PHYTOMEDICINE
·
2024
·
IF 6.7
Fang Wang,Fanxuan Zhang,Bingfeng Lin,Wenlong Xiao,Xuchen Wang,Nani Wang
Background Promoting the coupling of osteogenesis and angiogenesis is a crucial strategy for the treatment of postmenopausal osteoporosis (PMOP). Estrogen deficiency induces ferroptosis, which is closely associated with the pathophysiology of PMOP. Sarsasapogenin (SAR) is a natural sapogenin with anti-oxidative effects. However, it is unclear whether SAR has a protective role against the impaired osteogenesis and angiogenesis coupling in PMOP. In this study, we evaluated the efficacy of SAR in estrogen deficiency-induced osteoporosis and explored the underlying mechanisms. Methods Bone marrow mesenchymal stem cells (BMSCs) and human umbilical vein endothelial cells (HUVECs) were utilized to assess the in vitro effects of SAR on the coupling of osteogenesis and angiogenesis. In vivo experiments involved bilateral ovariectomy (OVX)-induced osteoporosis in mice and glutathione peroxidase 4 (GPX4)-knockout (KO) mice. Mice were orally administered SAR (5 or 10 mg/kg/d) for a duration of 12 weeks. The direct target of SAR was investigated through molecular docking, a cellular thermal shift assay, and surface plasmon resonance. Additionally, RNA sequencing was employed to elucidate the underlying mechanisms. Results SAR treatment improved cell viability and osteogenic differentiation while inhibiting ferroptosis in iron dextran-induced BMSCs. Furthermore, SAR enhanced the production of slit guidance ligand 3 (SLIT3) in these cells, which stimulated angiogenesis by activating its receptor, roundabout human homolog 1 (ROBO1), in HUVECs. An in vitro model of ferroptosis induced by erastin demonstrated that SAR promoted the coupling of osteogenesis and angiogenesis by upregulating the BMSCs-SLIT3/HUVECs-ROBO1 axis. Activation of GPX4 was identified as a contributing factor to the effects of SAR on this coupling. Transfection of GPX4 small interfering RNA (siRNA) in BMSCs negated the impact of SAR on the BMSCs-SLIT3/HUVECs-ROBO1 axis. Additionally, SAR was found to directly interact with GPX4, enhancing protein stability, with an equilibrium dissociation constant of 44.6 μM. Notably, SAR did not increase SLIT3, ROBO1, or indicators of osteogenesis or angiogenesis in GPX4-KO mice. Conclusions These findings underscore the significance of restoring the GPX4/SLIT3/ROBO1 axis in promoting the coupling of angiogenesis and osteogenesis. SAR mitigates PMOP, in part, by activating the BMSCs-SLIT3/HUVECs-ROBO1 axis, with GPX4 serving as an upstream signaling modulator responsible for SLIT3 production. Our observations provide experimental evidence supporting the clinical application of SAR in the treatment of PMOP.
研究领域:
医学
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分子生物学
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药理学
✓ 已验证
DOI
高影响因子
Translational Oncology
·
2024
·
IF 4.5
Wei An,Kai Zhang,Guangbing Li,Shunzhen Zheng,Yukun Cao,Jun Liu
Cholangiocarcinoma remains a challenging primary hepatobiliary malignancy with dismal prognosis. Photodynamic therapy (PDT),a less invasive treatment, has been found to inhibit the proliferation and induce ferroptosis, apoptosis and necrosis in other tumor cells in recent years. Regrettably, the role and exact molecule mechanism of PDT is still incompletely clear in cholangiocarcinoma cells. Ferroptosis is a novel regulated cell death(RCD), which is controlled by glutathione peroxidase4(GPX4) with the characteristics of iron dependent and excessive intracellular accumulation of lipid peroxides. This novel form of RCD has attracted great attention as a potential new target in clinical oncology during recent years. In this study, we observed that hypericin mediated PDT(HY-PDT) could significantly inhibit the proliferation of the cholangiocarcinoma cells and suppress migration and the epithelial mesenchymal transition (EMT) as well. Then, we conducted transcriptome sequencing and bioinformatics analysis and observed that HY-PDT was most likely involved in ferroptosis, apoptosis, the EMT process and AKT/mTORC1 signaling pathways in cholangiocarcinoma cells. Next, a series of in vitro and in vivo experiments were performed to confirm that HY-PDT could trigger cholangiocarcinoma cells ferroptosis through inhibiting the expression of GPX4 protein. In terms of molecular mechanism, we found that HY-PDT induced ferroptosis by decreasing GPX4 expression via suppression of the AKT/mTORC1 signaling pathway. In addition, we also found that HY-PDT inhibit cholangiocarcinoma cells migration and the EMT process by inhibiting the AKT/mTORC1 pathway. Our study illustrated a new mechanism of action for HY-PDT and might throw light on the individualized precision therapy for cholangiocarcinoma patients.
研究领域:
肿瘤学
·
分子生物学
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细胞生物学
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药理学
✓ 已验证
DOI
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2025
·
IF 5.4
Nana Gao,Zongyu Huang,Jianjie Xie,Shuang Gao,Biaobiao Wang,Huicong Feng,Cuifen Bao,He Tian,Xia Liu
Ethnopharmacological relevance The Cryptotanshinone (CT) is a kind of Chinese medicine extracted from salvia miltiorrhiza, which has various pharmacological activities and is widely used in the treatment of diseases. Aim of the study The objective is to delve into the mechanism by which cryptotanshinone (CT) exerts its effects on rats with the middle cerebral artery occlusion/reperfusion (MCAO/R) model. Additionally, it aims to further assess the interplay between inflammation and oxidative stress, along with the underlying mechanism of CT's anti-ferroptosis function. Materials and methods We constructed the middle cerebral artery occlusion/reperfusion (MCAO/R) model in rats. The effects of cryptotanshinone (CT) were evaluated using 2,3,5 - triphenyltetrazolium chloride (TTC) staining, behavioral assays, immunofluorescence, hematoxylin - eosin (HE) staining, and Nissl staining. Additionally, in vitro, cell viability was assessed by the Cell Counting Kit - 8 (CCK - 8) assay following experimental dosing. Oxygen - glucose deprivation/oxidation (OGD/R) models were established in PC12 and BV2 cells. Flow cytometry was employed to detect cellular reactive oxygen species (ROS) expression. The activities of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-px), andMitochondrial Membrane Potential Assay Kit with JC-1(JC-1) were measured using biochemical methods. Inflammatory factor levels were determined using enzyme-linked immunosorbent assay (ELISA) kits. Immunoblotting was used to detect the levels of rat phosphatidylinositol 3 - kinase (PI3K), phosphorylated-PI3K (P-PI3K), protein kinase B (AKT), phosphorylated - AKT (P-AKT), nuclear factor erythroid 2related factor 2 (Nrf2), solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4). Results In rats with the MCAO/R model, CT demonstrated the ability to decrease ROS levels, enhance the activity of glutathione (GSH), mitigate inflammation, augment the activity of glutathione peroxidase 4 (GPX4), inhibit ferroptosis, safeguard neurons, and facilitate the restoration of nerve function. Results from network pharmacology indicated that the action of CT might be mediated via the PI3K/Akt signaling pathway. Simultaneously, in-vivo investigations revealed that CT curbs ferroptosis through the PI3K/AKT/Nrf2 and SLC7A11/GPX4 signaling pathways. Conclusion CT can inhibit ferroptosis by inhibiting the vicious cycle between oxidative stress and inflammation, protect neurons and promote motor function recovery.
研究领域:
药理学
·
神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2025
·
IF 16
Mengsi Zhang,Hao Zheng,Xuanqi Zhu,Shuwei Liu,Hao Jin,Yang Chen,Lanlan Wan,Songling Zhang,Hao Zhang
Disulfidptosis and ferroptosis are recently identified programmed cell deaths for tumor therapy, both of which highly depend on the intracellular cystine/cysteine transformation on the cystine transporter solute carrier family 7 member 11/glutathione/glutathione peroxidase 4 (SLC7A11/GSH/GPX4) antioxidant axis. However, disulfidptosis and ferroptosis are usually asynchronous due to the opposite effect of cystine transport on them. Herein, systematic glucose deprivation, by both inhibiting upstream glucose uptake and promoting downstream glucose consumption, is proposed to synchronously evoke disulfidptosis and ferroptosis. As an example, Au nanodots and Fe-apigenin (Ap) complexes coloaded FeOOH nanoshuttles (FeOOH@Fe-Ap@Au NSs) are employed to regulate the SLC7A11/GSH/GPX4 axis for performing disulfidptosis- and ferroptosis-mediated tumor therapy synchronously. In this scenario, Au nanodots exhibit glucose oxidase-like activity when consuming massive glucose. Meanwhile, Ap can inhibit glucose uptake by downregulating glucose transporter 1, depriving glucose fundamentally. The systematical glucose deprivation limits the supplement of NADPH and suppresses cystine/cysteine transformation on the SLC7A11/GSH/GPX4 axis, thus solving the contradiction of cystine transport on disulfidptosis and ferroptosis. In addition, the efficient delivery of exogenous iron ions by FeOOH@Fe-Ap@Au NSs and self-supplied H2O2 through Au nanodots-catalytic glucose oxidation facilitate intracellular Fenton reaction and therewith help to amplify ferroptosis. As a result of synchronous occurrence of disulfidptosis and ferroptosis, FeOOH@Fe-Ap@Au NSs exhibit good efficacy in an ovarian cancer therapeutic model.
研究领域:
肿瘤治疗
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分子生物学
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纳米医学
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生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FREE RADICAL BIOLOGY AND MEDICINE
·
2024
·
IF 7.1
Deshan Yao,Liuxiang Bao,Sichuan Wang,Meng Tan,Yuanyuan Xu,Tianxu Wu,Zhengang Zhang,Kaizheng Gong
Ischemia-reperfusion (I/R) injury, a multifaceted pathological process, occurs when the prolongation of reperfusion duration triggers ferroptosis-mediated myocardial damage. Isoliquiritigenin (ISL), a single flavonoid from licorice, exhibits a wide range of pharmacological impacts, but its function in ferroptosis caused by myocardial I/R injury remains unclear. This study delved into the protective effect of ISL on myocardial I/R injury-induced ferroptosis and its mechanism. Neonatal mouse cardiomyocytes (NMCM) underwent hypoxia/reoxygenation (H/R) to simulate the pathological process of myocardial I/R. ISL significantly attenuated H/R-triggered production of reactive oxygen species in NMCM, reduced the expression of malondialdehyde and the activity of lactate dehydrogenase, enhanced superoxide dismutase and catalase activity, and increased the expression of nuclear factor E2-related factor 2 (Nrf2) and its downstream heme oxygenase 1 (HO-1), thereby mitigating oxidative stress damage. CCK8 experiment revealed that the ferroptosis inhibitor Ferrostatin-1 significantly improved myocardial cell viability after 24 h of reoxygenation, and ISL treatment showed a similar effect. ISL reduced intracellular free iron accumulation, up-regulated glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11) expression, and inhibited lipid peroxidation accumulation, thereby alleviating ferroptosis. The Nrf2-specific inhibitor ML385 counteracted ISL's defensive role against H/R-triggered oxidative stress damage and ferroptosis. In vivo experiments further confirmed that by regulating the translocation of Nrf2 into the nucleus, ISL treatment increased the levels of HO-1, GPX4, and SLC7A11, inhibited the expression of ACSL4, Drp1 to exert the antioxidant role, alleviated mitochondrial damage, and ferroptosis, ultimately reducing myocardial infarction area and injury induced by I/R. ML385 nearly abolished ISL's protective impact on the I/R model by inhibiting Nrf2 function. In summary, ISL is capable of mitigating oxidative stress, mitochondrial damage, and cardiomyocyte ferroptosis caused by I/R, thereby reducing myocardial injury. A key mechanism includes triggering the Nrf2/HO-1/SLC7A11/GPX4 pathway to prevent oxidative stress damage and cardiomyocyte ferroptosis caused by I/R.
研究领域:
药理学
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心脏病学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2025
·Vol. 31
·期 1
·79
·
IF 4.6
Ziqian Zhang,Xue Bai,Qian Du,Jianhong Yang
Diabetic cardiomyopathy (DCM) is a severe complication of diabetes, in which ferroptosis is a key pathogenic mechanism. This study examines how alpha-linolenic acid (ALA), a plant-derived omega-3 polyunsaturated fatty acid, protects against damage from ferroptosis in DCM. Using an in vitro model of H9C2 cardiomyocytes treated with high glucose/palmitate, combined with a high-fat diet and mouse model of low-dose streptozotocin (STZ)-induced diabetes, this research demonstrates for the first time that ALA significantly alleviates cardiac dysfunction and prevents ferroptosis. Mechanistically, ALA inhibits STAT3 phosphorylation by activating the AMPK signaling pathway, thereby reducing NCOA4-mediated ferritinophagy and mitigating mitochondrial iron overload and reactive oxygen species accumulation. It also enhances the function of the SLC7A11/GSH/GPX4 axis, reducing lipid peroxidation (LPO)-induced ferroptosis. Collectively, these findings indicate that ALA protects against diabetic cardiomyopathy by coordinating the regulation of ferritinophagy and antioxidant defense through the AMPK-STAT3 pathway, offering a potential therapeutic strategy for disease management.
研究领域:
心血管病学
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内分泌学
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分子生物学
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代谢性疾病
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氧化应激
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细胞死亡机制
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营养干预
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Cell and Developmental Biology
·
2022
·
IF 6.081
Fan Zhang,Hualong Zhen,Hengshun Cheng,Fengying Hu,Yunfei Jia,Binbin Huang,Minmin Jiang
As one kind of endocrine disrupting chemical, di-(2-ethylhexyl) phthalate (DEHP) has been reported to cause liver dysfunction in epidemiological and experimental studies. Abnormal liver function in pregnancy is associated with adverse maternal and perinatal outcomes. Few studies have investigated the potential effect of gestational DEHP exposure on the liver in pregnant mice, and the underlying mechanisms remain unclear. In the present study, pregnant ICR mice were exposed to doses (0, 500, 1,000 mg/kg/day) of DEHP in the presence or absence of 5 mg/kg/day ferrostatin-1 (Fer-1, ferroptosis inhibitor) by oral gavage from gestation day 4 to day 18. HepG2 cells were exposed to different doses of monoethylhexyl phthalate (MEHP, a major metabolite of DEHP) in vitro . Hepatic function and pathologic changes were observed. Oxidative stress, iron metabolism, and ferroptosis-related indicators and genes were evaluated both in vivo and in vitro . The results showed that gestational DEHP exposure induced disordered liver function and hepatocyte morphology changes in pregnant mice, along with increased malondialdehyde (MDA) and Fe 2+ content and decreased glutathione (GSH) levels. The expression levels of the selected ferroptosis-related genes Slc7a11 , Gpx4 , and Nfr2 were significantly decreased, and Ptgs2 and Lpcat3 were significantly increased. Notably, Fer-1 attenuated DEHP-induced liver injury and ferroptosis. Furthermore, MEHP exhibited a synergistic effect with RSL3 (a GPX4 inhibitor) in promoting ferroptosis in vitro . Taken together, the results demonstrated that DEHP induced liver injury and ferroptosis in pregnant mice, probably by inhibiting the GPX4 pathway through lipid peroxidation and iron accumulation.
研究领域:
毒理学
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药理学
·
分子生物学
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生殖健康
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food & Function
·
2025
·
IF 5.4
Dapeng Chen,Jiayi Li,Xinyu Li,Kexin Zhang,Shujie Zeng,Shenjun Zhang,Longyun Li,Yongjian Xiong
Hispidulin, a dietary flavonoid occurring naturally in brown algae, has attracted considerable interest owing to its functions in modulating inflammatory responses and neutralizing reactive oxygen species. This study examined the consequences of hispidulin in a model of chemically induced acute colitis. RNA sequencing (RNA-seq), 16s rRNA-seq, and non-targeted metabolome were conducted to determine the mechanisms underlying hispidulin-induced effects on colitis. The findings revealed that hispidulin exhibited significant therapeutic benefits against colitis. In addition, treatment with hispidulin led to a decrease in pro-inflammatory cytokine levels as well as serum FITC-dextran concentrations. RNA-seq analysis demonstrated a notable increase in colonic ACAT2 expression in mice with colitis following hispidulin treatment. Furthermore, hispidulin administration resulted in the upregulation of GPX4, a reduction in ROS levels, and inhibition of epithelial ferroptosis in mice with colitis. Both genetic inhibition of ACAT2 in vitro and AAV-mediated knockdown of ACAT2 in vivo substantially negated the effects of hispidulin on GPX4/GSH levels, ROS levels, and lipid hydroperoxide accumulation in both NCM460 cells and epithelial cells derived from DSS exposed murine models. 16s rRNA-seq results showed that hispidulin increased abundance of Lactobacillus, NK4A136_group, Oscillibacter, Peptococcus, Adlercreutzia and decreased abundance of Turicimonas in colitic mice. Non-targeted metabolome results showed that hispidulin facilitated the metabolism of galactose and promoted unsaturated fatty acid biosynthesis in colitic mice. In summary, hispidulin reduced the advancement of acute colitis in mice by lessening ACAT2-mediated ferroptosis in epithelial cells, as well as altering composition of gut microbiota.
研究领域:
营养科学
·
胃肠病学
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分子生物学
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微生物学
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药理学
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生物信息学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHINESE JOURNAL OF PHYSIOLOGY
·
2023
·Vol. 66
·期 6
·437
·
IF 1.8
Fan Wenbo,Zhou Jianwu
Parkinson's disease (PD) is recognized as a degenerative and debilitating neurodegenerative disorder. The novel protective role of icariside II (ICS II) as a plant-derived flavonoid compound in neurodegenerative diseases has aroused much attention. Herein, the definite impacts of ICS II on the process of PD and the relevant action mechanism were studied. Human neuroblastoma SK-N-SH cells were challenged with 1-methyl-4-phenylpyridinium ion (MPP + ) to construct the PD cell model. MTT assay and flow cytometry analysis, respectively, appraised cell viability and apoptosis. Caspase 3 Activity Assay examined caspase 3 activity. Corresponding kits examined oxidative stress levels. BODIPY 581/591 C11 assay evaluated lipid reactive oxygen species. Iron Assay Kit assessed iron content. Western blot tested the expression of apoptosis-, ferroptosis- and Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2)/glutathione peroxidase 4 (GPX4) signaling-associated proteins. Molecular docking verified the binding of ICS II with Keap1. The existing experimental results unveiled that ICS II elevated the viability whereas reduced the apoptosis, oxidative stress, and ferroptosis in MPP + -treated SK-N-SH cells in a concentration-dependent manner. Furthermore, ICS II declined Keap1 expression while raised Nrf2, heme oxygenase 1, and GPX4 expression. In addition, ICS II had a strong binding with Keap1 and Nrf2 inhibitor ML385 partially abolished the suppressive role of ICS II in MPP + -triggered apoptosis, oxidative stress, and ferroptosis in SK-N-SH cells. To summarize, ICS II might inhibit apoptosis, oxidative stress, and ferroptosis in the MPP + -stimulated PD cell model, which might be due to the activation of Keap1/Nrf2/GPX4 signaling.
研究领域:
神经科学
·
药理学
·
细胞生物学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL POLLUTION
·
2024
·
IF 7.6
Xiang Li,Jie Yang,Erbao Shi,Yiguang Lu,Xiaochao Song,Huifeng Luo,Jundong Wang,Chen Liang,Jianhai Zhang
Fluoride is widely found in groundwater, soil, animal and plant organisms. Excessive fluoride exposure can cause reproductive dysfunction by activating IL-17A signaling pathway. However, the adverse effects of fluoride on male reproductive system and the mechanisms remain elusive. In this study, the wild type and IL-17A knockout C57BL/6J mouse were treated with 24 mg/kg·bw·d sodium fluoride and/or 5 mg/kg·bw·d riboflavin-5′-phosphate sodium for 91 days. Results showed that fluoride caused dental fluorosis, increased the levels of ROS in testicular Leydig cells and GSSG in testicular tissue, and did not affect the iron and serum hepcidin levels in testicular tissue. Riboflavin alleviated above adverse changes, whereas IL-17A does not participate in the oxidative stress-mediated reproductive toxicity of fluoride. Based on this, TM3 cells were used to verify the injury of fluoride on Leydig cells. Results showed that fluoride increased mRNA levels of ferroptosis marker SLC3A2 , VDAC3 , TFRC , and SLC40A1 and decreased Nrf2 mRNA levels in TM3 cells. The ferroptosis inhibitor Lip-1 and DFO were used to further investigate the relationship between male reproductive toxicity and ferroptosis induced by fluoride. We found that the fluoride-induced decrease in cell viability, increase in xCT, TFRC, and FTH protein expression, and decrease in GPX4 protein expression, can all be rescued by Lip-1 and DFO. Similar results were also observed in the riboflavin treatment group. Moreover, riboflavin mitigated fluoride-induced increases in ROS levels and SLC3A2 protein levels. In all, our work revealed that riboflavin inhibited ferroptosis in testicular Leydig cells and improved the declined male reproductive function caused by fluoride. This study provides new perspectives for revealing new male reproductive toxicity mechanisms and mitigating fluoride toxicity damage.
研究领域:
毒理学
·
生殖生物学
·
细胞生物学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Advanced Science
·
2023
·Vol. 10
·期 13
·2207216
·
IF 15.1
Xiao Yang,Yan Chen,Jiadong Guo,Jiaxin Li,Pu Zhang,Huan Yang,Kewei Rong,Tangjun Zhou,Jingke Fu,Jie Zhao
Intervertebral disc degeneration (IVDD)-induced lower back pain (LBP) is a common problem worldwide. The underlying mechanism is partially accredited to ferroptosis, based on sequencing analyses of IVDD patients from the gene expression omnibus (GEO) databases. In this study, it is shown that polydopamine nanoparticles (PDA NPs) inhibit oxidative stress-induced ferroptosis in nucleus pulposus (NP) cells in vitro. PDA NPs scavenge reactive oxygen species (ROS), chelate Fe 2+ to mitigate iron overload, and regulate the expression of iron storage proteins such as ferritin heavy chain (FHC), ferritin, and transferrin receptor (TFR). More importantly, PDA NPs co-localize with glutathione peroxidase 4 (GPX4) around the mitochondria and suppress ubiquitin-mediated degradation, which in turn exerts a protective function via the transformation and clearance of phospholipid hydroperoxides. PDA NPs further down-regulate malondialdehyde (MDA) and lipid peroxide (LPO) production; thus, antagonizing ferroptosis in NP cells. Moreover, PDA NPs effectively rescue puncture-induced degeneration in vivo by targeting ferroptosis and inhibiting GPX4 ubiquitination, resulting in the upregulation of antioxidant pathways. The findings offer a new tool to explore the underlying mechanisms and a novel treatment strategy for IVDD-induced LBP.
研究领域:
纳米技术
·
生物医学工程
·
骨科
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food Bioscience
·
2024
·
IF 4.8
Mengmeng Zhang,Jingbo Liu,Yiding Yu,Wenshuo Ren,Rui Yuan,Xuanting Liu,Xiaomin Shang,Zhiyang Du,Meng-Lei Xu,Ting Zhang
Genistein (GEN) is the most abundant aglycone in soy isoflavones and is a key factor distinguishing soybeans from other food sources. It holds significant nutritional value and exhibits notable biological activity. However, the low water solubility of genistein limits its widespread application. To improve its water solubility, this study prepared γ-cyclodextrin (γ-CD)/GEN inclusion complexes and investigated their mechanism of action in alleviating hydrogen peroxide-induced oxidative stress damage in PC12 cells. The results showed that γ-CD/GEN could be uniformly and stably dispersed in the system. Cell experiments indicated that γ-CD/GEN significantly increased cell survival after treatment with organic hydrogen peroxide, and promoted the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and the expression of glutathione peroxidase 4 (GPx4). It also improved mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) levels, thereby alleviating cell damage caused by oxidative stress. Further Nrf2 knockdown experiments revealed that γ-CD/GEN failed to provide protection, and no protective effect was observed under RSL3 intervention. In conclusion, γ-CD/GEN exerts antioxidant effects by activating the Nrf2/GPx4 pathway, thereby reducing oxidative stress damage induced by organic hydrogen peroxide, providing a theoretical basis for the development of novel antioxidants.
研究领域:
药理学
·
分子生物学
·
神经科学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）