ACS Infectious Diseases
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2020
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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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DOI
PubMed
高影响因子
Oxidative Medicine and Cellular Longevity
·
2021
·
IF 6.543
Haiwen Zhang,Youming Liu,Xin Fang,Lihong Gu,Caiwei Luo,Lu Chen,Qian Wang
Vitamin D 3 , as an indispensable and fat-soluble micronutrient, plays an important role in the health of humans and animals. At present, studies are focusing on the calcium absorption and immunoregulation function of vitamin D 3 ; this study was aimed at exploring the antioxidative stress ability of vitamin D 3 on diquat-induced intestinal dysfunction of ICR mice and the underlying mechanism. The results showed that oral gavage of vitamin D 3 daily significantly improved the body weight gain and immune organ index and significantly reverted the abnormal changes of ALT, AST, SOD, GSH-Px, T-AOC, and MDA in the serum and jejunum induced by diquat. The addition of vitamin D 3 also significantly reduced the concentration of DAO, D-LA, and certain proinflammatory cytokines in serum. Moreover, vitamin D 3 improved the pathological morphology of the duodenum, jejunum, colon, liver, and kidney tissues, and it also largely attenuated the degree of inflammatory infiltration of macrophages and cell apoptotic index of jejunal epithelial tissue induced by diquat. The results demonstrated that vitamin D 3 significantly recovered the intestinal barrier injury by enhancing the expression of mucins and tight junction proteins in the jejunum. In addition, the results indicated that vitamin D 3 could significantly reduce the phosphorylation level of NF- κ B (p65) and enhance the expression of Nrf2 and HO-1 in the jejunum compared with the diquat-induced group. This study suggested that oral administration of vitamin D 3 can protect mice against oxidative damage by inhibiting the phosphorylation level of NF- κ B (p65) and activating Nrf2-related signaling pathways.
研究领域:
药理学
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免疫学
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分子生物学
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毒理学
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DOI
PubMed
高影响因子
CHEMICO-BIOLOGICAL INTERACTIONS
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2019
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IF 3.407
Jialin Xu,Leilei Zhou,Qi Weng,Linxia Xiao,Qingyong Li
Beta-amyloid (Aβ) has pivotal functions in the pathogenesis of Alzheimer's Disease (AD). In the present study, we adopted an vitro model that involved Aβ 25-35 -induced oxidative damage in PC12 cells. Aβ 25-35 (10 μΜ) treatment for 24 h induced significant cell death and oxidative stress in PC12 cells, as evidenced by cell viability reduction, LDH release, ROS accumulation and increased production MDA . (1E,4E)-1, 5-bis(4-hydroxy-3-methoxyphenyl) penta-1, 4-dien-3-one (CB) and (1E, 4E)-1-(3, 4-dimethoxyphenyl)-5-(4-hydroxy-3, 5-dime-thoxyphenyl) Penta-1, 4-dien-3-one (FE), two Curcumin (Cur) analogues displayed neuroprotective effects against Aβ 25-35 -induced oxidative damage and cellular apoptosis in PC12 cells. Here, we investigated three different treatment ways of CB and FE. It was interesting that post-treatment of CB and FE (restoring way) showed similar effect to the preventive way, while attenuating way did not show any protective effect. We found that low dose CB and FE increased transcriptional factor NF-E2-related factor 2 (Nrf2)/hemo oxygenase 1 (HO-1) protein expression and decreased Kelch-like ECH-associated protein 1 (Keap1) in PC 12 cells. In addition, CB and FE promoted the translation of Nrf2 into nuclear and enhanced the activity of superoxide dismutase (SOD)/catalase, which confirmed cytoprotection against Aβ 25-35 -induced oxidative damage. Moreover, CB and FE could increase Bcl-2 expression level, decrease the level of Bax and Cyt-c in Aβ 25-35 -treated PC12 cells. Ultimately, the neuroprotective effect of CB and FE provides a pharmacological basis for its clinical use in prevention and treatment of AD.
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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DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
·
2025
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IF 5.5
Yang Zhang,Han Wang,Ke Liu,Ruimeng Sun,Yurou Wang,Jiayu Guo,Wenxiang Zhou,Haoran Zheng,Yanfei Qi
Acute renal injury (AKI) has a high incidence rate and mortality, but current treatment methods are limited. As a kind of nanomaterial with enzyme-like activity, nanozyme has shown outstanding advantages in treating AKI according to recent reports. Herein, we assess the potential of manganese-based nanozymes (MnO2–BSA NPs) with excellent biosafety in effectively alleviating AKI. Our findings in vitro and in vivo reveal that MnO2–BSA NPs exert regulatory effects on oxidative stress, inflammation, and apoptosis. These effects are mediated through activation of the Nrf2/HO-1 and PI3K/Akt/NF-κB pathways. Notably, it was observed that the cytoprotective effect of MnO2–BSA NPs is abrogated upon inhibition of Nrf2 expression, highlighting the important role of this transcription factor in cellular protection. In summary, the study demonstrates the protective effect of MnO2–BSA NPs in AKI and provides the molecular mechanisms involved, which can contribute to the advancement of potential therapeutic interventions for nanozyme-based treatments.
研究领域:
医学
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生物化学
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纳米医学
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DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2026
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IF 5.2
Tianqi Wang,Shaoze Jing,Ke Ma,Fan Zhang,Bing Wang,Yu Lei,Jun Zhang
Osteoarthritis (OA) is a progressive degenerative joint disorder characterized by articular cartilage degradation, persistent oxidative stress, and chronic inflammation. Targeting oxidative damage within the joint microenvironment represents a promising avenue for disease modification, offering potential to preserve cartilage integrity, alleviate inflammatory cascades, and ultimately delay structural progression. Lipid nanoparticles were prepared by thin-film hydration and extrusion, then embedded into GelMA microspheres via a microfluidic droplet platform with UV crosslinking to form a sustained-release system. Biocompatibility, ROS-scavenging, anti-inflammatory, and chondroprotective effects were evaluated in vitro and in vivo, while transcriptome sequencing was applied to elucidate system-induced molecular alterations. In vitro , Api-LNP@GMS markedly attenuated ROS accumulation and inflammatory responses in IL-1β-stimulated chondrocytes, as demonstrated by ROS fluorescence imaging, immunofluorescence, Western blotting, and qRT-PCR analyses. In vivo , intra-articular administration in anterior cruciate ligament transection (ACLT) rats effectively alleviated joint inflammation while preserving cartilage integrity and functional capacity. Moreover, transcriptome-wide RNA sequencing, integrated with pathway enrichment analysis and validated by molecular assays, revealed robust activation of the Nrf2–HO-1 antioxidant signaling axis. Api-LNP@GMS is a multifunctional antioxidant biomaterial platform that integrates a natural therapeutic with a sustained-release delivery system, offering a safe and effective strategy to reprogram the osteoarthritic microenvironment and mitigate disease progression. Download: Download high-res image (281KB) Download: Download full-size image
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DOI
高影响因子
Frontiers in Neuroscience
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2019
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IF 3.648
Chen Xiao,Xi Zhiyu,Liang Huaibin,Sun Yuhao,Zhong Zhihong,Wang Baofeng,Bian Liuguan,Sun Qingfang
Secondary injuries mediated by oxidative stress lead to deterioration of neurological functions after intracerebral hemorrhage (ICH). Cortical astrocytes are among the most important cells in the central nervous system (CNS), and play key roles in maintaining redox homeostasis by providing oxidative stress defense. Hemin is a product of hemoglobin degradation, which has strong toxicity and can induce reactive oxygen species (ROS). Melatonin (Mel) and its metabolites are well tolerated without toxicity, prevent tissue damage as well as effectively assist in scavenging free radicals. We evaluated the hemin neurotoxicity to astrocytes and the resistance of Mel-treated astrocytes to hemin neurotoxicity. And we found Mel induced PKCα phosphorylation (p-PKC), nuclear translocation of Nrf2 in astrocytes, and upregulation of HO-1, which contributed to the reduction of ROS accumulation and cell apoptosis. Nrf2 and HO1 protein expression upregulated by Mel were decreased after administration of PKC inhibitor, Ro 31-8220 (Ro 31). Luzindole (Luz), a melatonin receptor inhibitor, suppressed p-PKCα, HO-1, and Nrf2 expression upregulated by Mel and increased cell apoptosis rate. The upregulation of HO-1 induced by Mel was depressed by knocking down Nrf2 expression by siRNA, which also decreased the resistance of astrocytes to toxicity of hemin. Mel activates astrocytes through PKCα/Nrf2/HO-1 signaling pathway to acquire resistance to toxicity of hemin and resist from oxidative stress and apoptosis. The positive effect of Mel on PKCα/Nrf2/HO-1 signaling pathway may become a new target for neuroprotection after intracerebral hemorrhage.
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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产品关联
DOI
PubMed
高影响因子
LIFE SCIENCES
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2018
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IF 3.234
Runxiao Lv,Lili Du,Lixin Zhang,Zhiqiang Zhang
Aims Spinal cord injury (SCI) is one of the most devastating central lesions, resulting in serious locomotor deficit. Polydatin is a glucoside of resveratrol with proven anti-cardiovascular, anti-inflammatory and anti-oxidative properties. The main purpose of this study was to investigate whether polydatin could alleviate SCI in rats and explore the underlying mechanisms. Materials and methods SCI rats induced by a weight-drop device were treated with intraperitoneal injection of 20 or 40 mg/kg polydatin. Then the locomotor function of SCI rats was evaluated by the Basso, Beattie and Bresnahan locomotor rating scale, spinal cord edema was measured by the wet/dry weight method, oxidative stress markers were detected by commercial kits and cell apoptosis status was measured by TUNEL staining. In addition, reactive oxygen species (ROS) generation, lactate dehydrogenase (LDH) production and apoptosis status were detected in murine microglia BV2 cells treated with 100 ng/ml lipopolysaccharides (LPS) and 4.0 μM polydatin. The expression of apoptosis-related proteins involved in nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway was measured by western blot. Key findings Our data showed that polydatin treatment improved locomotor performance of SCI rats, as well as reduced oxidative stress and inhibited apoptosis by enhancing Nrf2/HO-1 signaling. In addition, polydatin was found to up-regulate Nrf2 activity and the inhibitory effects of polydatin on oxidative stress and apoptosis in LPS-stimulated BV2 microglia was neutralized by silencing Nrf2 using specific siRNA. Significance We demonstrate that polydatin may protect the spinal cord from SCI by suppression of oxidative stress and apoptosis via improving Nrf2/HO-1 signaling in microglia.
研究领域:
神经科学
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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
FREE RADICAL BIOLOGY AND MEDICINE
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2026
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IF 8
Zhan Wang,Cheng Zheng,Wenzhen Li,Kaung Myat Kyaw,Yunmin Zhu,Yihan Lin,Zhen Lin,Di Wu,Zhiqi Hu,Yang Sun,Kaitao Li
Introduction Androgenetic alopecia (AGA), the most common form of hair loss, lacks ideal therapies due to the limitations of current drugs. Natural compounds with low toxicity and good biocompatibility present promising alternatives. Ginkgolide B (GB), a bioactive component of Ginkgo biloba , possesses multiple biological activities, yet its efficacy and mechanism against AGA remain unexplored. Objectives This study aimed to investigate the hair growth-promoting effect of GB in a dihydrotestosterone (DHT)-induced hair loss model and to elucidate the underlying molecular mechanism. Additionally, a novel detachable microneedle delivery system was developed and evaluated to overcome GB's poor transdermal permeability, thereby enhancing its therapeutic efficacy. Methods The AGA microenvironment was first simulated using DHT-stimulated human dermal papilla cells (HDPCs) in vitro. The molecular mechanism by which GB improves the secretory function of HDPCs was investigated through network pharmacology, western blot, transmission electron microscopy, and immunofluorescence. Subsequently, a detachable microneedle system was designed, in which GB was encapsulated in poly (lactic-co-glycolic acid) (PLGA) microspheres and integrated with the sulfobutylether-β-cyclodextrin (SCD)-based matrix (GB@MS-MN). The therapeutic efficacy of this system was evaluated in a DHT-induced hair loss model. Results GB rescued DHT-induced dysfunction in HDPCs, reversing the aberrant secretion of hepatocyte growth factor (HGF) and dickkopf-1 (DKK1). Mechanistically, GB alleviated DHT-induced endoplasmic reticulum stress (ERS) in HDPCs by activating the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. And GB promoted hair growth in DHT-induced hair loss mice. The GB@MS-MN system demonstrated excellent mechanical properties and targeted follicular delivery and showed superior hair growth promotion compared to free GB and minoxidil. It effectively suppressed follicular ERS, with no observed systemic toxicity. Conclusion In summary, this study confirms that GB protects HDPCs function by suppressing DHT-induced ERS through activation of the Nrf2/HO-1 pathway. Furthermore, a detachable microneedle delivery system based on a PLGA-SCD composite effectively overcomes the transdermal barrier of GB and demonstrates superior hair-promoting efficacy.
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DOI
高影响因子
JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE
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2026
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IF 4
Haixia Han,Juanjuan Gao,Quan Sun,Dandan Tong,Jian Liu,Xiuli Yang,Jingjing Sun,Yue Cui,Juan Wang,Zuoshan Feng,Mingxi Jia
BACKGROUND Acrylamide (ACR), an environmental neurotoxicant prevalent in thermally processed foods, contributes to brain injury via oxidative stress and neuroinflammation. The cumulative effects of long-term low-dose exposure are particularly alarming. As a traditional food ingredient, the inflorescence of Coreopsis tinctoria Nutt. is rich in polyphenolic compounds that exhibit significant anti-inflammatory and antioxidant properties. This study systematically evaluated the neuroprotective potential of Coreopsis tinctoria Nutt. polyphenols (CTNP) against chronic low-dose ACR exposure in mice. RESULTS Behavioral analyses demonstrated that CTNP (0.25–1.00 g kg −1 ) significantly ameliorated ACR-induced gait abnormalities and restored voluntary activity. CTNP mitigated neuronal misalignment and loss of synaptic density in the hippocampal CA1/CA3 regions and markedly reduced serum levels of brain injury markers MBP and GFAP by 30.6% and 41.7%, respectively. Mechanistic investigations revealed that CTNP attenuated oxidative damage via activation of the Nrf2/HO-1 pathway, leading to decreased brain reactive oxygen species and malondialdehyde levels while enhancing catalase, superoxide dismutase and glutathione peroxidase activities. Furthermore, CTNP suppressed MAPK pathway-mediated neuroinflammation, reducing pro-inflammatory factors such as COX-2, TNF- α and IL-1 β . CONCLUSION These findings demonstrate that CTNP, as diet-derived bioactives, mitigate ACR neurotoxicity through coordinated modulation of Nrf2/HO-1 antioxidant and MAPK anti-inflammatory pathways, supporting their potential as a functional food component for preventing environmental toxicant-associated neural damage. © 2026 Society of Chemical Industry.
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DOI
高影响因子
PHYTOMEDICINE
·
2026
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IF 11.3
Chunge Zhang,Shuai Huang,Wenxin Zhang,Hongbo Teng,Yuna Shao,Yihua Zhang,Shihang Ren,Qi Wu,Yan Zhao,Zhaowei Yan
Background Acanthopanax sessiliflorus ( A. sessiliflorus ) extract has been used in various traditional Chinese medicines and compound preparations for the treatment of arrhythmia. Our preliminary studies have demonstrated that A. sessiliflorus extract exerts significant protective effects against arrhythmia induced by barium chloride. The present study aims to elucidate the bioactive components of A. sessiliflorus and to investigate the underlying mechanisms by which it mitigates barium chloride-induced arrhythmia. Methods Network pharmacology was employed to predict the pharmacological profiles of chemical constituents from A. sessiliflorus, followed by a systematic screening of their biological activities. Subsequently, a barium chloride-induced arrhythmia model was established, and the potential therapeutic mechanisms were analyzed using transcriptomics. Functional and histopathological analyses of the rat hearts were performed. Western blot was used to detect the expression levels of the Nrf2/HO-1 axis, connexins, ion channels, and autophagy-related proteins in myocardial tissue and NRVMs. Subsequently, PCR, immunofluorescence, co-immunoprecipitation, and molecular docking were employed to verify the involvement of the targets in the intervention of arrhythmia. Results The results showed that after treatment with divaroside, the arrhythmia and redox system imbalance induced by BaCl₂ in rats were significantly restored. Divaroside can inhibit calcium overload by regulating the expression levels of RyR2 and SERCA2a in the sarcoplasmic reticulum, serving as a means to alleviate arrhythmia. In addition, we have confirmed that autophagy plays a crucial role in arrhythmia, and divaroside can activate autophagy, thereby protecting cardiomyocytes from BaCl₂-induced damage. Finally, it was confirmed that divaroside can weaken the interaction between the Keap1-Nrf2 complex and promote the nuclear translocation of Nrf2, activating the Nrf2/HO-1 axis and regulating the aforementioned pathways to counteract arrhythmia. Conclusion This study suggests that divaroside prevents the occurrence of arrhythmia by activating autophagy and reducing abnormal calcium ion homeostasis through the Nrf2/HO-1 axis.
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产品关联
DOI
PubMed
高影响因子
FASEB JOURNAL
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2022
·Vol. 36
·期 9
·e22505
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IF 5.834
Xia Wu,Xueliang Zhou,Songqing Lai,Jichun Liu,Jianwei Qi
The hallmark feature of Diabetes mellitus (DM) is hyperglycemia which can lead to excess production of reactive oxygen species (ROS) in the myocardium, contributing to diabetic cardiomyopathy (DCM). Nuclear factor erythroid2-related factor2 (Nrf2), a transcriptional activator, enhances its ability to resist oxidative stress by activating multiple downstream anti-oxidants, anti-inflammatory proteins, and detoxifying enzymes. However, the mechanism of Nrf2 signaling in HG-induced DCM is unclear. In this study, we used HG pretreated H9c2 cells as the experimental basis in vitro, and established a high fat-diet, streptozotocin (STZ) induced Type 2 diabetic rat model in vivo. Meanwhile, we used shRNA-Nrf2 and curcumin (CUR) (as an activator) to affect H9c2 cells, to verify the role of the Nrf2 signaling pathway in DCM. The results showed that the excessive production of ROS caused by HG, which could inhibit the activation of Nrf2-related signaling, resulting in a decrease in cell energy metabolism and an increase in cell apoptosis. Surprisingly, we found that the activation of the Nrf2 signaling pathway significantly increased cardiomyocyte viability, reduced ROS formation, increased antioxidant enzyme activity, and inhibited cardiomyocyte apoptosis. In conclusion, these findings conclusively infer that CUR activation of the Nrf2/HO-1 signaling pathway exerts myocardial protection by reducing ROS formation.
研究领域:
药理学
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心脏病学
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糖尿病研究
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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
CARBOHYDRATE POLYMERS
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2024
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IF 10.7
Hongliang Li,Yingmeng Hou,Shiyu Jia,Mingqian Tan,Haitao Wang
Fucoxanthin (Fx) has garnered significant interest due to its exceptional biological properties. However, its efficacy in enhancing food quality and human health is contingent upon the solubility of the compound in water and its physicochemical stability. Therefore, nanocarriers must be developed to enhance the stability and biocompatibility of Fx. In this study, oxidized paramylon and Fx self-assembled nanoparticles (Fx-OEP) were prepared via the anti-solvent method, with a loading rate of 82.47 % for Fx. The Fx-OEP exhibited robust storage and photostability. In vitro simulated digestion assays demonstrated that Fx-OEP effectively protected Fx from premature gastric release, while achieving a release efficiency of 72.17 % in the intestinal phase. Fx-OEP has the capacity to scavenge a range of reactive oxygen species (ROS) induced by cellular oxidative stress. Treatment with Fx-OEP resulted in a significant reduction in ROS accumulation in insulin-resistant HepG2 cells, which was attributed to the activation of the nuclear factor E2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) pathway. This, in turn, activated insulin receptor substrate 1/glucose transporter type 4 (IRS1/GLUT4), promoting cellular glucose absorption and utilization. These findings indicate the potential of self-assembled nanoparticles based on oxidized paramylon as a new type of nanocarrier for delivering hydrophobic substances.
研究领域:
营养学
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药理学
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分子生物学
✓ 已验证
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）