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
·
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
·
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
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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
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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产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2019
·
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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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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DOI
PubMed
高影响因子
EXPERIMENTAL EYE RESEARCH
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2023
·
IF 3.4
Jingfei Yang,Zhijuan Hua,Zhikun Zheng,Xuan Ma,Liang Zhu,Yan Li
Diabetes retinopathy (DR) is one of the most common microvascular complications of diabetes. Retinal pigment epithelial (RPE) cells exposed to a high glucose environment experience a series of functional damages, which is an important factor in promoting the progression of DR. Acteoside (ACT) has strong antioxidant and anti-apoptotic properties, but the mechanism of ACT in DR is not completely clear. Therefore, the purpose of the present study was to explore whether ACT inhibits the damage to RPE cells in a high glucose environment through antioxidative effects to alleviate the DR process. The DR in vitro cell model was constructed by treating RPE cells with high glucose, and the DR in vivo animal model was constructed by injecting streptozotocin (STZ) into the peritoneal cavity of mice to induce diabetes. The proliferation and apoptosis of RPE cells were detected by CCK-8 and flow cytometry assays, respectively. The expression changes in Nrf2, Keap1, NQO1 and HO-1 were evaluated by qRT‒PCR, Western blot and immunohistochemistry analyses. The MDA, SOD, GSH-Px and T-AOC contents were detected by kits. The changes in ROS and nuclear translocation of Nrf2 were observed by immunofluorescence assays. HE staining was used to measure the thickness of the outer nuclear layer (ONL) of the retina, and TUNEL staining was used to detect the number of apoptotic cells in the retinas of mice. In the present study, ACT effectively ameliorated outer retina damage in diabetic mice. In high glucose (HG)-induced RPE cells, ACT treatment had the following effects: improved proliferation, decreased apoptosis, inhibited Keap1 expression, promoted the nuclear translocation and expression of Nrf2, upregulated NQO1 and HO-1 (the target genes of Nrf2) expression, decreased ROS concentration, and increased the levels of the SOD, GSH-Px and T-AOC antioxidant indicators. However, knockdown of Nrf2 reversed the above phenomena, which indicated that the protective function of ACT in HG-induced RPE cells are closely related to Nrf2. In summary, the present study demonstrated that HG-induced oxidative stress injury is inhibited by ACT in RPE cells and the outer retina through the Keap1/Nrf2/ARE pathway.
研究领域:
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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糖尿病研究
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眼科学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2023
·
IF 5.6
Haochun Guo,Jiajia Chen,Hanxu Yu,Lei Dong,Ran Yu,Qingju Li,Jian Song,Haoyu Chen,Haijun Zhang,Juan Pu,Wanpeng Wang
Background Radiation-induced lung injury (RILI) is a common side effect of thoracic tumor radiotherapy, including early-stage radiation-induced lung injury (RP) and late-stage radiation-induced pulmonary fibrosis (RIPF). Currently, it is urgently needed to clarify the pathogenesis of RILI and find safe and effective RILI treatment methods. Irradiation causes DNA damage and oxidative stress in tissues and cells, induces cellular senescence, and promotes the occurrence and development of RILI. In recent years, Anisodamine (654-2) has shown potential therapeutic value in acute lung injury, acute kidney injury, chlamydial pneumonia, and COVID-19. However, there is currently no research on the mechanism of 654-2-mediated cellular senescence and its preventive and therapeutic effects on RILI. Purpose This study aimed to investigate the protective effect and mechanism of 654-2 on X-ray-induced RILI. Methods In vivo experiments involved a mouse RILI model with 18 Gy X-ray irradiation. Mice were divided into control, model, medication (control + 654-2), and treatment (model + 654-2) groups. And mice in medication and treatment groups were intraperitoneal injection of 5 mg/kg 654-2 every other day until being sacrificed at week 6. In vitro experiments used MLE-12 cells irradiated with 16 Gy and divided into control, model, and model + 654-2（2 μM and 10 μM） groups. Various assays were performed to evaluate lung tissue morphology, fibrosis, apoptosis, cytokine expression, cellular senescence, protein expression, and antioxidant capacity. Results 654-2 mitigated pulmonary pathological damage, inflammation, DNA damage, cellular senescence, and apoptosis in RILI mice and MLE-12 cells. It restored epithelial cell proliferation ability and enhanced antioxidant capacity. Additionally, 654-2 activated the Nrf2/ARE pathway, increased Nrf2 phosphorylation, and upregulated antioxidant gene expression. Inhibition of Nrf2 reversed the effects of 654-2 on ROS production, antioxidant capacity, and cell senescence. Conclusion 654-2 can activate the Nrf2/ARE pathway, enhance cellular antioxidant capacity, and inhibit cellular senescence, thereby exerting a protective effect against RILI.
研究领域:
药理学
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放射生物学
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分子生物学
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呼吸病学
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肿瘤学
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DOI
PubMed
高影响因子
NEUROCHEMICAL RESEARCH
·
2022
·Vol. 48
·期 2
·393-403
·
IF 4.414
Ma Zijian,Ma Yang,Cao Xuefeng,Zhang Yunpeng,Song Tieying
Postoperative neurocognitive impairment (POCD) is a common complication after surgery and anesthesia, especially in elderly patients. Avenanthramide-C (AVC) test is a vascular endothelial cell adhesion molecule inhibitor with strong anti-inflammatory and antioxidant effects. The aim of this study was to investigate the effect and mechanism of AVC on POCD in aged rats to clarify the effect of AVC on POCD in aged rats. The aging rat model was established by continuous 200 mg/kg propofol anesthesia. Repeated propofol anesthesia could severely impair spatial learning ability, memory and cognitive function, and could promote hippocampal apoptosis, oxidative stress injury, neuroinflammation and ferroptosis in aging rats. In addition, AVC not only improved cognitive dysfunction, but also significantly inhibited apoptosis, neuroinflammatory response, ferroptosis and oxidative stress level in the hippocampus of aging rats induced by repeated anesthesia. Further mechanistic studies manifested that the above protective effects of AVC on aging rats induced by repeated propofol anesthesia may be achieved by activating Nrf2/ARE pathway activity. AVC pretreatment has a preventive effect on cognitive dysfunction induced by repeated propofol anesthesia in aging rats, and the preventive effect of AVC may be realized by activating the Nrf2/ARE signaling pathway activity. Our results demonstrate that AVC preconditioning reduces postoperative neuronal loss and neuroinflammation, activates the Nrf2/ARE pathway, reduces oxidative stress injury, and improves POCD in aged rats.
研究领域:
神经科学
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药理学
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老年医学
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麻醉学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2018
·
IF 3.61
Zhisheng Xie,Lingjun Zhong,Yanrao Wu,Xiaomeng Wan,Hua Yang,Xiaojun Xu,Ping Li
Background Diabetic nephropathy (DN), one of the most serious complications of diabetes , is the leading cause of morbidity and mortality of end-stage renal disease. Our previous research found that carnosic acid (CA) or rosemary extract can effectively improve glucose and lipid metabolism disorder by inhibiting SREBPs . Purpose In this study, we aimed to explore the therapeutic effects of CA on the DN. Methods The mice glomerular mesangial cells (mGMCs) were used to evaluate the anti-oxidative and anti-inflammation effects of CA under high glucose (HG) condition. Furthermore, db/db mice and streptozotocin (STZ)-induced diabetic mice were used to investigate the effects of CA against DN in vivo . Results The results showed that CA activated Nrf2, inhibited NF-κB pathway and regulated related downstream genes in mGMC under HG condition. A 14-week treatment of mice with CA reduced water uptake and urine volume, attenuated diabetes-induced albuminuria , increased urine creatinine , and subsequently improved the glomerular sclerosis and mesangial expansion in db/db mice. Similarly, a 20-week oral administration of CA improved kidney damage in STZ-induced diabetic mice. In addition, CA inhibited the expression of profibrotic factors, such as TGF-β1, fibronectin and E-cadherin. Compared to irbesartan , CA exerted better glucose lowering effect, and in kidney, CA was more potent to reduce fibronectin and E-cadherin expression. In all the animal experiment, CA did not lead to abnormal damages to other tissues. Conclusion These findings suggest that CA is a safe compound which exerts the protective effects on diabetes-induced kidney complications.
研究领域:
药理学
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内分泌学
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肾病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）