RENAL FAILURE
·
2026
·
IF 3.8
Jia Wang,Jin-Wei E.,Jiong Zhang
Roxadustat (ROX) has a protective action against contrast-induced acute kidney injury (CI-AKI). Excessive production of reactive oxygen species (ROS) plays a significant role in exacerbating the deterioration of renal function. Notably, activation of Nrf2/HO-1 signaling can reduce ROS production. We constructed a mouse model of CI-AKI by iohexol injection. The effect of ROX on CI-AKI was assessed by measuring serum blood urea nitrogen (BUN) and creatinine (Cr), evaluating renal histopathology, and analyzing the expression level of Nrf2 and HO-1. Additionally, levels of ROS, malondialdehyde (MDA), proinflammatory cytokines (IL-6, TNF-α, and IL-1β), as well as the activities of antioxidant kinases superoxide dismutase (SOD) and glutathione (GSH), were examined. The results showed that ROX significantly suppresses the iohexol-induced decline in the activity of antioxidant enzymes, increases the levels of ROS, MDA, Cr, IL-6, IL-1β, BUN and TNF-α, and attenuates renal pathological injury. Furthermore, ROX enhanced the iohexol–induced increase in Nrf2 and HO-1 expression. However, these effects of ROX on CI-AKI were abolished by ML-385, a Nrf2 inhibitor. Our findings indicate ROX attenuates CI-AKI by down-regulating inflammation and restoring the balance between oxidative stress and anti-oxidant defenses. This may involve the activation of the Nrf2/HO-1 signaling pathway to clear excessive ROS.
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Aging-US
·
2018
·
IF 5.179
Xingting Liu,Xin Lin,Siyu Zhang,Changquan Guo,Jian Li,Yuling Mi,Caiqiao Zhang
After 480 days of age, high-producing hens are likely to be subject to ovarian aging, mainly due to oxidative stress. In this study, the amelioration of ovarian aging in chickens, using a plant antioxidant, lycopene, was investigated. The activity of the Nrf2/HO-1 pathway in chicken ovaries at different ages (90, 150, 280 and 580 days old) were compared to elucidate any age-related changes. Subsequently, the putative attenuating effect of lycopene (100 ng/mL) on ovarian aging was evaluated through the establishment of a D-gal-induced aging ovarian culture model. The cultured ovarian tissues of young (280 days) and old (580 days) hens were treated with lycopene for 72 h to verify protective effects of lycopene on naturally aged ovaries. Results showed that the Nrf2/HO-1 pathway was down-regulated during the ovarian aging process. Lycopene rescued the decreased antioxidant capacity by increasing the activities of antioxidases and activating the Nrf2/HO-1 pathway in both D-gal-induced and naturally aged ovaries. Moreover, lycopene promoted cell proliferation and inhibited apoptosis in both D-gal-induced and naturally aged ovaries. Lycopene also alleviated D-gal-induced mitochondrial damage in the living granulosa cells. In conclusion, lycopene can effectively ameliorate the oxidative stress in aging hen ovaries via the activation of the Nrf2/HO-1 pathway.
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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
·
生物化学
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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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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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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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Molecular Medicine Reports
·
2022
·Vol. 26
·期 6
·1-11
·
IF 3.423
Wenjuan Guo,Xiaodi Wang,Fang Liu,Shuo Chen,Shuai Wang,Qingrui Zhang,Lan Yuan,Shiyu Du
Ulcerative colitis (UC) is a significant burden on human health, and the elucidation of the mechanism by which it develops has potential for the prevention and treatment of UC. It has been reported that acteoside (ACT) exhibits strong anti‑inflammatory activity. In the present study, it was hypothesized that ACT may exert a protective effect against UC. The effects of ACT on inflammation, oxidative stress and apoptosis were evaluated using dextran sulphate sodium (DSS)‑treated mice and DSS‑treated human colorectal adenocarcinoma Caco‑2 cells, which have an epithelial morphology. The results demonstrated that the ACT‑treated mice with DSS‑induced UC exhibited significantly reduced colon inflammation, as demonstrated by a reversal in body weight loss, colon shortening, disease activity index score, inflammation, oxidative stress and colonic barrier dysfunction. Further in vivo experiments demonstrated that ACT inhibited DSS‑induced apoptosis in colon tissues, as demonstrated by the results of the TUNEL assay and the altered protein expression levels of Bax, cleaved caspase‑3 and Bcl‑2. Furthermore, DSS significantly stimulated the protein expression levels of high mobility group box 1 protein (HMGB1), which serves a central role in the initiation and progression of UC, an effect which was markedly inhibited by ACT. Finally, DSS significantly decreased the protein expression levels of heme oxygenase‑1 (HO‑1) in colon tissues and the effect of ACT on GSH, apoptotic proteins and HMGB1 was markedly attenuated in the presence of the HO‑1 inhibitor tin protoporphyrin. In conclusion, ACT ameliorated colon inflammation through HMGB1 inhibition in a HO‑1‑dependent manner.
研究领域:
药理学
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免疫学
·
胃肠病学
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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
·
心血管疾病
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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
·
分子生物学
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ACS Infectious Diseases
·
2020
·
IF 4.614
Chongshan Dai,Xilong Xiao,Yuan Zhang,Biao Xiang,Daniel Hoyer,Jianzhong Shen,Tony Velkov,Shusheng Tang
Peripheral neurotoxicity often occurs in patients receiving parenteral polymyxin therapy (i.e., colistin methanesulfonate or polymyxin B). The present study aimed to investigate the protective effect of curcumin on colistin-induced peripheral neurotoxicity using a murine model. Female C57BL/6 mice (n = 10 in each group) were randomly divided into the following: (1) control group (saline), (2) curcumin only group (200 mg/kg/day; orally), (3) colistin only group (18 mg/kg/day; i.p.), (4) colistin (18 mg/kg/day) plus curcumin 50 mg/kg/day group, (5) colistin (18 mg/kg/day) plus curcumin 100 mg/kg/day group, (6) colistin (18 mg/kg/day) plus curcumin 200 mg/kg/day group; all mice were treated for 7 days. Orally applied curcumin was detected in the brain, cerebellum, and sciatic nerve. Co-administration of oral curcumin markedly improved colistin-induced impaired sensory and motor dysfunctions in a dose-dependent manner. Curcumin supplementation at 100 and 200 mg/kg significantly decreased lipid peroxidation and upregulated catalase (CAT) and superoxide dismutase (SOD) activities, ATP levels, and Na+/K+-ATPase activity in sciatic nerve tissue, compared to the colistin alone group. Curcumin supplementation at 200 mg/kg upregulated the levels of AKT, NGF, mTOR, Nrf2, and HO-1 mRNA and concomitantly downregulated Bax, caspases-3, and -9 mRNA; it also decreased caspase-3 and caspase-9 activity. In summary, for the first time, our study reveals that the protective effect of oral curcumin on colistin induced peripheral neurotoxicity is associated with the activation of NGF/Akt and Nrf2/HO-1 pathways and inhibition of oxidative stress. This study highlights the potential clinical application of curcumin as an oral neuroprotective agent coadministered during colistin therapy.
研究领域:
药理学
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神经科学
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毒理学
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危险品化学品经营许可证（带存储）