NEUROCHEMISTRY INTERNATIONAL
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2019
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IF 3.994
Liping Liao,Jinguo Shi,Caibao Jiang,Liantao Zhang,Lisi Feng,Jiayong Liu,Jingxia Zhang
Oxidative stress is an important cause of neurodegenerative diseases . Antioxidant is an potential important method to treat such diseases. The aim of this study is to discover new and effective antioxidants and their mechanism. The neuroprotective effect of six curcumin pyrozole compounds were first evaluated on sodium nitroprusside (SNP) - induced PC12 cell injury by testing cell viability and LDH release. The results showed that four compounds (C1-C4) have more significant protective effects compared to curcumin and edaravone . Furthermore, compounds C1-C4 can attenuate the intracellular ROS , and compound C3 is the most effective one which can preservate the mitochondria function by inhibiting the mitochondrial membrane potential loss and enhance nuclear translocation of Nrf2 in PC12 cell. These results indicated that C3 may be a potential candidate drug for treating neurodegenerative diseases.
研究领域:
药理学
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神经科学
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DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2022
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IF 7.419
Ya Zhang,Qifang Wu,Jian Liu,Zhongshan Zhang,Xiaojing Ma,Yaoyue Zhang,Jiawen Zhu,Ronald W. Thring,Mingjiang Wu,Yitian Gao,Haibin Tong
Insulin resistance is a characteristic feature of type 2 diabetes. Sulforaphane (SFN) is a natural antioxidant extracted from the cruciferous vegetables. Recent study reported that SFN exhibits excellent anti-diabetic effects, however, the underlying mechanism is still unclear. This study aimed to investigate the therapeutic effects of SFN on a high-fat diet (HFD)-induced insulin resistance and potential mechanism. SFN was found to effectively reduce body weight, fasting blood glucose and hyperlipidemia, and improve liver function in HFD-fed mice. Furthermore, SFN effectively increased glucose uptake and improved insulin signaling in palmitic acid (PA)-induced HepG2 cells. SFN also led to increased expression of antioxidant genes downstream of Nrf2 and decreased accumulation of lipid peroxides MDA and 4-HNE, both in vivo and in vitro. Further studies revealed that SFN significantly reduced glutathione peroxidase 4 (GPx4) inactivation-mediated oxidative stress by activating the AMPK and Nrf2 signaling pathways. In PA-induced HepG2 cells and flies , the alleviation of insulin resistance by SFN was diminished by GPx4 inhibitor. Taken together, SFN ameliorated HFD-induced insulin resistance by activating the AMPK-Nrf2-GPx4 pathway, providing new insights into SFN as a therapeutic compound for the alleviation of insulin resistance.
研究领域:
药理学
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内分泌学
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分子生物学
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营养学
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产品关联
DOI
PubMed
高影响因子
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
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2025
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IF 3
Mengying Jin,Xiao Chen,Lanzhuoying Zheng,Yuanyuan Peng,Mingying Lin,Ke Liang,Xinran Liu,Zihan Xu,Yiming Yang,Baozhu Wei,Jing Wan
Background Astaxanthin (ASX), a fat-soluble carotenoid mainly sourced from Haematococcus pluvialis, shows promise for clinical applications in chronic inflammatory diseases. This study investigates whether ASX can mitigate atherosclerosis (AS) by modulating macrophage ferroptosis and provides astaxanthin-loaded polylactic acid-glycolic acid nanoparticles (ASX-PLGA NPs) as comparison. Method ApoE−/− mice were fed a high-fat diet with ASX or statin intervention. Plaque area, lipid aggregation, collagen content, and ferroptosis-related indicators were assessed. Moreover, ASX-PLGA NPs were synthesized and characterized and were used to pretreat macrophages induced with oxidized low-density lipoprotein (ox-LDL). Indicators linked to ferroptosis and oxidative stress were detected. Finally, the expression of nuclear factor erythroid -related factor 2 (NRF2) was evaluated. Results ASX intervention significantly delayed the progression of AS plaques, characterized by reductions in plaque area and increased collagen fibers. The observed improvements in AS were consistent with statins. ASX-PLGA NPs demonstrate good safety and stability and have better therapeutic effects than ASX alone. Indicators linked to ferroptosis and oxidative stress were significantly improved in groups containing ASX in vivo and vitro. Additionally, ASX facilitated the nuclear translocation of NRF2, which could be attenuated with ML385, a specific inhibitor of NRF 2. Conclusion ASX-PLGA NPs have better therapeutic effects than ASX alone. The regulation of NRF2/SLC7A11/GPX4 represents a novel mechanism by which ASX can counteract ferroptosis and impede AS progression.
研究领域:
医学
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药理学
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生物化学
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DOI
PubMed
高影响因子
INFLAMMATION RESEARCH
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2025
·Vol. 74
·期 1
·1-19
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IF 5.4
Weng Xiuhong,Wang Simin,Wang Qing,Wei Mingbo,Cheng Bo
Background Primary Sjögren’s syndrome (pSS) is an autoimmune disease characterized by xerostomia and autoimmune sialadenitis. Interferon-γ (IFN-γ) induces ferroptosis in salivary gland epithelial cells (SGECs), leading to salivary gland (SG) hypofunction. We previously demonstrated the beneficial effects of melatonin (MLT) in alleviating SG dysfunction and inflammation in a pSS animal model. However, the precise underlying mechanism remains unclear. Methods Female NOD/ltj and ICR mice were used as the pSS mouse model and control group, respectively. MLT was administered via intraperitoneal injection to NOD/ltj mice to detect its effect on ferroptosis in SGs. Primary human SGECs and A253 cells were treated with IFN-γand ferroptosis inducers, with or without MLT. Results Exogenous MLT alleviated pathological SG alterations and promoted saliva production through inhibiting SGEC ferroptosis. MLT inhibited SGEC ferroptosis induced by IFN-γ and ferroptosis inducers via nuclear factor erythroid 2-related factor 2/heme oxygenase-1/glutathione peroxidase 4 (NRF2/HO-1/GPX4) pathway activation. Moreover, MLT suppressed the nuclear factor-kappa B (NF-κB) pathway, which is triggered by ferroptosis in SGECs. Nevertheless, ML385-mediated NRF2 inhibition abrogated the antiferroptotic protective effects of MLT on SGECs. Conclusions MLT inhibits SGEC ferroptosis through NRF2/HO-1/GPX4 pathway activation and thus attenuates ferroptosis-triggered NF-κB activity. Melatonin represents a potential therapeutic approach for pSS owing to its capacity to regulate ferroptosis.
研究领域:
免疫学
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细胞生物学
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医学
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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
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2015
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IF 2.532
Pan Chen,Jingjie Li,Xiaomei Fan,Hang Zeng,Rongrong Deng,Dongshun Li,Min Huang,Huichang Bi
Obstructive cholestasis is characterized by impairment of hepatic canalicular bile efflux and there are no clinically effective drugs to cure except surgeries. Previously we revealed that oleanolic acid (OA) protected against lithocholic acid (LCA)-induced intrahepatic cholestasis in mice. Cholestasis caused by LCA is characterized by segmental bile duct obstruction, whether OA possesses the beneficial effect on completed obstructive cholestasis induced by bile duct ligation (BDL) remains unknown. In this study, we demonstrated that BDL-induced mice liver pathological change, and increase in serum levels of ALT, AST and ALP were all significantly reduced by OA (20 mg/kg, i.p.). Meanwhile, OA also lowered total bilirubin and total bile acids levels in serum, as well as total bile acids level in liver, in contrast, urinary total bile acids output was remarkably up-regulated by OA. Gene expression analysis showed that OA caused significant increased mRNA expression of MRP3 and MRP4 located at hepatic basolateral membrane , and restoration of MRP2 and BSEP located at hepatic cannalicular membrane. Furthermore, significant NRF2 protein accumulation in nucleus was also observed in OA treated mice. In mice primary cultured hepatocytes, the effects of OA on MRP2, MRP3 and MRP4 expression were directly proved to be mediated via NRF2 activation, and BSEP downregulation induced by OA was in part due to FXR antagonism. Luciferase assay performed in Hep G2 cells also illustrated that OA was a partial FXR antagonist. Taken together, we conclude that OA attenuates obstructive cholestasis in BDL mice, possibly via activation of NRF2-MRPs and FXR antagonism.
研究领域:
肝病学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
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2018
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IF 5.158
Shijie Li,Zhuoyue Song,Tingting Liu,Jian Liang,Jun Yuan,Zhanchi Xu,Zhanghua Sun,Xiaoping Lai,Qingping Xiong,Danyan Zhang
The purpose of this study was to investigate the effects of Ostrea rivularis polysaccharide (ORP) against testicular oxidative stress injury via kelch-like ECH-associated protein 1-nuclear erythroid 2-related factor 2/antioxidant response element (Keap1-Nrf2/ARE) pathway. In pharmacological experiments in vivo , ORP administration could dose-dependently inhibit body and testicular weight loss, ameliorate epididymal sperm quality and protect reproductive impairment in cyclophosphamide-induced male Balb/c mice. Moreover, the mechanism in vivo might be elucidated that ORP could increase expression level of Nrf2 and its downstream ARE gene battery in the testis, promote production of corresponding antioxidative enzymes and protein, and enhance Keap1-Nrf2/ARE signaling pathway to avoid male reproductive dysfunction. In addition, ORP treatment could improve survival capacity of H 2 O 2 -induced TM4 cells and its antioxidant mechanism in vitro also had been verified to activate Keap1-Nrf2/ARE signaling pathway. Overall, these results showed that ORP as a potent antioxidant could reduce reproductive oxidative stress damage related to Keap1-Nrf2/ARE pathway.
研究领域:
药理学
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生殖生物学
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分子生物学
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DOI
PubMed
高影响因子
TOXICOLOGY AND APPLIED PHARMACOLOGY
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2025
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IF 3.4
Jingjing Chen,Lu Zhou,Mengxin Li,Jun Wang,Yaru Chen,Jing Xia,Yue Lin,Huizhen Chen,Zibo Dong
Chronic Intermittent Hypoxia (CIH) is a central pathological feature of diseases such as obstructive sleep apnea hypopnea syndrome (OSAHS), which induces oxidative stress in lung tissues and leads to lung injury. Atraric acid (AA), a lichen-derived compound, has been reported to possess anti-inflammatory and antioxidant activities. In this study, we investigated the functions and mechanisms of AA in CIH-induced lung injury by constructing a CIH mouse model and an in vitro hypoxia/reoxygenation model in MLE-12 cells. Various methods were employed, including hematoxylin and eosin (H&E) staining, biochemical assay kits, quantitative polymerase chain reaction (qPCR) analysis, protein blotting, immunofluorescence, and flow cytometry. The results showed that AA pretreatment significantly attenuated pathological injury of mouse lung tissue, reduced pulmonary edema, reactive oxygen species (ROS) and malondialdehyde production, as well as the depletion of total antioxidant capacity, catalase and glutathione, and lowered the expression levels of inflammatory factors. Mechanistic studies showed that AA up-regulated solute transport family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) expression and down-regulated prostaglandin-endoperoxide synthase 2 (PTGS2) through activation of the Nrf2 signaling pathway, whereas the Nrf2 inhibitor ML385 completely blocked this protective effect. In conclusion, the present study demonstrates that AA targets the Nrf2 axis, attenuated CIH-induced inflammation, alleviates ROS accumulation, and blocks the vicious cycle of oxidative stress, ferroptosis, and inflammation, making it a promising therapeutic strategy for the treatment of CIH-induced lung injury.
研究领域:
药理学
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分子生物学
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呼吸病学
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生物化学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
EXPERIMENTAL CELL RESEARCH
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2017
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IF 3.546
Yong Yang,Zhiyu Xi,Yuan Xue,Jie Ren,Yuhao Sun,Baofeng Wang,Zhihong Zhong,Guo-yuan Yang,Qingfang Sun,Liuguan Bian
Oxidative stress mediated secondary injury contributes to neurological deterioration after intracerebral hemorrhage (ICH). Astrocytes, the most dominant cells in the central nervous system (CNS), play key roles in maintaining redox homeostasis by providing oxidative stress defense. Hemoglobin (Hb), the primary component released by hemolysis, is an effective activator of astrocytes. Hemin, the product of Hb degradation, is highly toxic due to the induction of reactive oxygen species (ROS). We speculate that Hb-activated astrocytes are resistant to hemin-induced toxicity. To verify our speculation, Hb-pretreated astrocytes were exposed to hemin, intracellular ROS accumulation and cell apoptosis were evaluated. Heme oxygenase 1 (HO-1) and nuclear transcription factor-erythroid 2 related factor (Nrf2) expression were observed to explore the potential mechanism. The results demonstrated that Hb induced upregulation and nuclear translocation of Nrf2 in astrocytes, resulted in HO-1 upregulation, which contributed to reduced ROS accumulation and apoptosis rate . Knocking down Nrf2 expression by siRNA suppressed Hb-induced upregulation of HO-1 expression and increased the susceptibility of Hb-pretreated astrocytes to hemin-induced toxicity. Taken together, Hb-activated astrocytes acquired resistance to hemin-induced toxicity via Nrf2/HO-1 pathway. This phenomenon can be considered as the adaptive self-defense in the pathological process of ICH. Hb pre-warned astrocytes and enhanced their capability of handling the coming hemin “flood”. Nrf2/HO-1 may be employed as a target for neuroprotection after ICH.
研究领域:
神经科学
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药理学
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
MOLECULES
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2018
·Vol. 23
·期 1
·215
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IF 3.098
Xinyan Peng,Chongshan Dai,Quanwen Liu,Junke Li,Jingru Qiu
This study aimed to investigate the protective effect of curcumin against carbon tetrachloride (CCl4)-induced acute liver injury in a mouse model, and to explain the underlying mechanism. Curcumin at doses of 50, 100 and 200 mg/kg/day were administered orally once daily for seven days prior to CCl4exposure. At 24 h, curcumin-attenuated CCl4induced elevated serum transaminase activities and histopathological damage in the mouse’s liver. Curcumin pre-treatment at 50, 100 and 200 mg/kg significantly ameliorated CCl4-induced oxidative stress, characterized by decreased malondialdehyde (MDA) formations, and increased superoxide dismutase (SOD), catalase (CAT) activities and glutathione (GSH) content, followed by a decrease in caspase-9 and -3 activities. Curcumin pre-treatment significantly decreased CCl4-induced inflammation. Furthermore, curcumin pre-treatment significantly down-regulated the expression of TGF-β1 and Smad3 mRNAs (bothp< 0.01), and up-regulated the expression of nuclear-factor erythroid 2-related factor 2 (Nrf2) and HO-1 mRNA (bothp< 0.01) in the liver. Inhibition of HO-1 attenuated the protective effect of curcumin on CCl4-induced acute liver injury. Given these outcomes, curcumin could protect against CCl4-induced acute liver injury by inhibiting oxidative stress and inflammation, which may partly involve the activation of Nrf2/HO-1 and inhibition of TGF-β1/Smad3 pathways.Keywords:curcumin;acute liver injury;Nrf2/HO-1 pathway;oxidative stress;TGF-β1/Smad3 pathway
研究领域:
药理学
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肝病学
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分子生物学
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DOI
PubMed
高影响因子
CHEMICAL & PHARMACEUTICAL BULLETIN
·
2022
·Vol. 70
·期 1
·66-73
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IF 1.903
Li Han,Aimei Chen,Ling Liu,Fang Wang
Despite the precise mechanisms for renal ischemia/reperfusion (I/R)-induced acute kidney injury (AKI) are poorly understood, nuclear factor erythroid 2 related factor 2 (Nrf2) and Toll-like receptor 4 (TLR4) pathways were considered as the important targets. Leonurine (LEO) is a special alkaloid extracted from Chinese motherwort (Leonurus japonicus Houtt), which has an anti-inflammatory effect and reduces oxidative stress. We conducted the study to explore the efficacy of LEO against I/R-induced AKI in rats and further investigated the underlying mechanisms. Ischemic renal injury was induced by temporary vascular clamping for 45 min. We have measured the levels of inflammation-related biomarkers and antioxidative stress markers. Next, Western blot analysis and Real-time PCR were performed to analyze whether the Nrf2 and TLR4/nuclear factor-kappaB (NF-κB) pathways were involved in this process. We found that LEO pretreatment remarkably decreased serum creatinine and blood urea nitrogen (BUN) in I/R rats and attenuated acute tubular damage. In addition, LEO markedly increased the expression of antioxidant proteins and decreased the levels of inflammatory factors. Further study revealed that LEO promoted Nrf2 into the nucleus, promoted the expression of heme oxygenase-1 (HO-1) and quinone oxidoreductase 1 (NQO-1), and suppressed the TLR4/NF-κB signal pathway in kidney tissues of ischemic AKI rats. The study reveals that LEO has a protective effect to prevent ischemic AKI through activation of Nrf2 nuclear translocation resisting oxidative stress injury and inhibition of the TLR4/NF-κB pathway mediated inflammatory gene expression.
研究领域:
药理学
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肾病学
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分子生物学
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免疫学
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产品关联
DOI
PubMed
高影响因子
POULTRY SCIENCE
·
2025
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IF 4.2
Yulong Li,Shu Wang,Rui Feng
Cadmium (Cd) is a non-essential heavy metal that is highly toxic to testicle. Selenium (Se) is known to possess antagonistic effects against Cd toxicity, yet the precise mechanisms through which Se counteracts Cd-induced testicular damage in chickens through Nuclear factor erythroid 2-related factor 2/Heme oxygenase-1 (Nrf2/HO-1) signaling pathway, oxidative stress (OS), apoptosis, and inflammation remained unclear. In the present study, the experimental model of chicken testis was established by incorporating CdCl 2 and Na 2 SeO 3 into the dietary intake. After 60 days, chickens from each group were euthanized, and testicular and serum samples were subsequently collected. Ultrastructural assessment revealed that Se supplementation significantly mitigated the testicular damage induced by Cd. Se effectively suppressed the Cd-induced elevation in ROS, MDA, and H 2 O 2 levels, while also preventing the downregulation of CAT, GSH, and T-AOC levels. Furthermore, Se administration ameliorated the reduction in the expression levels of Nrf2, HO-1, and Bcl-2 induced by Cd, and counteracted the overexpression of Caspase-3, Bax, Cyt-c, and Caspase-9, TNF-α, IL-2, IL-6, and IL-1β. Meanwhile, immunofluorescence data demonstrated that Se attenuated the Cd-induced decrease in Nrf2 and HO-1 expression and the upregulation of IL-6 expression. In conclusion, this study elucidated that Se might mitigate Cd-induced oxidative stress in chicken testicles through the stimulation of the Nrf2/HO-1 signaling pathway, thereby inhibiting apoptosis and inflammation, and was beneficial in reducing Cd-induced testicular injury.
研究领域:
毒理学
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生殖生物学
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营养学
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产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2024
·
IF 5.3
Mingyue Tan,Yunfei Yin,Weixiang Chen,Jun Zhang,Yifeng Jin,Yue Zhang,Lei Zhang,Tingbo Jiang,Bin Jiang,Hongxia Li
Ferroptosis is a newly defined mode of cellular demise. The increasing investigation supports that ferroptosis is a crucial factor in the complex mechanisms of myocardial ischemia–reperfusion (I/R) injury. Hence, targeting ferroptosis is a novel strategy for treating myocardial injury. Although evidence suggests that trimetazidine (TMZ) is potentially efficacious against myocardial injury, the exact mechanism of this efficacy is yet to be fully elucidated. This study aimed to determine whether TMZ can act as a ferroptosis resistor and affect I/R-mediated myocardial injury. To this end, researchers have constructed in vitro and in vivo models of I/R using H9C2 cardiomyocytes, primary cardiomyocytes, and SD rats. Here, I/R mediated the onset of ferroptosis in vitro and in vivo, as reflected by excessive iron aggregation, GSH depletion, and the increase in lipid peroxidation. TMZ largely reversed this alteration and attenuated cardiomyocyte injury. Mechanistically, we found that TMZ upregulated the expression of Sirt3. Therefore, we used si-Sirt3 and 3-TYP to interfere with Sirt3 action in vitro and in vivo, respectively. Both si-Sirt3 and 3-TYP partly mitigated the inhibitory effect of TMZ on I/R-mediated ferroptosis and upregulated the expression of Nrf2 and its downstream target, GPX4-SLC7A11. These results indicate that TMZ attenuates I/R-mediated ferroptosis by activating the Sirt3-Nrf2/GPX4/SLC7A11 signaling pathway. Our study offers insights into the mechanism underlying the cardioprotective benefits of TMZ and establishes a groundwork for expanding its potential applications.
研究领域:
心脏病学
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药理学
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
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