查找使用阿拉丁产品的科研文献

Chrysin alleviates pressure overload–induced myocardial remodeling through regulating the PI3K/AKT/NRF2 pathway–mediated oxidative stress response

Yijia Wang,Xing Feng,Shuhui Zhao,Yuchong Fu,Ao Zhang,Xiaofeng Shen,Bowen Yu,Yihao Wang,Jiahui Lin,Bing Zhang,Weiping Ji,Lianpin Wu,Xiaoling Guo

Background Oxidative stress plays a pivotal role in the pathogenesis of heart failure and is closely linked to myocardial remodeling, which includes myocardial hypertrophy and fibrosis. Chrysin (CHR) has multiple medicinal effects such as antioxidant, anti-inflammatory, and anti-apoptosis. This research seeks to investigate whether CHR can protect against pressure overload–induced myocardial remodeling and to explore the underlying mechanism. Methods Transverse aortic constriction (TAC) surgery was conducted to establish a model of cardiac hypertrophy on male C57BL/6J mice. A model of cardiomyocyte hypertrophy in H9C2 cells induced by angiotensin II (Ang II) was also established. Results The results showed that CHR significantly improved survival and cardiac function, reduced myocardial hypertrophy and fibrosis, inhibited the expression of inflammatory mediators TNF-α and IL-1β, suppressed cell apoptosis rate, downregulated the levels of Bcl-2 Associated X protein (BAX) and Cleaved-Caspase-3, and upregulated B-cell lymphoma/leukemia 2 (BCL-2) expression in TAC surgical mice or Ang II-treated H9C2 cells. CHR could also upregulate the levels of antioxidant enzymes SOD1 and HO-1 by mediating the nuclear translocation and expression of NRF2 to counteract oxidative stress response. The further mechanism investigation utilizing bioinformatics analysis and western blot revealed that the disease of heart failure is associated with the phosphatidylinositol‑3‑kinase (PI3K)/serine/threonine-protein kinase B (AKT) signaling pathway. Conclusions Collectively, our findings demonstrated that CHR might exert the improvement effects on pressure overload–induced myocardial remodeling with hypertrophy and fibrosis through regulating the PI3K/AKT/NRF2 pathway–mediated oxidative stress response to alleviate myocardial cell inflammation and apoptosis, suggesting that CHR may be a promising therapeutic agent for cardiac diseases induced by pressure overload.

Injectable GelMA microspheres encapsulating self-assembly apigetrin-loaded lipid nanoparticles for osteoarthritis via Nrf2–HO-1 pathway activation

Tianqi Wang,Shaoze Jing,Ke Ma,Fan Zhang,Bing Wang,Yu Lei,Jun Zhang

Osteoarthritis (OA) is a progressive degenerative joint disorder characterized by articular cartilage degradation, persistent oxidative stress, and chronic inflammation. Targeting oxidative damage within the joint microenvironment represents a promising avenue for disease modification, offering potential to preserve cartilage integrity, alleviate inflammatory cascades, and ultimately delay structural progression. Lipid nanoparticles were prepared by thin-film hydration and extrusion, then embedded into GelMA microspheres via a microfluidic droplet platform with UV crosslinking to form a sustained-release system. Biocompatibility, ROS-scavenging, anti-inflammatory, and chondroprotective effects were evaluated in vitro and in vivo, while transcriptome sequencing was applied to elucidate system-induced molecular alterations. In vitro , Api-LNP@GMS markedly attenuated ROS accumulation and inflammatory responses in IL-1β-stimulated chondrocytes, as demonstrated by ROS fluorescence imaging, immunofluorescence, Western blotting, and qRT-PCR analyses. In vivo , intra-articular administration in anterior cruciate ligament transection (ACLT) rats effectively alleviated joint inflammation while preserving cartilage integrity and functional capacity. Moreover, transcriptome-wide RNA sequencing, integrated with pathway enrichment analysis and validated by molecular assays, revealed robust activation of the Nrf2–HO-1 antioxidant signaling axis. Api-LNP@GMS is a multifunctional antioxidant biomaterial platform that integrates a natural therapeutic with a sustained-release delivery system, offering a safe and effective strategy to reprogram the osteoarthritic microenvironment and mitigate disease progression. Download: Download high-res image (281KB) Download: Download full-size image

Electroacupuncture Enhances Effectiveness of Omeprazole in Indomethacin-Induced Gastric Injury Mice via Nrf2 Activation and Vagus Nerve Conduction

Hou Yu-jun,Wang Wen,Ye Jiang-nan,Wang Lu,Zhou Si-yuan,Shi Yun-zhou,Chen Ying,Yao Jun-peng,Sun Lu-qiang,Li Ying

Objective To compare the effectiveness of electroacupuncture (EA) combined with omeprazole (Ome) and Ome alone on indomethacin-induced gastric injury mice and reveal the underlying mechanism of this combination. Methods Fourty-eight male C57BL/6J mice were randomly divided into 6 groups by a simple random method ( n =8), including control, model, Ome, Ome + EA, Ome + sham EA, and Ome + EA + ML385 groups. A gastric ulcer mouse model was constructed by intragastrically administering indomethacin at a dose of 30 mg/kg. EA and Ome treatment were performed twice daily with each session of EA treatment lasting 20 min. Gastric injury severity was determined by measuring the ulcer index. Sixteen mice with gastric ulcers underwent left cervical vagotomy (CV) were further divided into model + CV and Ome + EA + CV groups. Eight mice with gastric ulcers underwent sham vagotomy and EA combined with Ome treatment were included in the Ome + EA + SCV group. Following respective treatments, the gastric mucosal ulcer tissues were collected and pathologic scores were evaluated by HE staining. Oxygenase-1/tumor necrosis factor-α levels in gastric tissue were measured using ELISA. Colorimetric assay was conducted to measure oxidative stress levels. Real-time polymerase chain reaction was applied to detect the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) in gastric tissue. Immunofluorescence staining was performed to observe the locations and expressions of F4-80 and Nrf2 in the gastric mucosa. CV was conducted to evaluate the role of the vagus nerve in EA-mediated gastric injury improvement. Results EA combined with Ome alleviated gastric ulcers and decreased gastric pathologic scores (both P <0.01). Furthermore, it decreased gastric oxidative stress levels and inhibited macrophages activation (all P <0.01). However, vagotomy abolished the antioxidant function of EA. Meanwhile, we observed that Nrf2 plays a critical role in inducing the therapeutic effect of EA combined with Ome on gastric injury. Conclusion In mice with gastric ulcers, EA combined with Ome can better repair indomethacin-induced gastric injury via inactivation of macrophages and Nrf2-mediated antioxidant signaling pathway, which is primarily mediated by vagus nerve.

Dapagliflozin Alleviates Non-Alcoholic Fatty Liver Disease in Mice by Inhibiting Ferroptosis through Activating the SIRT1/Nrf2 Pathway

Min Liu,BiYing Meng,Jing Dong,Lin Xiang

Vitamin D3 Protects Mice from Diquat-Induced Oxidative Stress through the NF-κB/Nrf2/HO-1 Signaling Pathway.

Haiwen Zhang,Youming Liu,Xin Fang,Lihong Gu,Caiwei Luo,Lu Chen,Qian Wang

Vitamin D 3 , as an indispensable and fat-soluble micronutrient, plays an important role in the health of humans and animals. At present, studies are focusing on the calcium absorption and immunoregulation function of vitamin D 3 ; this study was aimed at exploring the antioxidative stress ability of vitamin D 3 on diquat-induced intestinal dysfunction of ICR mice and the underlying mechanism. The results showed that oral gavage of vitamin D 3 daily significantly improved the body weight gain and immune organ index and significantly reverted the abnormal changes of ALT, AST, SOD, GSH-Px, T-AOC, and MDA in the serum and jejunum induced by diquat. The addition of vitamin D 3 also significantly reduced the concentration of DAO, D-LA, and certain proinflammatory cytokines in serum. Moreover, vitamin D 3 improved the pathological morphology of the duodenum, jejunum, colon, liver, and kidney tissues, and it also largely attenuated the degree of inflammatory infiltration of macrophages and cell apoptotic index of jejunal epithelial tissue induced by diquat. The results demonstrated that vitamin D 3 significantly recovered the intestinal barrier injury by enhancing the expression of mucins and tight junction proteins in the jejunum. In addition, the results indicated that vitamin D 3 could significantly reduce the phosphorylation level of NF- κ B (p65) and enhance the expression of Nrf2 and HO-1 in the jejunum compared with the diquat-induced group. This study suggested that oral administration of vitamin D 3 can protect mice against oxidative damage by inhibiting the phosphorylation level of NF- κ B (p65) and activating Nrf2-related signaling pathways.

Curcumin analogues attenuate Aβ25-35-induced oxidative stress in PC12 cells via Keap1/Nrf2/HO-1 signaling pathways

Jialin Xu,Leilei Zhou,Qi Weng,Linxia Xiao,Qingyong Li

Beta-amyloid (Aβ) has pivotal functions in the pathogenesis of Alzheimer's Disease (AD). In the present study, we adopted an vitro model that involved Aβ 25-35 -induced oxidative damage in PC12 cells. Aβ 25-35 (10 μΜ) treatment for 24 h induced significant cell death and oxidative stress in PC12 cells, as evidenced by cell viability reduction, LDH release, ROS accumulation and increased production MDA . (1E,4E)-1, 5-bis(4-hydroxy-3-methoxyphenyl) penta-1, 4-dien-3-one (CB) and (1E, 4E)-1-(3, 4-dimethoxyphenyl)-5-(4-hydroxy-3, 5-dime-thoxyphenyl) Penta-1, 4-dien-3-one (FE), two Curcumin (Cur) analogues displayed neuroprotective effects against Aβ 25-35 -induced oxidative damage and cellular apoptosis in PC12 cells. Here, we investigated three different treatment ways of CB and FE. It was interesting that post-treatment of CB and FE (restoring way) showed similar effect to the preventive way, while attenuating way did not show any protective effect. We found that low dose CB and FE increased transcriptional factor NF-E2-related factor 2 (Nrf2)/hemo oxygenase 1 (HO-1) protein expression and decreased Kelch-like ECH-associated protein 1 (Keap1) in PC 12 cells. In addition, CB and FE promoted the translation of Nrf2 into nuclear and enhanced the activity of superoxide dismutase (SOD)/catalase, which confirmed cytoprotection against Aβ 25-35 -induced oxidative damage. Moreover, CB and FE could increase Bcl-2 expression level, decrease the level of Bax and Cyt-c in Aβ 25-35 -treated PC12 cells. Ultimately, the neuroprotective effect of CB and FE provides a pharmacological basis for its clinical use in prevention and treatment of AD.

6-Shogaol ameliorates experimental colitis and colitis-associated colorectal cancer in mice through the Nrf2-Keap1 signaling pathway

Na Li,Hehe Shi,Wei Du,Siqian Luo,Xianyue Yang,Xinyue Yang,Bingyue Jiang,Peng Xia,Guangji Zhang,Wanghui Jing

The progression from ulcerative colitis to colitis-associated colorectal cancer (CAC) represents a significant clinical challenge. 6-Shogaol, a bioactive phenolic compound of ginger, exhibits anti-inflammatory, antioxidant, and anti-tumor properties. This study aims to investigate the therapeutic efficacy of 6-shogaol against colitis and CAC, and explore the underlying mechanisms through network pharmacology and in vivo validation. Putative hub targets and pathways associated with 6-shogaol were identified through network pharmacology. Murine models of dextran sulfate sodium (DSS)-induced colitis and azoxymethane/DSS-induced CAC were established, and the mice were treated with 6-shogaol to assess the latter’s therapeutic effects. The targets of 6-shogaol predicted through network pharmacology were mainly associated with oxidative stress and reactive oxygen species (ROS) signaling pathways. I n vivo , 6-shogaol relieved colitis symptoms and reduced CAC tumor burden. Furthermore, 6-shogaol alleviated intestinal inflammation by decreasing the colonic levels of TNF-α and MPO, and reduced oxidative stress in the colon tissues, as indicated by lower ROS production and malondialdehyde content. Moreover, 6-shogaol restored intestinal barrier function by upregulating claudin-4, occludin, and ZO-1, and decreasing intestinal permeability. Mechanistically, 6-shogaol promoted Nrf2 nuclear translocation by upregulating nuclear Nrf2 expression while downregulating cytoplasmic Keap1, thereby activating antioxidant response element driver genes, including Hmox1 , Nqo1 , and Gclc . Molecular docking confirmed strong binding affinity between 6-shogaol and Keap1 receptor, with a low binding energy of -6.89 kcal/mol. These findings collectively suggested that 6-shogaol alleviated colitis and CAC in murine models by inhibiting colonic inflammation, relieving oxidative stress, and enhancing intestinal barrier function through the activation of the Nrf2-Keap1 pathway.

Artesunate overcomes oxaliplatin resistance in colorectal cancer by inducing ferroptosis through inhibition of the CDK5/Nrf2/GPX4 pathway

Lv Feng,Li Xiao-huan,Li Si-qi,Deng Hao-wei,Wei Hao-tang,Li Ke-zhi,Xie Ming-zhi,Xie Li-ye,Ning Shu-fang,Hu Bang-li

This study aimed to determine the effect of Artesunate (ART) on oxaliplatin-resistance of colorectal cancer (CRC) and the underlying mechanism. CRC parent and oxaliplatin-resistance cells were induced ferroptosis by ART, overexpression or silence of CDK5 and Nrf2 was conducted on CRC cells, and the function of cells were tested. The protein location, binding effect, protein–protein interaction, ART–CDK5 interaction were determined. Mice model was used to validated the effect of ART on CRC cells. ART induces ferroptosis and inhibits oxaliplatin-resistance of CRC cells. CDK5 promoted the viability, invasive, migration of CRC cells, but did not lead to increases cell apoptosis. CDK5 was associated with ferroptosis and oxaliplatin-resistance of CRC cells, and ART binding and inhibited the expression of CDK5. CDK5 inhibit CRC cells ferroptosis and promote oxaliplatin-resistance; CDK5 binding to Nrf2, increased stability and promote translocation of Nrf2 from cytosol to nuclear. By combination of overexpression of CDK5 and the overexpression or silence of Nrf2 in CRC cells, we found that CDK5 inhibited ferroptosis of CRC cells and enhance resistance to oxaliplatin via Nrf2/GPX4 pathway. The in vivo experiments exhibited that combination of ART and sh-CDK5 reduce the growth of tumors with low toxicity in xenograft models, and reduced Nrf2 and GPX4 expression. ART induced ferroptosis thereby overcomes oxaliplatin-resistance of CRC cells, this effect was via modulating the CDK5/Nrf2/GPX4 pathway. These findings highlight CDK5 as a critical regulator of redox homeostasis in CRC and the therapeutic potential of ART in treating chemoresistant tumors. Graphical abstract The alternative text for this image may have been generated using AI. The present study demonstrate that ART was able to induce ferroptosis via binding and regulation of CDK5, and CDK5 modulates the expression of Nrf2, thereby inhibited biological function of CRC cells and attenuates oxaliplatin-resistance of the cells, this effect was via orchestrating the Nrf2/GPX4 pathway.

Bioinspired zinc-doped carbon dots protect against polystyrene microplastic-induced spermatogenic dysfunction through Nrf2 activation and cuproptosis suppression

Tushuai Li,Kehui Li,Shiqing Yang,Hongying Pan,Zhihui Cai,Xiyao Hua,Guangfu Liao,Bing Luo,Jie Zhang

A zinc-doped trifolirhizin-derived carbon dots was developed. • ZnTFZCDs demonstrate favorable biosafety without overt cytotoxicity, hemolysis, or organ damage. • ZnTFZCDs administration ameliorates testicular histopathology, improves sperm count and morphology. • ZnTFZCDs reactivates the Nrf2/HO-1 antioxidant axis, and suppresses cuproptosis-associated alterations in testicular tissues. Polystyrene microplastics (PS-MPs) are increasingly recognized for their detrimental effects on reproductive health, particularly in the male reproductive system. While mitochondrial oxidative stress is recognized as a driver of MPs-induced reproductive injury, it remains unclear whether this process involves cuproptosis, a newly identified copper-dependent form of regulated cell death, and elucidating this potential link is critical for alleviating such damage. Here, we report that PS-MPs exposure induces testicular injury and spermatogenic dysfunction in mice, associated with redox imbalance, copper transport defects, and upregulation of the cuproptosis regulators Ferredoxin 1 (FDX1) and Lipoic Acid Synthetase (LIAS). In turn, zinc-doped trifolirhizin-derived carbon dots (ZnTFZCDs) were rationally designed via a one-step hydrothermal strategy, embedding the antioxidant properties of a natural flavonoid and the reproductive-protective role of zinc into a biocompatible carbon nanoplatform. ZnTFZCDs are well-dispersed carbon dots rich in oxygen/nitrogen-containing groups with Zn coordination, and demonstrate favorable biosafety without overt cytotoxicity, hemolysis, or organ damage. In vitro , ZnTFZCDs potently scavenge intracellular reactive oxygen species (ROS), maintain antioxidant enzyme activities, preserve mitochondrial membrane potential, suppress lipid peroxidation, and rescue Glutathione peroxidase 4 (GPX4) expression in MPs-exposed RAW264.7 and GC-2 cells. Notably, ZnTFZCDs modulate copper homeostasis by upregulating the copper exporter ATP7B, downregulating the importer SLC31A1, and reducing FDX1/LIAS expression, thereby inhibiting cuproptosis-related signaling. In vivo , ZnTFZCDs administration ameliorates testicular histopathology, improves sperm count and morphology, reactivates the Nrf2/HO-1 antioxidant axis, and suppresses cuproptosis-associated alterations in testicular tissues, confirming the translational potential of the in vitro findings. Collectively, ZnTFZCDs represent a bio-inspired nanoplatform that attenuates PS-MPs-induced male reproductive injury through coordinated modulation of redox and copper homeostasis, offering a new therapeutic strategy for environmental pollutant-related reproductive disorders by targeting the previously overlooked cuproptosis pathway. This work reports a novel zinc-doped trifolirhizin-derived carbon dots (ZnTFZCDs) for attenuating PS-MPs-induced male reproductive injury through coordinated restoration of redox and copper homeostasis. Download: Download high-res image (323KB) Download: Download full-size image

Febuxostat ameliorates APAP-induced acute liver injury by activating Keap1/Nrf2 and inhibiting TLR4/NF-κB p65 pathways

Jinhong Tian,Shuaishuai Zhang,Lu Li,Xueman Lin,Yongmei Li,Kunlu Zhao,Fengxin Zheng,Yongjun Chen,Yang Yang,Ting Wu,Jianxin Pang

Excessive acetaminophen (APAP) application is a major cause of drug-induced liver injury (DILI). Febuxostat (Feb), a drug for reducing uric acid (UA) levels, was demonstrated to relieve hepatic inflammation and reverse organ functions. However, the effect of Feb on APAP-induced DILI and its mechanisms have not been fully explored. In this study, Feb (10 mg/kg) was given to mice by gavage 1 h after APAP (300 mg/kg, i.g.) induction. Serum and liver samples were collected 12 or 3 h after APAP challenge. Feb treatment was found to remarkably improve APAP-induced DILI, as evidenced by reduced serum ALT, AST and UA levels, pathomorphology, inflammatory, and oxidative responses. Consistently, treatment with Feb also reduced the cell injury induced by APAP in LO2 cells. Mechanistically, Feb induced GPX4 expression, activated the Keap1/Nrf2 pathway, and inhibited the TLR4/NF-κB p65 pathway. Feb also inhibited glutathione (GSH) depletion and Jun N-terminal kinase (JNK) activation in the early injury phase. Notably, pretreatment with Feb for 3 days also revealed preventive effects against APAP-induced DILI in mice. Overall, our data revealed a potential health impact of Feb on APAP-mediated DILI in vivo and in vitro, suggesting that Feb might be a potential candidate for treating DILI.

Rutin modified selenium nanoparticles reduces cell oxidative damage induced by H2O2 by activating Nrf2/HO-1 signaling pathway

Mengyu Zhu,Yang Zhang,Chi Zhang,Lei Chen,Ying Kuang

Oxidative damage of neurons is one of the key pathological markers of Alzheimer’s disease (AD), which eventually leads to neuronal apoptosis and loss. Nuclear factor E2-related factor 2 (Nrf2) is a key regulator of antioxidant response and is considered to be an important therapeutic target for neurodegenerative diseases. In this study, the selenated derivative of antioxidant rutin (Se-Rutin) was synthesized with sodium selenate (Na2SeO3) as raw material by a simple electrostatic-compound in situ selenium reduction method. The effects of Se-Rutin on H2O2 induced oxidative damage in Pheochromocytoma PC12 cells were evaluated by cell viability, apoptosis, reactive oxygen species level and the expression of antioxidant response element (Nrf2). The results showed that H2O2 treatment significantly increased the level of apoptosis and reactive oxygen species, while the level of Nrf2 and HO-1 decreased. However, Se-Rutin significantly reduced H2O2 induced apoptosis and cytotoxicity, and increased the expression of Nrf2 and HO-1, both of which were better than that of pure rutin. Therefore, the activation of Nrf2/HO-1 signaling pathway may be the basis of Se-Rutin’s anti-oxidative damage to AD.

Nrf2 deficiency aggravates Angiotensin II-induced cardiac injury by increasing hypertrophy and enhancing IL-6/STAT3-dependent inflammation

Dandan Chen,Zhe Li,Peiqing Bao,Miao Chen,Miao Zhang,Fangrong Yan,Yitao Xu,Caoyu Ji,Xinyue Hu,Daniel Sanchis,Yubin Zhang,Junmei Ye

Background NF-E2-related factor 2 (Nrf2) is a transcription factor playing cytoprotective effects in various pathological processes including oxidative stress and cardiac hypertrophy. Despite being a potential therapeutic target to treat several cardiomyopathies, the signaling underlying Nrf2-dependent cardioprotective action remains largely uncharacterized. Aim This study aimed to explore the signaling mediating the role of Nrf2 in the development of hypertensive cardiac pathogenesis by analyzing the response to Angiotensin II (Ang II) in the presence or absence of Nrf2 expression, both in vivo and in vitro. Results Our results indicated that Nrf2 deficiency exacerbated cardiac damage triggered by Ang II infusion. Mechanistically, our study shows that Ang II-triggered hypertrophy and inflammation is exacerbated in the absence of Nrf2 expression and points to the involvement of the IL-6/STAT3 signaling pathway in this event. Indeed, our results show that IL-6 abundance triggered by Ang II is increased in the absence of Nrf2 and demonstrate the requirement of IL-6 in STAT3 activation and cardiac inflammation induced by Ang II. Conclusion Our results show that Nrf2 is important for the protection of the heart against Ang II-induced cardiac hypertrophy and inflammation by mechanisms involving the regulation of IL-6/STAT3-dependent signaling.