Translational Cancer Research
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2025
·Vol. 14
·期 11
·7641
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IF 1.7
Yuan Cheng,Liu Ruiwen,Xu Xinming,Sun Jun,Zhu Yi,Lu Rongzhu,Liu Yueyu,Chen Jian
Background Because of the high malignancy and subtle early symptoms of hepatocellular carcinoma (HCC), most patients lose the opportunity for surgery and opt for drug therapy. However, the current drugs for HCC treatment remain suboptimal, underscoring the urgent need to develop a novel anti-HCC agent. Curcumin is a natural chemical compound that has anti-cancer effects on various tumor cells, attracting sustained attention from researchers and clinicians. The present study aims to further elucidate curcumin’s anti-HCC mechanisms, thereby offering a promising therapeutic candidate for HCC patients. Methods The viability of HCC cells was evaluated by Cell Counting Kit-8 (CCK-8) assay. The levels of glutathione (GSH), malondialdehyde (MDA), and total iron in the cells were detected by biochemical kits. The levels of reactive oxygen species (ROS) and Fe 2+ in the cells were detected by fluorescent probes. The protein expressions of protein kinase RNA-like endoplasmic reticulum kinase (PERK), nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and glutathione peroxidase 4 (GPX4) in the cells were detected by western blotting. Results Curcumin exerted a notably suppressive impact on HCC cells, which could be reversed by ferrostatin-1 (Fer-1) and desferrioxamine (DFO). By detecting cellular metabolic products, we observed an increase in total iron, Fe 2+ , MDA, ROS, and a reduction in GSH levels in HCC cells after treatment with curcumin, and these effects could be attenuated by Fer-1. Western blot analysis showed that curcumin significantly downregulated GPX4 levels in HCC cells while upregulating PERK, Nrf2 and HO-1 expression. Additionally, using PERK inhibitor, HO-1 inhibitor, and endoplasmic reticulum (ER) stress inhibitor could partially reverse the inhibition of HCC cells viability by curcumin and alleviate the reduction of GPX4 expression caused by curcumin. Conclusions Curcumin may induce ferroptosis in HCC cells through the PERK/Nrf2/HO-1 signaling pathway, thereby exerting its anti-cancer effects, suggesting that curcumin could potentially be used as a drug for treating HCC.
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高影响因子
Molecular Medicine Reports
·
2019
·Vol. 20
·期 2
·1017-1024
·
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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Materials Today Bio
·
2025
·
IF 10.2
Qiang Zhang,Tuo Wang,Junyu Ren,Yanru Guo,Ziyi Yin,Chenrui Zhang,Honglin Fan,Yinting Ren,Junlong Da,Narisu Hu
Oral ulcers, a prevalent mucosal disorder with high recurrence rates, remain challenging to treat due to the oral cavity’s dynamic environment and the multifactorial nature of ulcer progression. Here, we report a multifunctional microneedle (MN) patch loaded with astragalus polysaccharide (APS-MN) that integrates rapid mucosal penetration, reactive oxygen species (ROS) scavenging, and ferroptosis inhibition to accelerate ulcer healing. Unlike conventional MN systems reliant on synthetic drugs or prolonged dissolution, APS-MN leverages the natural antioxidant and immunomodulatory properties of APS-a traditional Chinese medicine-derived polysaccharide-enabling complete drug release within 2 minutes and targeted delivery to ulcer bases. In vitro and in vivo studies demonstrate that APS-MN promotes M2 macrophage polarization, suppresses pro-inflammatory cytokines (TNF-α, IL-1β), and inhibits ferroptosis via the Nrf2/HO-1/SLC7A11 axis, achieving 88.2% wound closure in rats within 6 days. Notably, this work combined herbal polysaccharides with MN technology for oral ulcer therapy, offering a biocompatible, non-invasive alternative to corticosteroids and antibiotics. The rapid dissolution, dual antioxidant/anti-ferroptotic action, and scalability of APS-MN position it as a transformative platform for managing recurrent oral ulcers and other redox-imbalanced mucosal diseases.
研究领域:
药学
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生物医学工程
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免疫学
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高影响因子
CELL BIOLOGY INTERNATIONAL
·
2022
·Vol. 47
·期 3
·598-611
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IF 4.473
Yangyang Wu,Shuo Zhou,An Zhao,Yuling Mi,Caiqiao Zhang
Oxidative stress is a major cause of ovarian aging and follicular atresia. There is growing evidence that showed potential roles of rutin in antidiabetic, anti-inflammatory, antitumor, antibacterial and antioxidant, although it is yet unclear what the underlying mechanism is. Here, we looked into the potential effects of rutin on oxidative stress in the prehierarchical small white follicles (SWFs) from 580-day-old (D580) laying chickens. According to the findings, aging D580 layer ferroptosis was much higher than it was for laying hens during the peak period (280-day-old, D280). In both naturally aged and d -gal-induced chicken SWFs, rutin treatment concurrently boosted cell proliferation and prevented apoptosis. In addition, rutin inhibited the increased ferroptosis in aging hens. Meanwhile, rutin markedly suppressed the elevated ferroptosis and descending antioxidant capacity of D280-culture-SWFs from chicken elicited by d -gal. Rutin's activation of the Nrf2/HO-1 pathway hastened the SWFs' verbal battle with oxidative damage and reduced ferroptosis. Furthermore, activation of the ferroptosis signal increased the oxidative damage in SWFs. In conclusion, rutin alleviated oxidative stress that was induced by ferroptosis in aging chicken SWFs through Nrf2/HO-1 pathway. These findings point to a novel mechanism by which rutin protects SWFs from oxidative stress by suppressing ferroptosis, which is presumably a fresh approach to slowing ovarian aging in laying hens.
研究领域:
动物科学
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分子生物学
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营养学
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Current Nanoscience
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2024
·Vol. 21
·期 4
·757-765
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IF 1.4
Zirui Liu,Dan Li,Baofeng Zhao,Xifan Mei
BackgroundGouty arthritis, characterized by excruciating pain and discomfort, poses a significant burden on patients. While nanomedicines have shown promise in addressing this ailment, their complicated synthesis processes often involve potentially toxic procedures, contributing to adverse side effects in disease management.MethodsIn this study, we introduce a straightforward and elegant solution by utilizing easily prepared gold platinum (AuPt) nanoparticles for the treatment of gouty arthritis. The synthesis of these nanoparticles involves the use of gold and platinum precursors in conjunction with NaBH4, simplifying the manufacturing process. Experimental models of gout were established in both in vivo and in vitro settings through lipopolysaccharide and monosodium urate crystal induction.ResultsOur findings revealed that AuPt nanoparticles exhibited potent anti-inflammatory effects against gout. This effect was attributed to their ability to activate the Nrf2/HO-1 pathway, resulting in pain alleviation and the inhibition of inflammation, ultimately leading to the reduction of joint edema. With their uncomplicated synthesis and promising therapeutic potential, these simply prepared AuPt nanoparticles emerge as a compelling candidate for pharmaceutical intervention in the treatment of gouty arthritis.ConclusionThis approach not only holds the promise of delivering effective relief to patients but also minimizes the risk of unwanted side effects associated with complex nanomedicine synthesis processes.
研究领域:
药理学
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纳米医学
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炎症研究
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EUROPEAN JOURNAL OF PHARMACOLOGY
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2025
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IF 4.7
Ji-Ping Wei,Bo Zhao,Zi-Jian Jiang,Peng-Yu Wang,Yan Xu,Ning Ding,Yuan-Yuan Hu,Wei Wang,Bo-Tao Jiang
Renal ischemia/reperfusion (I/R) injury is the most common cause of acute kidney injury (AKI). It can progress to chronic injury and subsequently to chronic kidney disease (CKD) via the renal fibrosis pathway. Luteolin is one of the most commonly occurring flavonoids and exhibits potential therapeutic activity against various pathophysiological processes. In this study, we investigated the protective role of luteolin in counteracting renal I/R injury and its potential mechanisms through systematic network pharmacology, molecular docking, and in vivo experimental studies. Using network pharmacology, we constructed and analyzed a luteolin-renal I/R injury target network. We assessed the relationship between luteolin and renal I/R injury targets using molecular docking analysis. Subsequently, we established a rat model of AKI to CKD transition using unilateral ischemia/reperfusion injury (UIRI), and detected changes in the expression of related proteins using biochemical indices. Network pharmacological analysis and molecular docking showed that luteolin affected renal I/R injury through multiple targets and pathways. As demonstrated by in vivo experiments, luteolin significantly attenuated renal I/R-induced oxidative injury by inhibiting renal lipid peroxidation in rats through the modulation of the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. Luteolin attenuated the levels of relevant inflammatory markers, significantly upregulated the synthesis of apoptosis-related proteins, and downregulated the expression of anti-apoptotic proteins. Our results suggest that luteolin effectively inhibited oxidative damage, inflammation, apoptosis, and fibrosis caused by renal I/R injury, thus exerting a nephroprotective effect. The antioxidant effects of luteolin may be related to the regulation of Nrf2/HO-1 signaling.
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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Frontiers in Pharmacology
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2022
·
IF 5.988
Li Dafei,Zhao Haiyan,Xu Piao,Lin Qiongping,Zhao Tingting,Li Chubing,Cui Zhong-Kai,Tian Guangyong
Irreversible sensorineural hearing loss is one of the most common side effects after cisplatin treatment. Prevention and reversal of hearing loss caused by cisplatin are of great importance for cancer patients, especially children. Oxidative stress is an important cause of hearing loss resulted from cisplatin, unfortunately, there is no drug yet available that can completely prevent and reverse the ototoxicity from cisplatin. Polydatin (PD) possesses excellent antioxidant and anti-inflammatory effects, however, its role in the cisplatin-induced hearing loss has not been investigated. Herein, we have explored the preventive and therapeutic effects of PD on cisplatin-induced hearing loss and the possible underlying mechanisms. In the in vivo setting with guinea pigs, we have demonstrated that PD can reduce the threshold shift of auditory brainstem response (ABR) caused by cisplatin, promote the nuclear translocation of Nuclear factor erythroid-2 related factor 2 (Nrf2), increase the expression of Nrf2 and heme oxygenase-1 (HO-1), and thus reduce the loss of outer hair cells (OHCs). PD can ameliorate cisplatin-induced hearing loss through activating the Nrf2/HO-1 signaling pathway. This study provides a potential strategy for preventing and improving hearing loss resulted from cisplatin treatment in clinics.
研究领域:
药理学
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耳鼻喉科学
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肿瘤学
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CLINICAL AND EXPERIMENTAL HYPERTENSION
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2025
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IF 3.5
Hao Wang,Ke Zhou,Xiaoling Chen,Yao Tong,Qiuyan Jiang,Qiang She,Jun Xiao
Myocardial infarction (MI) is a leading cause of morbidity and mortality globally, primarily due to oxidative stress-induced cardiomyocyte apoptosis and adverse cardiac remodeling. OL-FS13, a neuroprotective peptide derived from Odorrana livida, has previously shown anti-apoptotic effects in cerebral ischemia models. However, its role in myocardial protection remains unclear. In this study, we investigated the cardioprotective effects of OL-FS13 in both in vitro and in vivo models of MI. Hydrogen peroxide (H₂O₂) was used to induce oxidative stress in primary neonatal rat cardiomyocytes, while permanent ligation of the left anterior descending (LAD) coronary artery was employed to establish a murine MI model. OL-FS13 treatment significantly attenuated cardiomyocyte apoptosis, reduced ROS accumulation, improved left ventricular function, and decreased infarct size. Mechanistically, OL-FS13 activated the Nrf2/HO-1 signaling pathway, restoring antioxidant protein levels and suppressing oxidative stress-induced apoptosis. Pharmacological inhibition of Nrf2 with ML385 abrogated the antioxidant and anti-apoptotic effects of OL-FS13 both in vitro and in vivo, confirming the central role of this pathway. These findings demonstrate that OL-FS13 exerts potent cardioprotective effects via Nrf2/HO-1 pathway activation and ROS suppression, suggesting its potential as a novel therapeutic agent for the treatment of myocardial infarction.
研究领域:
心血管病学
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分子药理学
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氧化应激生物学
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心肌缺血再灌注损伤
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信号转导
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FOOD AND CHEMICAL TOXICOLOGY
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2025
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IF 3.5
Ziyang Huang,Ruijia Xu,Zhongjun Wan,Chao Liu,Jinquan Li,Jun He,Li Li
Cadmium (Cd) is a prevalent heavy metal pollutant known to cause lung damage. However, the mechanisms underlying Cd-induced lung injury and the associated therapeutic strategies remain unclear. By establishing Cd-induced lung damage models both in vivo and in vitro , we observed that Cd inhibited the Nrf2/HO-1 signaling pathway, disrupted the redox balance in lung tissue, accelerated endoplasmic reticulum (ER) stress, and promoted ferroptosis, ultimately leading to lung injury. Melatonin (Mel), a potent reactive oxygen species (ROS) inhibitor with high antioxidative efficacy, mitigated the increasing in ROS and the decreasing in superoxide dismutase levels induced by Cd, as well as the upregulation of PERK-eIF2α-ATF4 signaling associated with ER stress, through the activation of the Nrf2/HO-1 signaling pathway. Furthermore, Mel administration not only prevented Cd-induced iron overload but also reduced lipid peroxidation levels, thereby improving mitochondrial morphological alterations. Collectively, our results demonstrated that Mel treatment alleviated Cd-induced lung injury by inhibiting oxidative stress, which in turn ameliorated ER stress and ferroptosis through the activation of the Nrf2/HO-1 pathway.
研究领域:
毒理学
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分子生物学
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呼吸系统医学
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Pharmaceuticals
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2022
·Vol. 15
·期 12
·1548
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IF 5.215
Fei Yang,Cuizhen Shen
On the basis of the mice pressure ulcers (PU) model, the protective effect and potential mechanism of sodium Danshensu (SDSS) cream against PU were investigated. The mice were randomly divided into three groups: the negative control group (cream without 0.5 g SDSS), the SDSS group (cream containing 0.5 g SDSS), and the positive group (0.5 g Hirudoid®). After 7 and 14 days of ointment application, the wound-healing rate of the SDSS and positive groups was significantly higher than that of the control group (p< 0.05). The results of hematoxylin–eosin staining also indicated that SDSS has the potential to promote the healing of PU. In addition, the serum IL-6, IL-1β, TNF-α, and MDA levels decreased significantly (p< 0.01) after 14 days of SDSS treatment, while the SOD, CAT, and GSH-Px activities increased significantly (p< 0.01). In addition, SDSS cream was able to significantly increase the expression of Nrf2, HO-1, GCLM, NQO1, NF-κB p65, NF-κB p50, IKKα, and IKKβ while decreasing the expression of Keap1 and IκBαin the Nrf2/HO-1 and NF-κB pathways. Our research will provide a foundation for the future clinical prevention and treatment of PU with SDSS cream.Keywords:pressure ulcers;sodium Danshensu cream;ischemia/reperfusion injury;Nrf2/HO-1 pathway;NF-κB pathway
研究领域:
药理学
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伤口愈合
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炎症
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氧化应激
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INFLAMMATION RESEARCH
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2025
·Vol. 74
·期 1
·1-19
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IF 5.4
Weng Xiuhong,Wang Simin,Wang Qing,Wei Mingbo,Cheng Bo
Background Primary Sjögren’s syndrome (pSS) is an autoimmune disease characterized by xerostomia and autoimmune sialadenitis. Interferon-γ (IFN-γ) induces ferroptosis in salivary gland epithelial cells (SGECs), leading to salivary gland (SG) hypofunction. We previously demonstrated the beneficial effects of melatonin (MLT) in alleviating SG dysfunction and inflammation in a pSS animal model. However, the precise underlying mechanism remains unclear. Methods Female NOD/ltj and ICR mice were used as the pSS mouse model and control group, respectively. MLT was administered via intraperitoneal injection to NOD/ltj mice to detect its effect on ferroptosis in SGs. Primary human SGECs and A253 cells were treated with IFN-γand ferroptosis inducers, with or without MLT. Results Exogenous MLT alleviated pathological SG alterations and promoted saliva production through inhibiting SGEC ferroptosis. MLT inhibited SGEC ferroptosis induced by IFN-γ and ferroptosis inducers via nuclear factor erythroid 2-related factor 2/heme oxygenase-1/glutathione peroxidase 4 (NRF2/HO-1/GPX4) pathway activation. Moreover, MLT suppressed the nuclear factor-kappa B (NF-κB) pathway, which is triggered by ferroptosis in SGECs. Nevertheless, ML385-mediated NRF2 inhibition abrogated the antiferroptotic protective effects of MLT on SGECs. Conclusions MLT inhibits SGEC ferroptosis through NRF2/HO-1/GPX4 pathway activation and thus attenuates ferroptosis-triggered NF-κB activity. Melatonin represents a potential therapeutic approach for pSS owing to its capacity to regulate ferroptosis.
研究领域:
免疫学
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细胞生物学
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医学
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高影响因子
MOLECULES
·
2018
·Vol. 23
·期 1
·215
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IF 3.098
Xinyan Peng,Chongshan Dai,Quanwen Liu,Junke Li,Jingru Qiu
This study aimed to investigate the protective effect of curcumin against carbon tetrachloride (CCl4)-induced acute liver injury in a mouse model, and to explain the underlying mechanism. Curcumin at doses of 50, 100 and 200 mg/kg/day were administered orally once daily for seven days prior to CCl4exposure. At 24 h, curcumin-attenuated CCl4induced elevated serum transaminase activities and histopathological damage in the mouse’s liver. Curcumin pre-treatment at 50, 100 and 200 mg/kg significantly ameliorated CCl4-induced oxidative stress, characterized by decreased malondialdehyde (MDA) formations, and increased superoxide dismutase (SOD), catalase (CAT) activities and glutathione (GSH) content, followed by a decrease in caspase-9 and -3 activities. Curcumin pre-treatment significantly decreased CCl4-induced inflammation. Furthermore, curcumin pre-treatment significantly down-regulated the expression of TGF-β1 and Smad3 mRNAs (bothp< 0.01), and up-regulated the expression of nuclear-factor erythroid 2-related factor 2 (Nrf2) and HO-1 mRNA (bothp< 0.01) in the liver. Inhibition of HO-1 attenuated the protective effect of curcumin on CCl4-induced acute liver injury. Given these outcomes, curcumin could protect against CCl4-induced acute liver injury by inhibiting oxidative stress and inflammation, which may partly involve the activation of Nrf2/HO-1 and inhibition of TGF-β1/Smad3 pathways.Keywords:curcumin;acute liver injury;Nrf2/HO-1 pathway;oxidative stress;TGF-β1/Smad3 pathway
研究领域:
药理学
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肝病学
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分子生物学
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高影响因子
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