Food & Function
·
2025
·
IF 5.4
Jiaxuan Li,Yu Li,Xunyu Song,Yuxiao Wang,Yinxu Zhang,Xinghua Gao,Mingqian Tan,Wentao Su
High-fat diets (HFDs) impair the intestinal barrier by increasing permeability and oxidative stress, which contributes to obesity-related disorders. Ulva lactuca, a marine green alga, produces extracellular vesicles (UEVs) that remain underexplored as functional food components. In this study, UEVs were isolated and characterized, showing a cup-like shape morphology with average diameter of 188.8 nm. Functional assays demonstrated that UEV treatment attenuated oxidative stress, reduced apoptosis, and restored tight junction proteins. In a gut-on-a-chip model, UEVs improved transepithelial electrical resistance (TEER) and enhanced mucin secretion under HFD-mimicking stress. Mechanistic studies revealed that UEVs activated the Nrf2/Keap1/HO-1 signaling pathway, promoting nuclear translocation of Nrf2 and upregulation of antioxidant genes. Collectively, these findings highlight UEVs as novel food-derived nanostructures with dual functions in oxidative stress reduction and intestinal barrier protection, supporting their potential in functional food applications targeting metabolic gut disorders.
研究领域:
海洋生物学
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营养科学
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分子生物学
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纳米技术
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胃肠病学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2026
·
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
ACS Biomaterials Science & Engineering
·
2025
·
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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产品关联
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
·
毒理学
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DOI
PubMed
高影响因子
CHEMICO-BIOLOGICAL INTERACTIONS
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2019
·
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
FREE RADICAL BIOLOGY AND MEDICINE
·
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
Antioxidants
·
2026
·Vol. 15
·期 9
·1114
·
IF 8.2
Wen-Xu Yao,Yao-Dan Ma,Shi-Yao Ding,Jian Lu,Hao-Lan Tang,Zeng-Ming Yang
Successful embryo implantation requires intimate crosstalk between the blastocyst and the uterine epithelium within a defined window of receptivity. However, the metabolic signals that mediate this process in mammals remain poorly understood. In this study, pregnant mice, primary uterine cell culture and uterine epithelial organoids were used to examine the regulation and function of heme oxygenase-1 (HO-1) during mouse embryo implantation and decidualization. We demonstrate that embryo-derived lactic acid drives heme catabolism and regulates epithelial receptivity in mice through a hypoxia-inducible factor 1α (HIF1α) -heme oxygenase-1 (HO-1) signaling axis. Specifically, lactic acid stabilizes HIF1α to induce HO-1 expression in uterine epithelial cells by promoting von Hippel-Lindau (VHL) nucleolar sequestration and downregulating PHD2/3. Additionally, lactic acid suppresses the transcriptional repressor BACH1, further facilitating HO-1 induction. At physiological heme levels, HO-1-derived bilirubin promotes epithelial receptivity by increasing phosphorylated STAT3 (p-STAT3) and downregulating MUC1. A low dose of hemin promotes epithelial receptivity and decidualization, whereas a high dose of hemin suppresses these processes. Pharmacological inhibition of HO-1 in mice markedly reduces implantation sites, establishing the functional necessity of this pathway. However, when heme levels exceed the regulatory capacity of HO-1, epithelial dysfunction ensues, characterized by reduced p-STAT3 and elevated MUC1, which ultimately disrupts implantation. Consistent with this, chronic heme exposure by oral gavage in mice increases uterine heme levels and upregulates BACH1, thereby suppressing HO-1 and trapping the uterus in a non-receptive state, causing implantation failure. Our findings define a lactic acid-HIF1α-HO-1-heme metabolic checkpoint that couples glycolytic signaling to heme regulation and endometrial receptivity. Dysregulation of this checkpoint may contribute to implantation disorders associated with heme stress, providing mechanistic insights into heme stress-related uterine receptivity failure.
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DOI
高影响因子
JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE
·
2026
·
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
·
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
JOURNAL OF HAZARDOUS MATERIALS
·
2021
·
IF 10.588
Yuhao Wu,Junke Wang,Tianxin Zhao,Jiadong Chen,Lian Kang,Yuexin Wei,Lindong Han,Lianju Shen,Chunlan Long,Shengde Wu,Guanghui Wei
Di-(2-ethylhexyl) phthalate (DEHP) is an extensively used plasticizer and has been shown to cause reproductive dysfunction in humans and model animals. However, the exact mechanisms of testicular injury induced by DEHP exposure have not been fully clarified. Using gas chromatography-mass spectrometry, we found that mono-2-ethylhexyl ester (MEHP, a major biometabolite of DEHP) and DEHP concentrations were elevated in mouse serum after DEHP exposure. Using RNA-seq, we found that ferroptosis and HIF-1 signaling pathways might be involved in testicular injury due to prepubertal DEHP exposure. Subsequent Western blotting, ferrous iron and MDA measurements, and immunofluorescence of testicular sections verified the RNA-seq findings. Consistently, based on the RNA-seq findings, we found that ferroptosis and HIF-1 signaling pathways might play crucial roles in Leydig and Sertoli cell injury due to MEHP exposure in vitro. Further experiments also confirmed ferroptosis in Leydig and Sertoli cells. Using Western blotting, cellular immunofluorescence and ChIP-qPCR, we found that MEHP exposure caused HIF-1α accumulation and stabilization, resulted in HIF-1α translocation into the nucleus, and induced HIF-1α/ Hmox1 binding in Leydig and Sertoli cells. To clarify whether HIF-1α plays a pivotal role in MEHP-induced ferroptosis, we knocked out Hif-1α using the CRISPR/Cas9 technique. We found that Hif-1α knockout rescued MEHP-induced ferroptosis. In summary, our findings certified that prepubertal DEHP exposure led to ferroptosis in mouse testes via the HIF-1α/HO-1 signaling pathway.
研究领域:
毒理学
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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
LIFE SCIENCES
·
2018
·
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
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
CHEMICO-BIOLOGICAL INTERACTIONS
·
2019
·
IF 3.407
Li-Ming Yu,Xue Dong,Xiao-Dong Xue,Jian Zhang,Zhi Li,Hong-Jiang Wu,Zhong-Lu Yang,Yang Yang,Hui-Shan Wang
Punicalagin has been found to exert cardiac protective effects against myocardial ischemia/reperfusion (MI/R) injury, although the detailed mechanisms remain largely unknown. This experiment was performed to explore the potential involvement of silent information regulator 1 (SIRT1)-NFE2-related factor 2 (NRF-2)-heme oxygenase-1 (HO-1) pathway in the cardiac protective actions of punicalagin. Sprague-Dawley (SD) rats were subjected to MI/R operation with or without punicalagin treatment (40 mg kg −1 d −1 ). We showed that punicalagin-treated group exhibited enhanced cardiac function, reduced myocardial infarction and decreased cleaved caspase-3 level. Furthermore, myocardial oxidative/nitrosative stress was ameliorated by punicalagin as evidenced by suppressed superoxide generation, gp91 phox and iNOS expressions, NO metabolites as well as myocardial nitrotyrosine level. Additionally, punicalagin decreased myocardial IL-6, TNF-α and the levels of ICAM-1, VCAM-1 and IKK-β expressions as well as IκB-α phosphorylation and NF-κB nuclear translocation. However, these effects were abolished by EX527 (5 mg kg −1 d −1 , a selective SIRT1 inhibitor). We further found that punicalagin dose-dependently enhanced SIRT1 nuclear distribution and NRF-2-HO-1 signaling. While EX527 treatment not only reduced SIRT1 activity, but also reversed the activation of NRF-2-HO-1 pathway. Collectively, these results revealed that punicalagin reduced cardiac oxidative/nitrosative stress and inflammatory response induced by MI/R operation through SIRT1-mediated activation of NRF-2-HO-1 signaling.
研究领域:
心脏病学
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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
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