NEUROMOLECULAR MEDICINE
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2025
·Vol. 27
·期 1
·1-14
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IF 3.9
Wang Yiming,Chen Yifei,Yang Jianbo,Sun Wei,Zhang Xiaoning
Post-stroke insomnia (PSI) is a common complication following stroke, which seriously affects patients’ life quality. Electro-acupuncture (EA) is an innovative form of traditional Chinese acupuncture that combines electricity with needles to achieve the prevention and treatment of diseases. However, there is limited understanding regarding the treatment mechanism of EA in PSI. In our study, we aimed to investigate the role of EA on PSI development. Our study findings indicated that the quality of sleep, levels of neurotransmitters 5-hydroxytryptamine (5-HT) and gamma-aminobutyric acid (γ-GABA), and antioxidant levels showed significant improvement following EA treatment in PSI clinical samples and rat models, while the levels of pro-inflammatory factor interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), and astrocyte damage were notably reduced. Furthermore, it was discovered that the levels of sirtuin 1 (Sirt1) were reduced in PSI, a condition that was significantly ameliorated by EA treatment. Additionally, the inhibition of Sirt1 caused a marked elevation in astrocyte apoptosis, inflammatory response, and oxidative stress. Besides, the nuclear factor E2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway was deactivated in the PSI rat model and Sirt1-silenced cells. However, the suppressive impact was successfully counteracted by EA or estazolam (ES), and the overexpression of Nrf2 partially alleviated the increase in apoptosis, inflammation, and oxidative stress caused by Sirt1 knockdown. Taken together, these findings indicated that EA improved sleep quality and silenced Sirt1-induced apoptosis, inflammation, and oxidative stress in PSI by activating the Nrf2-ARE pathway.
研究领域:
神经科学
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中医学
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2019
·
IF 3.571
Yanan Hou,Xinming Li,Shoujiao Peng,Juan Yao,Feifei Bai,Jianguo Fang
The mechanisms underlying neurodegenerative diseases are not fully understood yet. However, an increasing amount of evidence has suggested that these disorders are related to oxidative stress. We reported herein that lipoamide (LM), a neutral amide derivative of lipoic acid (LA), could resist oxidative stress-mediated neuronal cell damage. LM is more potent than LA in alleviating hydrogen peroxide- or 6-hydroxydopamine-induced PC12 cell injury. Our results reveal that LM promotes the nuclear accumulation of NFE2-related factor 2 (Nrf2), following with the activation of expression of Nrf2-governed antioxidant and detoxifying enzymes. Notably, silencing Nrf2 gene annuls the protection of LM, which demonstrates that Nrf2 is engaged in this cytoprotection. Our findings suggest that LM might be used as a potential therapeutic candidate for oxidative stress-related neurological disorders.
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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DOI
PubMed
高影响因子
BIOMEDICAL AND ENVIRONMENTAL SCIENCES
·
2025
·
IF 4.1
Jia Lin Liu,Min Wang,Rui Zhang,Ji Fang Zheng,Xi Xiu Jiang,Qiao Ni Hu
Objective: To explore the protective effects and underlying mechanisms of H 2 S against lipid peroxidation-mediated carbonyl stress in the uranium-treated NRK-52E cells. Methods: Cell viability was evaluated using CCK-8 assay. Apoptosis was measured using flow cytometry. Reagent kits were used to detect carbonyl stress markers malondialdehyde, 4-hydroxynonenal, thiobarbituric acid reactive substances, and protein carbonylation. Aldehyde-protein adduct formation and alcohol dehydrogenase, aldehyde dehydrogenase 2, aldo-keto reductase, nuclear factor E2-related factor 2 (Nrf2), and cystathionine β-synthase (CBS) expression were determined using western blotting or real-time PCR. Sulforaphane (SFP) was used to activate Nrf2. RNA interference was used to inhibit CBS expression. Results: GYY4137 (an H 2 S donor) pretreatment significantly reversed the uranium-induced increase in carbonyl stress markers and aldehyde-protein adducts. GYY4137 effectively restored the uranium-decreased Nrf2 expression, nuclear translocation, and ratio of nuclear to cytoplasmic Nrf2, accompanied by a reversal of the uranium-decreased expression of CBS and aldehyde-metabolizing enzymes. The application of CBS siRNA efficiently abrogated the SFP-enhanced effects on the expression of CBS, Nrf2 activation, nuclear translocation, and ratio of nuclear to cytoplasmic Nrf2 and concomitantly reversed the SFP-enhanced effects of the uranium-induced mRNA expression of aldehyde-metabolizing enzymes. Simultaneously, CBS siRNA reversed the SFP-mediated alleviation of the uranium-induced increase in reactive aldehyde levels, apoptosis rates, and uranium-induced cell viability. Conclusion: H 2 S induces Nrf2 activation and nuclear translocation, which modulates the expression of aldehyde-metabolizing enzymes and the CBS/H 2 S axis. Simultaneously, the Nrf2-controlled CBS/H 2 S axis may at least partially promote Nrf2 activation and nuclear translocation. These events form a cycle-regulating mode through which H 2 S attenuates the carbonyl stress-mediated NRK-52E cytotoxicity triggered by uranium.
研究领域:
毒理学
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细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
Animals
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2025
·Vol. 15
·期 4
·559
·
IF 2.7
Chunjie Hou,Zirou Yu,Chenyu Shi,Ya Huang,Hu Liu
Oxidative stress caused by weaning is widespread in pig breeding and poses a serious threat to the health of piglets. As a feed additive, Brown algae polysaccharides (BAPs) have a good application prospect and have antibacterial, anti-inflammatory, antioxidant, and antiviral activities. The present study was conducted to investigate the effects of BAP on oxidative stress in piglets. The results showed that BAPs alleviated the oxidative stress damage caused by diquat and improved the antioxidant capacity and intestinal barrier capacity of weaned piglets and IPEC-J2 cells. It is worth noting that BAPs also promoted the translocation of Nrf2 from the cytoplasm to the nucleus. These results provide a new way to illustrate the mechanism of BAPs alleviating oxidative stress in piglets. This study investigated the effect of Brown algae polysaccharides (BAPs) on diquat-induced oxidative stress in piglets and IPEC-J2 cells through Nrf2/ARE signaling pathway. In the in vivo model, 24 male piglets of the Duroc × Landrace × Large White breed were selected and divided into 4 groups (n = 6), including the CON group (basal diet), DIQ group (10 mg/kg Diquat), BAP group (1000 mg/kg BAP), and BAP+DIQ group (1000 mg/kg BAP + 10 mg/kg Diquat). Compared with the DIQ group, BAP improved growth performance and the BAP+DIQ group reduced the levels of IL-1β, IL-6, TNF-α, and DAO in plasma, increased VH and VCR, improved jejunal tissue morphology, decreased MDA levels, and increased T-AOC ( p < 0.05). Additionally, the BAP+DIQ group elevated mRNA levels of ZO-1 , and enhanced the protein levels of Occludin, Claudin1, CAT, SOD1, and HO-1 ( p < 0.05). In the in vitro model, the BAP+DIQ group decreased MDA levels, increased T-AOC, elevated mRNA levels of ZO-1 , CAT and SOD2 , as well as protein levels of Claudin1, SOD1, HO-1, and total Nrf2 compared with the DIQ group ( p < 0.05). Furthermore, BAP increased nuclear Nrf2 protein levels, and promoted the translocation of Nrf2 from the cytoplasm to the nucleus compared with the DIQ group ( p < 0.05). In conclusion, BAPs are crucial for enhancing piglets’ antioxidant capacity via Nrf2 pathway activation. These findings highlight BAP’s potential as a natural feed additive to mitigate oxidative stress and improve overall health in piglets. Further research is warranted to explore BAPs as a dietary supplement to support gut health and reduce oxidative stress.
研究领域:
动物营养学
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分子生物学
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DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2018
·
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
Stem Cells International
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2015
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IF 2.813
Meihui Chen,Yu Hou,Dingkun Lin
Polydatin, a glucoside of resveratrol, has been reported to possess potent antioxidative effects. In the present study, we aimed to investigate the effects of polydatin in bone marrow-derived mesenchymal stem cells (BMSCs) death caused by hydrogen peroxide (H2O2), imitating the microenvironment surrounding transplanted cells in the injured spinal cord in vitro. In our study, MTT results showed that polydatin effectively prevented the decrease of cell viability caused by H2O2. Hochest 33258, Annexin V-PI, and Western blot assay showed H2O2-induced apoptosis in BMSCs, which was attenuated by polydatin. Further studies indicated that polydatin significantly protects BMSCs against apoptosis due to its antioxidative effects and the regulation of Nrf 2/ARE pathway. Taken together, our results indicate that polydatin could be used in combination with BMSCs for the treatment of spinal cord injury by improving the cell survival and oxidative stress microenvironments.
研究领域:
药理学
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干细胞生物学
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神经科学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION
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2025
·
IF 3.5
Liang Yongchao,Huo Hongjin,Wei Wei,Wang Dongxuan,Lu Jingjing,Yi Wenjie,Jiang Fei
Purpose Perfluorooctane sulfonic acid (PFOS) is a representative persistent organic pollutant that has been shown to impair male reproductive function. Epidemiological studies and animal models suggest that vitamin D may modify male reproductive function. However, whether 1α,25(OH) 2 D 3 could mitigate the PFOS-induced damage of Sertoli cells, and the underlying mechanisms remain poorly defined. Methods Mouse Sertoli cell line TM4 were pretreated with or without 10 nM or 100 nM 1α,25(OH) 2 D 3 for 6 h, followed by 100 µM or 200 µM PFOS for 24 h. Cell viability was assessed using the CCK8 assay. Reactive oxygen species (ROS) were detected by fluorescent staining, while malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) levels were measured using commercial kits. siRNA transfection, quantitative real-time PCR (qRT‒PCR), and Western blotting were performed to elucidate the underlying mechanisms. Molecular docking studies were conducted to explore the potential binding of PFOS to Keap1. Results PFOS increased MDA contents, decreased GSH levels, and induced cytotoxicity in mouse Sertoli cells. Mechanistically, PFOS might directly bind to Keap1, facilitating its degradation, leading to persistent activation of the Nrf2-ARE pathway. Conversely, 1α,25(OH) 2 D 3 attenuated PFOS-induced cytotoxicity by alleviating the Nrf2-ARE pathway, a protective effect which was abolished by vitamin D receptor (VDR) knockdown. Conclusion PFOS induces cytotoxicity in Sertoli cells by binding to Keap1 and persistently activating the Nrf2-ARE pathway. 1α,25(OH) 2 D 3 emerges as a promising candidate for mitigating PFOS-induced testicular dysfunction. Graphical abstract
研究领域:
毒理学
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分子生物学
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内分泌学
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生殖生物学
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药理学
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DOI
PubMed
高影响因子
AQUACULTURE RESEARCH
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2021
·Vol. 53
·期 5
·1814-1822
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IF 2.082
Bin Xue,Huirong Lv,Yanli Liu,Yang Gao
This study was conducted to investigate the effects of replacing dietary lipid source FO with a terrestrial lipid blend (LB) on the growth performance, body composition and immunity of juvenile Japanese sea bass when the dietary n-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFAs) requirements are met ( Lateolabrax japonicus ). Two types of experimental diets were formulated with the total FO (the control) or the LB (linseed oil and lard = 1:1). A 56-day feeding trial was conducted in floating cages with three replicates for each treatment. The results indicated that a significantly higher specific growth rate (SGR) and feed efficiency ratio (FER) occurred in fish that were fed the LB diet compared with the control group ( p < 0.05). There was no significant difference in the survival rate, body composition or body indicates between the groups ( p > 0.05). The respiratory burst, alternative complement pathway activity, lysozyme activity, cytokine genes expression and air exposure test results indicated that the replacement of FO with LB did not significantly affect the nonspecific immunity or stress resistance ( p > 0.05). The serum antioxidant enzyme activities and liver tissue antioxidant-related gene expression were significantly higher in the control group than in the other group ( p < 0.05). Therefore, the terrestrial lipid blends from linseed and lard (1:1) could be used as an alternative for dietary fish oil without compromising the growth performance, nonspecific immunity and resistance to stress in juvenile Japanese sea bass.
研究领域:
水产养殖学
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营养学
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DOI
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2019
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IF 3.571
Dongwen Hu,Tao Bao,Yang Lu,Hongming Su,Huihui Ke,Wei Chen
This study was aimed to investigate the protective effects of three different mulberry fruit polysaccharide fractions (MFP-I, MFP-II, and MFP-III) against palmitic acid (PA)-induced hepatocyte lipotoxicity and characterize the functional polysaccharide fraction using gel permeation chromatography, high-performance liquid chromatography, Fourier transform infrared spectroscopy, and nuclear magnetic resonance analyses. MFP-I, MFP-II, and MFP-III were isolated from mulberry fruit by stepwise precipitation with 30, 60, and 90% ethanol, respectively. MFP-II at 0.1 and 0.2 mg/mL dramatically attenuated PA-induced hepatic lipotoxicity, while MFP-I and MFP-III showed weak protection. It was demonstrated that MFP-II not only increased nuclear factor erythroid-2-related factor 2 (Nrf2) phosphorylation and its nuclear translocation, thereby activating the Nrf2/ARE signaling pathway, but also enhanced heme oxygenase 1, NAD(P)H:quinone oxidoreductase 1, and γ-glutamate cysteine ligase gene expressions and promoted catalase and glutathione peroxidase activities, which protected hepatocytes against PA-induced oxidative stress and lipotoxicity. Further investigation indicated that the molecular weight of MFP-II was 115.0 kDa, and MFP-II mainly consisted of galactose (30.5%), arabinose (26.2%), and rhamnose (23.1%). Overall, our research might provide in-depth insight into mulberry fruit polysaccharide in ameliorating lipid metabolic disorders.
研究领域:
药理学
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生物化学
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细胞生物学
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营养学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2024
·
IF 4.8
Yilin Pi,Huaiwen Zuo,Yuxin Wang,Weiping Zheng,Huiyuan Zhou,Lamei Deng,Hongli Song
Severe steatosis in donor livers is contraindicated for transplantation due to the high risk of ischemia–reperfusion injury (IRI). Although Ho-1 gene-modified bone marrow mesenchymal stem cells (HO-1/BMMSCs) can mitigate IRI, the role of gut microbiota and metabolites in this protection remains unclear. This study aimed to explore how gut microbiota and metabolites contribute to HO-1/BMMSCs-mediated protection against IRI in severe steatotic livers. Using rat models and cellular models (IAR20 and THLE-2 cells) of steatotic liver IRI, this study revealed that ischemia–reperfusion led to significant liver and intestinal damage, heightened immune responses, impaired liver function, and altered gut microbiota and metabolite profiles in rats with severe steatosis, which were partially reversed by HO-1/BMMSCs transplantation. Integrated microbiome and metabolome analyses identified gut microbial metabolite oleanolic acid as a potential protective agent against IRI. Experimental validation showed that oleanolic acid administration alone alleviated IRI and inhibited ferroptosis in both rat and cellular models. Network pharmacology and molecular docking implicated KEAP1/NRF2 pathway as a potential target of oleanolic acid. Indeed, OA experimentally upregulated NRF2 activity, which underlies its inhibition of ferroptosis and protection against IRI. The gut microbial metabolite OA protects against IRI in severe steatotic liver by promoting NRF2 expression and activity, thereby inhibiting ferroptosis.
研究领域:
肝病学
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移植学
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药理学
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微生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF FOOD SCIENCE AND TECHNOLOGY
·
2024
·Vol. 59
·期 9
·6231-6242
·
IF 2.6
Mengmeng Zhang,Tianchui Wang,Sixian Ou,Yucong Zou,Xuan Xin
Summary Betaine is a natural antioxidant lacking the ability to scavenge free radicals. Although it has been shown to exert antioxidant function by enhancing the expression of antioxidant enzymes, its mechanism has not yet been elucidated. This study explored the role and mechanism of the transcription factor NF-E2-associated factor 2 (Nrf2)-Kelch-like epichlorohydrin-associated Protein 1 (Keap1) antioxidant reaction element (ARE) pathway in betaine-mediated enhancement of antioxidant enzyme expression. Results derived from real-time quantitative PCR, Western blot, quantitative methylation-specific PCR, and inhibitors assay experiments showed that betaine activated the Nrf2-Keap1-ARE pathway, leading to an increase in the mRNA level of superoxide dismutase, glutathione peroxidase, and heme oxygenase-1. The mechanism may involve betaine's promotion of DNA methyltransferase expression, resulting in increased methylation of Keap1 DNA promoter, which ultimately reduces the level of Keap1 mRNA. Therefore, betaine can directly activate the Nrf2-Keap1-ARE pathway by increasing the methylation level of Keap1 DNA promoter, thereby improving the expression of antioxidant enzymes. This study will contribute to unveiling a new antioxidant mechanism for betaine.
研究领域:
分子生物学
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药理学
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生物化学
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DOI
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2018
·Vol. 19
·期 4
·1135
·
IF 3.687
Maiquan Li,Tao Xu,Fei Zhou,Mengmeng Wang,Huaxin Song,Xing Xiao,Baiyi Lu
Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key transcription factor against oxidative stress and neurodegenerative disorders. Phenylethanoid glycosides (PhGs; salidroside, acteoside, isoacteoside, and echinacoside) exhibit antioxidant and neuroprotective bioactivities. This study was performed to investigate the neuroprotective effect and molecular mechanism of PhGs. PhGs pretreatment significantly suppressed H2O2-induced cytotoxicity in PC12 cells by triggering the nuclear translocation of Nrf2 and reversing the downregulated protein expression of heme oxygenase 1 (HO-1), NAD(P)H quinone oxidoreductase 1 (NQO1), glutamate cysteine ligase-catalytic subunit (GCLC), and glutamate-cysteine ligase modifier subunit (GCLM). Nrf2 siRNA or HO-1 inhibitor zinc protoporphyrin (ZnPP) reduced the neuroprotective effect. PhGs showed potential interaction with the Nrf2 binding site in Kelch-like ECH-association protein 1 (Keap1). This result may support the hypothesis that PhGs are activators of Nrf2. We demonstrated the potential binding between PhGs and the Keap1-activated Nrf2/ARE pathway, and that PhGs with more glycosides had enhanced effects.Keywords:Keap1;Nrf2;Neuroprotective;PC12 cells;PhGs
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
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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