Increased SOD Activity Research Articles

N-acetylneuraminic acid promotes ferroptosis of H9C2 cardiomyocytes with hypoxia/reoxygenation injury by inhibiting the Nrf2 axis.

To investigate the mechanism through which N-acetylneuraminic acid (Neu5Ac) exacerbates hypoxia/reoxygenation (H/R) injury in rat cardiomyocytes (H9C2 cells). H9C2 cells were cultured in hypoxia and glucose deprivation for 8 h followed by reoxygenation for different durations to determine the optimal reoxygenation time. Under the optimal H/R protocol, the cells were treated with 0, 5, 10, 20, 30, 40, 50, and 60 mmol/L Neu5Ac during reoxygenation to explore the optimal drug concentration. The cells were then subjected to H/R injury followed by treatment with Neu5Ac, Fer-1 (a ferroptosis inhibitor), or both. The changes in SOD activity, intracellular Fe2+ and lipid ROS levels in the cells were evaluated, and the cellular expressions of Nrf2, GPX4, HO-1, FSP1, and xCT proteins were detected using Western blotting. Following hypoxia and glucose deprivation for 8 h, the cells with reoxygenation for 6 h, as compared with other time lengths of reoxygenation except for 9 h, showed the lowest expression levels of Nrf2, GPX4, HO-1, and FSP1 proteins (P<0.001). Neu5Ac treatment of dose-dependently decreased the viability of the cells with H/R injury with an IC50 of 30.07 mmol/L. Reoxygenation for 3 h with normal glucose supplementation and a Neu5Ac concentration of 30 mmol/L were selected as the optimal conditions in the subsequent experiments. The results showed that Neu5Ac could significantly increase SOD activity, Fe2+ and lipid ROS levels and reduce Nrf2, GPX4, HO-1, and FSP1 protein expressions in H9C2 cells with H/R injury, but its effects were significantly attenuated by treatment with Fer-1. Neu5Ac exacerbates ferroptosis of myocardial cells with H/R injury by inhibiting the Nrf2 axis to promote the production of ROS and lipid ROS.

Trehalose Inhibits ferroptosis Through Activating SIRT3/SOD2 Signaling Axis and Alleviates Brain Injury After Traumatic Brain Injury.

Trehalose has neuroprotective effects in neurodegenerative diseases. This study aimed to explore the impact of trehalose on traumatic brain injury (TBI) by investigating its role in neuroprotection. The TBI mice model was established utilizing the cortical impact technique followed by trehalose treatment. Traumatic neuronal injury induced by scratch followed by trehalose treatment was performed to mimic TBI in vitro. Memory function was assessed using the Water maze test. Brain damage was evaluated through various methods including brain water content analysis, Nissl staining, Evans blue exudation, and TUNEL staining. Biochemical and morphological changes related to ferroptosis post-TBI were also examined. The results showed that trehalose was found to enhance spatial memory, reduce brain injury, and inhibit ferroptosis in TBI mice, similar to ferroptosis inhibitors. The influence of trehalose on TBI was reversed by the SIRT3 inhibitor. Trehalose upregulated SIRT3 to increase SOD activity in TBI, which could also be counteracted by the SIRT3 inhibitor. Combining trehalose with a ferroptosis inhibitor had a more significant effect on reducing brain injury and inhibiting ferroptosis. Furthermore, in TBI mice treated with trehalose and SIRT3 inhibitors, the effect of trehalose was reversed by SIRT3 inhibitors, but the addition of ferroptosis inhibitors reversed the effect of SIRT3 inhibitors, as shown by decreased ferroptosis and neuronal apoptosis in damaged brain tissue. In summary, this study provides initial evidence that trehalose plays a crucial role in neuroprotection post-TBI through the SIRT3/SOD2 pathway-mediated ferroptosis.

FOXA2 regulates endoplasmic reticulum stress, oxidative stress, and apoptosis in spermatogonial cells by the Nrf2 pathway under hypoxic conditions.

Hypoxia-caused spermatogenesis impairment may contribute to male infertility. FOXA2 has been found to be abundant in spermatogonial stem cells and critical for spermatogenesis. Here we aimed to explore the roles of FOXA2 in regulating spermatogonial cells against hypoxia stimulation. Our results showed that FOXA2 expression was downregulated in hypoxia-stimulated spermatogonial cells. Overexpression of FOXA2 prevented hypoxia-induced endoplasmic reticulum (ER) stress with decreased expression levels of associated markers including GRP78, CHOP, and ATF-4. FOXA2 overexpression caused a decrease in MDA content and an increase in activities of SOD, CAT, and GSH-Px in spermatogonial cells under hypoxic conditions, implying its inhibitory effect on oxidative stress. Besides, cell apoptosis under hypoxic conditions was also prevented by FOXA2 overexpression, as shown by reduced apoptotic rate and caspase-3 activity. Moreover, we found that hypoxia stimulation inactivated the Nrf2 pathway, which could be prevented by FOXA2 overexpression. Nrf2 knockdown attenuated the effects of FOXA2 overexpression on hypoxia-induced ER stress, oxidative stress, and apoptosis in spermatogonial cells. In conclusion, FOXA2 exerted protective effects on spermatogonial cells against hypoxia-induced ER stress, oxidative stress, and apoptosis via regulating Nrf2/HO-1 signaling. These findings suggested that FOXA2 might be a therapeutic target for treating hypoxia-induced spermatogenesis impairment.

Scutellaria barbata D.Don and Hedyotis diffusa Willd herb pair combined with cisplatin synergistically inhibits ovarian cancer progression through modulating oxidative stress via NRF2-FTH1 autophagic degradation pathway

BackgroundCisplatin (DDP) is one of the most effective anticancer drugs, commonly used to treat advanced ovarian cancer (OC). However, DDP has significant limitations of platinum-based drugs, including chemical resistance and high-dose toxic side effects. Traditional Chinese medicines (TCMs) often presented in the form of formula, in which the herb pair was the basic unit. Scutellaria barbata D.Don and Hedyotis diffusa Willd (SB-HD) are famous TCMs herb pair that have been shown to help treat multiple types of cancers. However, the synergistic effects and mechanism of combination of SB-HD and DDP to enhance DDP chemosensitivity in OC are still unknown.ResultsIn vitro, we found that the optimal proportion of SB-HD to inhibit the proliferation of OC cells was 2:1, SB-HD and DDP were shown to synergistically reduce the viability of OC cells, inhibit the colony formation, promote cell cycle arrest and apoptosis, as well as inhibit cell migration and invasion. In vivo, combination treatment significantly inhibited the growth of subcutaneous tumors in BALB/c nude mice and reduced the toxic side effects of DDP. Mechanistically, SB-HD and DDP combination treatment significantly promoted oxidative stress response, decreased MMP, inhibited ATP production, decreased ROS levels and increased SOD activity, increased the expression of NRF2, HO-1, ATG5 and LC3, decreased the expression of p62 and FTH1 both in OC cells and tumor tissue of mice. Inhibitor 3-MA (Methyladenine, autophagy inhibitor) and Fer-1 (Ferrostatin-1, iron ion inhibitor) can effectively reverse the expression changes of the key target proteins, but not ZnPP (Zinc protoporphyrin, HO-1 inhibitor). Through bioinformatics analysis, it was found that the abnormal expression level of NRF2 and FTH1 mRNA has a high prognostic value, at the same time, the other four key proteins respectively or interacting with NRF2 and FTH1, also play important roles in the occurrence and development of OC.ConclusionOur findings uncover a synergistic effect of SB-HD and DDP against OC through modulating oxidative stress via NRF2-FTH1 autophagic degradation pathway, which may provide an important theoretical foundation for the use of SB-HD and a new strategy for enhancing DDP chemosensitivity as well as reducing toxic side effects.

Clonal Integration Promotes the Photosynthesis of Clonal Plant Under Heterogeneous Pb and/or Pyrene Stress.

Clonal plants can support the growth of their ramets in heterogeneous environments through clonal integration between the ramets. However, the role of clonal integration in modulating ramet photosynthesis under toxic stress, especially combined stress, is unclear. This study examines the impact of clonal integration on Zoysia japonica under three heterogeneous stresses (Pb, pyrene, and Pb+Pyrene) with two stolon connection conditions (connected and disconnected). Our results show that clonal integration significantly enhances PN, gs, Ci, E, and CE while reducing WUE. It also improves ΦPSII, Fv'/Fm', Fv/Fm, Fv/F0, and qP while reducing NPQ. Clonal integration lowers MDA levels, increases SOD activity, and mitigates the decline in CAT and POD activity, resulting in increased biomass under stress. Furthermore, we observed that the synergistic effects of the Pb+Pyrene mixture negatively impacted the adaptability of clonal integration. Our study underscores the role of clonal integration in maintaining photosynthesis and supporting the success of clonal plants in toxic environments.

Investigating the antiproliferative and antioxidant potential of xanthoxylin and of essential oil isolated from Pulicaria incisa (Lam.) DC. herbal medicine.

In this study have been evaluated the antiproliferative and antioxidant activities of Israeli Pulicaria incisa (Lam.) DC. essential oil (Pi1), of essential oil partially purified by xanthoxylin (Pi2), one of its feature metabolites, and the isolated xanthoxylin (Xan). From the compositional analysis carried out by GC-MS oxygenated monoterpenes class was the main class (71.18 %), with cis-chrysanthenol (55.66 %) as the most abundant components, following by carvotanacetone (11.68 %). Other metabolites represented the second class (20.33 %), being xanthoxylin (15.35 %) the principal metabolites, isolated and characterized by NMR tecniques. Pi1 and Xan showed good antioxidant activity causing a clear reduction in ROS levels and an increase in CAT and SOD activity, while Pi2 showed a reduction in enzymatic activity. Furthermore, Pi1 and Xan demonstrated an apoptotic antiproliferative effect in a dose-dependent manner on solid and hematological tumors, unlike Pi2 which showed lower activity. These data showed that P. incisa EO had interesting antioxidant and antitumor activity and that the biological activities exhibited by the essential oil as a whole are mainly due to xanthoxylin.

LncRNA UCA1 enhances NRF2 expression through the m6A pathway to mitigate oxidative stress and ferroptosis in aging cardiomyocytes.

To explore the regulatory mechanism of lncRNA UCA1 and NRF2 in cardiomyocyte aging. In this study, we explored how lncRNA UCA1 regulates NRF2 and its effect on cardiomyocyte aging. H9c2 cardiomyocytes were cultured and treated with H2O2 to simulate cardiomyocyte aging in vitro. The expression levels of lncRNA UCA1 and NRF2 in cells were detected using qRT-PCR. Cell viability was assessed using the CCK8 assay, and cell aging was detected via Sa-β-gal staining. The levels of oxidative stress markers (SOD, MDA, ROS) and the expressions of ferroptosis-related proteins (ACSL4, TFR1, FTH1, GPX4) were measured. The regulatory mechanism between UCA1 and NRF2 was investigated using RIP-qPCR. Additionally, changes in m6A modification levels and the expression of m6A modification-related proteins in cells after UCA1 overexpression were analyzed by western blot. Our results indicate that H2O2 treatment significantly downregulated the expression of lncRNA UCA1 and NRF2. UCA1 overexpression promoted H9c2 cell proliferation, inhibited cell aging, increased SOD activity and the expression of FTH1 and GPX4 proteins, and decreased MDA and ROS content as well as ACSL4 and TFR1 protein expression. RIP-qPCR verified that UCA1 can promote the expression of NRF2 in cells. Overexpression of UCA1 significantly increased the expression of the demethylase FTO, leading to a reduction in m6A modification levels. Furthermore, there was significant enrichment between FTO and NRF2, and overexpression of FTO improved the expression of NRF2 protein in cells. Taken together, lncRNA UCA1 inhibits oxidative stress and ferroptosis, thereby preventing cardiomyocyte aging. This protective effect is likely mediated by increasing the expression of demethylase FTO and reducing m6A modification, which promotes the expression of NRF2.

Shramahara Mahakasya, a traditional polyherbal formulation, induces anti-anxiety activity in hippocampal neurons by effectuating SOD2-mediated protection against oxidative stress

BackgroundShramahara Mahakasya (SM) is an Ayurvedic polyherbal formulation known for its anti-fatigue and anti-anxiety effects on the human body. However, its mechanism of action remains largely unexplored. In this study, we investigated the intricate mechanisms through which SM polyherbal extract exerts neuroprotective and anxiolytic effects in cultured HT-22 cells and rodent models. MethodIn this study, the chemical composition of SM was first identified using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS). The antioxidant potential of SM was evaluated through antioxidant assays such as DPPH, ABTS and FRAP. The neuroprotective activity of SM (200 and 600 μg/mL) was investigated in glutamate (10 mM) assaulted HT-22 cells. The anxiolytic activity of SM (50 and 100 mg/kg) was assessed in a caffeine (50 mg/kg) induced anxiety model of Sprague Dawley rats. The possible underlying mechanisms for the neuroprotective and anxiolytic activities of SM were explored through biochemical assays and brain histology. ResultsOur findings suggest that SM has antioxidant and neuroprotective potential, as evidenced by a decrease in ROS accumulation, Ca2+ overload, mitochondrial membrane potential (MMP) loss, and apoptosis in HT-22 cells subjected to glutamate-induced oxidative stress. The extract also increased SOD2 levels and decreased cleaved caspase-3 levels across various treatment sets. The anxiolytic activity of SM was demonstrated by improved behavior of the animals in the elevated plus maze test and increased SOD activity in the brain. SM exhibited the most effective improvements in anxiety disorder at a dose of 100 mg/kg body weight in rats. ConclusionsThis study is a pioneering investigation depicting the antioxidant, neuroprotective, anti-apoptotic, and anxiolytic potential of SM formulation against glutamate/caffeine-induced oxidative stress and anxiety in both in vitro and in vivo situations. Overall, our study suggests that the regular consumption of SM formulation could effectively prevent anxiety symptoms by reducing oxidative stress in neuronal cells.

Effects of Soluble and Insoluble Fibre on Glycolipid Metabolism and Gut Microbiota in High-Fat-Diet-Induced Obese Mice.

Dietary fibre can alleviate or reduce the risk of obesity and obesity-induced abnormalities in glycolipid metabolism. However, the effects of different types of dietary fibre or their combinations on obesity remain unclear. Here, we explored the effects of different ratios of inulin soluble dietary fibre (ISDF) and barley leaf insoluble dietary fibre (BLIDF) on the body weight, glycolipid metabolism and gut microbiota of obese mice. Seven experimental groups were treated with different combinations of soluble and insoluble fibre, comprising HFD (high-fat diet without dietary fibre), BLIDF, ISDF, I3S1DF (insoluble/soluble = 3:1), I2S2DF (insoluble/soluble = 1:1), I1S3DF (insoluble/soluble = 1:3) and MIX (inulin, BLIDF and matcha powder fibre; insoluble/soluble = 3.6:1) groups. Our results showed that the BLIDF, ISDF and MIX treatments decreased the body weight gain of the HFD mice significantly after eight-week interventions. All the fibre intervention groups except the MIX group displayed lower fasting blood glucose and glycosylated serum protein levels than the HFD group. BLIDF, ISDF, I3S1DF and I2S2DF improved the glucose tolerance of the mice. Moreover, none of the dietary fibre interventions affected the liver lipid metabolism, while I3S1DF and I1S3DF improved the abnormal serum lipid metabolism. BLIDF, ISDF, I3S1DF and I2S2DF reduced the serum IL-6 levels, and BLIDF and I1S3DF increased SOD activity significantly. Additionally, all the dietary fibre interventions decreased the Firmicutes to Bacteroidota (F/B) ratio and increased the abundance of beneficial gut microbes differently. In short, our results suggest that different ratios of soluble and insoluble dietary fibre have unique impacts on mice body weight, glycolipid metabolism, inflammation and gut microbiota. The ratio of soluble to insoluble dietary fibre intake should be considered for specific health goals in the future.

Synergistic antimicrobial effects of ammonium persulfate, ultrasound, and mild heat on Staphylococcus aureus under varied conditions

This study elucidated the antimicrobial effect of ammonium persulfate (PS), ultrasound (US), and 40–60 °C mild heat on Staphylococcus aureus ATCC 27213 under various growth conditions, including non-adaptation, pH-adaptation, and aridity-adaptation, in buffered peptone water (BPW) and on orange peel surfaces. For non-adapted, pH-adapted, and aridity-adapted S. aureus, the combined treatment of PS, US, and mild heat showed a synergistic effect, with log reductions of 2.05, 6.44, and 1.11 log CFU/mL in BPW after 6 min, respectively. Mechanistic experiments showed that pH-adapted S. aureus had increased SOD activity due to oxidative stress from the acidic environment, but the introduction of PS further elevated this stress, leading to greater cell death primarily through membrane damage, as confirmed by TEM, with leakage of nucleic acids and proteins. This technique was applied to an orange peel washing system, effectively inactivating aridity-adapted S. aureus, resulting in 3.51 log CFU/cm2 and 3.20 log CFU/mL reductions on orange peel and in BPW washing water, respectively, after a 6-min treatment, without any quality changes, including color and texture attributes. The enhanced inactivation on orange peel may be attributed to the presence of compounds such as ascorbic acid and limonene, which further activate persulfate and exhibit antimicrobial properties, thereby contributing to the increased efficacy of the treatment. The combined PS, US, and mild heat treatment provides an effective strategy for controlling resilient bacterial strains in the food industry, enhancing food safety through oxidative stress and mild thermal effects.

Isoxanthohumol improves hepatic lipid metabolism via regulating the AMPK/PPARα and PI3K/AKT signaling pathways in hyperlipidemic mice.

Hyperlipidemia presents a significant global healthcare challenge, necessitating innovative therapeutic strategies for more effective outcomes. Recent studies have highlighted the beneficial impact of moderate beer intake on metabolic diseases. The purpose of this research is to explore the possible molecular mechanisms of isoxanthohumol (IXN), the major hop flavonoid in beer, in the treatment of hyperlipidemia. The mice model of acute hyperlipidemia was constructed by intraperitoneal injection of Triton WR-1339. The therapeutic effect of IXN was assessed by biochemical and histological analyses. Furthermore, comprehensive data mining across various public databases was conducted to identify underlying therapeutic targets of IXN on hyperlipidemia. A protein-protein interaction network was constructed to pinpoint hub targets, and subsequent GO and KEGG enrichment analyses were used to elucidate underlying biological functions. Molecular docking was utilized to validate the binding affinity between hub targets and IXN. Western blotting analysis further verified the protein expression of potential IXN targets. IXN administration significantly improved blood lipid and hepatic lipid levels, alongside increased SOD activity and decreased MDA content in hyperlipidemia mice. Histological analyses, including H&E and Oil Red O staining, showed the improvement of hepatic steatosis with IXN treatment. At the molecular level, IXN significantly increased protein levels of p-AMPK, PPARα, p-PI3K, and p-AKT. IXN activates AMPK/PPARα and PI3K/AKT signaling pathways, leading to reduction in lipid accumulation and oxidative stress, and ultimately ameliorating hyperlipidemia.

Purification of mulberry anthocyanins by macroporous resin and its protective effect against H2O2-induced oxidative stress in vascular endothelial cells

Vascular endothelial cells (VECs), which are cells located in the inner layer of the vessel wall, maintain the homeostasis of the microenvironment; however, a large accumulation of reactive oxygen species can cause cellular damage. In this study, mulberry anthocyanins were enriched and purified by macroporous resin; the protective effect of mulberry anthocyanins against H2O2-induced injury to VECs was investigated. The results showed AB-8 macroporous resin was suitable for the purification of mulberry anthocyanins, the purity was as high as 82.37% ± 1.79%. Mulberry anthocyanins were effective in restoring H2O2-induced reduction in vascular cell viability, and showcased protective effects against apoptosis. Meanwhile, mulberry anthocyanins increased SOD activity, while it decreased the level of MDA and Xanthine oxidase-1 (XO-1), thus further enhancing the antioxidant defense of VECs. This shows that mulberry anthocyanins can be used as antioxidants and play a positive role in the prevention of cardiovascular diseases, and have certain development value.

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.

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 &gt; 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 &lt; 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 &lt; 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.

Selenomethionine and Allicin Synergistically Mitigate Intestinal Oxidative Injury by Activating the Nrf2 Pathway.

Oxidative stress frequently contributes to intestinal barrier injury in animals and humans. It was reported that both Selenomethionine (SeMet) and allicin exhibit protective effects against a range of diseases caused by oxidative stress. This study aimed to investigate the synergistic antioxidant effects and underlying mechanisms of SeMet and allicin on a H2O2-induced intestinal barrier injury model using IPEC-J2 cells and mice. The results showed that H2O2 induced severe oxidative stress, including a decrease in cell viability, antioxidant level, migration capacity, and cell integrity. SeMet and allicin exhibited significant synergistic anti-oxidative effects on intestinal epithelial cells. The combined use of SeMet and allicin increased SOD activity, GSH content, and GSH/GSSG ratio while decreasing MDA, NO, and ROS content levels. Furthermore, we found that SeMet and allicin synergistically activated the nuclear factor erythroid-related factor 2 (Nrf2)-NAD(P)H dehydrogenase [quinone] 1 (NQO1) signaling pathway and down-regulated endoplasmic reticulum stress (ER stress)-related proteins. However, the synergistic antioxidative and intestinal barrier protective effects of SeMet and allicin were abolished by Nrf2 inhibitor ML385 in vitro and in vivo. In conclusion, SeMet and allicin synergistically attenuate intestinal barrier injury induced by excessively oxidative stress through the activation of the Nrf2 signaling pathway and inhibition ER stress. These findings support that the combined use of SeMet and allicin could enhance antioxidative properties and alleviate intestinal injury in further clinical practice.

Screening the active ingredients of plants via molecular docking technology and evaluating their ability to reduce skin photoaging.

The active ingredients of plants were screened by molecular docking technology and the result were verified. According to the verification results of molecular docking, the five active ingredients were combined in equal proportions to form a compound drug. In the HaCaT photoaging model, the effects of the compound drug on antioxidant and senescence-associated secretory phenotype (SASP) factors of the NF-κB and MAPK pathways were studied via SOD and MDA kits, DCFH-DA fluorescent probes and ELISA. In the skin photoaging model, the effects of the compound drug on antioxidants and the SASP factors of the NF-κB and MAPK pathways were studied via SOD, MDA, and CAT kits and ELISA. The results revealed that the compound drug increased SOD activity, decreased the MDA content and intracellular ROS, inhibited IL-6 in the NF-κB pathway, and inhibited MMP-1 and collagen I in the MAPK pathway. The results of HE, Masson and Victoria blue skin staining revealed that the compound drug inhibited abnormal thickening of the epidermis, abnormal breaking and accumulation of collagen fibers and elastic fibers, and maintained their orderly arrangement. Moreover, the results revealed that the compound drug increased SOD, CAT and collagen I, and reduced the MDA content, the SASP factors IL-6 and TNF-α of the NF-κB pathway, and the SASP factors MMP-1 of the MAPK pathway. The above results indicate that the active ingredients of the compound drug screened by molecular docking have the potential to reduce skin photoaging.

M6A methyltransferase ZC3H13 improves pulmonary fibrosis in mice through regulating Bax expression

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease. N6-methyladenosine (m6A) is a reversible RNA modification that was shown to be associated with IPF development. The present study aimed to explore the function and potential mechanism of the m6A methylation enzyme zinc finger CCCH-type containing 13 (ZC3H13) in IPF. In the study, bioinformatic screening yielded a differentially expressed m6A gene, ZC3H13, which was down-regulated in GEO microarrays, BLM-induced mouse models, and cellular models. Overexpression of ZC3H13 reduced histopathological damage of lung tissues in mice, mitigated fibrosis (including reduced α-SMA, collagen Ⅰ, and Vimentin levels, and elevated E-cadherin levels), decreased lung/body weight ratio and lung hydroxyproline levels, reduced oxidative stress (increased SOD activity and GSH-Px activity and decreased MDA levels), suppressed apoptosis within lung tissues and MLE-12 cells, promoted Bcl-2 expression, and inhibited Bax expression. Bax expression was found to be negatively correlated with ZC3H13 expression by correlation analysis. ZC3H13 could bind Bax mRNA and promote its m6A methylation through reading protein YTHDC1, thereby inhibiting its stability. Bax inhibition ameliorated BLM-induced MLE-12 cell dysfunction and partially abrogated the inhibition of MLE-12 cell function by ZC3H13 downregulation. In conclusion, m6A methyltransferase ZC3H13 impedes lung epithelial cell apoptosis and thus improves pulmonary fibrosis by promoting Bax mRNA m6A methylation and down-regulating Bax expression through reading protein YTHDC1.

Neuroprotective effect of Lannea egregia Alkaloid-rich leaf extracts in streptozotocin-induced diabetic rats

BackgroundStudies suggest that medicinal plant extracts can help reduce the neuron degeneration associated with diabetes. In this study, the neuroprotective effect of the alkaloid-rich extract from the leaves of Lannea egregia was assessed in rats with diabetes induced by streptozotocin (STZ). MethodsLannea egregia alkaloid-rich analysis was carried out via a known procedure. The rats were randomly assigned into five treatment groups (n = 8): normal control, diabetic-induced rats (45 mg/kg STZ), and diabetic rats treated with low doses of Lannea egregia leaf alkaloid-rich extract (50 mg/kg b.w, LEL) and high (100 mg/kg b.w, LEH) (300 mg/kg and 150 mg/kg), and metformin (200 mg/kg). On 22nd day of the experiment, animals were sacrificed, and their blood and brains were collected for neuro-biomarker analysis. ResultsDiabetic-induced rats that received metformin, LEL and LEH exhibited considerably reduced levels of dopamine, serotonin, norepinephrine, NO, MDA, and AChE, BChE activities when compared to untreated diabetic animals. Additionally, rats with diabetes that received treatment with metformin, LEL and LEH displayed a noticeable increase in ENTPDase, Na/K ATPase, GST, CAT, GPx, and SOD activities when compared to the untreated diabetic rats. Histological examination revealed improved brain architecture in the treated groups in contrast to those in diabetic-induced rats. ConclusionThe alkaloid-rich extracts of Lannea egregia might be effective in normalizing brain damage caused by complications of diabetes mellitus.

The use of chitosan as an antioxidant in the feed of cultivated P. vannamei shrimp against oxidative stress induced by exposure to microplastics

Microplastics (MP) are omnipresent in aquaculture and can induce several toxic effects, mainly oxidative stress. Therefore, alternatives to minimize these effects are welcome. In this study, chitosan (1 and 3 g/kg) was supplemented through the feed of farmed shrimp P. vannamei for 30 days. After this period, the shrimp were exposed to MP (0.5 mg/L) for 7 days. The results showed the presence of MP in hepatopancreas, gills and muscle. Hepatopancreas morphological alterations, as well as lipid peroxidation, a decrease in GSH level, and an increase in SOD activity indicated an oxidative stress that was reversed by chitosan. The muscle was also affected by MP, showing decreased CAT activity and increased SOD activity, though no lipid peroxidation was observed. In muscle, chitosan reversed the SOD increase to basal activity. The results obtained showed that chitosan was more effective against oxidative stress than in preventing accumulation and histological damage.

Fermented Fish Collagen Attenuates Melanogenesis via Decreasing UV-Induced Oxidative Stress.

Excessive melanogenesis leads to hyperpigmentation-related cosmetic problems. UV exposure increases oxidative stress, which promotes melanogenesis-related signal pathways such as the PKA, microphthalmia-associated transcription factor (MITF), tyrosinase (TYR), tyrosinase-related protein-1 (TRP1), and tyrosinase-related protein-2 (TRP2) pathways. Glycine is a source of endogenous antioxidants, including glutathione. Fermented fish collagen (FC) contains glycine; thus, we evaluated the effect of FC on decreasing melanogenesis via decreasing oxidative stress. The glycine receptor (GlyR) and glycine transporter-1 (GlyT1) levels were decreased in UV-irradiated keratinocytes; however, the expression levels of these proteins increased upon treatment with FC. The FC decreased oxidative stress, as indicated by the decreasing expression of NOX1/2/4, increased expression of GSH/GSSG, increased SOD activity, and decreased 8-OHdG expression in UV-irradiated keratinocytes. Administration of conditioned media from FC-treated keratinocytes to melanocytes led to decreased p38, PKC, MITF, TRP1, and TRP2 expression. These changes induced by the FC were also observed in UV-irradiated animal skin. FC treatment increased the expression of GlyR and GlyT, which was accompanied by decreased oxidative stress in the UV-irradiated skin. Moreover, the FC negatively regulated the melanogenesis signaling pathways, leading to decreased melanin content in the UV-irradiated skin. In conclusion, FC decreased UV-induced oxidative stress and melanogenesis in melanocytes and animal skin. FC could be used in the treatment of UV-induced hyperpigmentation problems.