Increased Superoxide Dismutase Research Articles

GhAGL16 (AGAMOUS-LIKE16) Negatively Regulates Tolerance to Water Deficit in Transgenic Arabidopsis and Cotton.

Cotton is one of the most economically important crops in the world, and drought is a key abiotic factor that can significantly reduce cotton yield. MADS-box transcription factors play essential roles in various aspects of plant growth and development as well as responses to biotic and abiotic stress. However, the use of MADS-box transcription factors to regulate water stress responses has not been fully explored in cotton. Here, we showed that GhAGL16 acts as a negative regulator of water deficit in cotton, at least in part by regulating ABA signaling. GhAGL16-overexpressing (GhAGL16-OE) transgenic Arabidopsis had lower survival rates and relative water contents (RWCs) under water stress. Isolated leaves of GhAGL16-OE Arabidopsis had increased water loss rates, likely attributable to their increased stomatal density. GhAGL16-OE Arabidopsis also showed reduced primary root lengths in response to mannitol treatment and decreased sensitivity of seed germination to ABA treatment. By contrast, silencing GhAGL16 in cotton enhanced tolerance to water deficit by increasing proline (Pro) content, increasing superoxide dismutase (SOD) and peroxidase (POD) activities, and reducing malondialdehyde (MDA) and hydrogen peroxide (H2O2) contents under water stress. Subcellular localization and transcriptional activation assays confirmed that GhAGL16 is a nuclear protein that lacks transcriptional self-activation activity. The expression of ABA biosynthesis-related genes (GhNCED3/7/14), a catabolism-related gene (GhCYP707A), and a gene related to the ABA signaling pathway (GhABF4) was altered in GhAGL16-silenced plants. Taken together, our data demonstrate that GhAGL16 plays an important role in cotton resistance to water stress.

Triphenyltin isoselenocyanate: a novel nuclear retinoid X receptor ligand with antiproliferative and cytotoxic properties in cell lines derived from human breast cancer

Several commercially available triorganotin compounds were previously found to function as agonist ligands for nuclear retinoid X receptor (RXR) molecules. Triphenyltin isoselenocyanate (TPT-NCSe), a novel selenium atom containing a derivative of triorganotin origin, was found to represent a new cognate bioactive ligand for RXRs. TPT-NCSe displayed a concentration- and time-dependent decrease in the cell viability in both human breast carcinoma MCF-7 (estrogen receptor positive) and MDA‑MB‑231 (triple negative) cell lines. Reactive oxygen species levels generated in response to TPT-NCSe were significantly higher in both carcinoma cell lines treated with TPT-NCSe when compared to mock-treated samples. Treatment with 500 nM TPT-NCSe caused a decrease in SOD1 and increased SOD2 mRNA in MCF-7 cells. The levels of SOD2 mRNA were more increased following the treatment with TPT-NCSe along with 1 μM all-trans retinoic acid (AtRA) in MCF-7 cells. An increased superoxide dismutase SOD1 and SOD2 mRNA levels were also detected in combination treatment of 500 nM TPT-NCSe and 1 μM AtRA in TPT-NCSe-treated MDA-MB-231 cells. The data have also shown that TPT-NCSe induces apoptosis via a caspase cascade triggered by the mitochondrial apoptotic pathway. TPT-NCSe modulates the expression levels of apoptosis‑related proteins, Annexin A5, Bcl‑2 and BAX family proteins, and finally, it enhances the expression levels of its cognate nuclear receptor subtypes RXRalpha and RXRbeta.

Huangqi Baihe Granules alleviate hypobaric hypoxia-induced acute lung injury in rats by suppressing oxidative stress and the TLR4/NF-κB/NLRP3 inflammatory pathway

Ethnopharmacological relevanceHuangqi Baihe Granules (HQBHG) are a modified formulation based on the traditional recipe “Huangqi Baihe porridge” and the Dunhuang medical prescription “Cistanche Cistanche Soup.” The Herbal medicine moistens the lungs and tones the kidneys in addition to replenishing Qi and feeding Yin, making it an ideal choice for enhancing adaptability to high-altitude hypoxic environments. Aim of the studyThe purpose of this study was to examine a potential molecular mechanism for the treatment and prevention of hypoxic acute lung injury (ALI) in rats using Huangqi Baihe Granules. Materials and methodsThe HCP-III laboratory animal low-pressure simulation chamber was utilized to simulate high-altitude environmental exposure and establish an ALI model in rats. The severity of lung damage was evaluated using a battery of tests that included spirometry, a wet/dry lung ratio, H&E staining, and transmission electron microscopy. Using immunofluorescence, the amount of reactive oxygen species (ROS) in lung tissue was determined. Superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), and myeloperoxidase (MPO) levels in lung tissue were determined using this kit. Serum levels of proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1 beta), and antiinflammatory cytokines like interleukin-10 (IL-10) were measured using an enzyme-linked immunosorbent assay kit. Gene expression changes in lung tissue were identified using transcriptomics, and the relative expression of proteins and mRNA involved in the toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB p65)/Nod-like receptor protein 3 (NLRP3) pathway were determined using western blotting and quantitative real-time PCR. ResultsHQBHG was shown to enhance lung function considerably, decrease the wet/dry ratio of the lungs, attenuate lung tissue damage, suppress ROS and MDA formation, and increase SOD activity and GSH expression. The research also demonstrated that HQBHG inhibited the activation of the TLR4/NF-κB p65/NLPR3 signaling pathway in lung tissue, reducing the release of downstream pro-inflammatory cytokines. ConclusionsHQBHG exhibits potential therapeutic effects against ALI induced by altitude hypoxia through suppressing oxidative stress and inflammatory response. This suggests it may be a novel drug for treating and preventing ALI.

Mitochondria-Targeted Nitronyl Nitroxide Radical Nanoparticles for Protection against Radiation-Induced Damage with Antioxidant Effects.

Radiotherapy is a non-invasive method that is widely applied to treat and alleviate cancers. However, radiation-induced effects in the immune system are associated with several side effects via an increase in oxidative stress and the inflammatory response. Therefore, it is imperative to develop effective clinical radiological protection strategies for the radiological protection of the normal organs and immune system in these patients. To explore more effective radioprotective agents with minimal toxicity, a mitochondria-targeted nitronyl nitroxide radical with a triphenylphosphine ion (TPP-NIT) was synthesized and its nanoparticles (NPs-TPP-NIT) were prepared and characterized. The TPP-NIT nanoparticles (NPs-TPP-NIT) were narrow in their size distribution and uniformly distributed; they showed good drug encapsulation efficiency and a low hemolysis rate (<3%). The protective effect of NPs-TPP-NIT against X-ray irradiation-induced oxidative damage was measured in vitro and in vivo. The results show that NPs-TPP-NIT were associated with no obvious cytotoxicity to L-02 cells when the concentration was below 1.5 × 10-2 mmol. NPs-TPP-NIT enhanced the survival rate of L-02 cells significantly under 2, 4, 6, and 8 Gy X-ray radiation exposure; the survival rate of mice was highest after 6 Gy X-ray irradiation. The results also show that NPs-TPP-NIT could increase superoxide dismutase (SOD) activity and decrease malondialdehyde (MDA) levels after the L-02 cells were exposed to 6.0 Gy of X-ray radiation. Moreover, NPs-TPP-NIT could significantly inhibit cell apoptosis. NPs-TPP-NIT significantly increased the mouse survival rate after irradiation. NPs-TPP-NIT displayed a marked ability to reduce the irradiation-induced depletion of red blood cells (RBCs), white blood cells (WBCs), and platelets (PLTs). These results demonstrate the feasibility of using NPs-TPP-NIT to provide protection from radiation-induced damage. In conclusion, this study revealed that NPs-TPP-NIT may be promising radioprotectors and could therefore be applied to protect healthy tissues and organs from radiation during the treatment of cancer with radiotherapy.

A sodium alginate intervention strategy to enhance therapeutic effects of bone-targeted alpha therapy via remodeling 223RaCl2 distribution

Radium-223 dichloride is the first approved alpha particle-emitting radiopharmaceutical for patients with castration-resistant prostate cancer with symptomatic bone metastases and no known visceral metastases. A large percentage of intestinal enrichment and a slow clearance rate were the main causes of gastrointestinal adverse events after 223RaCl2 administration. The molecular weight of sodium alginate in aqueous solution was determined to be 656 kDa. Sodium alginate exhibits a higher affinity for adsorbing Ra2+ compared to other metal ions belonging to the second main group. Sodium alginate as low as 0.5 g/rat reduced intestinal damage by remodeling 223RaCl2 distribution without affecting bone resorption. Intestinal villi were preserved and enterocyte activity was maintained after sodium alginate intervention. Sodium alginate reduced DNA oxidative damage and lipid peroxidation and maintained endogenous antioxidant status by increasing superoxide dismutase levels and total antioxidant capacity. Furthermore, sodium alginate treatment mitigated DNA damage and apoptosis. The administration of sodium alginate effectively maintained the integrity of the intestinal microbiota, which had undergone perturbations due to radiation exposure. This study demonstrated that sodium alginate could be applied to reduce the adverse effects caused by radiation exposure to the intestine during 223RaCl2-treated and reduced intestinal damage resulted from 223RaCl2 accumulation without affecting bone uptake.

Polypropylene packaging alleviates the quality deterioration of Lentinus edodes through antioxidant system and phenylpropane pathway

Lentinus edodes (L. edodes) is a popular edible mushroom, which is very easy to rot and deteriorate after harvest. The quality of L. edodes were significantly affected by different packaging materials. Hence, polypropylene (PP) or polyethylene (PE) packaging were employed to explore the effects and underlying mechanisms on the post-harvested quality of L. edodes. Compared with PE packaging, PP packaging could maintain good storage quality and membrane integrity of L. edodes by reducing oxidative damage, which might be related to the significantly decreased relative electrolyte leakage and malondialdehyde content at the later stage of storage. Also, PP packaging could improve the antioxidant ability and inhibit the production of H2O2 by the decreased catalase and increased superoxide dismutase content. Phenylalanine ammonia lyase, phenylalanine ammonia lyase and cinnamaldehyde dehydrogenase, as the key enzymes in the metabolic pathway of phenylpropane, increased at the later storage of PP-packaged L. edodes. It helped the synthesis of phenolic substances and lignin accumulation. These results indicated PP packaging could be an effective material for maintaining the postharvest storage quality of L. edodes, which might be related to the antioxidant system and phenylpropane pathway.

Unraveling the Role of miR-200b-3p in Attention-Deficit/Hyperactivity Disorder (ADHD) and Its Therapeutic Potential in Spontaneously Hypertensive Rats (SHR).

Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder in children with unknown etiology. Impaired learning ability was commonly reported in ADHD patients and has been associated with dopamine uptake in the striatum of an animal model. Another evidence also indicated that micro-RNA (miR)-200b-3p is associated with learning ability in various animal models. However, the association between miR-200b-3p and ADHD-related symptoms remains unclear. Therefore, the current study investigated the role of miR-200b-3p in ADHD-related symptoms such as inattention and striatal inflammatory cytokines. To verify the influence of miR-200b-3p in ADHD-related symptoms, striatal stereotaxic injection of miR-200b-3p antagomir (AT) was performed on spontaneously hypertensive rats (SHR). The antioxidant activity and expressions of miR-200b-3p, slit guidance ligand 2 (Slit2), and inflammatory cytokines in the striatum of SHR were measured using quantitative real-time polymerase chain reaction (RT-qPCR), immunohistochemistry (IHC), immunoblotting, and enzyme-linked immunosorbent assay (ELISA). The spontaneous alternation of SHR was tested using a three-arm Y-shaped maze. The administration of miR-200b-3p AT or taurine significantly decreased striatal tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in SHR, along with increased super-oxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities and significantly higher spontaneous alternation. In this paper, we show that miR-200b-3p AT and taurine alleviates ADHD-related symptoms in SHR. These findings provide insights into ADHD's molecular basis and suggest miR-200b-3p as a potential therapeutic target. Concurrently, this study also suggests broad implications for treating neurodevelopmental disorders affecting learning activity such as ADHD.

Effect of Substituting Soybean Meal in Oreochromis niloticus Diets with Pumpkin (Cucurbita maxima) Seed Cake on Water Quality, Growth, Antioxidant Capacity, Immunity, and Carcass Composition.

A 10-week feeding experiment was performed to determine the impacts of partial substitution of soybean meal (SB) with pumpkin seed cake (PSC) in Oreochromis niloticus diets on water quality, growth rate, antioxidant capacity, immunity, and carcass composition. One hundred and fifty tilapia fish (average weight, 11.93 ± 0.17 g) were randomly allocated to five diets. The first diet (the basal diet) contained 420 g of SB per kg of feed. The remaining four diets, namely, D1, D2, D3, and D4, had SB partially replaced by PSC at 10%, 20%, 30%, and 40%, respectively. The results revealed that D4 and D1 significantly improved dissolved oxygen levels, while water temperature, pH, total ammonia, and nitrate levels were not significantly affected. Replacing SB with PSC significantly improved specific growth performance indicators and feed conversion compared to the control, with the D4 group showing the best values. Increasing PSC levels decreased serum glucose, aspartate aminotransferase, alanine aminotransferase, cholesterol, and triglyceride levels. In contrast, the D4 group had higher globulin, albumin, total protein, and lysozyme serum levels. Moreover, fish-fed PSC had significantly increased superoxide dismutase, glutathione peroxidase, and catalase activities and significantly decreased malondialdehyde levels. Increasing PSC substitution levels in fish diets increased the ash and crude lipid contents in the bodies of the fish, while crude protein and moisture decreased. In conclusion, replacing SB with PSC in fish diets significantly enhances growth performance, feed conversion, and fish health. Moreover, the findings suggest that PSC can be a promising alternative protein source for sustainable aquaculture practices.

Assessing physiological responses and oxidative stress effects in Rhamdia voulezi exposed to high temperatures.

Exposure to high temperatures induces changes in fish respiration, resulting in an increased production of reactive oxygen species. This, in turn, affects the enzymatic and non-enzymatic components of antioxidant defenses, which are essential for mitigating cellular stress. Rhamdia voulezi, an economically important fish species endemic to Brazil's Iguaçu River, served as the subject of our study. Our goal was to assess enzymatic antioxidant biomarkers (superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase, glutathione reductase, glucose-6-phosphate dehydrogenase), non-protein thiol levels (reduced glutathione), and markers of oxidative damage (lipoperoxidation and carbonylation) in the liver, gills, and kidneys of R. voulezi after acute exposure to high temperatures (31°C) for 2, 6, 12, 24, and 96 h. Control groups were maintained at 21°C. Our findings revealed that the liver exhibited increased superoxide dismutase levels up to 12 h and elevated glutathione S-transferase levels at 12 and 96 h at 31°C. In the gills, superoxide dismutase levels increased up to 24 h, along with increased lipoperoxidation at 2, 6, 12, and 96 h of exposure to high temperatures. The kidneys responded to heat stress at 12 h, with an increase in superoxide dismutase and catalase activity, and lipid peroxidation was observed at 2 and 6 h at 31°C. The three tissues evaluated responded differently to heat stress, with the liver demonstrating greater physiological adjustment to high temperatures. The intricate interplay of various antioxidant defense biomarkers and oxidative damage suggests the presence of oxidative stress in R. voulezi when exposed to high temperatures.

Exploring the effects of astragalus polysaccharide food supplementation on growth performance, immunity, antioxidant capacity, and intestinal microflora in Chinese mitten crabs

Astragalus polysaccharide (APS) is the main active ingredient in astragalus membranaceus, which is composed of rhamnose, arabinose, xylose, mannose, galactose, and glucose. This research evaluated dietary addition with APS effects on growth, non-specific immune, antioxidant status and intestinal microbiota of Chinese mitten crabs. Altogether 288 crabs with intact appendages were irregularly assigned 12 crabs per replicate to 24 tanks with 6 replicates per treatment. Crabs were given a basal diet in different groups containing 0 (control group), 500, 1000, and 2000 mg/kg of APS, respectively. The results indicated that the dietary APS addition increased the specific growth rate and percentage weight gain, serum phenoloxidase and lysozyme activities, increased superoxide dismutase and glutathione peroxidase activities of serum and hepatopancreas, reduced the feed conversion ratio of Chinese mitten crabs (P < 0.05). APS addition quadratically increased acid phosphatase levels, decreased the malondialdehyde levels of Chinese mitten crabs (P < 0.05). APS inclusion linearly and quadratically increased hepatopancreas mRNA expression levels of TLR2, MyD88 and Tube of crabs (P < 0.05). Principal component analysis showed that the four groups had different composition of the intestinal microbiota in Chinese mitten crabs. On the other hand, this addition decreased the Chao1, Shannon indexes, abundance of phyla Bacteroidota, increased the abundance of phyla Firmicutes and genus Candidatus_Bacilloplasma in intestine microbiota of Chinese mitten crabs compared with the control (P < 0.05). The level of APS to the diet of Chinese mitten crabs with a 1000 mg/kg inclusion was better compared to its counterparts with 500 and 2000 mg/kg inclusions according to the better results on growth, immunity, and antioxidant capacity. In summary, dietary APS inclusion enhanced growth performance via improving antioxidant function, non-specific immunity, modulating the Toll/NF-κB pathway and proPO system, and ameliorating the intestinal flora in Chinese mitten crabs. The optimal level of supplemented APS in the diet was 1000 mg/kg.

Toxicity Profile and Reincarnation of Antioxidant Activity of Annona squamosa L (Sugar apple) Ethanol Leaves Extract in Wistar Albino rats

Abstract The toxicity profile and antioxidant properties of natural compounds from plants like Annona squamosa L. (Sugar apple) have garnered significant research interest due to their potential health benefits, as antioxidants are crucial in combating oxidative stress, which is implicated in various diseases.This study investigates the Annona squamosa L ethanol leaf extract (ASELE) in Wistar Albino rats to elucidate its toxicity profile and its ability to reincarnate antioxidant activity. Phytochemical screening was conducted using specified reagents, confirming the presence of bioactive secondary metabolites such as alkaloids, saponins, flavonoids, phenols and anthraquinones. Quantitative analysis revealed varying concentrations, with the highest in alkaloids (18.47±0.06 mg/ml) followed by Saponins (16.33±0.05mg/ml and Anthraquinones (9.60±0.04mg/ml) Flavonoids (4.08±0.04mg/ml) and Phenol (0.80±0.03mg/ml) were present in lower amounts. The LD50 of Annona squamosa L ethanol leaf extract (ASELE) exceeded 3000mg/kg body weight, showing no fatality within a 14-day observation period. ASELE treatment resulted in a significant reduction (p&lt;0.05) in oxidative stress markers. Similarly, ASELE (150-1200mg/kg) exhibited a notable decrease (p&lt;0.05) in Aspartate Amino Transferase and Alanine Amino Transferase during a 28-day oral toxicity trial. However, other biochemical parameters, including alkaline phosphate, albumin, total protein, direct bilirubin, urea, uric acid, and creatinine, showed no significant differences compared to the control. In terms of hematological parameters, platelets and mean corpuscular volume exhibited significant differences (p&lt;0.05) between the extract-treated groups and the control. Moreover, ASELE demonstrated significant antioxidant effects, as evidenced by increased superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and decreased malondialdehyde (MDA) levels. The study demonstrates that the Annona squamosa ethanol leaf extract (ASELE) exhibits a favorable toxicity profile with an LD50 exceeding 3000 mg/kg, no significant biochemical alterations, and notable antioxidant effects, highlighting its potential therapeutic benefits in reducing oxidative stress and validating its traditional medicinal uses; therefore, it is recommended to further investigate ASELE's therapeutic potential through extended preclinical and clinical trials, explore the mechanisms behind its antioxidant properties, and consider its incorporation into nutraceutical formulations for controlled and standardized health benefits

Sodium butyrate and rosemary herb improve growth performance, biochemical profile, immunity, and carcass traits in broiler chickens

Background: Feed additives are products used in poultry nutrition to improve the quality of feed and safety of food byproducts from animal origin. They are promising antibiotic alternatives for production of broilers. Aim: This study aimed to investigate the effect of sodium butyrate (SB) and rosemary leaves (RL) on growth performance, biochemical profile, immunity, and carcass traits of broilers. Methods: Five hundred-one-day old chicks of Hubbard breed were reared on floor pens in a privet farm, Giza. The chicks were weighed on arrival (each chick weighted 43-45 gm) and randomly assigned into five equal groups, with four replicates each (25 chicks/replicate). Group 1 was fed on a broiler diet without any additions (control). The diets of groups 2 and 3 were supplemented with 500 g/ton SB and 4 kg/ton RL, respectively. In group 4, the diet was enriched with 250g/ton SB plus 2 kg/ton RL. Chicks in group 5 were fed on diet fortified with 500 g/ton SB plus 4 kg/ton RL. Results: Supplementation of broiler diet with 500 g/ton SB plus 4 kg /ton RL increased Body weight gain (BWG) and feed efficiency ratio (FER) of birds. It decreased serum levels of aspartate aminotransferase, alanine aminotransferase, total cholesterol triglycerides, malondialdehyde, but increased superoxide dismutase, catalase, and immunoglobulins, phagocytic activity, lysozyme activity, and nitric oxide concentrations. Antibody titers against Newcastle disease virus were also elevated. Conclusion: Supplementation of broiler diet with 500 g/ton SB plus 4 kg/ton RL gives the best result regarding productive efficiency and immunity of broiler chickens.

Ameliorative effect of Odontonema cuspidatum extract against testicular damage induced by sodium nitrite in rats.

Sodium nitrite (NaNO2) is a chemical substance used to enhance taste, add color, and keep food products fit for consumption for a longer time. NaNO2 gives rise to a negative adverse effect on male reproductive function. Odontonema cuspidatum (OC) is a natural plant that possesses antioxidant capacity. Our research evaluates the potential beneficial effect of OC extract on the harmful effects caused by NaNO2 on the testicular tissue and sperm characteristics of male rats. Four groups with a total of forty rats: the control, the NaNO2-received group, the OC-administered group, and the fourth group received both NaNO2 and OC. All groups were administered daily for two months. Sperm characteristics, testicular antioxidant status, qRT-PCR, and histopathological changes were evaluated. Coadministration of NaNO2 and OC, in comparison with NaNO2 alone, contributed to a notable enhancement in acrosomal integrity, decreasing sperm abnormalities and restoring serum testosterone levels. Moreover, such coadministration reduced the oxidative stress marker, malondialdehyde (MDA), and increased superoxide dismutase (SOD) in testicular tissue, lowering TNF-α gene expression, and increasing the expression of P450scc and StAR genes. In addition, the NaNO2 and OC combination decreased the testicular histopathological changes and the Caspase-3 and Proliferating cell nuclear antigen (PCNA) immunoexpression in seminiferous tubules compared with the NaNO2 group. The extract of OC exhibited the ability to decrease oxidative stress and ameliorate the detrimental effects caused by NaNO2.

Unacylated ghrelin attenuates acute liver injury and hyperlipidemia via its anti-inflammatory and anti-oxidative activities.

Liver injury and hyperlipidemia are major issues that have drawn more and more attention in recent years. The present study aimed to investigate the effects of unacylated ghrelin (UAG) on acute liver injury and hyperlipidemia in mice. UAG was injected intraperitoneally once a day for three days. Three hours after the last administration, acute liver injury was induced by intraperitoneal injection of carbon tetrachloride (CCl4), and acute hyperlipidemia was induced by intraperitoneal injection of poloxamer 407, respectively. Twenty-four hours later, samples were collected for serum biochemistry analysis, histopathological examination, and Western blotting. In acute liver injury mice, UAG significantly decreased liver index, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), reduced malondialdehyde (MDA) concentration and increased superoxide dismutase(SOD) in liver tissue. NF-kappa B (NF-κB) protein expression in the liver was down-regulated. In acute hyperlipidemia mice, UAG significantly decreased serum total cholesterol (TC), triglyceride (TG), ALT, and AST, as well as hepatic TG levels. Meanwhile, hepatic MDA decreased and SOD increased significantly. Moreover, UAG improved the pathological damage in the liver induced by CCl4 and poloxamer 407, respectively. Intraperitoneal injection of UAG exhibited hepatoprotective and lipid-lowering effects on acute liver injury and hyperlipidemia, which is attributed to its anti-inflammatory and anti-oxidant activities.

Protective effects of hesperidin in gastric damage caused by experimental ischemia-reperfusion injury model in rats.

This study evaluated the protective effect of hesperidin on injury induced by gastric ischemia-reperfusion. Fifty male Sprague Dawley rats (250-300g) were divided into five groups: control (C), sham (S), ischemia (I), ischemia-reperfusion (I/R) and hesperidin + ischemia-reperfusion (Hes + I/R). Hesperidin was injected intraperitoneally at the dose of 100mg/kg one hour before the experimental stomach ischemia-reperfusion. Celiac artery was ligated. After 45minutes ischemia and 60minutes reperfusion period, blood samples were obtained under anesthesia. Then, animals were sacrificed, stomach tissues were excised for biochemical, and histopathological analyses were performed. Malondialdehyde levels and superoxide dismutase, glutathione peroxidase activities and total antioxidant status (TAS), total oxidant status (TOS), protein, total thiol parameters were measured in plasma, and tissue homogenate samples. H + E, periodic acid-Schiff, hypoxia inducible factor, terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end-labeling (TUNEL), and proliferating cell nuclear antigen (PCNA) for cell proliferation as immunohistochemical parameters were determined. Upon biochemical and histopathological assessment, hesperidin decreased stomach tissue changes in comparison with IR group. Ischemia-reperfusion injury led to a considerably increase in malondialdehyde, protein, and TOS levels (p < 0.001) in stomach tissue. Hesperidin treatment significantly decreased malondialdehyde, protein, and TOS levels (p < 0.001). Hesperidin increased superoxide dismutase, TAS, total thiol and glutathione peroxidase activities in comparison with IR group. Hesperidin reduced damage and also increased TUNEL and PCNA immunoreactivity in stomach tissue. Hesperidin was able to decrease I/R injury of the stomach tissue due to inhibition of lipid peroxidation and protein oxidation, duration of antioxidant, and free radical scavenger properties. Consequently, hesperidin can provide a beneficial therapeutic choice for preventing stomach tissue ischemia-reperfusion injury in clinical application.

Comprehensive fecal metabolomics and gut microbiota study of the protective mechanism of herbal pair Polygonum hydropiper-Coptis chinensis in rats with stress-induced gastric mucosal damage.

Introduction: Stress-related gastric mucosal lesions (SGMLs) are the most common complication in critical care patients. Previous studies have demonstrated that herbal pair (HP), Polygonum hydropiper-Coptis chinensis (HP P-C) has the anti-SGML effect. However, the underlying mechanism of HP P-C against SGML remains elusive. This study aimed to elucidate how HP P-C extracts exert their protective effects on SGML by examining the role of gut microbiota and metabolites. Methods: SD rats were pretreated with different doses of HP P-C extracts for 6 days, followed by inducing SGML with water-immersion restraint stress (WIRS). After a comprehensive evaluation of serum and gastric tissue indicators in rats, 16S rRNA sequencing and metabolomics analyses were conducted to assess the impact of HP P-C on the fecal microorganisms and metabolites and their correlation. Results: Animal experiment suggested that pretreatment with HP P-C effectively reduced the gastric mucosal lesions, remarkably increased superoxide dismutase (SOD) activity in SGML model rats induced by WIRS. 16S rRNA sequencing analysis showed that HP P-C altered the composition of gut microbiota by raising the abundance of Lactobacillus and Akkermansia. In addition, metabolomics data identified seventeen main differential metabolites related to WIRS-induced gastric mucosal injury, primarily involving in tyrosine metabolism and betalain biosynthesis. HP P-C was found to regulate tyrosine metabolism and betalain biosynthesis by down-regulating the tyramine, L-tyrosine and L-dopa and up -regulating the gentisic acid and dopaquinone. Conclusion: Taken together, this study indicated that HP P-C could effectively protect against WIRS-induced gastric mucosal lesions by modulating intestinal flora and metabolites.

Metformin enhanced the effect of pirfenidone on pulmonary fibrosis in mice.

The aim of the study is to observe the anti-inflammatory and antioxidative stress effects of metformin on bleomycin (BLM)-induced pulmonary fibrosis in mice. Mice with BLM-induced pulmonary fibrosis were treated with pirfenidone, metformin, pirfenidone plus metformin and the NADPH oxidase 4 (NOX4) inhibitor diphenyleneiodonium chloride (DPI). Pathological changes and hydroxyproline (HPO) levels were examined in the lung tissue of mice with pulmonary fibrosis. Superoxide dismutase (SOD) activity and malonaldehyde (MDA) levels in lung tissue were determined. Compared with pirfenidone, pirfenidone plus metformin could reduce alveolar damage and collagen fibre deposition and alleviate BLM-induced pulmonary fibrosis. Lung HPO levels were significantly lower in the PFD + MET group than in the BLM group (p < 0.05). SOD levels in the lungs of mice were increased in the PFD + MET group than in the BLM group (p < 0.05). Metformin and pirfenidone plus metformin can reduce MDA levels (p < 0.05). Pirfenidone plus metformin could reduce HPO levels, increase SOD levels, and reduce MDA levels in the lungs of mice. There was a significant correlation between the HPO level and the Ashcroft score (r = 0.520, p < 0.001). Metformin enhanced the antifibrotic effects of pirfenidone on BLM-treated mice. Moreover, these findings provide an experimental basis for examining whether metformin can improve the antifibrotic effects of pirfenidone on patients with idiopathic pulmonary fibrosis (IPF). It has broad therapeutic prospects for patients with IPF.

Carthamin yellow attenuates brain injury in a neonatal rat model of ischemic-hypoxic encephalopathy by inhibiting neuronal ferroptosis in the hippocampus.

Hypoxic-ischemic encephalopathy (HIE) is a common neurological disorder characterized by ischemia and hypoxia in the perinatal period, which seriously affects the growth and development of newborns. To date, there is no specific drug for the treatment of HIE. Previous studies have shown that ferroptosis plays an important role in the pathogenesis of HIE. Carthamin yellow (CY) is believed to have antioxidant and anti-inflammatory effects. However, no studies have reported the role of CY in ferroptosis in HIE in vivo until now. The aim of this study was to investigate the effect and mechanism of CY on HIE in vivo and to provide an experimental basis for the clinical treatment of HIE. The results demonstrated that CY increased the expression of NeuN in the neonatal rat hypoxic-ischemic brain damage (HIBD) model. Further exploration revealed that CY increased the expression of glutathione peroxidase 4 and ferritin heavy chain 1 while it decreased the expression of PTGS2 and ACSL2. Moreover, CY decreased malondialdehyde expression and increased superoxide dismutase and glutathione expression in vivo. The findings also indicated that CY downregulated the expression of Nrf2 and Keap-1. In conclusion, this study demonstrated that CY attenuated brain injury in an experimental HIBD model, potentially by alleviating hippocampal neuronal ferroptosis through inhibition of the Nrf2/Keap-1 signaling pathway. These findings provide a novel therapeutic strategy for the clinical treatment of HIE.

Electroacupuncture improves cognitive function in APP/PS1 mice by inhibiting oxidative stress related hippocampal neuronal ferroptosis

BackgroundElectroacupuncture, recognized as a crucial non-pharmacological therapeutic approach, has demonstrated notable efficacy in enhancing cognitive function among Alzheimer's disease (AD) patients. This study aimed to investigate the neuroprotective properties of electroacupuncture in APP/PS1 mice with AD. MethodsA total of thirty APP/PS1 mice were randomly assigned to three groups: the Alzheimer's disease group (AD), the electroacupuncture treatment group (EA), and the ferroptosis inhibitor deferasirox treatment group (DFX). Additionally, ten C57BL/6 mice were included as a control group (Control). In the EA group, mice underwent flat needling at Baihui and Yintang, as well as point needling at Renzhong, once daily for 15 min each time. In the DFX group, mice received intraperitoneal injections of deferasirox at a dosage of 100 mg/kg/day. Following the 28-day treatment period, behavioral evaluation, morphological observation of neurons, and detection of neuronal ferroptosis were conducted. ResultsThe electroacupuncture treatment demonstrated a significant improvement in spatial learning, memory ability, and neuronal damage in mice with AD. Analysis of neuronal ferroptosis markers indicated that electroacupuncture interventions reduced the elevated levels of malondialdehyde, iron, and ptgs2 expression, while also increasing superoxide dismutase activity, Ferroportin 1 and glutathione peroxidase 4 expression. Moreover, the regulatory impact of electroacupuncture on ferroptosis may be attributed to its ability to enhance the expression and nuclear translocation of Nrf2. ConclusionsThis study suggested that electroacupuncture could inhibit the neuronal ferroptosis by activating the antioxidant function in neurons through p62/Keap1/Nrf2 signal pathway, thereby improve the cognitive function of AD mice by the neuronal protection effect.

Effect of Serum Breadfruit Leaf Extract (Artocarpus Altilis) on TNF-Α and Sod Levels (Experimental Study on Guinea Pigs Exposed to UVB Light)

Continuous exposure to ultraviolet B (UVB) light can increase the amount of melanin, causing hyperpigmentation on the skin. This process involves the important role of Tumor Necrosis Factor-α (TNF-α) and Superoxide Dismutase (SOD). Artocarpus Altilis contain flavonoids that have anti-inflammatory potential, can reduce TNF-α levels and increase SOD which affects the melanogenesis process. To determine the effect of administering Artocarpus Altilis extract serum on TNF-α and SOD levels in guinea pigs exposed to UVB. This research is an in vivo experimental study with Post Test Only Group design, which was conducted at the IBL FK Laboratory (Integrated Biomedical Laboratory Faculty of Medicine) Unissula. A total of 30 male guinea pigs were divided into 5 groups, namely: Group 1 sham, group 2 negative control, group 3 treated with 2% Artocarpus Altilis extract serum, group 4 treated with 4% serum and group 5 treated with 6% serum. Then analyzed using the One-way ANOVA test to determine differences between groups. The lowest mean TNF-α levels were found in group P2 (4.958), other values were P1 (5.820), P3 (5.964), KS (6.069) and KN (5.811). Meanwhile, the average SOD levels in all groups were not much different, P2 (5.802), P1 (5.975), P3 (5.906), KS (6.054) and KN (6.000). In the One-way ANOVA test on TNF-α and SOD there was no significant difference, p&gt;0.05. Administration Artocarpus Altilis extract serum, especially 4%, caused a decrease in TNF-α levels but was not significant, and there was no increase in SOD levels, in guinea pigs exposed to UVB light.