of 6 mg/kg. ROF group: Rats received a dosage of 1.2 mg/kg orally daily for 11 days. SeNPs group: animals orally received 0.5 mg/kg of ROF daily for 11 days. The ROF + SeNPs group was administered both after receiving a Cis injection for 11 days. Animals were sacrificed at 5 and 11 days, and the urine and blood samples were collected on day 5 and day 11 for chemical analysis, while kidney samples were obtained for molecular, histological, and immunohistochemical studies. ResultsThe levels of serum creatinine, Blood urea nitrogen (BUN), and total protein were elevated in the Cis group compared to the control group (p < 0.05). While the combination of ROF and SeNPs dramatically decreased these values after 5 and 11 days (p < 0.05). In addition, Cis caused renal oxidative stress by elevating MDA levels and suppressing the activities of SOD, GSH, and CAT. Similarly, these effects were modulated by ROF and SeNPs after 11 days (p < 0.05). Furthermore, the concurrent administration of ROF and SeNPs resulted in a significant increase in the expression of HO-1, Nrf2, and Bcl2, while decreasing the expression of BAX and IL-6 compared to the Cis group after 11 days (P < 0.05). ConclusionThe study showed that both ROF and SeNPs had significant therapeutic potential in reducing the pathological alterations caused by Cis.