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
Frontiers in Immunology
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2026
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IF 7
Jinli Ma,Luya Pu,Yundong Zhang,Baiao Wu,Rui Fei,Dongmei Han,Miao Hao,Jianshi Du
BackgroundSecondary lymphedema leads to progressive tissue remodeling and immune dysregulation. Dysregulation of macrophage polarization critically influences pathological progression. Oxidative stress and mitochondrial homeostasis are the critical components of secondary lymphedema.MethodsA secondary lymphedema model and an LPS-induced in vitro cell injury model were established. Mitochondrial dynamics were evaluated using the ROS assay, mitochondrial membrane potential analysis and mPTP opening assays. Mechanistic investigations included Nrf2 nuclear translocation analysis via immunofluorescence, western blotting, and pharmacological inhibition of exosome biogenesis using GW4869.ResultsSecondary lymphedema tissues exhibited a significant imbalance in M1/M2 macrophage infiltration (with an increase in M1 and decrease in M2), along with elevated IL-1β levels. M2-Exo significantly prevents the proliferation, migration, and tube formation of human lymphatic endothelial cells and alleviated the mitochondrial damage induced by LPS. This mechanism may involve activation of Keap1-Nrf2 signaling.ConclusionM2 macrophage exosomes activated the Nrf2 anti-oxidative stress pathway. This activation improves mitochondrial homeostasis and enhances the function of human lymphatic endothelial cells by delivering active ingredients, offering a new strategy for the treatment of secondary lymphedema.
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DOI
PubMed
高影响因子
EXPERIMENTAL BIOLOGY AND MEDICINE
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2023
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IF 3.2
Jinhong Tian,Shuaishuai Zhang,Lu Li,Xueman Lin,Yongmei Li,Kunlu Zhao,Fengxin Zheng,Yongjun Chen,Yang Yang,Ting Wu,Jianxin Pang
Excessive acetaminophen (APAP) application is a major cause of drug-induced liver injury (DILI). Febuxostat (Feb), a drug for reducing uric acid (UA) levels, was demonstrated to relieve hepatic inflammation and reverse organ functions. However, the effect of Feb on APAP-induced DILI and its mechanisms have not been fully explored. In this study, Feb (10 mg/kg) was given to mice by gavage 1 h after APAP (300 mg/kg, i.g.) induction. Serum and liver samples were collected 12 or 3 h after APAP challenge. Feb treatment was found to remarkably improve APAP-induced DILI, as evidenced by reduced serum ALT, AST and UA levels, pathomorphology, inflammatory, and oxidative responses. Consistently, treatment with Feb also reduced the cell injury induced by APAP in LO2 cells. Mechanistically, Feb induced GPX4 expression, activated the Keap1/Nrf2 pathway, and inhibited the TLR4/NF-κB p65 pathway. Feb also inhibited glutathione (GSH) depletion and Jun N-terminal kinase (JNK) activation in the early injury phase. Notably, pretreatment with Feb for 3 days also revealed preventive effects against APAP-induced DILI in mice. Overall, our data revealed a potential health impact of Feb on APAP-mediated DILI in vivo and in vitro, suggesting that Feb might be a potential candidate for treating DILI.
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DOI
PubMed
高影响因子
Advanced Healthcare Materials
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2024
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IF 10
Lulu Liu,Chenxin Lu,Zhenchao Tao,Zhengbao Zha,Hua Wang,Zhaohua Miao
Polydopamine nanomaterials have emerged as one of the most popular organic materials for management of oxidative stress-mediated inflammatory diseases. However, their current anti-inflammatory ability is still unsatisfied because of limited phenolic hydroxyl groups and oxidation reaction-medicated reactive oxygen and nitrogen species (RONS) scavenging. Herein, via fusing dimension engineering and surface charge engineering, we reported two-dimension (2D) cationic polydopamine nanosheets (PDA NSs) capable of scavenging multiple danger signals to enhance anti-inflammatory capability. Compared with conventional spherical polydopamine nanoparticles, 2D PDA NSs exhibited 3∼4-fold enhancement in RONS scavenging capability, which should be attributed to high specific surface area and abundant phenol groups of 2D ultrathin structure. To further enhance the anti-inflammatory ability, polylysine molecules were absorbed on the surface of PDA NSs to endow the scavenging capability of cell-free DNA (cfDNA), another typical inflammatory factor to exacerbate the pathogenesis of inflammation. Molecular mechanisms revealed that cationic PDA NSs could concurrently activate Keap1-Nrf2 and block TLR9 signaling pathway, achieving synergistical inflammation inhibition. As a proof of concept, cationic PDA NSs with RONS and cfDNA dual-scavenging capability effectively alleviated the inflammatory bowel disease in both delayed and prophylactic models, much better than the clinical drug 5-aminosalicylic acid. This article is protected by copyright. All rights reserved
研究领域:
材料科学
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纳米技术
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药学
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炎症研究
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产品关联
DOI
PubMed
高影响因子
FOOD RESEARCH INTERNATIONAL
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2025
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IF 8
Chi Feng,Xichuang Cheng,Mula Na,Fenglun Zhang,Jiufang Duan,Li Ji,Jianxin Jiang
Galactomannan comes from a wide range of plant resources and has some biological activities, but its bioavailability is limited due to its large molecular weight and complex structure. In this study, three degradation methods (H 2 O 2 , ultrasound, and β-mannanase) combined with ethanol fractional precipitation (25 %, 50 %, and 75 %) were used to degrade and separate Gleditsia sinensis galactomannans (GSG), and the physicochemical properties and biological activities of GSG after degradation were analyzed. Comprehensive comparison indicates that H 2 O 2 exhibits had a better degradation effect. After 4 h of degradation using 4 % H 2 O 2 , the yield of GSG precipitated with 50 % ethanol was 37.06 % (the yield of undigested GSG is 1.80 %). Simultaneously, the molecular weight (reduced from 225.25 to 36.87 kDa) and viscosity were significantly reduced under this condition, while the solubility was increased. In addition, the low-molecular-weight GSG (LGSG) obtained by 4 % H 2 O 2 /50 % ethanol showed the strongest free radical scavenging activity in vitro . Furthermore, the results of in vivo antioxidant assays showed that LGSG inhibited Aflatoxin B1-induced developmental toxicity by regulating gene expression in the Keap1 / Nrf2 pathway. LGSG also promoted Nrf2 -mediated expression of the lipid metabolism genes ppar-α and cpt1 , while suppressing expression of the fatty acid synthesis genes fas and scd-1 . Therefore, the liver recovered from lipid peroxidation induced nonalcoholic fatty liver disease (NAFLD). The present study introduces a method for green and efficient preparation of LGSG, indicates its potential as a nutritional product.
研究领域:
食品科学
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生物化学
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医学
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产品关联
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
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2025
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IF 3.5
Yue Che,Xiaozhu Wang,Qian Li,Xiyi Peng,Zhen Liu,Wenhui Xu,Mei Jing,Ting Wang,Jian Gao,Weiling Wang
A B S T R A C T Exposure to 4-vinylcyclohexene diepoxide (VCD) has been associated to reproductive toxicity, However, the dynamic ovarian function alterations over time in rats and the underlying mechanisms remain unclear. This study investigated the effects of VCD on ovarian function in female Sprague-Dawley (SD) rats on the 25, 60 and 135 days after VCD injection and discovered related mechanisms. Our results showed that VCD had little ovotoxicity on the 25 th day, as no significant changes were observed except for the reduction of preantral follicles. However, on the 60 th day and 135 th day, rats exhibited irregular estrous cycles, abnormal serum sex hormone levels, ovarian morphological damage, decreased primordial and preantral follicles, and increased atretic follicles. We further found that on the 60 th and 135 th day, VCD might exert ovotoxicity by decreasing antioxidant enzyme levels, inhibiting of the Kelch-like ECH-associated protein 1 (KEAP1)/nuclear factor erythroid 2-related factor 2 (NRF2) and PTEN-induced putative kinase 1 (PINK1)/E3 ubiquitin ligase (Parkin) signaling pathway. Interestingly, on the 25 th day, KEAP1/NRF2 and PINK1/Parking signaling pathway were activated. This study provided a wider application in using laboratory rodents as a model of ovarian failure and highlighted that VCD-induced ovotoxicity was linked to the regulation of the KEAP1/NRF2 and PINK1/Parkin signaling pathways.
研究领域:
生殖毒理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2026
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IF 12.5
Yana Ma,Wen Luo,Weijia Zhu,Zhichao Deng,Shijun Xu,Hang Yuan,Wei-jun Fan,Quanjun Yao,Wei Yao,Ho-Young Song,Mingzhen Zhang,Jizhao Wang,Hongtao Hu
Oxidative stress, resulting from excessive reactive oxygen species (ROS), is critically involved in the development and progression of inflammatory diseases such as inflammatory bowel disease. Therefore, targeting ROS for the treatment of inflammation holds great potential, and the underlying mechanism is of great significance for clinical medication. In this work, carbon dots (C-dots) based on chrysanthemum as carbon source were obtained through a hydrothermal method. The as-prepared C-dots exhibited favorable ROS scavenging capacity and biocompatibility. The ROS level and the oxidative damage were reversed, the expression of proinflammatory factors was reduced, and the disrupted barrier was recovered by chrysanthemum-derived C-dots in the cellular inflammatory model. The anti-inflammatory effects were also validated in mice colitis model. Mechanistically, the chrysanthemum-derived C-dots regulated the Keap1/Nrf2 antioxidant signaling and inhibited the NF-κB/NLRP3 inflammasome-mediated inflammatory signaling, thereby restoring redox homeostasis and modulating the inflammatory microenvironment. Collectively, the C-dots from chrysanthemum with preferable biocompatibility hold a bright prospect in inflammation resolution through remodeling redox and inflammatory microenvironment.
✓ 已验证
DOI
高影响因子
FOOD RESEARCH INTERNATIONAL
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2025
·
IF 8
Wei Cui,Yong Xie,Yinghui Zhang,Xinlian Su,Tianqi Cui,Xingguang Chen,Zhaoming Wang,Feiran Xu,Hui Zhou,Baocai Xu
Achieving the therapeutic goal of treating diseases by effectively controlling the excessive accumulation of intracellular free radicals is still very challenging, which motivates researchers to develop efficient novel antioxidant peptides from sustainable resources continuously. This study first pioneered a probiotic-assisted enzymatic hydrolysis of hemoglobin, which obtained 149 peptides. Two antioxidant peptides were rapidly screened using advanced molecular dynamics simulation techniques, revealing their molecular interaction mechanisms with Keap1. It was found that GLWGKV occupied six binding sites for Keap1 to form hydrogen bonds with Nrf2, whereas LIVYPW occupied two binding sites, and the binding free energy of GLWGKV to Keap1 was lower binding more stable. Cellular experiments confirmed that GLWGKV up-regulated the expression of related proteins and increased antioxidant enzyme activities, thereby attenuating H 2 O 2 -induced oxidative damage in Caco-2 cells. This research increases the economic added value of animal blood and demonstrates its great potential for development in functional foods.
CAS / MDL:
研究领域:
食品科学
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生物化学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food & Function
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2023
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IF 6.1
Yuzhou Wan,Kexu Chen,Shaopeng Wang,Lin Liu,Xiaoqian Wang,Bo Zhang,Lin Hu,Shunmei Liu,Tingting Zhao,Huimin Qi
Nephrotic syndrome (NS) is characterized by proteinuria, hyperlipidemia, and hypoalbuminemia. Ulva pertusa, a green seaweed, is a nutritional supplement. In this study, the high-sulfated derivative of Ulva pertusa polysaccharide (HU) was prepared by combining U pertusa polysaccharide with chlorosulfonic acid. The NS rat model was established by tail vein single injection of Adriamycin (6.0 mg/kg). Normal rats were used as the control group. NS rat models were treated with HU or U (173 mg/kg/day). After treatment for 6 weeks, we assessed urine protein, renal function, and blood lipids, and observed morphology and histologic injury of the kidney and glomerular microstructure. Furthermore, we detected antioxidant enzyme activity and expression level of the Keap1/Nrf2 signaling pathway to explore the potential mechanism of HU. Results showed that HU not only alleviated hyperlipidemia and hypoalbuminemia, but also reduced urine protein by inhibiting podocyte detachment, thickening of the glomerular basement membrane, and expression of kidney fibrosis markers (collagens Ⅰ and Ⅳ). In addition, HU enhanced antioxidant enzyme activity (GSH-Px, CAT, SOD) in both serum and the kidney, which may be due to upregulating the expression of Nrf2 and downregulating the expression of Keap1. In conclusion, HU appears to be effective in attenuating NS in rats through suppressing oxidative stress by regulating the Keap1/Nrf2 signaling pathway.
研究领域:
药理学
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肾病学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEUROSCIENCE
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2025
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IF 2.8
Siqi Quan,Mengyuan Li,Zhouli Yue,Hui Liu,Shuaijun Peng,Roujia Guo,Xiaoyan Fang,Yucheng Li
Neuroinflammation and oxidative stress are major pathogenic drivers of depression, with the Keap1/Nrf2/HO-1 pathway serving as a key regulator of both processes. Formononetin (FMN) is a naturally occurring isoflavone with anti-inflammatory and antioxidant activities; however, its potential to exert antidepressant effects through activation of this pathway has not been investigated. In this study, lipopolysaccharide (LPS, 1 mg/kg, i.p.) was used to induce neuroinflammation and depressive-like behaviors in mice, and FMN (20 or 40 mg/kg) was administered for seven days prior to LPS challenge. FMN dose-dependently alleviated LPS-induced behavioral deficits, including reduced sucrose preference, decreased locomotor activity, and prolonged immobility in the tail suspension test. Hematoxylin-eosin (HE) and Nissl staining revealed that FMN markedly attenuated LPS-induced hippocampal neuronal damage. FMN also inhibited microglial activation, as evidenced by reduced Iba-1 expression, decreased NF-κB phosphorylation, and downregulation of both mRNA and protein levels of pro-inflammatory cytokines, including IL-1β, TNF-α, and IL-6. Furthermore, LPS-induced lipid peroxidation was significantly attenuated, as indicated by lower levels of 4-hydroxynonenal (4-HNE). Molecular docking suggested a potential direct interaction between FMN and Keap1, while Western blot analysis confirmed that FMN downregulated Keap1 and upregulated Nrf2 and HO-1 protein expression. Collectively, these findings demonstrate that FMN alleviates LPS-induced neuroinflammation and depressive-like behaviors, likely through activating the Keap1/Nrf2/HO-1 pathway, supporting its potential as a preventive candidate for inflammation-associated depression.
研究领域:
神经药理学
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分子生物学
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精神病学
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炎症研究
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氧化应激
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Nutrition
·
2026
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IF 5.5
Maoru Li,Zefeng Wang,Huan Zhai,Jiajiao Li,Ji Ma,Bin Qiu
BackgroundMetabolic dysfunction-associated steatotic liver disease (MASLD) is a rapidly growing metabolic disorder with no FDA-approved treatment. Pachymic acid (PA; synonym: 3-O-acetyltumulosic acid), a lanostane-type triterpenoid, shows potential for treating MASLD. However, its mechanisms remain underexplored.ObjectiveThis work evaluated the therapeutic efficacy and mechanisms of PA in treating MASLD.MethodsThe high-cholesterol diet (HCD)-induced zebrafish model, high-fat diet induced C57BL/6 mice model and free fatty acid (FFA)-treated BRL-3A cells was used to assess PA’s anti- MASLD effects in vivo and in vitro.ResultsPA improved lipid metabolism disrupted by HCD, reduced hepatic oxidative stress, as indicated by decreased MDA levels and increased SOD activity, and lowered inflammatory markers, including TNF-α, IL-6, and IL-1β. PA also enhanced antioxidant activity by regulating the Keap1-Nrf2-HO-1 pathway. PA decreased Keap1 mRNA expression induced by reactive oxygen species (ROS), upregulated Nrf2 and HO-1 expression, and promoted Nrf2 nuclear translocation. These effects suggest that PA inhibits ROS production by activating the Keap1-Nrf2-HO-1 pathway and possibly by inhibiting Nrf2 degradation.ConclusionPA improves MASLD through lipid metabolism regulation and antioxidant effects, primarily by activating the Keap1-Nrf2-HO-1 pathway. These findings highlight PA’s potential as a therapeutic agent for MASLD.
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DOI
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2026
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IF 6.2
Yanan Zhao,Rui Wang,Ziyang Huang,Siting Ju,Binghua Dong,Hui Teng,Lei Chen
The gut is often referred to as the “second brain” and is highly vulnerable to alcohol exposure. Galangin, a flavonoid extracted from traditional medicinal herbs, Alpinia officinarum Hance, has manifested auspicious clinical application potential. This study aims to explore the regulatory effect of galangin on ferroptosis in an alcohol-related intestinal injury model and its underlying mechanism. In vivo, we confirmed that galangin administration could alleviate alcohol-induced iron metabolism dysfunction and ferroptosis and activate the SESN2/KEAP1/NRF2 signaling pathway in mice colon. In vitro, alcohol-caused disruption of iron homeostasis and ferroptosis could also be significantly reduced by galangin. Using specific small interfering RNA targeting SESN2 (Si-SESN2) or the NRF2 inhibitor ML385 significantly abrogated the protective effect of galangin. Molecular docking and Co-IP results further revealed that galangin activates NRF2 nuclear translocation by promoting KEAP1/SESN2 formation as well as KEAP1/NRF2 dissociation. Collectively, galangin suppressed ferroptosis by activating the SESN2/KEAP1/NRF2 pathway in mice and Caco-2 cells.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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