EXPERIMENTAL CELL RESEARCH
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2017
·
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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高影响因子
HISTOCHEMISTRY AND CELL BIOLOGY
·
2025
·Vol. 163
·期 1
·1-15
·
IF 2.1
Zhong Wen-Jing,Xiong Jian-Bing,Zhang Chen-Yu,Jin Ling,Yang Nan-Shi-Yu,Sha Han-Xi,Liu Yu-Biao,Duan Jia-Xi,Guan Cha-Xiang,Zhou Yong,Su Feng
Pulmonary fibrosis (PF) is an insidious, progressive, and fatal age-associated disease that occurs primarily in older adults and has a poor prognosis. Alveolar epithelial cell (AEC) senescence is the critical pathological mechanism of PF. The accumulation of oxygen radicals, commonly referred to as reactive oxygen species (ROS), strongly contributes to cellular senescence. The triggering receptor expressed on myeloid cells-1 (TREM-1) is a pattern recognition receptor. Triggering via TREM-1 results in ROS, leading to the amplification of inflammation. However, whether TREM-1 is involved in PF by inducing oxidative stress to exacerbate AEC senescence remains unclear. We first observed that blockade of TREM-1 during the fibrotic phase attenuated bleomycin (BLM)-induced PF in mice, with decreased expression of senescence-related proteins, including p16, p21, p53, and γ-H2AX, in the lung tissue. Moreover, TREM-1 blockade during the fibrosis stage restored antioxidant levels by increasing the percentage of Nrf2- and HO-1-positive cells in mice with PF. Notably, TREM-1 was highly expressed in surfactant-associated protein (SPC)-positive AECs in mice with PF. In vitro, blocking TREM-1 activated Nrf2 antioxidant signaling, thereby decreasing intracellular ROS levels and diminishing BLM-induced senescence in AECs. Furthermore, inhibition of Nrf2/HO-1 partially counteracted the anti-senescence effect of blocking TREM-1 in BLM-treated AECs. In this study, we reported that TREM-1 stimulated the senescence of AECs, induced ROS and exacerbated PF. We also provide compelling evidence suggesting that the Nrf2/HO-1 signaling pathway underpins TREM-1-triggered senescence. Therefore, our findings provide new insights into the molecular mechanisms associated with TREM-1 and AEC senescence in the pathogenesis of PF.
研究领域:
医学
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分子生物学
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PubMed
高影响因子
MOLECULES
·
2025
·Vol. 30
·期 5
·1103
·
IF 4.6
Bin Zhang,Xiaoyu Wei,Peiwen Du,Huangqun Luo,Lanfang Hu,Liping Guan,Guangying Chen
Polysaccharides are very promising molecules in the field of pharmacotherapy. Knowing this, the aim of this study was to extract, characterize, and evaluate the action of the polysaccharides in noni juice, using biological models of Type 2 diabetes mellitus processes. In this study, one polysaccharide named NJSPd−1 was separated from fermented noni fruit juice. The characterization assay showed that NJSPd−1 had a molecular weight ( Mw ) of 18,545 Da. NJSPd−1 consisted of galacturonic acid, galactose, rhamnose, and arabinose, with a molar ratio of 28.79:20.34:19.80:18.84 according to HPGPC analysis, and the glycosidic bond mainly included →4)- α -D-GalA p -(1→, 4)- β -D-Glc p -(1→, →2)- α -L-Rha p -(1→, and →3)- α -L-Ara f -(1→. The prevention of oxidative stress activities by NJSPd−1 was evaluated using high-glucose-induced oxidative stress in HepG2 cells. In vitro results showed that NJSPd−1 influenced the downregulation of the proteins and genes Nrf2, Keap1, HO-1, and NQO1 in HepG2 cells. These results suggest that NJSPd−1 exerted a protective effect against oxidative stress in HepG2 cells by activating the Nrf2/HO-1/NQO1 signaling pathway.
研究领域:
药理学
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生物化学
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PubMed
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Frontiers in Pharmacology
·
2022
·
IF 5.988
Qian Wang,Xiaoyan Yang,Changwei Zhu,Guodong Liu,Weili Han,Yujun Sun,Lisheng Qian
Benincasa hispida Cogn. ( B. hispida ) is a popular vegetable in China, and studies have been reported on B. hispida polysaccharides (BPS) preparation. However, few studies have been reported on its physicochemical and skincare properties. In this study, we analyzed the physicochemical properties of BPS, free radical scavenging capability, moisturizing and antioxidant activities in vitro and in vivo , respectively. Our results show that BPS was an inhomogeneous acidic polysaccharide that could scavenge a variety of free radicals. Also, BPS had a good moisturizing and antioxidant capability both in vitro and in vivo . Specifically, BPS could alter some key antioxidant enzyme activities and pro-inflammatory factor levels via activating the NRF2/HO-1 pathway, thereby preventing H 2 O 2 -induced reactive oxygen species (ROS) production and apoptosis of HDF-1 cells. Our results suggest that BPS exhibited favorable moisturizing and anti-aging properties and might be an attractive candidate for the development of anti-aging skincare products.
研究领域:
药学
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化妆品科学
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生物化学
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药理学
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高影响因子
Frontiers in Nutrition
·
2022
·
IF 6.59
Feng Y,Gao S,Zhu T,Sun G,Zhang P,Huang Y,Qu S,Du X,Mou D
Context Hyperlipidemia is a highly prevalent risk factor for atherosclerosis and stroke. The currently available medications used to treat Hyperlipidemia cannot improve its oxidative stress damage. Consumption of hawthorn can regulate blood sugar and blood lipids, and its rich fruit acid is a natural antioxidant that can improve oxidative stress damage. Objective The present research aimed to investigate the protective effect of hawthorn fruit acid (HFA) on hyperlipidemia and to determine its potential molecular mechanism. Materials and methods Sprague-Dawley rats were fed a high-fat diet (HFD) to induce hyperlipidemia and treated orally with hawthorn fruit acids (HFA). Serum and liver levels of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), superoxide dismutase (SOD), hydrogen peroxide (CAT), and malondialdehyde (MDA) were measured. Human hepatocellular carcinoma cell lines (HepG2) cells were treated with 0.1 mM oleic acid and HFA (0.125, 0.25 mg/mL), and intracellular TC, TG, HDL-C, SOD, CAT and MDA were measured. Changes in LDLR, HMGCR, Nrf2, HO-1, NQO1 protein and gene expression were analyzed by Western blot and qPCR. Results This study found that HFA treatment effectively reduced the level of triglyceride, cholesterol, and glucose, and attenuated hepatic steatosis in rats. Additionally, oxidative stress damage of rats was effectively reduced by treatment with HFA. Western blot and qPCR analysis indicated that HFA treatment inhibited fat accumulation in HepG2 cells by upregulating LDLR and downregulating HMGCR gene expression. HFA inhibits oleic acid (OA)-induced oxidative damage to HepG2 by activating the Nrf2/HO-1 signaling pathway. Conclusion HFA administration can provide health benefits by counteracting the effects of hyperlipidemia caused by an HFD in the body, and the underlying mechanism of this event is closely related to the activation of the Nrf2/HO-1 signaling pathway.
研究领域:
药理学
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生物化学
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分子生物学
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BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
·
2026
·
IF 4.3
Jingjing Li,Xiaoxia Feng,Ranran Si,Yuanyuan Liu,Zhifang Huo,Huanqing Song,Chuan Zhou
Bronchopulmonary dysplasia (BPD), characterized by inflammation, is a severe pulmonary condition of preterm infants. This study aimed to investigate the role of secreted frizzled related protein 2 (SFRP2) in BPD and to elucidated its underlying mechanisms, focusing on inflammation, apoptosis, and the Nrf2/HO-1 signaling pathway. In vivo neonatal mouse models and in vitro murine lung epithelial-12 (MLE-12) models were established by hyperoxia induction. Administration of recombinant SFRP2 (rSFRP2) aggravated hyperoxia-induced lung injury, reduced alveolation, and increased inflammatory cytokines (TNF-α, IL-1β, and IL-6) in both lung tissues and cells (all P < 0.05). This demonstrated that SFRP2 aggravated hyperoxia-induced inflammation. These results were also evidenced by elevated numbers of inflammatory cells in the BALF and increasing counts of MAC-3 positive cells in the lung tissues of rSFRP2-treated BPD mice (all P < 0.05). rSFRP2 treatment promoted hyperoxia-induced apoptosis of lung tissue in mice and MLE-12 cells, reflected in increased count of TUNEL-positive cells. The Nrf2/HO-1 pathway was inhibited in the lung tissues of mice and MLE-12 cells after hyperoxia induction, and rSFRP2 therapy further suppressed its activity. Rescue experiments demonstrated that the activation of Nrf2 expression mitigated rSFRP2-induced inflammation and apoptosis in MLE-12 cells. Mechanically, SFRP2 promoted competitive binding of BACH1 to the ARE sequence of HO-1, impaired Nrf2 binding, and suppressed antioxidant signaling. We concluded that SFRP2 might exacerbate lung inflammation and apoptosis by inhibiting the Nrf2/HO-1 pathway, thus promoting the progression of BPD.
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FREE RADICAL BIOLOGY AND MEDICINE
·
2024
·
IF 7.1
Deshan Yao,Liuxiang Bao,Sichuan Wang,Meng Tan,Yuanyuan Xu,Tianxu Wu,Zhengang Zhang,Kaizheng Gong
Ischemia-reperfusion (I/R) injury, a multifaceted pathological process, occurs when the prolongation of reperfusion duration triggers ferroptosis-mediated myocardial damage. Isoliquiritigenin (ISL), a single flavonoid from licorice, exhibits a wide range of pharmacological impacts, but its function in ferroptosis caused by myocardial I/R injury remains unclear. This study delved into the protective effect of ISL on myocardial I/R injury-induced ferroptosis and its mechanism. Neonatal mouse cardiomyocytes (NMCM) underwent hypoxia/reoxygenation (H/R) to simulate the pathological process of myocardial I/R. ISL significantly attenuated H/R-triggered production of reactive oxygen species in NMCM, reduced the expression of malondialdehyde and the activity of lactate dehydrogenase, enhanced superoxide dismutase and catalase activity, and increased the expression of nuclear factor E2-related factor 2 (Nrf2) and its downstream heme oxygenase 1 (HO-1), thereby mitigating oxidative stress damage. CCK8 experiment revealed that the ferroptosis inhibitor Ferrostatin-1 significantly improved myocardial cell viability after 24 h of reoxygenation, and ISL treatment showed a similar effect. ISL reduced intracellular free iron accumulation, up-regulated glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11) expression, and inhibited lipid peroxidation accumulation, thereby alleviating ferroptosis. The Nrf2-specific inhibitor ML385 counteracted ISL's defensive role against H/R-triggered oxidative stress damage and ferroptosis. In vivo experiments further confirmed that by regulating the translocation of Nrf2 into the nucleus, ISL treatment increased the levels of HO-1, GPX4, and SLC7A11, inhibited the expression of ACSL4, Drp1 to exert the antioxidant role, alleviated mitochondrial damage, and ferroptosis, ultimately reducing myocardial infarction area and injury induced by I/R. ML385 nearly abolished ISL's protective impact on the I/R model by inhibiting Nrf2 function. In summary, ISL is capable of mitigating oxidative stress, mitochondrial damage, and cardiomyocyte ferroptosis caused by I/R, thereby reducing myocardial injury. A key mechanism includes triggering the Nrf2/HO-1/SLC7A11/GPX4 pathway to prevent oxidative stress damage and cardiomyocyte ferroptosis caused by I/R.
研究领域:
药理学
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心脏病学
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分子生物学
·
细胞生物学
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高影响因子
Molecular Medicine Reports
·
2026
·Vol. 33
·期 4
·1-14
·
IF 5
Xiaoyu Zheng,Jinping Li,Tianyang Hu,Li Tan,Ding Lan,Ying Deng
Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.
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高影响因子
NEUROCHEMICAL RESEARCH
·
2022
·Vol. 48
·期 2
·579-590
·
IF 4.414
Shen Mengya,Zheng Yuantie,Li Ge,Chen Yinqi,Huang Lili,Wu Jianzhang,Hong Chenglv
Abstract Antioxidants represent a potential therapy for cerebral ischemia–reperfusion injury (CIRI). Compounds which exhibit both direct and indirect antioxidative activity may potentially exert improved effects. Hence, we aimed to assess whether the dual antioxidant DH-217, a derivative of DHAP clinically used to treat coronary heart disease, can reduce oxidative stress damage and elucidate the underlying mechanism. Hydrogen peroxide (H 2 O 2 )-induced and Middle Cerebral Artery Occlusion (MCAO)-induced damages were used to imitate oxidative stress. The antioxidation of DH-217 was determined by MTT, ROS, colony and DPPH assay. Besides, immunofluorescence, Real-Time PCR Analyses, western blotting and si-RNA/Plasmid-induced protein expression were used for mechanism validation. DPPH scavenging assay evidenced DH-217 was a well free radical scavenger. Cell survival assay also showed that DH-217 had a significant cytoprotection through direct and indirect clearance mechanisms. Further, it clearly inhibited oxidative stress-induced IkappaB kinase beta (IKKβ) phosphorylation and increased heme oxygenase-1 (HO-1) expression. Significantly, these antioxidant beneficial effects were reversed by HO-1 inhibitor, si-nuclear erythroid 2-related factor 2 (Nrf2) and IKKβ plasmid. Meanwhile, DH-217 had a good neuroprotective effect on CIRI rats. The dual antioxidant DH-217 has potential reference value for drug development of CIRI. Furthermore, inhibition of IKKβ phosphorylation and activation of Nrf2/HO-1 could be a promising antioxidant pathway. Graphical Abstract Dual antioxidant DH-217 not only has the ability of directly scavenging ROS, but also can clear it by targeting IKKβ/Nrf2/HO-1 signal axis. Inhibition of IKKβ phosphorylation and activation of Nrf2/HO-1 may be a promising antioxidant pathway for CIRI.
研究领域:
药理学
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神经科学
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分子生物学
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细胞生物学
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PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
·
2023
·
IF 4.7
Haitong Wu,Haoye Li,Haihua Huo,Xinrun Li,Heyun Zhu,Lijiao Zhao,Jianzhao Liao,Zhaoxin Tang,Jianying Guo
Terbuthylazine (TBA) is one of the most commonly used and effective herbicides. However, due to its affinity for soil organic matter and water solubility, TBA can lead to biological health concerns. This study exposed broilers to TBA (0 mg/kg bw, 0.4 mg/kg bw, 4 mg/kg bw) for 28 days. The results showed significant pathological damage in broiler myocardial tissue, such as widening of the interstitial space, rupture of muscle fibers, and deposition of myocardial collagen fibers. In addition, Under the 0.4 mg/kg bw TBA exposure, myocardial oxidative stress was observed in broilers, which was accompanied by the activation of Nrf2/HO-1 pathway and the increased protein and mRNA levels of NQO1, NOX2 and SOD2 antioxidant enzymes . However, Nrf2/HO-1 protein and mRNA levels were reversed at 4 mg/kg bw TBA exposure. Meanwhile, the Nrf2/HO-1 mediated antioxidant defense was impaired. In contrast with the low dose, the protein and gene expression levels of NQO1, NOX2, and SOD2 were reduced in 4 mg/kg bw TBA group. The expression of GPX4 and SLC7A11 was significantly downregulated at both protein and mRNA levels. Beyond that, ACSL4 expression was significantly up-regulated, and the protein result was consistent with the mRNA expression, demonstrating the occurrence of ferroptosis . In general, TBA exposure activated the Nrf2/HO-1 pathway, resulting in ferroptosis . This study links ferroptosis to the Nrf2/HO-1 pathway, providing new insights into the potential role of TBA in myocardial toxicity.
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FITOTERAPIA
·
2025
·
IF 2.6
Zongchao Li,Ruoxuan Xu,Can Li,Chenglin Chi,Xiaoli Yang,Shufang Yang,Rongxia Liu
The pericarp of Zanthoxylum bungeanum Maxim. (ZBM) is an edible spice with medicinal value, and it has anti-obesity, anti-inflammatory, and cardiovascular protective effects. This study investigated the therapeutic effect of ZBM on atherosclerosis (AS) and its potential mechanisms. An in vivo experimental model of AS was established on apolipoprotein-E deficient (ApoE −/− ) mice to evaluate the efficacy of ZBM. Serum metabolomics combined with the vascular smooth muscle cell (VSMC) proliferation model were subsequently conducted to analyze the mechanisms. Results showed that ZBM effectively alleviated blood lipid disorders, aortic lipid accumulation, and intimal thickness in mice. Metabolomics indicated that ZBM mainly regulated 5 major metabolic pathways, including TCA cycle, steroid hormone biosynthesis, sphingolipid metabolism, glyoxylate and dicarboxylate metabolism, glycerophospholipid metabolism, which affected lipid metabolism and cell proliferation. Further experiments showed that ZBM inhibited VSMC proliferation likely because it blocked the signal transducer activator of transcription 3 (STAT3) phosphorylation and activated nuclear factor E2-related factor-2 (Nrf2)/heme oxygenase-1 (HO-1) pathway, resulting in G0/G1 phase arrest and reactive oxygen species (ROS) clearance.
研究领域:
药理学
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代谢组学
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心血管疾病
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高影响因子
Frontiers in Veterinary Science
·
2021
·
IF 3.412
Peng Xinyan,Dai Chongshan,Zhang Min,Das Gupta Subhajit
Copper overload is an established cause of nephrotoxicity, but the precise molecular mechanism remains unknown. Our study aimed to investigate the molecular mechanism of copper sulfate (CuSO4)-induced nephrotoxicity and the protective effect of the natural compound quercetin using a mouse model. Mice were orally administered CuSO4 only (200 mg/kg per day), or co-administered CuSO4 (200 mg/kg per day) plus quercetin (25, 50, or 100 mg/kg per day), or quercetin only (100 mg/kg per day), or vehicle for 28 days. The blood and kidneys were collected for the examination of serum biomarkers, oxidative stress biomarkers, changes in histopathology and gene and protein expression. Our results show that quercetin supplementation attenuates CuSO4-induced renal dysfunction and tubular necrosis in a dose-dependent manner. Quercetin supplementation at 50 and 100 mg/kg significantly attenuated CuSO4-induced oxidative damage. Quercetin supplementation also inhibited the activities of caspases-9 and−3, and the expression of p53 and Bax mRNAs. Furthermore, quercetin supplementation markedly activated the expression of Nrf2 and HO-1 mRNAs, but inhibited the expression of NF-κB, IL-1β, IL-6, and TNF-α mRNAs. In conclusion, our results revealed that quercetin supplementation could inhibit CuSO4-induced nephrotoxicity in mice via the inhibition of mitochondrial apoptotic and NF-κB pathways and the activation of Nrf2/HO-1 pathway. Our study highlights quercetin as a potential candidate in treating copper overload-induced nephrotoxicity.
研究领域:
药理学
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毒理学
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分子生物学
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高影响因子
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