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CELL BIOCHEMISTRY AND BIOPHYSICS · 2025 · IF 2.5

Luteolin Inhibits Ferroptosis of HUVEC by Regulating the Sirt1/Nrf2 Pathway

Xiang Ming,Lin Xiangdong,Chen Haiying

Coronary heart disease (CHD) is a disease caused by organic and functional coronary artery stenosis, resulting in a reduced oxygen supply to the heart. This study aimed to investigate the mechanism via which Luteolin regulates the Sirt1 / Nrf2 pathway to inhibit ferroptosis in human umbilical vein endothelial cells (HUVEC) associated with CHD. An ox-LDL-induced HUVEC cell model with Sirt1 silencing and Luteolin treatment was established. The silencing efficiency of Sirt1 was validated using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot analysis. The results of molecular docking and DARTS experiments showed that Luteolin could effectively bind Sirt1 . Subsequently, we measured the expression of Nrf2 and Sirt1 , cell viability, MDA, GSH, Fe 2+ levels, lipid ROS content, expression of ferroptosis-related proteins GPX4, FTH, FTL, and cell migration parameters. The results showed that Luteolin could activate the Sirt1 / Nrf2 axis and effectively inhibit ox-LDL-induced ferroptosis in HUVEC. Experimental results revealed that Luteolin could enhance HUVEC cell viability, decrease MDA, Fe 2+ , and ROS levels, increase GSH levels, promote the expression of HO-1, GPX4, FTH, FTL, inhibit the expression of ACSL4 and TFRC, and enhance the migration capability of HUVEC cells. Moreover, silencing Sirt1 reversed the effects of Luteolin on the activation of Sirt1 and Nrf2 , confirming the dependence of these effects on the Sirt1 / Nrf2 signaling pathway. In conclusion, this study indicates that Luteolin could inhibit ferroptosis in HUVEC in CHD by modulating the Sirt1 / Nrf2 axis, providing a basis for further research on strategies for preventing and treating CHD and related diseases.

CAS / MDL: 9036-06-0 9073-78-3
研究领域: 药理学 · 分子生物学 · 心脏病学 · 细胞生物学 · 生物化学
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JOURNAL OF MOLECULAR STRUCTURE · 2025 · IF 4.7

Virtual screening and experimental validation of luteolin cocrystals for enhanced solubility

Jia Xu,Hongjian Ji,Guozhe Zhang,Jin Cheng,Qin Shi,Jie Zhang

Luteolin, a bioactive flavonoid known for its anti-inflammatory, antioxidant, and anticancer properties, is limited in its clinical application due to poor water solubility and low bioavailability. In this study, we applied an integrated approach combining virtual screening and experimental validation to identify potential coformers that can form cocrystals with luteolin, improving its physicochemical properties. A total of 28 coformers were analyzed using virtual screening, with predictions based on hydrogen bond strength. From this, 12 promising coformers were selected for experimental trials. Our experimental results led to the successful synthesis of five novel luteolin cocrystals with 4,4′-bipyridine, l -ascorbic acid, nicotinic acid, and isonicotinic acid. Notably, the coformers that formed cocrystals in the experiments ranked highly in the virtual screening results, demonstrating the feasibility of the virtual cocrystal screening method. Notably, all synthesized cocrystals exhibited substantially enhanced solubility profiles, achieving a maximum 4.51-fold increase in solubility relative to pure luteolin. These findings not only validate the virtual screening approach but also highlight its potential applications in pharmaceutical cocrystal design to overcome solubility and bioavailability challenges in drug development.

研究领域: 药学 · 化学
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MICROCHEMICAL JOURNAL · 2022 · IF 5.304

Ag doped Co/Ni bimetallic organic framework for determination of luteolin

Jing Tang,Tao Hu,Nali Li,Yanli Zhu,Jie Li,Shengbiao Zheng,Jiahao Guo

Electrochemical determination of luteolin is vital to food industry owing to its bioactive properties such as anti-viral, anti-ulcer. However, bare electrode of traditional electrochemical sensors generally have narrow linear range and low sensitivity, which sets limit on their practical application. Accordingly, a new nano-architecture fabricated with Ag doped CoNi-bimetal metal–organic frameworks (Ag-CoNi-MOF) is developed as a material for electrochemical determination of luteolin. The introduction of Ag to three-dimensional (3D) flower-like hierarchical structure greatly increases specific surface area and electrical conductivity, which subsequently provides more excellent active sites for luteolin oxidation. Under optimal conditions, Ag-CoNi-MOF sensor presents a broader linear response to luteolin concentration of 0.002 – 1.0 μM with the detection limit as low as 0.4 nM (S/N = 3). Ag-CoNi-MOF has good anti-interference according to compared amperometric current response of luteolin within different organic analytes and metal ions. Finally, the sensor platform is implemented directly to determine luteolin in human urine for evaluation of its practical application. In general, Ag-CoNi-MOF sensors fabricated perform larger linear range with high sensitivity and anti-interference properties, which can be used as a potential material for electrochemical determination of luteolin.

研究领域: 食品科学 · 材料科学 · 分析化学
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BIODEGRADATION · 2015 ·Vol. 26 ·期 3 ·197-210 · IF 2.336

Biodegradation of the phytoestrogen luteolin by the endophytic fungus Phomopsis liquidambari

Wang Hong-Wei,Zhang Wei,Su Chun-Lun,Zhu Hong,Dai Chuan-Chao

Phytoestrogens are plant-derived hormonally-active compounds known to cause varied reproductive, immunosuppressive and behavioral effects in vertebrates. In this study, biodegradation of luteolin, a common phytoestrogen, was investigated during incubation with endophytic fungus Phomopsis liquidambari . The optimum concentration of luteolin as sole carbon source supplied in culture was 200 mg L −1 , which allowed 97 and 99 % degradation of luteolin by P. liquidambari in liquid culture and soil conditions, respectively. The investigation of the fungal metabolic pathway showed that luteolin was first decomposed to caffeic acid and phloroglucinol. These intermediate products were degraded to protocatechuic acid and hydroxyquinol, respectively, and then rings were opened by ring-cleavage dioxygenases. Two novel genes encoding the protocatechuate 3,4-dioxygenase and hydroxyquinol 1,2-dioxygenase were successfully cloned. Reverse-transcription quantitative polymerase chain reaction demonstrated that expression levels of mRNA of these two genes increased significantly after P. liquidambari was induced by the intermediate products caffeic acid and phloroglucinol, respectively. These results revealed that P. liquidambari can biodegrade luteolin efficiently and could potentially be used to bioremediate phytoestrogen contamination.

研究领域: 环境科学 · 微生物学 · 分子生物学
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Acta Crystallographica Section E-Crystallographic Communications · 2026 ·Vol. 82 ·期 4 · IF 0.5

Crystal structure and Hirshfeld surface analysis of luteolin dimethyl sulfoxide monosolvate

Xu J.

The title compound, 3′,4′,5,7-tetrahydroxyflavone dimethyl sulfoxide monosolvate (LUT-DMSO), C2H6OS·C15H10O6, crystallizes in the monoclinic space group P21. The LUT mol­ecule adopts a planar conformation, and the crystal structure is consolidated by extensive hydrogen-bonding inter­actions. Hirshfeld surface analysis indicates that the predominant inter­molecular inter­actions are O⋯H/H⋯O, C⋯H/H⋯C, and H⋯H, with these contacts contributing significantly to the overall cohesion of the crystal.

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JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY · 2019 · IF 2.606

Luteolin cocrystals: Characterization, evaluation of solubility, oral bioavailability and theoretical calculation

Yumiao Luo,Siqi Chen,Jianle Zhou,Jiamen Chen,Liwen Tian,Wei Gao,Yingyi Zhang,Ande Ma,Liang Li,Zhengzheng Zhou

Luteolin is an important flavonoid with low water solubility and oral bioavailability properties, which limit its further clinical applications. In the present study, two new cocrystals of luteolin monohydrate with isoniazid and caffeine have been synthesized successfully using liquid assisted grinding method. Solid characterizations including X-ray diffraction, thermal and spectroscopic analysis were carefully performed to identify the two new cocrystals. Temperature-composition phase diagrams for both cocrystals were plotted through differential scanning calorimetry data. The maximum and minimum extreme values of all the compounds on molecular electrostatic potential surfaces that can be converted into hydrogen driving forces were calculated and illustrated. The luteolin-isoniazid cocrystal presents the solubility (112.3 μg mL −1 ) about three times better than luteolin monohydrate. In the pharmacokinetic analysis, the integrated AUC 0-∞ of luteolin-isoniazid and luteolin-caffeine cocrystals performed 2.7 folds and 1.4 folds respectively more enhancements than luteolin monohydrate.

CAS / MDL: 54-85-3
研究领域: 药理学 · 药物化学 · 理论计算
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NEUROTOXICITY RESEARCH · 2021 ·Vol. 39 ·期 6 ·1800-1811 · IF 3.911

Luteolin Suppresses Microglia Neuroinflammatory Responses and Relieves Inflammation-Induced Cognitive Impairments

Zhou Wei,Hu Mengmeng,Hu Jingrong,Du Zhiyun,Su Qing,Xiang Zhangmin

Microglia-mediated neuroinflammation in response to injurious self and non-self-stimuli exerts detrimental effects on neurons, which may lead to cognitive impairment. Luteolin, a typical kind of natural flavonoid in honeysuckle, chrysanthemum, and Herba Schizonepetae , is widely recognized to be anti-inflammatory and antioxidant against peripheral inflammation. However, its protective effect against inflammation-induced cognitive impairment is currently unknown. In this paper, we investigated the relief potential of luteolin against lipopolysaccharide (LPS)-induced cognitive impairment and neuroinflammation and its possible anti-inflammatory mechanisms in lipopolysaccharide-stimulated BV2 microglia cells. In this study, luteolin ameliorated LPS-induced cognitive impairments, indicated by behavioral performance of neuroinflammatory model mice in Morris water maze tests. Protein analyses and histological examination also revealed protective effect of luteolin against neuronal damage, through inhibiting overproduction of inflammatory cytokines in both hippocampus and cortex of mice. We also observed luteolin in vitro significantly suppressed the levels of pro-inflammatory cytokines, such as tumor necrosis factor alpha (TNF-α) and interleukin-1 β (IL-1β), and inflammatory mediators like nitric oxide. Taken together, these results demonstrated luteolin was effective in alleviating cognitive impairment and limited neuronal damage via inhibiting the release of inflammatory mediators, suggesting luteolin is potential for further therapeutic research of neuroinflammation-related neurodegenerative diseases.

CAS / MDL: 298-93-1
研究领域: 神经科学 · 药理学 · 免疫学 · 神经退行性疾病
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Antioxidants · 2025 ·Vol. 14 ·期 12 ·1495 · IF 6.6

Luteolin in Safflower Leaves Suppresses Microglial Inflammation Through FOXO3-Mediated Trem2 Transcription

Tiantian Zhang,Shuangxi Zhang,Jiayang Ma,Dmitrii Atiakshin,Shujun Han,Mami Noda,Midori Hiramatsu,Jiankang Liu,Yunhua Peng,Jiangang Long

Neuroinflammation driven by microglial activation is a hallmark of Alzheimer’s disease (AD). Triggering receptor expressed on myeloid cells 2 (TREM2) is a key regulator of microglial inflammation, yet strategies to modulate its expression remain limited. Safflower leaves, a vegetable rich in flavonoids—particularly luteolin—were previously shown to attenuate neuroinflammation, reduce oxidative stress, and ameliorate cognitive impairment in APP/PS1 mice. Here, we demonstrated that safflower leaves inhibit microglial inflammation and upregulate TREM2 in APP/PS1 mice. Luteolin, the major active flavonoid in safflower leaves, exerted anti-inflammatory effects in lipopolysaccharides (LPS)-activated microglia. Mechanistically, luteolin enhancedTrem2transcription by activating forkhead box protein O3 (FOXO3), a novel transcriptional regulator ofTrem2identified through promoter analysis. FOXO3 binding to theTrem2promoter was essential for this regulation, and luteolin further promoted FOXO3 nuclear translocation. Crucially,Trem2knockdown attenuated luteolin’s anti-inflammatory effects, confirming TREM2 as a key mediator. Overall, our study reveals the FOXO3-TREM2 axis as a potential therapeutic target for neuroinflammation and highlights luteolin present in safflower leaves as a candidate dietary intervention for AD, providing new mechanistic insights into the anti-inflammatory activity of this natural antioxidant.

CAS / MDL: 117-39-5 491-70-3
研究领域: 神经科学 · 分子生物学 · 免疫学 · 营养科学 · 药理学
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FOOD CHEMISTRY · 2025 · IF 9.8

Effect of anthocyanin-luteolin copigmentation on beef color stability: Interaction with myoglobin

Handan Zhang,Xinyue Ren,Yanjie Guo,Lianhong Guo,Jie Zhu

In this study, the effect of anthocyanin (AC)-luteolin (LUT) on meat color stability during postmortem aging and the molecular mechanisms of color protection were investigated. During postmortem aging, ROS-mediated lipid oxidation in muscle increased over time, whereas AC-LUT treatment inhibited ROS generation and slowed the rate of lipid oxidation. Compared with the control, the addition of AC-LUT increased the a ⁎ value of bovine muscle, thereby significantly enhancing postmortem meat color stability. AC-LUT delayed the decrease of myoglobin (Mb) peaks at the Soret and Q bands, helping to maintain the structure of the hydrophobic heme pocket and inhibiting Mb oxidation. Changes in heme iron and free iron content also confirmed that the addition of AC-LUT maintains heme structure, thereby enhancing meat color stability. In addition, the inhibition of denaturing aggregation of Mb by AC-LUT was also observed by atomic force microscopy. In conclusion, the addition of AC-LUT improved meat color stability and provided a safe and simple new strategy to protect meat color.

研究领域: 食品科学 · 肉类科学 · 生物化学 · 氧化稳定性
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ENVIRONMENT INTERNATIONAL · 2026 · IF 10.2

Trimethyltin chloride triggers ferroptosis in myocardial injury: mitochondria-dependent protection by luteolin

Pengyu Wang,Xia Zhang,Ning Ding,Aimei Liu,Shuo Zhang,Yan Song,Leiming Yang,Huiting He,Mi Chen,Xiying Guo,Youzhi Zhang

Trimethyltin chloride (TMT), a poison from water and soil, has been linked to bradycardia. Ferroptosis, an iron-driven type of regulated cell death, is critically involved in cardiovascular diseases. However, the mechanism of TMT-induced myocardial injury remains unclear. This study aims to investigate the toxicological mechanism of TMT-induced myocardial injury and evaluate the protective effect of Lut. In this study , RNA sequencing identified Gpx4 as the key ferroptosis-related gene of TMT-induced cardiomyopathy. In vitro , TMT induced ferroptosis, which was reversed by Ferrostatin-1. Notably, TMT also suppressed mitophagy, co-treatment with chloroquine (CQ) aggravated TMT-induced ferroptosis, whereas Urothione A reversed this effect. In vivo and in vitro , TMT caused bradycardia and myocardial ferroptosis, while Luteolin (Lut) exerted anti-ferroptosis effects. Furthermore, TMT increased DRP1 phosphorylation and reduced the expression of mitochondrial fusion and mitophagy proteins, which were restored by Lut. And the anti-ferroptosis effect of Luteolin was abolished by CQ. Collectively, it revealed that TMT induced ferroptosis in vitro and vivo, while Lut alleviated TMT-induced myocardial injury by activating mitophagy, inhibiting ferroptosis, then restoring mitochondrial function.

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PHYTOMEDICINE · 2025 · IF 8.3

Luteolin alleviates estrogen deficiency-induced muscle atrophy via targeting SLC7A11-mediated ferroptosis

Yu Liu,Honglin Chen,Kun Chen,Qi Shang,Feng Lin,Peng Zhang,You Zhang,Weicheng Qin,Huiwen Liu,Weiyu Qiu,Xingda Chen,Yan Gong,Yixuan Jiang,Yuzhuo Zhang,Jiahui He,Wenhua Zhao,Hui Ren,Gengyang Shen,Xiaobing Jiang

Background Skeletal muscle atrophy, which is a debilitating condition exacerbated by estrogen deficiency, lacks effective therapeutic interventions. Although ferroptosis (an iron-dependent form of cell death driven by lipid peroxidation) has emerged as a contributor to muscle degeneration, its regulatory mechanisms remain poorly defined. In this study, we identified luteolin, which is a natural flavonoid, as a potent inhibitor of ferroptosis that mitigates estrogen deficiency-induced muscle atrophy by targeting SLC7A11. Purpose The aim of this study was to investigate the role of ferroptosis in the anti-muscle atrophy effects of luteolin. Methods Via database screening, luteolin was identified as a potential drug for improving muscle atrophy, and the promotion of C2C12 myogenic differentiation by luteolin was detected by using immunofluorescence (IF), quantitative reverse transcription PCR (RT-qPCR) and western blot (WB). The mechanism of luteolin-mediated ferroptosis in muscle atrophy was confirmed by RNA-seq, transmission electron microscopy (TEM), and GSH, MDA, SOD and Fe 2+ assays. Molecular docking, molecular dynamics simulation, surface plasmon resonance (SPR), cellular thermal shift assay (CETSA), drug affinity responsive target stability (DARTS) and siRNA-mediated gene knockout were applied to validate the notion that the mechanism of luteolin treatment of muscle atrophy involves target binding to SLC7A11. In addition, this study confirmed the role of luteolin in ameliorating muscle atrophy via the modulation of the SLC7A11-mediated ferroptosis pathway in vivo . Finally, the effect of luteolin on the myogenic differentiation of HsKMCs was investigated. Results Luteolin promotes myogenic differentiation and significantly inhibits myotube atrophy, with the main mechanism of these effects involving the direct binding of luteolin to the SLC7A11 protein to inhibit the occurrence of ferroptosis. We confirmed that luteolin can inhibit ferroptosis in muscle tissue and improve the loss of muscle mass and strength due to muscle atrophy in vivo . In addition, luteolin significantly inhibited myotube atrophy in HsKMCs and promoted their myogenic differentiation by modulating the SLC7A11-mediated ferroptosis. Conclusions Our findings demonstrate that luteolin regulates myogenesis and prevents muscle atrophy ​​through binding to SLC7A11 and subsequently inhibiting ferroptosis. This study elucidates the critical role of the SLC7A11-ferroptosis axis in preserving muscle physiology during atrophy, while identifying luteolin as a therapeutic agent capable of targeting SLC7A11 to suppress ferroptosis and alleviate muscle atrophy.

研究领域: 医学 · 分子生物学 · 药理学
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JOURNAL OF PHYSICAL CHEMISTRY B · 2024 · IF 2.8

Fluorescence Enhancement of Nonemissive Monodeprotonated Luteolin in a Poly(vinyl alcohol) Film

Weili Wang,Yan Liu,Xiaolan Cheng,Qin Yu,Siyu Hou,Jie Zhao,Jian Luo

Solid polymer matrixes can modulate the electronic states of embedded chromophores and have been widely used in flexible optoelectronic and optical materials. Luteolin is one of the most common natural flavonoids, and its neutral and monodeprotonated forms are nonemissive in aqueous solution induced by ultrafast excited-state proton transfer (ESPT) followed by nonradiative relaxation. In this study, we have incorporated luteolin into poly(vinyl alcohol) (PVA) films and studied their fluorescence behaviors. Neutral and one monodeprotonated luteolin coexist in the PVA film. Weak steady-state fluorescence of neutral luteolin peaking at about 440 nm is observed for the first time. In addition, the monodeprotonated luteolin in PVA film exhibits obvious fluorescence peaking at 500 nm, with a fluorescence quantum yield of as high as 0.4 and a fluorescence lifetime of as long as 2.4 ns. Time-dependent density functional theory calculations have determined that the ESPT of neutral luteolin is barrierless but that of monodeprotonated luteolin needs to surmount a barrier, explaining their distinct emission properties. These results indicate the modulation ability of the PVA film in both ground-state deprotonation and ESPT, broadening the application areas of the solid polymer matrix.

研究领域: 材料科学 · 光化学 · 植物化学
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