ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
·
2026
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IF 3.5
Yurou Li,Zhenzhen Yan,Wanrong Zhang,Xin Zheng,Zhengping Wu,Yinjie Jiang,Jie Zhou
Sodium aescinate (SA), a triterpenoid saponin derived from Aesculus hippocastanum seeds, is widely used clinically but has been linked to hepatotoxicity, nephrotoxicity, and phlebitis. We previously reported that SA triggers hepatocyte ferroptosis, and enhancing GSH synthesis via the CTH/cysteine axis activation only partially mitigates liver injury. In this study, we showed that SA disrupted redox homeostasis, promoted lipid peroxidation (LPO), and induced ferroptosis in hepatocytes, concomitant with suppressed Nrf2/PRDX6/GPX4 pathway activity. Mechanistically, SA downregulated the expression and transcriptional activity of Nrf2, reducing its binding to antioxidant response elements (AREs) in the promoters of PRDX6 and GPX4, thereby decreasing their expression. Nrf2 overexpression restored PRDX6 and GPX4 levels, enhanced antioxidant capacity, and attenuated SA-induced ferroptosis. Notably, PRDX6 regulated GPX4 expression and activity by modulating selenium utilization and selenoprotein biosynthesis during SA-induced hepatotoxicity. Both PRDX6 overexpression and selenium supplementation rescued GPX4 and protected against SA-induced ferroptotic damage. The protection conferred by Nrf2/PRDX6 overexpression or selenium supplementation was fully abrogated upon GPX4 knockdown or inhibition with RSL3. Collectively, SA induced ferroptotic liver injury by disrupting the Nrf2/PRDX6/GPX4 axis, culminating in GPX4 deficiency and redox collapse. This study suggests that this cascade represents a promising therapeutic target for SA-induced hepatotoxicity.
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PubMed
高影响因子
REDOX REPORT
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2025
·
IF 7.4
Jingyi Ren,Ziyi Wang,Yadong Zhang,Huanting Pei,Rui Wen,Zhenao Zhang,Siqi Zhu,Xiaoya Sun,Bowen Yin,Shenghe Li,Yuxia Ma
Background: Acetaminophen (APAP) overdose is the leading cause of drug-induced acute liver failure. Sesamin (Ses), a natural polyphenolic compound, possesses diverse pharmacological properties. This study was to explore the effects of Ses on APAP-induced liver injury and the underlying molecular mechanism.Methods: In vivo, C57BL/6J mice were treated with different doses of Ses for 28 days. After overnight food deprivation, mice were intraperitoneally injected with a single dose of APAP. In vitro, the AML12 and HepG2 cells were pre-treated with Ses and then treated with APAP.Results: Ses dramatically alleviated APAP-induced hepatocellular injury in vitro and in vivo. Proteomic analysis suggested that the differentially expressed proteins were enriched in ferroptosis, autophagy, and FoxO signaling pathways between the APAP group and the Ses-treated groups. We subsequently found that ferroptosis was significantly inhibited, and autophagy was significantly enhanced in the Ses-treated group. Consistently, Ses obviously reduced the expression of Foxo1. However, hepatocyte-specific knockout Foxo1 abolished the effect of Ses on hepatocyte autophagy and ferroptosis caused by APAP in mice.Conclusions: Our findings demonstrate that Ses attenuates APAP-induced hepatotoxicity through Foxo1, which mediates both the activation of autophagy and the inhibition of ferroptosis. It provides a new strategy for the prevention and treatment of drug-induced liver injury.
研究领域:
药理学
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毒理学
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分子生物学
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肝脏病学
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PubMed
高影响因子
Small Methods
·
2025
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IF 9.1
Zheng Chen,Qiyue Wang,Sirui Cui,Xi Hu,Peihua Lin,Bo Zhang,Daishun Ling,Fangyuan Li
Piezoelectric materials have emerged as versatile tools for ultrasound-triggered cancer therapy, yet their clinical application is constrained by inefficient charge separation and the limited availability of catalytic substrates in the tumor microenvironment. Here, an electronegativity-modulated piezoelectric metal–organic framework (CapMOF@HA) is reported through controlled heteroepitaxial growth of CaO 2 on pMOFs, followed by surface functionalization with hyaluronic acid (HA) for tumor-targeting capability for enhanced piezocatalytic therapy. Of note, the electronegativity-modulated heterogeneous interfaces between CaO 2 and pMOF promote the separation of electron–hole pairs while suppressing recombination through the electronegativity effect, significantly amplifying piezocatalytic reactive oxygen species (ROS) generation (•OH, 1 O 2 , and •O 2 ⁻) under ultrasound stimulation. Furthermore, the controlled decomposition of calcium peroxide provides a continuous supply of H 2 O 2 and O 2 as catalytic substrates, while releasing Ca 2+ to induce calcium overload, triggering mitochondrial dysfunction and glutathione peroxidase 4 inhibition for ferroptosis induction. This strategy integrates enhanced piezoelectric catalysis with ferroptosis induction, overcoming long-standing limitations in piezocatalytic systems to achieve precise and robust tumor ablation. By combining substrate self-sufficiency with multifunctional therapeutic mechanisms, this work establishes tumor piezocatalytic ferroptosis as a transformative platform for next-generation piezoelectric cancer therapy.
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高影响因子
Journal of Materials Chemistry B
·
2025
·
IF 5.7
Lanfu Zheng,Wei Jiang,Shuming Tian,Zepeng Feng,Yanan Qi,Hongyang Fu,Liting Qi,Lianrui Chen
Photothermal therapy (PTT) represents a non-invasive therapeutic modality with considerable potential for tumor ablation. However, the complex tumor microenvironment (TME) presents substantial challenges to conventional PTT monotherapy. In this study, we developed a nanomedicine (Fe 3 O 4 @GOx@PDA) designed to synergistically eradicate tumor cells by integrating PTT with starvation therapy and ferroptosis induction. Glucose oxidase (GOx) catalyzes the oxidation of intratumoral glucose to gluconic acid and hydrogen peroxide (H 2 O 2 ). Simultaneously, the resultant H 2 O 2 facilitates intracellular Fenton-like reactions, generating reactive oxygen species (ROS) that trigger lipid peroxidation. Furthermore, Fe 2+ ions liberated within the TME react with H 2 O 2 via a Fenton-like reaction to produce abundant ROS. This ROS surge stimulates macrophage polarization towards the M1 phenotype, thereby further suppressing the proliferation and metastatic potential of colorectal cancer (CRC) cells. This multimodal therapeutic strategy, leveraging Fe 3 O 4 @GOx@PDA, demonstrates potent synergistic antitumor efficacy coupled with favorable biosafety, presenting a promising therapeutic approach for clinical colorectal cancer management.
研究领域:
纳米医学
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癌症治疗
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免疫治疗
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活性氧
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药物递送
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PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2025
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IF 11.5
Congcong Lin,Jiamin Sun,Yun Yang,Xinyao Pan,Shiyu Wang,Xiaoyang Li,Yan Zhang,Huile Gao,Chunli Gan
The development of chemotherapy resistance poses a major challenge in cancer therapy. Ferroptosis, a unique type of cell death, offers a promising strategy to combat this resistance. Herein, a peptide-based nanoassembly (PTX@CPG) consisting of paclitaxel (PTX), chlorin e6 (Ce6), and FFVLKPLGLAGK-(PEG8) 3 was constructed to promote ferroptosis through reactive oxygen species (ROS) accumulation and overcome chemoresistance. Specifically, the small-sized PTX@CPG nanoparticles effectively penetrate tumors, where the microenvironment-responsive peptide is selectively cleaved by the high expression of matrix metalloproteinase 2. This process facilitates the targeted release of PTX and its reassembly into nanofibers, improving the tumor retention of Ce6 and enhancing its cellular uptake. The synergistic therapeutic effects of PTX in combination with photodynamic therapy on triple-negative breast cancer cells were validated through both in vitro and in vivo experiments. Impressively, upon laser irradiation, PTX@CPG significantly increased ROS production, thereby amplifying the ferroptosis-inducing effects of PTX. Moreover, ferroptosis triggered by PTX@CPG with laser reduced the levels of P-glycoprotein and glutathione peroxidase 4, contributing to the alleviation of chemoresistance. Overall, PTX@CPG with laser demonstrated effective spatial targeting and drug retention, enhancing ferroptosis through ROS accumulation and showcasing a promising approach for overcoming chemotherapy resistance in cancer therapy.
研究领域:
肿瘤学
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纳米医学
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药理学
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DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2025
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IF 8.3
Yang Tang,Zheng Wang,Feng Zhou,Ling Li,Chen Sun,Linhui Li,Fei Tang,Dongqin Huang,Zewei Li,Yang Tan,Gang Pei
Background Ulcerative colitis (UC) is a clinically refractory diseases of the digestive system. Benzoylpaeoniflorin (BP) is a compound from Baishao, a Chinese herbal medicine documented with effects of anti-enteritis. However, the potential of BP in treating UC, along with its underlying mechanisms, requires further elucidation. Purpose This research was conducted to assess the effects of BP on dextran sulfate sodium (DSS)-induced UC and to elucidate its underlying mechanisms. Methods The C57BL/6 mouse model of UC was developed by administering the mice to freely drink DSS solution for 7 days. The mice were also subjected to intragastric administration of BP. Histopathology, nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathways, and ferroptosis indicators were determined in vivo . Besides, NCM460 cells were used to further evaluate the anti-ferroptosis effect of BP and its potential mechanisms. Ferroptosis agonists iron-dextrin (ID) and Erastin were employed to investigate whether BP exerts anti-UC effect by inhibiting ferroptosis. Similarly, Nrf2 inhibitor ML385 was conducted to ascertain the role of the Nrf2 signaling pathway in the downregulating ferroptosis effect of BP. Moreover, an ultra-performance liquid chromatography coupled with mass spectrometry was utilized to evaluate the changes in glucose metabolism within colon tissues of UC mice following BP treatment. Cellular thermal shift assay (CETSA), surface-plasmon resonance (SPR) and molecular docking were carried out to reveal the binding ability of BP and phosphogluconate dehydrogenase (PGD) protein. The PGD inhibitor, 6PGD-IN-S3 was used to evaluated whether BP inhibits anti-ferroptosis effect by upregulating the expression of PGD. Results BP exhibited significant anti-UC activity, leading to a reduction in both the disease activity index and histological damage in mice afflicted with UC. BP effectively mitigated DSS-induced ferroptosis both in vivo and in vitro . Additionally, ID and Erastin treatment diminished the therapeutic efficacy of BP against UC. A similar trend was observed in mice treated with ML385. Metabolomics analysis indicated that BP had a notable effect in restoring the pentose phosphate pathway (PPP) of colon tissues following DSS administration. The treatment of BP upregulated the activity of PGD. The inhibition of PGD weakened the anti-ferroptosis effect of BP. Subsequent analysis revealed that BP has the potential to effectively bind to PGD, thereby inhibiting PGD entries lysosomes. Conclusion The above findings provide robust evidence for the anti-UC mechanism of BP in inhibiting ferroptosis through upregulation of the Nrf2 signal. PGD, a key enzyme in the PPP, is proved as the target protein of BP to inhibit ferroptosis first time. BP has been further proved to inhibit the lysosomal degradation pathway of PGD.
研究领域:
药理学
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胃肠病学
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分子生物学
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生物化学
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中医学
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细胞生物学
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PubMed
高影响因子
BIOMATERIALS
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2025
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IF 12.9
Chunxue Dai,Yingjiao He,Hongyan Lu,Xiaotong Feng,Naling Long,Qile Song,Yuwei Li,Yifan Wang,Lisandra L. Martin,Cundong Fan,Dongdong Sun
Hydrogen therapy as an emerging strategy for anticancer medicine is attracting attention. However, the limitations of effective hydrogen storage and release have hindered its development and application for hydrogen therapy. Herein, a high hydrogen storage nanoquadruplex (PdH 0.2 ) 4 Se based on a palladium-selenium core has been designed and shows enhanced intratumoral accumulation via an enhanced permeability and retention (EPR) effect. High-efficiency hydrogen can be released from (PdH 0.2 ) 4 Se, activated by near infrared irradiation (NIR), and combines with available selenium (Se) to produce highly toxic hydrogen selenide (H 2 Se), which in turn unbalances the GSH/GSSG ratio and induces ROS overproduction. The effect demonstrates that (PdH 0.2 ) 4 Se irradiated by NIR significantly inhibits cancer cell proliferation, migration, invasion and angiogenesis in vitro . Furthermore, irradiation of (PdH 0.2 ) 4 Se by NIR can induce significant ferroptosis of cancer cells by triggering mitochondrial dysfunction, ROS generation and lipid peroxidation-mediated oxidative damage in vitro . Finally, NIR irradiated (PdH 0.2 ) 4 Se also exhibits tumor-targeted photothermal imaging, and inhibition of tumor growth in vivo activating cancer ferroptosis. Importantly, (PdH 0.2 ) 4 Se demonstrates excellent safety and biocompatibility in vitro and in vivo . Thus together, our findings support the rational design of an effective hydrogen storage (PdH 0.2 ) 4 Se nanoquadruplex with NIR-controlled release causing an unbalance of cellular GSH/GSSG and inducing cancer ferroptosis could be a highly efficient strategy for hydrogen-mediated cancer therapy.
研究领域:
纳米医学
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癌症生物学
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光疗
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药物输送
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生物无机化学
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PubMed
高影响因子
Advanced Composites and Hybrid Materials
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2025
·Vol. 8
·期 4
·1-18
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IF 21.8
Wang Pengfei,Sun Xinxin,Feng Chengcheng,Liu Shiwen,Chen Qin,Zhang Shenwu,Sun Jin,He Zhonggui,Wang Yuequan,Luo Cong
Ferroptosis has emerged as a promising anticancer target, while the clinical translation of ferroptosis inducers is greatly obstructed by the heterogeneous iron levels and inherent antioxidant defense in tumors. Given that most ferroptosis inducers alone fail to elicit cellular lipid peroxidation storm, we here design a ferroptosis booster to synergize with inducers to trigger cellular ROS eruption. Inspired by the pharmacological mechanisms of artesunate (ART), a functional ART-ferrocene (ART-Fc) conjugate is synthesized by esterification reaction. Encouragingly, ART-Fc remarkably sensitizes a variety of ferroptosis inducers through close-by iron supply and productive ROS generation, establishing it as a potential ferroptosis booster. To validate the concept, a binary nanohybrid of sorafenib (Sor) and ART-Fc is fabricated to cooperatively induce tumor ferroptosis. ART-Fc renders iron overload and raises ROS storm through close-by iron supply and intramolecular electron transfer from Fc to ART, which significantly boosts Sor-induced ferroptosis in heterotopic and orthotopic triple-negative breast cancer mouse models. This study presents a broad-spectrum synergist designed to enhance the efficacy of ferroptosis-based cancer therapies and advances an iron overload/ROS eruption/GSH depletion "triple punch" nanotherapeutics towards clinical treatment of triple-negative breast cancer.
研究领域:
纳米技术
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肿瘤学
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药理学
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生物化学
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材料科学
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高影响因子
AMERICAN JOURNAL OF CHINESE MEDICINE
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2025
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IF 5.5
Mei Luo,Yuelian Wang,Xiaodong Liu,Lin Liu,Li Zhu,Guo Chen,Qing Ye,Chengshi He,Xujue Xiao,Jike Li
Among the spectrum of digestive system cancers, hepatocellular carcinoma (HCC) poses a particularly formidable challenge due to its poor prognosis. Geniposide, an iridoid glucoside extracted from the fruit of Gardenia jasminoides Ellis, exhibits a diverse array of biological activities. The goal of this study is to delineate the specific roles and underlying mechanisms of geniposide on the progression of HCC. Cell viability, apoptosis and migration of Huh7 and HepG2 cells were, respectively, assessed via CCK-8, flow cytometry and trans-well assays. The level of reactive oxygen species (ROS) was assessed with a dihydroethidium (DHE) probe. The measurement of mitochondrial membrane potential (MMP) was conducted using JC-1 staining. Ferroptosis-related markers were evaluated by Western Blot assay. Transcriptome sequencing was performed in HCC cells both treated and untreated with geniposide. In vivo experiments were applied with the subcutaneous xenograft tumor model. In vitro experiments revealed that geniposide exerted a concentration-dependent suppression on cell viability and migration, concurrently eliciting apoptosis in HCC cells. Ferroptosis was identified as the main form of geniposide-induced cell death in HCC. Geniposide promoted the iron ions levels, ROS accumulation, and the expression of ferroptosis markers, which were partially reversed by the addition of deferoxamine (DFO, ferroptosis inhibitor). Intersection analysis was applied between upregulated genes of HCC cells and ferroptosis-related genes. DUOX1 was proven to be involved in geniposide-mediated roles in HCC. In vivo experiments further clarified the suppressive effects of geniposide on tumors. Geniposide treatment increased intracellular iron ions and induced ferroptosis in HCC. Geniposide attenuated tumor progression and oxidative stress via DUOX1-mediated ferroptosis.
研究领域:
生物医学
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分子生物学
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药理学
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PubMed
高影响因子
Food Science & Nutrition
·
2025
·Vol. 13
·期 5
·e70254
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IF 3.8
Yujie Pan,Mingyan Xia,Jin Luo,Shuai Lu
Diabetic wound healing critically depends on functional endothelial cells for angiogenesis, yet the hyperglycemic microenvironment induces endothelial dysfunction through oxidative stress, inflammation, and senescence. Although ferroptosis has been recognized as a critical pathological factor contributing to impaired diabetic wound healing, the therapeutic potential of resveratrol (Res), a natural polyphenol with well‐documented antioxidant and anti‐ferroptotic properties, remains underexplored in this context. This study aimed to investigate the protective effects of Res on endothelial cells and elucidate its underlying mechanisms in diabetic wound healing. In vitro experiments systematically evaluated Res's impact on cellular inflammatory responses, senescence levels, and angiogenic capacity. Subsequent in vivo studies assessed Res's therapeutic potential by monitoring diabetic wound healing progression and analyzing associated histological changes. To clarify the mechanisms underlying Res's promotion of diabetic wound healing, we conducted comprehensive analyses measuring intracellular reactive oxygen species, lipid peroxidation levels, mitochondrial membrane potential and morphology, ferroptosis‐related marker expression, and upstream signaling pathway regulation. Res significantly reduced HG‐induced inflammatory responses and cellular senescence in human umbilical vein endothelial cells while enhancing their angiogenic potential in vitro. In vivo results showed that Res not only markedly accelerated diabetic wound healing but also demonstrated multiple beneficial effects, including effective suppression of cellular senescence, decreased ferroptosis levels, and significantly promoted angiogenesis. Mechanistic investigations confirmed that Res achieves these effects by inhibiting ferroptosis through activation of the PI3K‐AKT‐Nrf2 signaling axis. Our results demonstrate that Res protects endothelial cells from HG‐induced ferroptosis by activating PI3K‐AKT‐Nrf2 signaling, thereby promoting angiogenesis and diabetic wound healing. These findings highlight Res as a promising therapeutic candidate for impaired diabetic wound repair and justify further clinical investigation. Resveratrol attenuates intracellular inflammatory responses and cellular senescence by inhibiting ferroptosis via activating the PI3K‐AKT‐Nrf2 signaling pathway, ultimately facilitating angiogenesis and healing of diabetic wounds.
研究领域:
医学
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药理学
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分子生物学
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PubMed
高影响因子
Cell Death Discovery
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2025
·Vol. 11
·期 1
·1-17
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IF 7
Wei Guojiang,Huang Ying,Li Wenya,Xie Yuxin,Zhang Deyi,Niu Yuanjie,Zhao Yang
Metabolic reprogramming in prostate cancer has been widely recognized as a promoter of tumor progression and treatment resistance. This study investigated its association with ferroptosis resistance in prostate cancer and explored its therapeutic potential. In this study, we identified differences in the epithelial characteristics between normal prostate tissue and tissues of various types of prostate cancer using single-cell sequencing. Through transcription factor regulatory network analysis, we focused on the candidate transcription factor, SREBF1. We identified the differences in SREBF1 transcriptional activity and its association with ferroptosis, and further verified this association using hdWGCNA. We constructed a risk score based on SREBF1 target genes associated with the biochemical recurrence of prostate cancer by combining bulk RNA analysis. Finally, we verified the effects of the SREBPs inhibitor Betulin on the treatment of prostate cancer and its chemosensitization effect. We observed characteristic differences in fatty acid and cholesterol metabolism between normal prostate tissue and prostate cancer tissue, identifying high transcriptional activity of SREBF1 in prostate cancer tissue. This indicates that SREBF1 is crucial for the metabolic reprogramming of prostate cancer, and that its mediated metabolic changes promoted ferroptosis resistance in prostate cancer in multiple ways. SREBF1 target genes are associated with biochemical recurrence of prostate cancer. Finally, our experiments verified that SREBF1 inhibitors can significantly promote an increase in ROS, the decrease in GSH, and the decrease in mitochondrial membrane potential in prostate cancer cells and confirmed their chemosensitization effect in vivo. Our findings highlighted a close association between SREBF1 and ferroptosis resistance in prostate cancer. SREBF1 significantly influences metabolic reprogramming in prostate cancer cells, leading to ferroptosis resistance. Importantly, our results demonstrated that SREBF1 inhibitors can significantly enhance the therapeutic effect and chemosensitization of prostate cancer, suggesting a promising therapeutic potential for the treatment of prostate cancer.
研究领域:
肿瘤学
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分子生物学
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生物信息学
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PubMed
高影响因子
CELL BIOCHEMISTRY AND BIOPHYSICS
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2025
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IF 2.5
Xiang Ming,Lin Xiangdong,Chen Haiying
Coronary heart disease (CHD) is a disease caused by organic and functional coronary artery stenosis, resulting in a reduced oxygen supply to the heart. This study aimed to investigate the mechanism via which Luteolin regulates the Sirt1 / Nrf2 pathway to inhibit ferroptosis in human umbilical vein endothelial cells (HUVEC) associated with CHD. An ox-LDL-induced HUVEC cell model with Sirt1 silencing and Luteolin treatment was established. The silencing efficiency of Sirt1 was validated using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot analysis. The results of molecular docking and DARTS experiments showed that Luteolin could effectively bind Sirt1 . Subsequently, we measured the expression of Nrf2 and Sirt1 , cell viability, MDA, GSH, Fe 2+ levels, lipid ROS content, expression of ferroptosis-related proteins GPX4, FTH, FTL, and cell migration parameters. The results showed that Luteolin could activate the Sirt1 / Nrf2 axis and effectively inhibit ox-LDL-induced ferroptosis in HUVEC. Experimental results revealed that Luteolin could enhance HUVEC cell viability, decrease MDA, Fe 2+ , and ROS levels, increase GSH levels, promote the expression of HO-1, GPX4, FTH, FTL, inhibit the expression of ACSL4 and TFRC, and enhance the migration capability of HUVEC cells. Moreover, silencing Sirt1 reversed the effects of Luteolin on the activation of Sirt1 and Nrf2 , confirming the dependence of these effects on the Sirt1 / Nrf2 signaling pathway. In conclusion, this study indicates that Luteolin could inhibit ferroptosis in HUVEC in CHD by modulating the Sirt1 / Nrf2 axis, providing a basis for further research on strategies for preventing and treating CHD and related diseases.
研究领域:
药理学
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分子生物学
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心脏病学
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细胞生物学
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生物化学
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PubMed
高影响因子
危险品化学品经营许可证（带存储）