Bioactive Materials
·
2021
·
IF 14.593
Yujuan Tian,Ying Li,Jialin Liu,Yi Lin,Jian Jiao,Bo Chen,Wanmeng Wang,Shuilin Wu,Changyi Li
Periodontitis is an inflammatory disease initiated by bacterial infection, developed by excessive immune response, and aggravated by high level of reactive oxygen species (ROS). Hence, herein, a versatile metal-organic framework (MOF)-based nanoplatform is prepared using mesoporous Prussian blue (MPB) nanoparticles to load BA, denoted as MPB-BA. The established MPB-BA nanoplatform serves as a shelter and reservoir for vulnerable immunomodulatory drug BA, which possesses antioxidant, anti-inflammatory and anti-bacterial effects. Thus, MPB-BA can exert its antioxidant, anti-inflammatory functions through scavenging intracellular ROS to switch macrophages from M1 to M2 phenotype so as to relieve inflammation. The underlying molecular mechanism lies in the upregulation of phosphorylated nuclear factor erythroid 2-related factor 2 (Nrf2) to scavenge ROS and subsequently inhibit the nuclear factor kappa-B (NF-κB) signal pathway. Moreover, MPB-BA also exhibited efficient photothermal antibacterial activity against periodontal pathogens under near-infrared (NIR) light irradiation. In vivo RNA sequencing results revealed the high involvement of both antioxidant and anti-inflammatory pathways after MPB-BA application. Meanwhile, micro-CT and immunohistochemical staining of p -Nrf2 and p-P65 further confirmed the superior therapeutic effects of MPB-BA than minocycline hydrochloride. This work may provide an insight into the treatment of periodontitis by regulating Nrf2/NF-κB signaling pathway through photothermal bioplatform-assisted immunotherapy.
研究领域:
牙科学
·
药理学
·
免疫学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
REDOX REPORT
·
2021
·
IF 4.412
Nabila Jahan,Apu Chowdhury,Ting Li,Ke Xu,Fen Wei,Sicen Wang
Background Progression of Benign Prostate hyperplasia (BPH) is vulnerable to oxidative stress (OS) and prostatic enlargement among the aging males through apoptosis deregulation. Our present study aimed to investigate the effect of neferine (NF) in the regulation of oxidative stress and apoptosis in human BPH-1 cells.Methods BPH epithelial cell line BPH-1 was treated with NF for 24 and 48 h. To measure oxidative stress (OS) we investigated MDA, SOD, and GST expression along with Nrf2 and its downstream gene and protein expression. Cell proliferation and apoptosis regulation was assayed with respective methods.Results Investigation revealed NF remarkably activate Nrf2 and its downstream proteins HO-1 and NQO1 at 48 h more substantially. Nrf2/Keap1 relative gene and protein expression indicated that NF might trigger Nrf2 upregulation by decreasing Keap1 expression. Both NF concentrations (3 µM and 9 µM) were able to deplete ROS and lipid peroxidation, concurrently, up-regulated SOD and GST. NF reduced cell proliferation significantly along with the regulation of apoptotic proteins Bax, Bcl2, Cyt-C, Caspase 9, and Caspase 3 at the same time (48 h).Conclusion This study is the first to manifest that NF may potentially regulate BPH by counterbalancing between OS and apoptosis through the activation of Nrf2-ARE pathway.
研究领域:
药理学
·
泌尿学
·
细胞生物学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
EXPERIMENTAL NEUROLOGY
·
2026
·
IF 4.8
Shiyao Feng,Boyu Sun,Longlong Tian,Mingkang Li,Guozhu Sun
Traumatic brain injury (TBI) is one of the most prevalent neurological disorders and a major cause of death and disability worldwide. Cuproptosis is a recently identified form of cell death. Nuclear factor erythroid 2-related factor 2 (Nrf2), a key transcription factor that has been widely investigated in TBI, may contribute to the regulation of cuproptosis. In this study, we investigated the role of cuproptosis in TBI and the regulatory mechanisms of Nrf2. We found that cuproptosis was induced following TBI in both patients and mouse models. In TBI mice, cuproptosis peaked at 3 days post-injury and predominantly occurred in neurons. Nrf2 deficiency aggravates neuronal cuproptosis after TBI, primarily through IRF7-mediated upregulation of SLC31A1. The Nrf2 activator dimethyl fumarate (DMF) suppresses neuronal injury and improves neurological function in TBI mice by inhibiting cuproptosis. Our results establish that cuproptosis is an important mechanism in TBI and that activation of Nrf2 mitigates TBI-induced cuproptosis by regulating the IRF7–SLC31A1 axis.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2026
·
IF 4.9
Zhang Shuhao,Zou Yanlong,Long Jundong,Wang Yufan,Chen Jian,Teng Miao
Osteoarthritis (OA) involves oxidative stress-induced chondrocyte senescence and extracellular matrix (ECM) dysregulation, yet disease-modifying therapies remain elusive. This study investigates the effects of cycloastragenol (CAG), a telomerase-activating triterpenoid from Astragalus membranaceus, on OA progression with a focus on NRF2/NF-κB signaling. In vitro, CAG suppressed oxidative stress-induced senescence in primary rat chondrocytes, evidenced by reduced SA-β-gal positivity, partially restored EdU proliferation, and downregulated senescence related proteins expression. In addition, CAG concurrently attenuated senescence-associated secretory phenotype (SASP) and partially restored ECM homeostasis. Mechanistically, molecular docking analysis suggested a potential interaction between CAG and the Kelch domain of KEAP1. Consistent with this, CAG treatment was associated with NRF2 pathway activation and attenuation of TBHP-induced NF-κB signaling. Importantly, genetic inhibition of NRF2 significantly attenuated the protective effects of CAG, supporting a required role for NRF2 in mediating CAG-induced suppression of oxidative stress and inflammatory signaling. In vivo, intra-articular CAG administration in monosodium iodoacetate (MIA)-induced OA rats reduced cartilage degradation, rescued ECM homeostasis, and enhanced NRF2 activation. Collectively, CAG mitigates the degradation of the extracellular matrix and suppresses the senescence-associated secretory phenotype (SASP) induced by osteoarthritis (OA).
✓ 已验证
DOI
PubMed
高影响因子
Cancer Cell International
·
2026
·Vol. 26
·期 1
·211
·
IF 7
Yan Ping,Luo Yunhai,Peng Dadi,Mou Tong,Lei Dengliang,Li Shanshan,Yu Huarong,Huang Zuotian,Wu Zhongjun
Background Hepatocellular carcinoma (HCC) is frequently associated with serious metabolic disorders, resulting in a bleak prognosis. Although ADH4 is implicated in the metabolism of fatty acids, its exact function in tumourigenesis is still unclear. Methods Our study initially examined proliferation potential in vitro and in vivo using various approaches, such as CCK8, EdU incorporation, colony formation assays, and a tumourigenicity assay in mice, which included orthotopic injection into the left liver lobe. Next, we conducted a quantitative analysis of oxylipins to investigate the correlation between ADH4 and lipid peroxidation in hepatoma cells. Additionally, we examined the intracellular ratio of NADP+/NADPH and measured the production of reactive oxygen species (ROS) and malondialdehyde (MDA) in other hepatoma cells. Furthermore, we employed mRNA sequencing to identify the downstream targets of ADH4 in hepatoma cells. Results The results indicate that there is a significant association between ADH4 levels and lipid peroxidation in hepatoma cells. It has been shown that there is a downregulation of ADH4 expression in hepatocellular carcinoma, and that ADH4 deficiency is a contributing factor in tumour progression and overall poor prognosis. Both gain- and loss-of-function studies have demonstrated that ADH4 has an anti-proliferative effect on hepatocellular carcinoma both in vitro and in vivo. Inhibition of ADH4 leads to the accumulation of oxylipin metabolites and an increase in the NADP+/NADPH ratio, ROS and MDA production, ultimately resulting in the activation of the KEAP1/NRF2 pathway and the nuclear translocation of NRF2. Furthermore, the results of mRNA sequencing indicate a close correlation between ADH4 expression and the cytokine-cytokine receptor pathway, with the strongest negative association found with CSF1 expression. This has been validated in other hepatoma cells and clinical patient samples. Flow cytometric analysis has confirmed ADH4’s ability to suppress CSF1-mediated polarization of M2-type macrophages in an NRF2 signaling-dependent manner. In conclusion, ADH4 plays a significant role in the regulation of macrophage polarization. Conclusion These findings suggest that downregulation of ADH4 may exert protumourigenic effects on hepatocellular carcinoma by increasing lipid peroxidation levels, NADP+/NADPH ratio, ROS and MDA levels, leading to activation of the KEAP1/NRF2 pathway, upregulation of CSF1 and M2-type polarisation of tumour-associated macrophages (TAMs), suggesting a potential therapeutic strategy for hepatocellular carcinoma.
✓ 已验证
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2025
·
IF 8.3
Mengdi Cui,Yi An,Jingling Zhao,Miaoxin Hui,Zhili Xiong,Bing Guan,Yinfeng Shen,Yinshui Zou,Chengyin Li,Rui Wang
Background: Acute kidney injury (AKI) is a leading complication of sepsis, necessitating the exploration of novel treatment modalities. The traditional Chinese medicine Dahuang Gancao Decoction (DHGC) has potential in the treatment of sepsis-associated acute kidney injury (SA-AKI). However, its specific mechanisms require further investigation. Purpose: This study aimed to validate the antiferroptotic effects of DHGC in the treatment of SA-AKI in vivo and in vitro . Methods: C57BL/6 mice and C57BL/6-background sirtuin-3 (SIRT3) -/- mice were induced with Reagents Lipopolysaccharide (LPS), while normal and si-SIRT3 human proximal tubular epithelial (HK-2) cells were induced with erastin to establish a ferroptosis phenotype, followed by DHGC treatment. First, the DHGC components were identified via liquid chromatography-tandem mass spectrometry (LC‒MS/MS), and the potential active components were further screened through comparison with the high-performance liquid chromatography (HPLC) reference standards. Ferroptosis levels and the protective mechanisms of DHGC in vivo and in vitro were evaluated using biochemical assays, transmission electron microscopy, immunohistochemistry, immunofluorescence, and Cell Counting Kit-8 (CCK-8) assays. Key pathways were identified by RNA-seq and validated via enzyme-linked immunosorbent assay (ELISA) and western blotting. Finally, the potential active components were subjected to molecular docking with SIRT3 to select candidate monomers for subsequent in vitro functional validation. Results: LPS was used to induce SA-AKI in mice, and erastin was used to induce ferroptosis in HK-2 cells. DHGC can improve renal function, increase cell viability, and reverse abnormal changes in key ferroptosis indicators. Mechanistically, the expression levels of SIRT3/nuclear factor erythroid-2 related factor 2 (NRF2) pathway-associated proteins were downregulated, and NRF2 nuclear translocation was restricted after modeling; in contrast, DHGC upregulated the expression of SIRT3/NRF2 pathway-related proteins, promoted NRF2 nuclear translocation, and activated downstream glutathione peroxidase 4 (GPX4) expression. Importantly, DHGC failed to improve the above indicators in SIRT3-deficient models. Potential active components of DHGC were screened via HPLC reference standard comparison, and subsequent molecular docking with SIRT3 identified candidate monomers. These monomers exerted ferroptosis-inhibiting effects consistent with those of the parent compound DHGC. Conclusions: The present study offers the first demonstration that DHGC retards SA-AKI progression through stimulating SIRT3-driven deacetylation of NRF2, promoting NRF2 nuclear translocation, and inhibiting ferroptosis. These findings suggest that DHGC is a potential therapeutic candidate for SA-AKI, warranting further clinical investigation.
研究领域:
中医中药
·
肾脏病学
·
分子生物学
·
药理学
·
氧化应激
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Toxicology
·
2025
·
IF 4.6
Liu-Dan Liang,Xiao-Yue Zhao,Li Li,Sheng Liang,Jin-Min Zhang,Jian-Nan Lv,Feng-Lian Deng,Chun-Lei Lu,Qian Li,Qi-Wen Huang,Mei-Jin Huang,Hui-Xin Peng
Aluminum is toxic to both humans and animals. Exposure to AlCl 3 can lead to kidney function damage, yet the specific underlying mechanism remains elusive. This study aimed to investigate whether ferroptosis is involved in the renal toxicity induced by AlCl 3 exposure in mice and to elucidate its potential molecular mechanism. Forty-eight C57BL mice were randomly assigned to six groups, with eight mice in each group: a control group, low -, medium -, and high - dose aluminum exposure groups, a ferroptosis inhibitor group, and a ferroptosis inhibitor + high - dose aluminum exposure group. Mice in the aluminum exposure groups received intraperitoneal injections of different doses of AlCl 3 solution for 4 weeks (5 times per week), while the ferroptosis inhibitor group was intraperitoneally injected with Fer - 1 for 4 weeks (2 times per week). After the experimental period, multiple indicators were examined. The results demonstrated that AlCl 3 exposure impaired the renal function and structure of mice. It also led to an increase in lipid peroxidation products, Fe 2+ , and Al content in renal tissue. Moreover, the expression levels of genes and proteins such as GPX4 and Nrf2 were decreased, whereas the expression levels of the ACSL4 gene and protein were increased.However, after pretreatment with Fer - 1, the aforementioned indicators were ameliorated. Specifically, the expression of ACSL4 decreased, and the expression of GPX4 and other related factors increased.In conclusion, this study suggests that AlCl 3 exposure may trigger ferroptosis in renal tissue cells by inhibiting the NRF2 pathway, thereby causing kidney function damage in mice. These findings provide a novel perspective on the mechanism of AlCl 3 - induced renal toxicity.
研究领域:
毒理学
·
分子生物学
·
环境健康
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PLoS One
·
2025
·Vol. 20
·期 6
·e0325189
·
IF 2.6
Yu Wang,Chaofan Chen,Yushan Li,Ran Li,Jinghan Wang,Chao Wu,Haonan Chen,Yingchao Shi,Shengfang Wang,Chuanyu Gao
Kaempferol exhibits various biological activities, including antioxidant and anti-inflammatory effects. Its role in modulating lipid metabolism and inhibiting inflammatory responses to suppress the progression of atherosclerosis has been confirmed. However, its impact on macrophage pyroptosis and the underlying mechanisms remain unclear. This study aims to investigate the effects of kaempferol (Kae) on lipopolysaccharide (LPS)-induced macrophage pyroptosis and its potential mechanisms. In the experiments, we used the CCK8 assay to evaluate cell viability, ROS detection kits to measure intracellular reactive oxygen species (ROS) levels, Western Blot to detect the expression of proteins such as NOD-like receptor family pyrin domain-containing 3 (NLRP3), nuclear factor erythroid 2-related factor 2 (NRF2), gasdermin D (GSDMD), and heme oxygenase-1 (HO-1), and immunofluorescence to observe NRF2 nuclear translocation. The results showed that kaempferol alleviated LPS-induced cell viability decline and lactate dehydrogenase (LDH) release, inhibited excessive ROS generation, and suppressed NLRP3 inflammasome activation by increasing glutathione (GSH) and HO-1 levels, thereby reducing the expression of inflammatory factors. Additionally, kaempferol promoted NRF2 nuclear translocation, and the application of the NRF2 inhibitor ML385 reversed its antioxidant and anti-inflammatory effects. In vivo experiments further confirmed that kaempferol inhibited oxidative stress and reduced macrophage pyroptosis by activating the NRF2 pathway.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TOXICOLOGY
·
2026
·
IF 4.6
Jin Chen,Hanwen Hu,Jing Fu,Yaolin He,Hui Zhou,Jingwei Lei,Ming Huang,Jianqi Wang,Anfei Liu,Zhenzhong Liu
Trimethyltin chloride (TMT), a pervasive environmental organic tin pollutant, has been implicated in cardiac injury, though its underlying mechanisms remain unclear. TMT exposure triggers excessive reactive oxygen species (ROS) generation, a key inducer of ferroptosis—a regulated form of cell death driven by iron-dependent lipid peroxidation. NADPH oxidase 4 (NOX4), highly expressed during cardiac development, plays a critical role in myocardial ROS production, while the Keap1/Nrf2 pathway regulates cellular ROS homeostasis. We hypothesized that TMT induces cardiac developmental defects by activating NOX4/Keap1/ROS-mediated ferroptosis. TMT exposure induced cardiac malformations, pericardial edema, and reduced heart rate in zebrafish embryos. Further studies revealed that TMT upregulated nox4 expression in embryonic hearts. Notably, pharmacological inhibition or genetic knockdown of nox4 markedly attenuated TMT-induced cardiac defects. Moreover, nox4 suppression antagonized TMT-triggered dysregulation of the Keap1/Nrf2 axis, ROS overaccumulation, mitochondrial damage, and ferroptosis-related abnormalities—including Fe²⁺ accumulation, elevated lipid peroxidation, and downregulated glutathione peroxidase 4 (GPX4) expression. Crucially, inhibition or knockdown of keap1 similarly mitigated TMT-induced ROS bursts, mitochondrial injury, and ferroptosis progression. Intervention with ferroptosis-specific inhibitors (Liproxstatin-1 and Myricetin) confirmed that ferroptosis directly contributes to TMT-induced cardiac developmental defects. This study demonstrates that TMT induces cardiac malformations by activating ferroptosis via the nox4/Keap1/Nrf2/ROS signaling axis. These findings reveal a novel mechanism underlying TMT cardiotoxicity, provide theoretical insights for assessing TMT exposure as a risk factor for congenital heart disease, and identify potential molecular targets for therapeutic intervention.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
·
2026
·Vol. 40
·期 7
·e70982
·
IF 3.6
Zimeng Liu,Yunpeng Gao,Musen Li,Qingsong Sun,Yunhe Fu,Yue Zhang
Mastitis is a prevalent gynecological disorder in women, with Staphylococcus aureus ( S. aureus ) serving as a primary etiological pathogen of this condition. Cryptotanshinone (CPT) has been demonstrated to exert anti-oxidative stress and anti-inflammatory effects, conferring therapeutic benefits for a diverse range of inflammatory diseases. However, its efficacy and underlying regulatory mechanisms in ameliorating S. aureus -induced mastitis remain elusive. Therefore, the present study was designed to elucidate the protective effects and molecular regulatory mechanisms of CPT against S. aureus -induced mastitis. A murine model of S. aureus -induced mastitis was established via intramammary injection of S. aureus , and CPT was administered to the model mice for therapeutic intervention. In vivo experiments revealed that CPT administration mitigated S. aureus -induced mastitis in mice by suppressing the production of pro-inflammatory cytokines and inhibiting ferroptosis. In vitro, CPT abrogated the S. aureus -induced elevation of TNF-α, IL-1β, MDA, ROS, and Fe 2+ levels in mouse mammary epithelial cells (MMECs); additionally, it restored the ATP and GSH levels that were reduced by S. aureus stimulation in these cells. Furthermore, CPT concentration-dependently upregulated the expression of GPX4, Nrf2 and HO-1 in MMECs. Notably, the inhibitory effects of CPT on S. aureus -induced inflammatory responses and ferroptosis were abrogated in Nrf2-knockdown MMECs. In conclusion, this study demonstrates that CPT exerts a robust protective effect against S. aureus -induced mastitis by suppressing inflammatory responses and inhibiting ferroptosis through the activation of the Nrf2/GPX4 signaling pathway.
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2025
·
IF 6.2
Jie Zhou,Yurou Li,Chen Xi,Wupei Pan,Qin Yu,Zhengping Wu
Fumonisin B1 (FB1) is a common mycotoxin known to cause hepatotoxicity in various species. However, whether ferroptosis is involved in its toxicity remains unclear, and effective interventions are lacking. Apigenin (AG) is a natural antioxidant with recognized cytoprotective properties. In this study, we investigated ferroptosis in FB1-induced liver injury and explored AG’s protective effects via the Nrf2/FSP1 pathway. FB1 triggered ferroptosis in hepatocytes, evidenced by decreased ubiquinol (CoQ10H2), Nrf2, and ferroptosis suppressor protein 1 (FSP1) levels, and increased Fe2+ levels, NAD+/NADH ratio, and lipid peroxidation (LPO). Both ferrostatin-1 and AG attenuated FB1-induced ferroptosis by upregulating CoQ10H2 and suppressing LPO, with effects similar to those of Nrf2 or FSP1 overexpression. However, knockdown of either Nrf2 or FSP1 abolished AG’s protective effects against FB1-induced ferroptosis. Collectively, this study reveals a novel mechanism by which AG activates the Nrf2/FSP1 pathway to counteract FB1-induced hepatotoxicity, suggesting its potential as a hepatoprotective agent against environmental toxins.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2023
·
IF 7.5
Jie-Ru Hong,Chen-Yu Zhang,Wen-Jing Zhong,Hui-Hui Yang,Jian‑Bing Xiong,Ping Deng,Nan-Shi-Yu Yang,Hui Chen,Ling Jin,Cha-Xiang Guan,Jia-Xi Duan,Yong Zhou
Alveolar epithelial cell (AEC) senescence is considered to be a universal pathological feature of many chronic pulmonary diseases. Our previous study found that epoxyeicosatrienoic acids (EETs), produced from arachidonic acid (ARA) through the cytochrome P450 cyclooxygenase (CYP) pathway, have significant negative regulatory effects on cellular senescence in AECs. However, the exact mechanisms by which EETs alleviate the senescence of AECs still need to be further explored. In the present study, we observed that bleomycin (BLM) induced enhanced mitophagy accompanied by increased mitochondrial ROS (mito-ROS) content in the murine alveolar epithelial cell line MLE12. While EETs reduced BLM-induced mitophagy and mito-ROS content in MLE12 cells, and the mechanism was related to the regulation of NOX4/Nrf2-mediated redox imbalance. Furthermore, we found that inhibition of EETs degradation could significantly inhibit mitophagy and regulate NOX4/Nrf2 balance to exert anti-oxidant effects in D-galactose-induced premature aging mice. Collectively, these findings may provide new ideas for treating age-related pulmonary diseases by targeting EETs to improve mitochondrial dysfunction and reduce oxidative stress.
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）