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rutin attenuates zearalenone-induced ferroptosis of endometrial stromal cells in piglets through the p53 signaling pathway

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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2025年 290卷 117546页

作者： Wang, Chenlong Chen, Chuangjiang Wang, Mengya Rahman, Sajid Ur Wei, Bin Ding, Hongyan Huang, Wanyue Wang, Xichun Anhui Agr Univ Coll Vet Med 130 West Changjiang Rd Hefei 230036 Peoples R China Huangyuan Cty Anim Husb & Vet Stn Xining 812100 Qinghai Peoples R China Anhui Acad Agr Sci Inst Anim Sci & Vet Med Anhui Prov Key Lab Livestock & Poultry Prod Safety Hefei 230031 Peoples R China Anhui Prov Engn Lab Anim Food Qual & Biosafety Hefei 230036 Peoples R China

Zearalenone (ZEA) is an environmentally widespread mycotoxin capable of posing a serious threat to food safety and public health, and porcine endometrial stromal cells (ESCs) are particularly sensitive to the toxic effects of ZEA. We hypothesized that rutin, a flavonoid antioxidant, could significantly alleviate ZEA-induced ferroptosis through the p53 signaling pathway. In this study, we used porcine ESCs as a research model. When porcine ESCs were co-cultured with the addition of rutin and ZEA following p53 gene silencing via siRNA transfection, rutin significantly mitigated ZEA-induced mitochondrial damage, oxidative stress, and Fe2 + content through the p53 pathway. Additionally rutin lowered the expression of p53, ALOX12, and ACSL4 while significantly improving cytokinesis, antioxidant enzyme activity, and SLC7A11, GPX4, Nrf2, FTH1, thereby inhibiting cellular ferroptosis. These findings suggested a novel programmed death mechanism for alleviating the cytotoxic effects of ZEA, involving the knockdown of p53.

关键词： ZEA rutin ESCs Ferroptosis p53 signaling pathway

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rutin ameliorates stress-induced blood-brain barrier dysfunction and cognitive decline via the endothelial HDAC1-Claudin-5 axis

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FLUIDS AND BARRIERS OF THE CNS 2025年第1期22卷 1-18页

作者： Sun, Zhao-Wei Sun, Zhao-Xin Zhao, Yun Zhang, Ling Xie, Fang Wang, Xue Li, Jin-Shan Zhou, Mao-Yang Feng, Hong Qian, Ling-Jia Beijing Inst Basic Med Sci Beijing 100850 Peoples R China Tianjin Univ Sport Inst Sport Exercise & Hlth Tianjin Key Lab Exercise Physiol & Sports Med Tianjin 301617 Peoples R China

Background Emerging evidence suggests that chronic stress compromises blood-brain barrier (BBB) integrity by disrupting brain microvascular endothelial cells (BMECs), contributing to the development of cognitive impairments. Thus, targeting the BBB is expected to be a promising treatment strategy. The biological function of rutin has been investigated in neurological disorders;however, its regulatory role in stress-induced BBB damage and cognitive decline and the underlying mechanisms remain elusive. Methods In a chronic unpredictable mild stress (CUMS) mouse model, a fluorescent dye assay and behavioral tests, including a novel object recognition test and Morris water maze, were performed to evaluate the protective effects of rutin on BBB integrity and cognition. The effects of rutin on BMEC function were also investigated in hCMEC/D3 cells (a human brain microvascular endothelial cell line) in vitro. Furthermore, the molecular mechanisms by which rutin restores BBB endothelium dysfunction were explored via RNA-seq, quantitative real-time PCR, western blotting, immunofluorescence and chromatin immunoprecipitation. Finally, biotinylated tumor necrosis factor-alpha (TNF-alpha) was employed to test the influence of rutin on the ability of circulating TNF-alpha to cross the BBB. Results We identified that rutin attenuated BBB hyperpermeability and cognitive impairment caused by the 8-week CUMS procedure. Moreover, rutin promoted the proliferation, migration and angiogenesis ability of BMECs, and the integrity of the cellular monolayer through positively regulating the expression of genes involved. Furthermore, rutin impeded histone deacetylase 1 (HDAC1) recruitment and stabilized H3K27ac to increase Claudin-5 protein levels. Ultimately, normalization of the hippocampal HDAC1-Claudin-5 axis by rutin blocked the infiltration of circulating TNF-alpha into the brain parenchyma and alleviated neuroinflammation. Conclusions This work establishes a protective role of rutin in

关键词： rutin Stress-induced cognitive decline BBB BMEC function Claudin-5

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rutin ameliorates calcium oxalate crystal-induced kidney injury through anti-oxidative stress and modulation of intestinal flora

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UROLITHIASIS 2025年第1期53卷 1-15页

作者： Zhang, Haoyu Yang, Huixuan Du, Sha Ren, Jiaxin Qiao, Guofeng Ren, Jie Shanxi Agr Univ Coll Vet Med Jinzhong 030801 Peoples R China Shanxi Agr Univ Coll Anim Sci Jinzhong 030801 Peoples R China Shanxi Med Univ Coll Clin 1 Taiyuan 030000 Peoples R China

Kidney stones are a common urological disease. Although there are many ways to treat them, their high recurrence rate remains unresolved. Research has demonstrated that Lysimachia christinae Hance influences kidney stone development;however, the exact mechanism remains unclear. In this experiment, we investigated the protective effect of Lysimachia christinae Hance extract, rutin, on renal injury and its mechanism of action in a mouse model of glyoxalate-induced renal calculi. A kidney stone model was established in Balb/c mice by continuous intraperitoneal injection of glyoxalate (80 mg/kg) for 6 days. Simultaneous gavage of 30, and 60 mg/kg of rutin was administered for 6 days. Samples were collected for determination of index coefficients. Mouse kidney tissue was collected for RNA-seq, and segments of mouse colon were analyzed with 16 S RNA sequencing. We found that rutin significantly reduced renal calcium oxalate deposition and renal tissue injury in the glyoxylate-induced kidney stone model of mice. rutin also significantly inhibited calcium oxalate deposition-induced apoptosis. In addition, rutin attenuates oxidative stress damage and inhibits the expression of signaling pathways associated with inflammation. 16 S RNA sequencing revealed that rutin regulated intestinal flora composition, significantly increasing the relative abundance of short-chain fatty acid-producing flora and promoting short-chain fatty acid production. In summary, rutin ameliorated renal tubular damage and apoptosis caused by renal stone deposition and reduced oxidative stress. It also regulates the intestinal flora, increases the enrichment of intestinal probiotics, and promotes the production of short-chain fatty acids, thereby inhibiting the formation of kidney stones.

关键词： rutin Nephrolithiasis Calcium oxalate Oxidative stress Short-chain fatty acids

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rutin attenuates iron overload induced-ferroptosis in rats' heart tissue

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NATURAL PRODUCT RESEARCH 2025年 1-11页

作者： Abdullah, Haidy A. Moawed, Fatma S. M. Ahmed, Esraa S. A. Hamid, Fatma F. Abdel Haroun, Riham Abdel-Hamid Ain Shams Univ Fac Sci Biochem Dept Cairo Egypt Atom Energy Author Natl Ctr Radiat Res & Technol Hlth Radiat Res Dept Cairo Egypt Egyptian Atom Energy Author Natl Ctr Radiat Res & Technol Radiat Biol Res Dept Cairo Egypt

rutin is a natural flavonoid with antioxidant and iron chelating properties. Therefore, this study aimed to investigate the ameliorative effects of rutin against iron-overload and ionising radiation induced (IR)-ferroptosis in rats' heart tissue. Rats were divided into nine groups;control, rutin, IR, Fe, Fe + IR, Fe + rutin, IR+rutin, Fe + IR+rutin and Fe + IR+Deferasirox. Serum iron profiles total iron, TIBC, ferritin, transferrin, and hepicidin were determined. Moreover, MDA, GSH, and NO levels and GPx, and SOD activities were also determined. Levels of gene expression of GPX4, Nrf2, DMT1, ACSL4, and caspase3 genes were evaluated by using RT-qPCR. Finally, histopathological examination of rat heart tissues of different groups was done. After rutin treatment, our results revealed that TIBC, ferritin, transferrin, hepicidin, MDA&NO were significantly decreased, while GSH level and GPx&SOD activities were significantly increased. Also, rutin exerting its protective role by increasing GPX4&Nrf2 expressions and decreasing DMTN, ACSL4, and caspase3 expressions. rutin can be proposed as a therapeutic candidate to attenuate ferroptosis.

关键词： Ferroptosis iron overload rutin flavonoids iron chelation antioxidant deferasirox

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rutin Attenuates Distraction Spinal Cord Injury by Inhibiting Microglial Inflammation Through Downregulation of P38 MAPK/NF-κB/STAT3 Pathway

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MOLECULAR NEUROBIOLOGY 2025年第5期62卷 6027-6040页

作者： Hai, Junrui Jonathan Liang, Weishi Sun, Duan Yin, Peng Han, Bo Qu, Xianjun Capital Med Univ Joint Lab Res & Treatment Spinal Cord Injury Spina Lab Clin Med Beijing 100069 Peoples R China Princeton Int Sch Math & Sci Princeton NJ 08540 USA Capital Med Univ Beijing Chaoyang Hosp Dept Orthoped Surg Chaoyang Dist Beijing 100020 Peoples R China Capital Med Univ Sch Basic Med Sci Dept Pharmacol Beijing 100069 Peoples R China Capital Med Univ Beijing Jishuitan Hosp Dept Radiol 31 Xinjiekou East St Beijing 100035 Peoples R China

Distraction spinal cord injury (DSCI) is a severe complication following scoliosis correction surgery, for which there are currently no effective clinical treatments. This study aims to evaluate the inhibitory effects of rutin, a natural product, on inflammation in DSCI and to investigate the underlying mechanisms. In vitro, microglial cells were exposed directly to rutin to assess its ability to inhibit lipopolysaccharide (LPS)-induced inflammation. In rats with DSCI, the inhibitory effect of rutin on DSCI was evaluated using behavioral tests. mRNA sequencing was performed on spinal cord tissues to elucidate the mechanism of rutin's action. rutin significantly suppressed the LPS-induced increase in inflammatory factors in microglial cells. In DSCI rats treated with rutin, scores in the Basso-Beattie-Bresnahan (BBB) were significantly improved. The mechanism of rutin's action was found to be related to its ability to reduce inflammatory infiltration in spinal cord tissue, protecting neurons from apoptosis and microstructural demyelination. Through assays of transcriptomic differentially expressed genes (DEGs), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and RT-qPCR validation of the top DEGs, MAPK13 (also known as P38 MAPK) was finally identified as the key target gene in promoting DSCI development. Further molecular docking analysis indicated an interaction between rutin and P38 MAPK, supporting the rutin's action and the underlying mechanism in anti-inflammation. In conclusion, rutin effectively inhibited the development of DSCI in rats. The mechanism of rutin's action was associated with its activity in blocking the P38 MAPK/NF-kappa B/STAT3 pathway in the microglial cells of spinal cord. rutin could be developed as a potential anti-DSCI drug for clinical applications.

关键词： Distraction spinal cord injury (DSCI) rutin Inflammation Rat model P38 MAPK/NF-kappa B/STAT3 pathways

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Stabilization and sustained release of rutin dye via eco-friendly Zn/Al-LDH adsorbent: Kinetic, thermodynamic, and antioxidant investigations

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JOURNAL OF MOLECULAR STRUCTURE 2025年第Part1期1319卷

作者： Bahman, Habibollah Gharanjig, Kamaladin Ghasemi, Ebrahim Kazemian, Hossein Hosseinnezhad, Mozhgan Gharanjig, Hamid Inst Color Sci & Technol ICST Dept Organ Colorants Tehran Iran Inst Color Sci & Technol ICST Dept Inorgan Pigment & Glazes Tehran Iran Univ Northern British Columbia Mat Technol & Environm Res MATTER Lab Prince George BC Canada Univ Northern British Columbia Northern Analyt Lab Serv Northern BCs Environm & Climate Solut Innovat Hub Prince George BC Canada Univ Northern British Columbia Fac Environm Environm Sci Program Prince George BC V2N 4Z9 Canada

This study focuses on the stabilization of rutin dye by intercalating it within Zn/Al-LDH (R-Z/A-L) through coprecipitation (CO) and ion exchange (IO) methods. For the IO method, rutin was intercalated onto Z/A-L using a circulator, achieving an optimal intercalation efficiency of 86.37 % and a capacity of 43.18 mg g(-1). Comprehensive characterization of the intercalated compounds was performed using XRD, FTIR, FE-SEM, TEM, TGA, DSC, BET, and XPS techniques, confirming efficient intercalation of rutin into LDH. Kinetic analysis indicated that the pseudo-second-order and intraparticle diffusion models best illustrate the intercalation and release mechanisms, respectively. Isotherm data supported the Langmuir model as the most accurate for describing rutin's intercalation behavior. Thermodynamic investigation disclosed the process to be endothermic and spontaneous. Using the CO method, R-Z/A-L was synthesized under optimal conditions with varying rutin concentrations (5%, 15%, and 25%), achieving maximum intercalation efficiencies and capacities up to 98.15 % and 49.07 mg g(-1), respectively. Additionally, the antioxidant activity of the intercalated rutin was evaluated, showing that its integration into the adsorbent allowed for prolonged and consistent release. These results confirm the effectiveness of the Z/A-L adsorbent in enhancing stability.

关键词： rutin Layered double hydroxide Stabilization Intercalation Antioxidant activity

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One-Step Synthesis of Zr/Cl-Doped Carbon Dots as Fluorescent Probes for the Determination of rutin

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JOURNAL OF APPLIED SPECTROSCOPY 2025年第1期92卷 175-182页

作者： Han, Dan Niu, Xiaoxue Wang, Jing Yan, Zihong Kashi Univ Coll Chem & Environm Sci Lab Xinjiang Native Med & Edible Plant Resource Ch Kashi Peoples R China

Zr and Cl double-doped carbon dots (Zr/Cl-CDs) were prepared by a one-step hydrothermal method using citric acid, urea, and ZrCl4 as precursors. Zr/Cl-CDs were characterized by ultra-violet-visible spectroscopy (UV-Vis), transmission electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, and X-ray photoelectron spectroscopy (XPS). Experimental analysis revealed that the average size of Zr/Cl-CDs was 2-3 nm, while XPS analysis revealed the presence of C-Cl and Zr-O bonds. The fluorescence quantum yield of the final CDs was 17.5% at the excitation of 360 nm. In addition, Zr/Cl-CDs exhibited excellent performance in the detection of rutin with a concentration of 30-110 and 100-160 mu mol/L, respectively. Linear correlation coefficients (R2) were 0.9931 and 0.9962. The underlying mechanism was that rutin had an excellent quenching effect on the emission of the Zr/Cl-CDs as the fluorescence intensity exhibited a good linear relationship between rutin concentration and fluorescence intensity. These findings provide a new strategy for synthesizing double-doped CDs for rutin detection.

关键词： carbon dots double-doped carbon dots ZrCl4 rutin

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Air plasma assisted directional electrodeposition of Ag nanoparticles on carbon cloth for electrochemical detection of rutin

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MICROCHIMICA ACTA 2025年第4期192卷 1-11页

作者： Ren, Jing An, Yutong Yin, Shiqi Wang, Jun Yu, Qingxian Li, Chunfang Zhan, Tianrong Qingdao Univ Sci & Technol Coll Chem & Mol Engn Key Lab Opt Elect Sensing & Analyt Chem Life Sci Minist Educ Qingdao 266042 Peoples R China

The air plasma-induced defects and O-related groups are employed as anchoring sites for the directional electrochemical deposition of Ag nanoparticles (AgNPs) with even distribution and a narrow size range on carbon cloth (CC). The strategy of integrating the air plasma and AgNPs provides plentiful adsorption and catalytic sites, a large electroactive area, superhydrophilic interface, and a smooth charge and mass-transfer pathway. As a consequence, the fabricated self-supporting electrode of AgNPs@CC - P displays an excellent sensing performance toward rutin with a large linear concentration window (0.05 similar to 30 mu M), a small LOD (4.2 nM, S/N = 3) and LOQ (32 nM, S/N = 10), as well as good stability and reproducibility. The fabricated sensor is successfully applied to the practical detection of rutin in tablets and beverages with good accuracy. The self-supporting sensor also shows potential for fabricating flexible and soft sensing devices for real-time monitoring.

关键词： Carbon cloth Air plasma Directional deposition of Ag nanoparticles rutin Electrochemical sensor Differential pulse voltammetry

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rutin resists Aspergillus fumigatus keratitis by activating Nrf2/HO-1 pathway, inhibiting Dectin-1/p-Syk pathway and affecting fungal structures

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EXPERIMENTAL EYE RESEARCH 2025年 254卷 110323页

作者： Li, Yuqi Tian, Xue Zhang, Lina Lin, Jing Wang, Qian Gu, Lingwen Li, Hong Yu, Bing Wang, Ziyi Chi, Menghui Zhao, Guiqiu Li, Cui Qingdao Univ Affiliated Hosp Dept Ophthalmol 16 Jiangsu Rd Qingdao 266003 Shandong Peoples R China

Fungal keratitis (FK) is a severe vision-threatening eye disease. The fungal invasiveness and excessive inflammatory response contribute to corneal tissue damage. rutin (RT) possesses anti-inflammatory, antimicrobial, antioxidant, and improved wound-healing characteristics. This study aimed to evaluate antifungal, antiinflammatory, and therapeutic effects of RT in FK. The results showed that RT exerted antifungal effects by inhibiting fungal growth, altering hyphal morphology, destroying biofilm, and disrupting fungal cellular structures. RT exhibited anti-inflammatory benefits by suppressing the Dectin-1/p-Syk pathway, activating the Nrf2/ HO-1 pathway, and decreasing the expression of inflammatory factors in vivo and in vitro. RT demonstrated therapeutic effects by reducing clinical scores, fungal load, macrophage recruitment, and neutrophil activity. In conclusion, RT exhibited anti-inflammatory, antifungal, and therapeutic effects in Aspergillus fumigatus keratitis, and has the potential to become a novel therapeutic strategy for FK.

关键词： rutin Aspergillus fumigatus keratitis Nrf2/HO1 Dectin-1/p-Syk Inflammation

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rutin engages opioid/benzodiazepine receptors towards anti-neuropathic potential in a rat model of chronic constriction injury: relevance to its antioxidant and anti-inflammatory effects

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NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY 2025年 1-15页

作者： Zamani, Kimia Fakhri, Sajad Kiani, Amir Abbaszadeh, Fatemeh Farzaei, Mohammad Hosein Kermanshah Univ Med Sci Student Res Comm Kermanshah Iran Kermanshah Univ Med Sci Hlth Inst Pharmaceut Sci Res Ctr Kermanshah *** Iran Kermanshah Univ Med Sci Hlth Technol Inst Regenerat Med Res Ctr Kermanshah Iran Shahid Beheshti Univ Med Sci Inst Neurosci & Cognit Neurobiol Res Ctr Tehran Iran

Neuropathic pain is a chronic type of pain caused by damage or dysfunction in the nervous system. It can be quite bothersome and often doesn't well respond to common painkillers. Among natural compounds, rutin (Rut) stands out for its remarkable antioxidant, and anti-inflammatory properties. In this research, our objective is to investigate the impact of Rut on an animal model of chronic constriction injury (CCI). A total of 54 adult Wistar rats were divided randomly into nine separate groups. Groups included sham, CCI, gabapentin (GBP, 100 mg/kg), Rut (10, 25 mg/kg), flumazenil (FLU, 0.5 mg/kg), naloxone (NAL, 0.1 mg/kg), Rut (10 mg/kg) + FLU (0.5 mg/kg), and Rut (10 mg/kg) + NAL (0.1 mg/kg). The aforementioned drug injection (intraperitoneal, i.p.) and sensorimotor behavioral tests were performed on days 1, 3, 5, 7, 9, 11, and 14. Biochemical (e.g., nitrite, catalase, glutathione), zymography (matrix-metalloproteinase 2 and 9), and histopathological tests were performed on day 14 after surgery. The findings demonstrated that Rut administration effectively alleviated symptoms of allodynia/hyperalgesia, and improved locomotor activity following CCI. Additionally, Rut administration resulted in increased catalase and glutathione activity, while reducing serum nitrite levels, as well as matrix metalloproteinase 2 and 9 activity. Additionally, histological results indicated that Rut improved sciatic nerve regeneration. Since the aforementioned effects of Rut were reversed by using opioid and benzodiazepine receptor antagonists (i.e., NAL and FLU, respectively), the receptors' involvement was revealed in the anti-neuropathic effects of Rut. In conclusion, Rut emerged as a potentially effective candidate for treating neuropathic pain and improving motor function by increasing antioxidant mediators, suppressing inflammation, and activating opioid/benzodiazepine receptors.

关键词： Neuropathic pain rutin Oxidative stress Inflammation Opioid pathway Benzodiazepine pathway Chronic constriction injury

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