查找使用阿拉丁产品的科研文献

Qingyu formula inhibits ferroptosis in HK-2 cells and in a diabetic nephropathy mouse model via the Nrf2/SLC7A11/GPX4 pathway

Jie Liu,Yuan-Yuan Xu,Tian-Ye Gao

Background Diabetic kidney disease (DKD) is a severe microvascular complication, and ferroptosis is a major contributor to its pathogenesis. This study investigated the protective effects of Qingyu formula (QYF), a traditional Chinese medicine prescription, against ferroptosis in high glucose-induced renal injury. Methods In vitro, human renal tubular cells (human kidney 2 [HK-2]) under high glucose conditions were treated with QYF. In vivo, the induced diabetic mice received QYF interventions. Biochemical and molecular assays assessed cell viability, oxidative stress, ferroptosis markers (Fe²⁺, glutathione [GSH], malondialdehyde) and nuclear factor erythroid 2-related factor 2/solute carrier family 7 member 11/glutathione peroxidase 4 (Nrf2/SLC7A11/GPX4) pathway activity. Results Qingyu formula enhanced cell viability and reduced reactive oxygen species in high glucose-treated HK-2 cells. It mitigated ferroptosis by decreasing Fe²⁺ accumulation and increasing GSH levels both in vivo and in vitro. Mechanistically, QYF upregulated GPX4, Nrf2 and SLC7A11. In diabetic mice, it improved metabolic parameters and reduced proteinuria in a dose-dependent manner, with high doses showing efficacy similar to that of clinically used irbesartan. Conclusions Qingyu formula protects against high glucose-induced renal injury by suppressing ferroptosis via the activation of the Nrf2/SLC7A11/GPX4 pathway. These findings support QYF as a promising candidate for targeting ferroptosis in DKD. Future studies should identify its active constituents and evaluate its efficacy in clinical trials.

Resveratrol Alleviates Polycystic Ovary Syndrome Symptoms by Reducing Inflammation, Oxidative Stress, and Ferroptosis Features in a Mouse Model: A Prospective Study

Jiao Cai,Fengqi Wan,Jumei Yang,Yalan Wang,Jiao Wang

Background:Polycystic ovary syndrome (PCOS) is related to persistent low-grade inflammation and oxidative stress (OS). Resveratrol (RSV) exhibits potent anti-inflammatory and antioxidant effects, suggesting therapeutic potential for PCOS. However, its precise mechanisms of action, particularly concerning ferroptosis remain unclear. This study aimed to investigate whether RSV ameliorates PCOS by modulating inflammation, OS and ferroptosis features, thereby offering novel insights into its therapeutic role.Methods:PCOS was induced in mice through once-daily subcutaneous dosing of dehydroepiandrosterone (DHEA: 0.6 mg/kg), alongside a 21-day continuous high-fat diet regimen. Following successful model induction, the mice were assigned to the PCOS group or the RSV group. RSV was orally gavaged at doses of 20 and 40 mg/kg/day for 30 days. The body weight, ovarian weight and estrous cycle were monitored. Serum is used for the detection of hormones [follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T) and inflammatory markers [interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α)]. Then the ovarian tissue samples were utilized for the assessment of OS indicators [malondialdehyde (MDA), glutathione (GSH)], glutathione peroxidase 4 (GPX4), and transcriptomic profiling.Results:RSV was shown to reduce body weight and ovarian weight. RSV also ameliorated symptoms of PCOS by decreasing chronic inflammation, OS and ferroptosis features in the ovaries. All the detected inflammatory factors in the PCOS group were significantly higher than those in the control group (IL-1β, p < 0.0001; IL-6, p < 0.001; TNF-α, p < 0.01) and were significantly decreased with the supplementation of RSV. Ovarian tissue MDA levels were markedly elevated in PCOS mice compared to controls (p < 0.0001), with RSV treatment significantly attenuating this increase. While GSH levels were significantly depleted in PCOS ovaries compared to controls (p < 0.0001), with RSV treatment effectively restoring concentrations. Western blot analysis revealed that GPX4 expression in ovaries was significantly diminished in the PCOS group compared with the control group (p < 0.01), but this reduction was effectively reversed by RSV treatment.Conclusions:RSV demonstrated therapeutic efficacy in PCOS mice by normalizing hormonal profiles and mitigating chronic inflammatory responses and oxidative damage. Furthermore, our investigation also revealed that RSV ameliorates PCOS pathology by modulating GPX4 pathways, which is consistent with ferroptosis features.

A Proanthocyanidins-Rich Cili (Rosa roxburghii) Fruit Extract Protects CCl4-Induced Mouse Hepatic Fibrosis via Modulation of Ferroptosis and Gut Microbiota

Yang Liu,Jingzhong Zheng,Xin Zheng,Dan Zhou,Hang Ma,Xue Zhou,Fahuan Ge

Background:Cili (Rosa roxburghiiTratt) is a unique fruit native to China’s Yunnan–Guizhou Plateau, rich in vitamin C, polyphenols, and triterpene, with broad health-promoting effects. Although cili’s hepatoprotective properties are reported, the bioactive components and underlying mechanisms remain poorly defined.Methods:We enriched proanthocyanidins from cili using column chromatography, identified their components via UPLC-Q-TOF-MS/MS, and validated their anti-liver fibrosis effects through in vitro and in vivo experiments.Results:Herein, we developed a novel proanthocyanidin-rich cili fruit extract (PACs-CFE) containing 84.2% total proanthocyanidins, comprising catechins, epicatechins, and diverse B-type dimers, trimers, tetramers, and gallate esters, as characterized by UPLC-Q-TOF-MS/MS. PACs-CFE inhibited LX-2 activation, suppressed collagen III and α-SMA expression, and induced ferroptosis via mitochondrial injury, reactive oxygen species accumulation, and GPX4/ferritin downregulation. In vivo, PACs-CFE ameliorated liver fibrosis, restored hepatic architecture, and improved serum alanine aminotransferase, aspartate aminotransferase, and bilirubin profiles. Moreover, PACs-CFE modulated the TGF-β1/Smad3 signaling pathway and beneficially reshaped the gut microbiota, enriching anti-inflammatory and hepatoprotective genera while reducing pathogenic taxa.Conclusions:Our findings show that PACs-CFE exerts multi-targeted anti-fibrotic effects through hepatic stellate cell inactivation, ferroptosis induction, TGF-β1/Smad3 suppression, and gut–liver axis modulation. This study provides useful insight into the hepatoprotective potential of cili fruit and supports its development as standardized functional ingredients for liver health.

Mechanistic insights into cadmium-induced nephrotoxicity: NRF2-Driven HO-1 activation promotes ferroptosis via iron overload and oxidative stress in vitro

Tongwang Luo,Shengzhe Song,Shujie Wang,Sheng Jiang,Bin Zhou,Quanjiang Song,Lingjun Shen,Xiaodu Wang,Houhui Song,Chunyan Shao

Cadmium (Cd), a pervasive environmental toxicant, poses significant threats to human and animal health through multi-organ toxicity. While ferroptosis has been implicated in Cd-induced pathologies, the molecular mechanisms underlying Cd-mediated nephrotoxicity remain poorly understood. This study elucidates the ferroptosis pathway in CdCl 2 -exposed PK-15 cells and murine kidney, characterized by iron overload, lipid peroxidation, and mitochondrial dysfunction, which were ameliorated by ferroptosis inhibitor ferrostatin-1. Transcriptomic analysis revealed substantial upregulation of heme oxygenase-1 (HO-1) following CdCl 2 exposure. Mechanistically, CdCl 2 triggered nuclear translocation of nuclear factor erythroid 2-related factor-2 (NRF2), subsequently activating HO-1 transcription. Over-activated HO-1 catalyzes the decomposition of heme and releases free iron, accompanied with the degradation of ferritin heavy chain 1 (FTH1) induced by CdCl 2 exposure, which leads to intracellular iron overload and excessive lipid peroxides production through Fenton reaction, resulting in ferroptosis ultimately. In vivo validation confirmed NRF2/HO-1-mediated ferroptosis in CdCl 2 -induced murine nephrotoxicity. Both pre-treatment with HO-1 competitive inhibitor Zinc protoporphyrin IX (ZnPP) and knockout of HO-1 gene remarkably alleviated PK-15 cells against ferroptosis induced by CdCl 2 treatment. Our findings demonstrate that Cd exposure initiates NRF2-mediated HO-1 overexpression, driving iron-dependent lipid peroxidation and subsequent ferroptosis. This mechanistic insight provides potential therapeutic targets for mitigating Cd-induced renal damage, advancing our understanding of heavy metal toxicity and its cellular consequences.

The Bach1/HO-1 pathway regulates oxidative stress and contributes to ferroptosis in doxorubicin-induced cardiomyopathy in H9c2 cells and mice

Wang Yanwei,Qiu Jingru,Yan Hua,Zhang Nan,Gao Shixuan,Xu Ning,Wang Cuiyan,Lou Haiyan

Doxorubicin (DOX) is one of the most frequently used chemotherapeutic drugs belonging to the class of anthracyclines. However, the cardiotoxic effects of anthracyclines limit their clinical use. Recent studies have suggested that ferroptosis is the main underlying pathogenetic mechanism of DOX-induced cardiomyopathy (DIC). BTB-and-CNC homology 1 (Bach1) acts as a key role in the regulation of ferroptosis. However, the mechanistic role of Bach1 in DIC remains unclear. Therefore, this study aimed to investigate the underlying mechanistic role of Bach1 in DOX-induced cardiotoxicity using the DIC mice in vivo (DOX at cumulative dose of 20 mg/kg) and the DOX-treated H9c2 cardiomyocytes in vitro (1 μM). Our results show a marked upregulation in the expression of Bach1 in the cardiac tissues of the DOX-treated mice and the DOX-treated cardiomyocytes. However, Bach1 −/− mice exhibited reduced lipid peroxidation and less severe cardiomyopathy after DOX treatment. Bach1 knockdown protected against DOX-induced ferroptosis in both in vivo and in vitro models. Ferrostatin-1 (Fer-1), a potent inhibitor of ferroptosis, significantly alleviated DOX-induced cardiac damage. However, the cardioprotective effects of Bach1 knockdown were reversed by pre-treatment with Zinc Protoporphyrin (ZnPP), a selective inhibitor of heme oxygenase-1(HO-1). Taken together, these findings demonstrated that Bach1 promoted oxidative stress and ferroptosis through suppressing the expression of HO-1. Therefore, Bach1 may present as a promising new therapeutic target for the prevention and early intervention of DOX-induced cardiotoxicity.

Wuwei Shaji powder alleviates OVA-induced allergic asthma by protecting bronchial epithelial cells from ferroptosis via the S-sulfhydration of Keap1

Huimei Zhao,Haiyan Zhang,Jianyu Shi,Yanru Liu,Jingao Yu,Yuangui Yang,Jingyu Weng,Zhongxing Song,Rui Zhou,Hong Min,Jian Yao,Mei Wang,Zhen Zhang

Ethnopharmacological relevance Asthma is a chronic inflammatory airway disease. Current treatments have limited efficacy and often cause severe side effects. Wuwei Shaji Powder (WSP), a traditional Mongolian remedy, is used for treating chronic pulmonary diseases, but its efficacy against asthma and underlying mechanisms are still unclear. Aim of the study To investigate the therapeutic effect of WSP on asthma and elucidate its molecular mechanisms. Materials and methods An ovalbumin (OVA)-induced allergic asthma model was established in rats. Ferroptosis or apoptosis was induced in BEAS-2B cells using Erastin or CdCl 2 . Various techniques including histopathological staining, ELISA, Western blot, flow cytometry, and transmission electron microscopy were employed to assess WSP's effects and mechanisms. Results WSP alleviated OVA-induced allergic asthma in rats without the immunosuppressive side effects observed with dexamethasone. WSP suppressed ferroptosis in bronchial epithelial cells both in vivo and in vitro. It reduced thiol- and sulfonic-based oxidative stress through Keap1 S-sulfhydration, disrupted the Keap1-Nrf2 interaction, and promoted Nrf2 nuclear translocation. Notably, we discovered that CdCl 2 can induce ferroptosis in BEAS-2B cells, and WSP prevented both ferroptosis and apoptosis in these cells. Conclusion WSP alleviates OVA-induced allergic asthma by protecting bronchial epithelial cells from ferroptosis via S-sulfhydration of Keap1, providing new insights for its clinical application.

Long noncoding RNA ADAMTS9-AS1 represses ferroptosis of endometrial stromal cells by regulating the miR-6516-5p/GPX4 axis in endometriosis

Wan Yiting,Gu Cancan,Kong Jueying,Sui Jin,Zuo Ling,Song Yanhua,Chen Jing

Endometriosis (EMs) is one of the most frequent diseases of reproductive-age women and is characterized by the growth of endometrial tissues beyond the uterus. The enhanced proliferative and migratory potential of endometrial stromal cells (ESCs) plays an important role in the progression of EMs. Mounting studies have demonstrated that long noncoding RNAs (lncRNAs) exert an important role in regulating the development and progression of EMs. Given the aberrant expression of lncRNA ADAMTS9-AS1 in ectopic endometrium (ecEM), we investigated the biological effect of ADAMTS9-AS1 on ESC proliferation and migration and explored the underlying mechanism. The current data showed that ADAMTS9-AS1 expression was significantly upregulated in ecEM compared with eutopic endometrium (euEM) in patients with EMs and in a murine model of EMs. Functionally, ADAMTS9-AS1 knockdown in ectopic ESCs (EESCs) decreased cell viability and migration, whereas ADAMTS9-AS1 overexpression in normal ESCs (NESCs) enhanced cell viability and migration. More importantly, the effect of ADAMTS9-AS1 inhibition on decreasing ESC viability was significantly blocked by ferrostatin-1 (Fer-1, a ferroptosis inhibitor), and ADAMTS9-AS1 overexpression repressed erastin (a ferroptosis activator)-induced cell death. Furthermore, the regulatory role of ADAMTS9-AS1 in ferroptosis was defined and evidenced by increased reactive oxygen species (ROS) levels and malonyl dialdehyde (MDA) content and decreased expression of glutathione peroxidase 4 (GPX4) after ADAMTS9-AS1 inhibition. Mechanistically, ADAMTS9-AS1 functioned as a competing endogenous RNA (ceRNA) by sponging miR-6516-5p to derepress the expression of GPX4, the critical repressor of ferroptosis. Taken together, these results demonstrate that upregulated ADAMTS9-AS1 accelerates ESC proliferation and migration by regulating miR-6516-5p/GPX4-dependent ferroptosis and may be a potential target for the treatment of EMs.

Cepharanthine Attenuates Early Brain Injury after Subarachnoid Hemorrhage in Mice via Inhibiting 15-Lipoxygenase-1-Mediated Microglia and Endothelial Cell Ferroptosis

Shiqi Gao,Liuzhi Zhou,Jianan Lu,Yuanjian Fang,Haijian Wu,Weilin Xu,Yuanbo Pan,Junjie Wang,Xiaoyu Wang,Jianmin Zhang,Anwen Shao

Background. Ferroptosis is a newly identified form of programmed cell death caused by iron-dependent lipid peroxidation. Our study was designed to determine the expression patterns and role of 15-lipoxygenase-1 (ALOX15) in subarachnoid hemorrhage (SAH) and to investigate whether cepharanthine (CEP) can inhibit ferroptosis by inhibiting ALOX15 in specific cell types. Methods. A mouse model of SAH was developed by the endovascular perforation method. bEend.3 endothelial cells and BV2 microglial cells as well as RSL3 and hemin were used to simulate SAH in vitro. Mice and cell lines were treated with CEP and a group of specific oxygenase inhibitors to explore the protection effect from ferroptosis. Lipid peroxidation staining with BODIPY 581/591 C11 and transmission electron microscopy were used to identify ferroptosis in vitro and in vivo. Results. In the present study, the accumulation of lipid peroxide, a defect in the glutathione peroxidase 4 (GPx4)/glutathione (GSH) antioxidant system, highly expressed ALOX15 in microglia and endothelium, and ferroptotic changes in microglial mitochondria confirmed the occurrence of ferroptosis after SAH in vivo. Further, CEP was shown to inhibit ferroptosis and improve neurological function by downregulating the expression of ALOX15. During in vitro experiments, we investigated the important role ALOX15 in RSL3-induced endothelial ferroptosis. In addition, we found that M2-type microglia are more sensitive to RSL3-induced ferroptosis than M1-type microglia and that hemin probably induced ferroptosis in M2-type microglia by increasing ALOX15 levels and decreasing GPx4 levels. The effect of CEP treatment was also demonstrated in vitro. Conclusions. In summary, to the best of our knowledge, this is the first study demonstrating that ferroptosis occurred in the microglia and endothelium after SAH, and this process was facilitated by increased ALOX15 levels. More importantly, treatment with CEP could inhibit ferroptosis through downregulating the expression of ALOX15.

Synergistic Induction of Ferroptosis by GPX4 Inhibitor and GSH-Depleted Nanoparticles Effectively Reverses Gemcitabine Resistance in Pancreatic Ductal Adenocarcinoma PDX Model

Chen-Song Huang,Chunlei Dai,Qi Liu,Si-Yun Chen,Ya-Hao Guo,Jie-Qin Wang,An-Da Zheng,Xi-Tai Huang,Jun Wu,Xiao-Yu Yin

Ferroptosis has emerged as a critical mechanism in overcoming drug resistance in various tumors; however, its role in gemcitabine-resistant pancreatic ductal adenocarcinoma (PDAC) has not been thoroughly explored. Additionally, the effectiveness of ferroptosis in many cancer therapies has been limited. In our study, we found that GPX4 is upregulated in gemcitabine-resistant (GR) PDAC patient tissues and cell lines. Notably, inhibiting GPX4 can reverse gemcitabine resistance in PDAC through the induction of ferroptosis, highlighting it as a potential therapeutic target. To address this, we developed a novel nanomedicine, GSH-depleted and ferroptosis-induced (FiN), designed to encapsulate and deliver the GPX4 inhibitor RSL3, resulting in a dual ferroptosis-induced nanomedicine (DFiN). In a PDAC patient-derived xenograft (PDX) mouse model exhibiting gemcitabine resistance, DFiN demonstrated significant accumulation in GR PDAC tumors, leading to a reduction in intracellular GSH levels and inhibition of GPX4. This dual action promoted lipid peroxidation and synergistically induced ferroptosis, effectively reversing gemcitabine resistance. Both in vitro and in vivo experiments confirmed that DFiN is effective in overcoming gemcitabine resistance in GR PDAC cells and PDX tumors, with minimal toxicity observed. This study presents a promising strategy for addressing drug resistance in cancer therapy.

Engineered exosomes mediated siNox4 delivery loaded polyzwitterionic hydrogel with electrophysiologic conductivity for synergistic treatment of spinal cord injury via suppressing neuronal ferroptosis.

Chenyu Wu,Yueman Tang,Zhichen Jiang,Chenglong Hong,Qi Yang,Zhouwei Wu,Jiangwei Zhu,Kaijie Guo,Jiang Liu,Si Yu Zheng,Lei Guo,Hui Xu,Wenfei Ni,Xiangyang Wang,Sunren Sheng,Jian Xiao,Chenggui Wang

Microenvironment-Adaptive Smart Hydrogel with 2D Vanadium Nitride MXenzyme Rescues Osteoarthritis via Coordinated ROS Scavenging and Hspa5/GPX4 Axis-Mediated Ferroptosis Suppression

Yanlin Li,Xiaotian Jiang,Jiale Li,Hanwen Gu,Qi Li,Jiaxin Li,Yunqing Ji,Xiang Min,Bin Chen,Qingjia Xu,Junhao Lin

Osteoarthritis (OA), a prevalent degenerative joint disorder characterized by articular cartilage deterioration, represents a major global health challenge. Recent studies highlight the pivotal role of reactive oxygen species (ROS)-mediated ferroptosis in OA pathogenesis. Here, we report a microenvironment-adaptive hydrogel system based on 2D vanadium nitride (V 2 N) MXene nanoenzyme (hereafter denoted as V 2 N MXenzyme@Gel). This system features a dual-crosslinked network that optimally balances between mechanical robustness and flexibility. Crucially, the V 2 N MXenzyme establishes a self-sustaining “capture-conversion-recycling” catalytic cycle, mimicking both superoxide dismutase (SOD) and catalase (CAT) activities. The cycle not only neutralizes detrimental ROS into water (H 2 O) and oxygen (O 2 ) but also generates nitric oxide (NO), collectively alleviating oxidative damage. Mechanistically, V 2 N MXenzyme@Gel effectively scavenges ROS, attenuates oxidative stress, and suppresses ferroptosis by regulating the Hspa5/GPX4 axis, while concurrently restoring the metabolic homeostasis of chondrocyte extracellular matrix (ECM). Meanwhile, intra-articular administration of V 2 N MXenzyme@Gel significantly attenuates cartilage degradation and inflammation levels in OA rats. Collectively, our work presents a V 2 N MXenzyme@Gel with dual capabilities for ROS elimination and ferroptosis blockade, demonstrating its efficacy in arresting OA progression and proposing a novel precision strategy for managing chronic joint diseases.

Integrated multi-omics analysis reveals NRF2-dependent ferroptosis regulation underlying the renoprotective effects of p-coumaric acid in folic acid–induced AKI

Hongchuang Ma,Nan Shen,Xin Liu,Fangfang Zhou,Chuanming Hao,Qun Luo

Background Acute kidney injury (AKI) remains a major clinical challenge lacking effective pharmacological interventions. Ferroptosis has emerged as a critical mechanism contributing to renal tubular injury. While p -coumaric acid (pCA), a natural phenolic compound, has been reported to exert renoprotective effects, its regulatory role in ferroptosis, particularly under different pathological contexts of AKI, remains incompletely understood. Methods A folic acid (FA, 250 mg/kg)–induced AKI model was established in mice treated with pCA (10 and 50 mg/kg). Renal function, histopathology, inflammatory responses, and ferroptosis-related markers were evaluated. Integrated transcriptomic and metabolomic analyses were performed to identify global regulatory alterations. Mechanistic studies were conducted in erastin-treated HK-2 cells. NRF2 signaling involvement was further assessed using pharmacological inhibition. Results pCA treatment significantly improved renal function, attenuated tubular injury, and suppressed inflammatory responses in FA-induced AKI. Multi-omics integration revealed that pCA markedly reprogrammed metabolic and transcriptional networks associated with ferroptosis and redox homeostasis. Mechanistically, pCA restored antioxidant capacity and normalized the expression of ferroptosis-related proteins. Notably, pCA activated NRF2 signaling, leading to upregulation of downstream targets involved in ferroptosis regulation. Inhibition of NRF2 partially abolished the cytoprotective and anti-ferroptotic effects of pCA in vitro. Conclusion pCA alleviates FA-induced AKI by suppressing ferroptosis through NRF2-dependent regulation of redox and metabolic homeostasis, highlighting NRF2 as a potential therapeutic target for AKI.