JOURNAL OF COLLOID AND INTERFACE SCIENCE
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2025
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IF 9.7
Fang Wang,Ke Wang,BaoRu Fang,SiQi Geng,Ying Li,HuiFeng Qian,YiNuo Lin,ZhangSen Yu
Doxorubicin-induced cardiomyopathy (DIC) is a toxic side effect that cannot be ignored during chemotherapy for malignant tumors. In this work, we synthesized a novel nano-chemotherapeutic drug based on Prussian blue nanozyme to alleviate DIC. Hollow mesoporous Prussian blue (HmPB) nanoparticles were used as a carrier to load doxorubicin (DOX) through electrostatic adsorption and obtain a novel chemotherapy drug, HmPB(DOX). I n vivo and in vitro chemotherapy efficacy and acute toxicity evaluation experiments were conducted. The results suggest that HmPB(DOX) exhibits pH-responsive characteristics and minimizes the release of DOX from within HmPB(DOX) in cardiomyocytes. However, in the acidic tumor microenvironment, the release of DOX from HmPB(DOX) is notably enhanced. More importantly, HmPB(DOX) possesses excellent antioxidant enzyme activity, effectively clearing DOX-induced reactive oxygen species (ROS) and alleviating oxidative stress in cardiomyocytes. Doxorubicin is pivotal in the chemotherapy of malignant tumors. This study presents novel insights for mitigating the toxic and side effects of DOX, offering new strategies to enhance tolerance to chemotherapy.
研究领域:
药理学
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纳米医学
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肿瘤学
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DOI
PubMed
高影响因子
MOLECULAR NUTRITION & FOOD RESEARCH
·
2025
·
IF 4.2
Bin Xu,Yan Zhuang,Ying Zhang,Suoning Liu,Rongjun Fan,Weiru Jiang
Epithelial barrier dysfunction, critically involved in intestinal ischemia/reperfusion (I/R) injury, is significantly regulated by Nrf2-mediated oxidative stress. Apigenin, a flavonoid commonly found in fruits and vegetables with diverse biological properties, has an unclear impact on intestinal I/R injury. We hypothesize that apigenin improves intestinal barrier dysfunction by activating Nrf2 signaling. Thirty rats were randomly divided into five groups to establish an I/R model using superior mesenteric artery occlusion. Hypoxia and re-oxygenation (H/R) model was developed utilizing Caco-2 and IEC-6 cells, which were exposed to hypoxic conditions followed by re-oxygenation. Apigenin protected against intestinal mucosal damage by suppressing inflammatory cytokines release (TNF-α, IL-1β, IL-6, MPO, p < 0.01), ameliorating oxidative stress (MDA, SOD, GSH, GSH-Px, p < 0.01), and improving barrier dysfunction (DAO and TEER, p < 0.01) both in vivo and in vitro, without causing significant changes in the corresponding normal controls ( p > 0.05). Apigenin up-regulated the protein expression of Nrf2, HO-1, and tight junction (TJ) proteins ( p < 0.01). Furthermore, the knockdown of Nrf2 significantly abrogated apigenin-enhanced the TJ expression. Apigenin pretreatment alleviates intestinal I/R-induced barrier damage through Nrf2 activation and TJ upregulation, offering new strategies for preventing or treating I/R-associated intestinal diseases.
研究领域:
药理学
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分子生物学
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消化系统疾病
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DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2025
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IF 5.6
Ruoxin Tu,Yining Wang,Ru Xu,Shusheng Wang,Jiabin Cai,Lin Sun,Pengfei Gao
Despite therapeutic advances, hepatocellular carcinoma (HCC) remains a leading cause of cancer mortality worldwide. While dihydrotanshinone I (DHT) shows promising anticancer potential, its molecular mechanisms in HCC remain unexplored. Here, we unveil a novel chemokine (C-C Motif) receptor 5(CCR5)-mediated regulatory network targeted by DHT in HCC treatment. This study identifies CCR5 as a crucial survival factor in HCC, uncovers a novel CCR5-Nuclear factor erythroid 2-related factor 2(NRF2) regulatory axis, and reveals a dual-targeting mechanism of DHT through direct CCR5 inhibition and Reactive oxygen species(ROS)-dependent cell death induction, validating its therapeutic efficacy by disrupting redox homeostasis. This study uncovers a novel CCR5-ROS-NRF2 signaling axis in HCC and establishes DHT as a promising therapeutic agent through its unique targeting mechanism. These findings provide new insights into HCC pathogenesis and present an innovative therapeutic strategy for HCC treatment.
研究领域:
肿瘤学
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药理学
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分子生物学
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生物化学
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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2025
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IF 4.7
Yanmin Zhang,Jianqiang Hu,Yan Zhang,Xiaolin Yang,Weihua Tong,Xinxin Ci
Background The transition from acute kidney injury (AKI) to chronic kidney disease (CKD) is a significant cause of kidney failure. Although the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) has been demonstrated to inhibit ferroptosis and alleviate cisplatin-induced AKI, the specific roles of Nrf2 and the alkaloid leonurine in modulating the AKI-CKD transition remain incompletely elucidated. Methods Murine and human proximal tubular epithelial cell models of the AKI-CKD transition were established using repeated low-dose cisplatin (RLDC) to investigate the roles of Nrf2 and leonurine in ferroptosis regulation and disease progression. Key results In mice, RLDC administration induced persistent tubular injury, ferroptosis, and progressive renal fibrosis. In HK-2 cells, RLDC triggered oxidative stress and ferroptosis. Although Nrf2 expression was transiently upregulated during the acute phase (4 weeks post-RLDC), it was downregulated by the chronic phase (8 weeks post-RLDC), correlating with impaired antioxidant capacity and exacerbated ferroptosis. Nrf2 knockout mice exhibited more severe oxidative damage, ferroptosis, and renal dysfunction following RLDC challenge. Pharmacological activation of Nrf2 by leonurine attenuated oxidative injury and ferroptosis and promoted tubular repair. Leonurine also suppressed the epithelial–mesenchymal transition and aberrant extracellular matrix deposition, ultimately mitigating renal fibrosis. The protective effects of leonurine were abolished in Nrf2 knockout mice. Conclusion These findings demonstrate that Nrf2 activation mitigates cisplatin-induced AKI-CKD transition by counteracting oxidative stress and ferroptosis, thereby attenuating renal fibrosis. Leonurine, as a potent Nrf2 activator, represents a promising therapeutic agent for preventing AKI-CKD transition.
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DOI
PubMed
高影响因子
Aging-US
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2019
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IF 5.515
Peng Chen,Fuchao Chen,Ben-hong Zhou
Aging is a complex physiological phenomenon associated with oxidative stress damage. The objective of this study was to investigate the potential effects of leonurine on D-galactose-induced aging in mice and its possible mechanisms. In this study, we first tested the antioxidant activity of leonurine in vitro . A subcutaneous injection of D-galactose in mice for 8 weeks was used to establish the aging model to evaluate the protective effects of leonurine. The results showed that treatment with 150 mg·kg -1 leonurine could improve the mental condition, organic index, and behavioural impairment; significantly increase the activities of antioxidative enzymes including SOD, CAT, and T-AOC; and ameliorate the advanced glycation end product (AGE) level and histopathological injury. Furthermore, the Western blotting data revealed that leonurine supplementation noticeably modulated the suppression of the Nrf2 pathway and upregulated the downstream expression of HO-1 and NOQ1 in aging mice. Additionally, leonurine treatment activated Nrf2 nuclear translocation in both aging mice and normal young mice, and the expression levels of Nrf2 in normal young mice was higher than those in naturally aging mice. In conclusion, our findings suggest that leonurine is a promising agent for attenuating the aging process, and the underlying molecular mechanisms depend on activating the Nrf2 pathway.
研究领域:
老年学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
Food Bioscience
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2023
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IF 5.2
Hengju Ge,Jiaxin Li,Yang Xu,Jiahong Xie,Naymul Karim,Fujie Yan,Jianling Mo,Wei Chen
Fructus Gardeniae (FG) is the dried ripe fruit of Gardenia jasminoides Ellis, having beneficial effects for human health. In this study, we discovered that the most relevant pathway influenced by Fructus Gardeniae extract (FGE) is lipid metabolism according to the analysis of network pharmacology. Furthermore, the protective effect of FGE against palmitic acid-induced lipotoxicity was investigated. In L02 cells, FGE significantly promoted cellular proliferation after being treated with palmitic acid , and reduced the accumulation of lipid droplets and triglyceride level . Palmitic acid led to an increase of ROS content, which was reduced by FGE. Additionally, FGE could facilitate Nrf2 localized to nuclear and followed by activating its downstream targets. ML385 (a Nrf2 inhibitor) treatment further proved that FGE attenuated lipotoxicity through regulating Nrf2/ARE pathway. Consequently, we demonstrated for the first time FGE could be regarded as potential functional food materials for hepatic protection.
研究领域:
药理学
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肝脏病学
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产品关联
DOI
高影响因子
EXPERIMENTAL EYE RESEARCH
·
2023
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IF 3.4
Jingfei Yang,Zhijuan Hua,Zhikun Zheng,Xuan Ma,Liang Zhu,Yan Li
Diabetes retinopathy (DR) is one of the most common microvascular complications of diabetes. Retinal pigment epithelial (RPE) cells exposed to a high glucose environment experience a series of functional damages, which is an important factor in promoting the progression of DR. Acteoside (ACT) has strong antioxidant and anti-apoptotic properties, but the mechanism of ACT in DR is not completely clear. Therefore, the purpose of the present study was to explore whether ACT inhibits the damage to RPE cells in a high glucose environment through antioxidative effects to alleviate the DR process. The DR in vitro cell model was constructed by treating RPE cells with high glucose, and the DR in vivo animal model was constructed by injecting streptozotocin (STZ) into the peritoneal cavity of mice to induce diabetes. The proliferation and apoptosis of RPE cells were detected by CCK-8 and flow cytometry assays, respectively. The expression changes in Nrf2, Keap1, NQO1 and HO-1 were evaluated by qRT‒PCR, Western blot and immunohistochemistry analyses. The MDA, SOD, GSH-Px and T-AOC contents were detected by kits. The changes in ROS and nuclear translocation of Nrf2 were observed by immunofluorescence assays. HE staining was used to measure the thickness of the outer nuclear layer (ONL) of the retina, and TUNEL staining was used to detect the number of apoptotic cells in the retinas of mice. In the present study, ACT effectively ameliorated outer retina damage in diabetic mice. In high glucose (HG)-induced RPE cells, ACT treatment had the following effects: improved proliferation, decreased apoptosis, inhibited Keap1 expression, promoted the nuclear translocation and expression of Nrf2, upregulated NQO1 and HO-1 (the target genes of Nrf2) expression, decreased ROS concentration, and increased the levels of the SOD, GSH-Px and T-AOC antioxidant indicators. However, knockdown of Nrf2 reversed the above phenomena, which indicated that the protective function of ACT in HG-induced RPE cells are closely related to Nrf2. In summary, the present study demonstrated that HG-induced oxidative stress injury is inhibited by ACT in RPE cells and the outer retina through the Keap1/Nrf2/ARE pathway.
研究领域:
药理学
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细胞生物学
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分子生物学
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糖尿病研究
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眼科学
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产品关联
DOI
PubMed
高影响因子
TOXICOLOGY AND APPLIED PHARMACOLOGY
·
2025
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IF 3.4
Shijie Fan,Ying Zhao,Qingqing Zhao,Diyun Xu,Xi Chen,Jibo Han,Ziming Fang,Guang Liang,Yunjie Zhao
Hypertension engenders numerous complications, including hypertensive renal disease (HRD). Recent studies have underscored the significance of redox homeostasis in hypertension-associated kidney disorders. Carnosol (Car) has been identified as a potent antioxidant in other diseases. Nevertheless, its role in HRD remains uncertain. This research evaluated the therapeutic impact of Car on HRD and explored its pharmacological mechanism. Car (40 mg/kg) effectively ameliorated kidney injury and oxidative stress (OS) induced by angiotensin II (Ang II) both in vitro and in vivo. Mechanistically, Car facilitates the phosphorylation of p62 through its interaction with mTOR, leading to the degradation of KEAP1, the release of NRF2, and the subsequent upregulation of antioxidant genes. Blocking mTORC1 eliminated Car-induced p62 activation and its antioxidant functions. In summary, our research has demonstrated that Car activates the p62-KEAP1-NRF2 pathway to alleviate the kidney injury and OS caused by Ang II. Consequently, Car may emerge as a promising candidate for the prevention and treatment of Ang II-induced kidney injury.
研究领域:
药理学
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分子生物学
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肾脏病学
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生物化学
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产品关联
DOI
PubMed
高影响因子
Molecular Medicine Reports
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2019
·Vol. 20
·期 2
·1017-1024
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IF 1.851
Duzhen Zhang,Man Li
Puerarin is the major bioactive ingredient isolated from the dry root of Pueraria lobata, a plant used in traditional Chinese medicine. Puerarin has been used to treat diabetes and cataracts in China; however, its underlying mechanism of action remains unclear. The aim of the present study was to investigate the effectiveness and mechanism of puerarin in preventing cataracts in diabetic rats. Diabetes was induced by streptozocin (STZ) administration and rats were intraperitoneally injected with puerarin (25, 50 and 100 mg/kg). Blood glucose levels and cataract development were examined in the different experimental groups. In addition, the expression levels of markers associated with oxidative stress, including nuclear factor erythroid 2 like 2 (Nrf2) and heme oxygenase‑1 (HO‑1), were analyzed. The present results suggested that treatment with puerarin at 25, 50 and 100 mg/kg significantly reduced blood glucose levels and the incidence of cataract in STZ‑induced diabetic rats. Additionally, puerarin treatment reduced oxidative stress, restoring the levels of malondialdehyde and glutathione, and the activity of glutathione peroxidase. Furthermore, puerarin administration decreased the expression levels of retinal vascular endothelial growth factor and interleukin‑1β and increased the mRNA expression levels of Nrf2 and HO‑1, thus inhibiting oxidative stress. The present findings suggested that puerarin had hypoglycemic effects and that it prevented cataract development and progression in diabetic rats by reducing oxidative stress through the Nrf2/HO‑1 signaling pathway.
研究领域:
药理学
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糖尿病研究
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眼科学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
TOXICOLOGY
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2016
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IF 3.817
Chuanyang Su,Qiong Shi,Xiufang Song,Juanli Fu,Zixuan Liu,Yawen Wang,Yuxin Wang,Xiaomin Xia,Erqun Song,Yang Song
Our previous studies demonstrated that tetrachlorobenzoquinone (TCBQ), an active metabolite of pentachlorophenol, has effects on the generation of reactive oxygen species (ROS) and oxidative stress in vitro and in vivo . Nuclear factor erythroid-derived 2-like 2 (Nrf2) is a cellular sensor of electrophilic or oxidative stress that regulates the expression of antioxidant enzymes and defensive proteins. We have illustrated that TCBQ activates Nrf2 signaling by promoting the formation of the Kelch-like ECH-associated protein 1 (Keap1) cross-linking dimer and the formation of an ubiquitination switch from Nrf2 to Keap1. The activation of Nrf2 by TCBQ may serve as an adaptive response to a TCBQ-induced oxidative insult. BTB and CNC homolog 1 (Bach1) compete with Nrf2, leading to the negative regulation of the antioxidant response element (ARE). In this report, we propose that TCBQ induces the dynamic inactivation of Bach1. We observed a rapid nuclear efflux of Bach1 and an accumulation of Nrf2 in nuclei upon TCBQ treatment that precedes the binding of Nrf2 with ARE. We found that the nuclear export of Bach1 is dependent on its chromosomal region maintenance 1 (Crm1) interaction and tyrosine phosphorylation. Although TCBQ induces the ubiquitination of Bach1, TCBQ also increases the mRNA and protein levels of Bach1, returning Bach1 to normal levels. Moreover, we found that TCBQ-induced activation of Nrf2 involves c-Jun N-terminal kinase (JNK)-P62 signaling.
研究领域:
分子生物学
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细胞信号传导
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毒理学
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氧化应激
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产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2025
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IF 5.6
Tianfeng Yang,Suyu Zhang,Kun Nie,Xiuhong Peng,Jian Huo,Xiao Fu,Yanmin Zhang
Although ferroptosis as an emerging way exhibits tremendous promising in the therapy of hepatocellular carcinoma (HCC), the novel therapeutic agents targeting ferroptosis are still scarce. In our previous study, we found that the natural products toosendanin (TSN) possessed significant anti-proliferative efficacy by regulating WW domain-containing oxidoreductase (WWOX) in HCC. However, there is very limited understanding about TSN-induced ferroptosis, and the role of WWOX in ferroptosis has not been studied. In present study, we investigated the effect and underlying molecular mechanisms of TSN in WWOX-mediated ferroptosis in HCC. We found that TSN induced ferroptosis in HCC cells and its effect was dependent on WWOX. RNA-seq and RT-qPCR assay identified that TSN significantly increased spermidine/spermine N1-acetyltransferase 1 (SAT1) expression while decreased solute carrier family 40 member 1 (SLC40A1) expression, which play vital roles in ferrous ion transport. Further dual-luciferase reporter assay and Co-IP assay revealed that TSN-induced WWOX activation controlled the transcriptional activity of p53 and NF-E2-related factor 2 (NRF2) by regulating their interaction. Meanwhile, IF assay and WB assay confirmed that TSN increased the nuclear distribution of p-WWOX and p-p53 dimers, but impeded the nuclear translocation of NRF2 by inducing its ubiquitination degradation, ultimately regulating the transcription of their downstream target genes. In addition, the results from cell viability assay and the tumor xenograft model verified that co-treatment of TSN, ML385 (NRF2 inhibitor), and MIRA-1 (p53 activator) could effectively inhibit HCC cells growth in the presence of Fer-1 (ferroptosis inhibitor) in vitro and in vivo. Overall, our study contributes to the necessary understanding of the molecular mechanisms of WWOX-mediated ferroptosis regulation, and identifies TSN as a potential therapeutic agent targeting ferroptosis for HCC.
研究领域:
肿瘤学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
International Journal of Endocrinology
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2025
·Vol. 2025
·期 1
·4473803
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IF 2.3
Song Xue,Wei Fan,Qingping Li,Hong Huang,Yibo Tang,Min Wu
Background: This study aimed to investigate the potential mechanisms of puerarin in alleviating diabetic nephropathy (DKD) in mice. Method: The DKD model was induced by multiple low-dose injections of streptozotocin (STZ) and a high-sugar and high-fat diet in male C57BL/6J mice. After confirming the onset of DKD, mice were given irbesartan, distilled water, or different concentrations of puerarin (40 and 80 mg/kg/d) by gavage for 8 weeks. HE staining and PAS staining were adopted to assess the pathological changes in the kidney tissues. Meanwhile, the levels of superoxide dismutase, catalase, creatinine, and cystatin C in the serum and the urine albumin and creatinine were measured, and the renal indices as well as the urinary albumin-to-creatinine ratio (UACR) were calculated. The changes of podocin and protein expression levels associated with AMPK/Nrf2 signaling pathway were evaluated by western blot. Results: Puerarin significantly reduced the level of fasting blood glucose, renal index, glomerular mesangial expansion index, renal function, and oxidative stress induced by STZ ( p < 0.05). The pathological injuries in kidney tissues were also alleviated. Furthermore, we demonstrated that the expression level of podocin and protein related to the AMPK/Nrf2 signaling pathway was also decreased significantly by the treatment of puerarin. At the same time, the efficacy of puerarin in the treatment of DKD was better than that of irbesartan, and the treatment effect of the high-dose group (80 mg/kg/d) was also significantly better than that of the low-dose group (40 mg/kg/d). Conclusion: Puerarin could attenuate the severity of DKD and protect the podocyte in mice in a dose-dependent way. Also, it might be performed by regulating the AMPK/Nrf2 pathway. These findings may provide a theoretical basis for updating the clinical management of DKD.
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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产品关联
DOI
PubMed
高影响因子
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