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JOURNAL OF CONTROLLED RELEASE · 2023 · IF 10.8

Inducing in situ M2 macrophage polarization to promote the repair of bone defects via scaffold-mediated sustained delivery of luteolin

Yan Hu,Lixi Tang,Zheng Wang,Honghan Yan,Xinzeyu Yi,Huimin Wang,Liya Ma,Changying Yang,Jiabing Ran,Aixi Yu

Immunoregulation mediated bone tissue engineering (BTE) has demonstrated huge potential in promoting repair of critical-size bone defects (CSBDs). The trade-off between stable immunoregulation function and extended immunoregulation period has posed a great challenge to this strategy. Here, we reported a 3D porous biodegradable Poly(HEMA- co -3APBA)/LUT scaffold, in which reversible boronic acid ester bond was formed between the 3APBA moiety and the catechol moiety of luteolin (LUT). The boronic acid ester bond not only protected the bioactivity of LUT but also extended the release period of LUT. The rationale behind the phenomenon of sustained LUT release was explained using a classical transition state theory. In vitro/in vivo assays proved the immunoregulation function of the scaffold in inducing M 2 polarization of both M 0 and M 1 M φ . The crosstalk between the scaffold treated Raw 264.7 and BMSCs were also investigated through the in vitro co-culture assay. The results demonstrated that the scaffold could induce immunoregulation mediated osteogenic differentiation of BMSCs. In addition, CSBDs model of SD rats was also applied, and the corresponding data proved that the scaffold could accelerate new bone formation, therefore promoting repair of CSBDs. The as-prepared scaffold might be a promising candidate for repair of CSBDs in the future.

CAS / MDL: 52628-03-2
研究领域: 生物医学工程 · 组织工程 · 材料科学 · 免疫学 · 骨再生
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TOXICON · 2023 · IF 2.8

Integrating network pharmacology and experimental validation to explore the mechanisms of luteolin in alleviating fumonisin B1–induced intestinal inflammatory injury

Defeng Wen,Wantong Han,Quan Chen,Guanhui Qi,Mengling Gao,Pu Guo,Yu Liu,Zhongyuan Wu,Shulin Fu,Qirong Lu,Yinsheng Qiu

Contamination with fumonisin B1 (FB1) represents a global health problem. FB1 exposure may also trigger intestinal injury by activating inflammatory responses, leading to a reduction in production performance and economic benefits. However, the mechanism of FB1-induced intestinal inflammatory injury is still unclear. At the same time, it is urgent to develop antibiotic alternatives and therapeutic targets to alleviate antibiotic resistance and to ensure effective treatment of intestinal inflammatory injury. We combined network pharmacology and in vitro experiments to explore the core therapeutic targets and potential mechanism of luteolin in FB1-induced intestinal inflammatory injury. Network pharmacology and molecular docking revealed that nuclear factor kappa B (NF-κB) p65, extracellular signal-regulated kinase (ERK), interleukin 6 (IL-6) and IL-1β are the important targets, and the NF-κB and ERK signalling pathways are critical in FB1-induced intestinal inflammatory injury. Besides, in vitro experiments further demonstrated that luteolin can inhibit FB1-induced intestinal inflammatory injury by inhibiting activation of the NF-κB and ERK signalling pathways and reducing the expression of IL-6 and IL-1β in IPEC-J2 cells. We have comprehensively illustrated the potential targets and molecular mechanism by which luteolin can alleviate FB1-induced intestinal inflammatory injury. Luteolin may be an effective antibiotic alternative to prevent intestinal inflammatory injury.

CAS / MDL: 116355-83-0 491-70-3
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Immunity Inflammation and Disease · 2023 ·Vol. 11 ·期 4 ·e820 · IF 3.2

Luteolin suppresses inflammation and oxidative stress in chronic obstructive pulmonary disease through inhibition of the NOX4-mediated NF-κB signaling pathway

Mingfei Li,Huifang Wang,Yun Lu,Jinwen Cai

Introduction Chronic obstructive pulmonary disease (COPD) is associated with chronic inflammation that predominantly affects the lung and peripheral airways. Previous investigation has underlined the efficacy of luteolin in the treatment of inflammation-related symptoms. Accordingly, our study concentrates on unveiling the effect of luteolin on COPD. Methods Mice or A549 cells were treated with cigarette smoke (CS) to establish COPD models in vivo and in vitro. Then, the serum and bronchoalveolar lavage fluid of mice were harvested. The lung tissues of mice were subjected to hematoxylin-eosin staining to observe the degree of damage. The inflammation and oxidative stress factors level were calculated via enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction. The expressions of nuclear factor-kappa B (NF-κB) pathway-related factors were detected by Western blot. Results In in vivo experiments, CS treatment reduced the weight of mice and promoted lung tissue damage, while luteolin attenuated the effect of CS on the mice. Moreover, luteolin inhibited the inflammation factors level, oxidative stress, and NADPH oxidase 4 (NOX4)-mediated NF-κB signaling pathway in CS-induced COPD mice. Similar results were obtained in in vitro experiments that luteolin alleviated CS-induced inflammation, oxidative stress, and NOX4-mediated NF-κB signaling pathway activation in CS-treated A549 cells. Besides, NOX4 overexpression offset the impacts of luteolin on the CS-induced A549 cells. Conclusion Luteolin alleviates inflammation and oxidative stress in COPD via NOX4-mediated NF-κB signaling pathway, which provides a theoretical basis for the treatment of COPD with luteolin.

研究领域: 药理学 · 肺病学 · 分子生物学
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY · 2026 · IF 6.7

Green Extraction of Luteolin from Chrysanthemi Indici Flos Using Deep Eutectic Solvents: Mechanistic Insights, Antioxidant Activities, and Synergistic α-Glucosidase Inhibition

Xueying Hu,Yue Sun,Junyu Zhou,Khitab Ur Rahman,Xuan Tang,Yueyuan Chen,Zhifang Cui

Luteolin, a flavonoid, exhibits inhibitory activity against α-glucosidase, an enzyme target relevant to glycemic regulation. This study reports the development of a green extraction process employing deep eutectic solvents (DESs). From a COSMO-SAC (Conductor-like Screening Model for Segment Activity Coefficient)-based screening of 128 candidate DESs, choline chloride/1,4-butanediol was identified as the optimal solvent and experimentally validated. Response surface optimization yielded a maximum luteolin yield of 1.394 mg/g under conditions of 40 mL/g liquid-to-solid ratio, 30% water content, 48 °C, and 30 min, representing 1.37- and 1.34-fold yields of methanol and ethanol, respectively. Molecular dynamic simulations indicated that electrostatic interactions predominantly govern extraction efficiency. Greenness metrics (Modified Green Analytical Procedure Index (MoGAPI) and Analytical GREEnness calculator (AGREE)) confirmed favorable sustainability. The extract displayed notable antioxidant capacity and mixed-type inhibition of α-glucosidase with synergistic potentiation of acarbose. These findings support sustainable luteolin extraction and its further investigation in postprandial glycemic regulation.

CAS / MDL: 491-70-3
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LIFE SCIENCES · 2026 · IF 6.4

Targeting the AMPK/ACC pathway with luteolin suppresses de novo lipogenesis and limits tumor burden in a MASH-HCC mouse model

Gaoxuan Shao,Chenceng Sun,Chenhao Ye,Ying Liu,Jiashu Pan,Yujing Liu,Lu Lu,Lei Wang,Zemin Lin,Fan Yang,Guang Ji,Hanchen Xu

Luteolin significantly reduces tumor burden and fibrosis in a MASH-HCC mouse model. • Luteolin attenuates hepatic lipid accumulation by inhibiting de novo lipogenesis. • The protective effects of luteolin are mediated via the AMPK/ACC signaling pathway. • Inhibition of AMPK abolishes the lipid-lowering benefits of luteolin in hepatocytes. Aims Metabolic dysfunction-associated steatohepatitis (MASH) is a primary driver of hepatocellular carcinoma (HCC), yet effective therapeutic interventions remain limited. While luteolin is known for its anti-inflammatory properties, its efficacy and underlying mechanism in the MASH-HCC transition are not fully understood. This study investigated the protective effects of luteolin against MASH-HCC and the role of the AMPK/ACC signaling pathway in this process. Materials and methods In vivo , a MASH-HCC mouse model was established using diethylnitrosamine (DEN) combined with a high-fat, high-cholesterol (HFHC) diet. Mice were treated with vehicle or luteolin (50 or 100 mg/kg) for 26 weeks. Progression was monitored via serum alpha-fetoprotein (AFP), histological analysis, and Western blotting. In vitro , HepG2 and Huh-7 cells were challenged with cholesterol and treated with luteolin. The AMPK inhibitor BAY-3827 was employed to verify whether the metabolic benefits of luteolin were pathway-dependent. Key findings Luteolin treatment significantly reduced tumor burden, lowered serum AFP levels, and attenuated hepatic lipid accumulation and fibrosis in MASH-HCC mice. In vitro results mirrored these findings, showing that luteolin reduced cholesterol-induced lipid loading. Mechanistically, luteolin increased the phosphorylation of AMPK and its downstream target, ACC. Furthermore, pharmacological inhibition of AMPK with BAY-3827 abolished the lipid-lowering effects of luteolin in hepatic cells, confirming that its therapeutic benefits are mediated through AMPK activation. Significance Luteolin suppresses the progression of MASH to HCC by activating the AMPK/ACC signaling pathway and subsequently inhibiting de novo lipogenesis. These findings highlight luteolin as a promising potential therapeutic candidate for the prevention and treatment of MASH-related liver cancer. Download: Download high-res image (314KB) Download: Download full-size image

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POULTRY SCIENCE · 2026 · IF 4.5

Targeted intestinal delivery of luteolin microcapsules as a precision nutritional strategy to alleviate heat stress and enhance growth performance in broilers

Xubin Du,Dong Zhao,Junjun Yuan,Chengjie Wang,Hongbing Gui,Moolchand Malhi,Jamila Soomro,Yong-Hao Ma,Minghui Wu,Fei Liu,Yanke Shan

Heat stress ( HS ) poses a significant threat to poultry production by impairing the growth and health of broilers. Luteolin ( Lut ) is a natural flavonoid with potent antioxidant properties. In vitro , Lut mitigated HS-induced oxidative injury and reactive oxygen species accumulation, decreased p38 MAPK phosphorylation, and downregulated Hsp70 expression. To improve its delivery, pH‑dependent spray‑dried microcapsules were engineered using tributyrin as a functional carrier. A 30-day oral toxicity study in mice confirmed the safety of Lut microcapsules at doses up to 10 g/kg/day. The efficacy of Lut microcapsules was then evaluated in broilers subjected to HS. Dietary supplementation with Lut microcapsules significantly increased average daily feed intake and average daily gain, while significantly reducing the feed/gain ratio compared with the HS group. In addition, Lut microcapsules alleviated metabolic disturbances and multi-organ histopathological damage. Lut microcapsules also reduced hepatic p38 MAPK phosphorylation and lowered Hsp70 and Hsp90 expression. However, because the in vivo study did not include Lut‑only or tributyrin‑only control groups, despite the convincing in vitro work it is not possible to definitively attribute the responses noted to Lut alone. Collectively, these findings suggest that Lut microcapsules may improve growth performance and heat tolerance in broilers. Therefore, the Lut microcapsule formulation shows potential as a feed supplement to mitigate heat stress‑related losses in broilers.

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Nutrients · 2025 ·Vol. 17 ·期 22 ·3607 · IF 5

Luteolin Alleviates Vascular Senescence Through Retinoic Acid–Peroxisome Proliferator-Activated Receptor Signaling and Lipid Metabolism Remodeling Combined with Multi-Omics Analysis

Huasong Bai,Hongchen Jin,Tong Liu,Yulong Yin,Hengyan Wang,Siyu Ruan,Yunliang Li,Zhanzhong Wang

Background:Although luteolin (Lut) is well recognized for its anti-inflammatory and antioxidant effects, its potential role in preventing vascular senescence remains underexplored in primary vascular aging. This study aimed to investigate the anti-vascular-aging effects of Lut in both cellular and murine aging models and to elucidate its conserved molecular mechanisms across species.Methods:Canine and feline vascular endothelial cells (cVECs and fVECs) were subjected to doxorubicin-induced senescence, while senescence-accelerated mice prone 8 (SAMP8) received an 8-week dietary supplementation with Lut. Senescence markers, inflammatory cytokines, antioxidant activities, vascular biomechanics, and histological changes were assessed. Transcriptomic and metabolomic analyses were combined to identify molecular pathways. Statistical significance was determined by one-way analysis of variance with Tukey’s or Games–Howell post hoc tests (p< 0.05).Results:Lut markedly reduced senescence-associated β-galactosidase activity, suppressed interleukin-6 and matrix metalloproteinase expression (p< 0.05), and enhanced superoxide dismutase activity and nicotinamide adenine dinucleotide levels (p< 0.05) in cVECs, fVECs, and SAMP8 sera. In aged mice, Lut alleviated arterial wall thickening and vascular inflammation, improved vascular biomechanics and systemic oxygenation (p< 0.05), and attenuated cardiac and hepatic inflammatory infiltration. Multi-omics analyses in cVECs revealed that Lut targets aldehyde dehydrogenase 1 to increase 9-cis retinoic acid, thereby activating the retinol X receptor–peroxisome proliferator-activated receptor (PPAR) network, which accelerates lipid clearance and oxidation. Consistent activation of this pathway was validated in murine vascular transcriptomes.Conclusions:These findings demonstrate that Lut delays vascular aging by activating the retinoic acid–PPAR axis and reprogramming lipid metabolism. This conserved mechanism was consistently observed in doxorubicin-induced cVEC senescence and the SAMP8 model, underscoring the robustness of Lut’s action across distinct contexts of vascular aging.

CAS / MDL: 25316-40-9
研究领域: 衰老生物学 · 心血管研究 · 分子药理学 · 代谢组学 · 转录组学 · 营养生物化学
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Food Bioscience · 2025 · IF 5.9

Protective effect of covalently coupled polyphenols on hydroxyl radical-damaged potato protein isolate: laccase-mediated functional modification of resveratrol and luteolin

Yushun Chen,Songyu Wang,Kefan Ouyang,Qin Zhang,Xiaojuan Dai,Xing Hu,Qiang Zhao

Potato protein isolate (PPI) is a major byproduct of potato starch processing, and its effective utilization is of great significance in reducing waste, conserving resources, and promoting environmental sustainability. However, the functional characteristics of PPI, such as solubility and emulsifying properties, are insufficient. This study explores a novel enzymatic strategy that utilizes laccase catalysis to covalently couple PPI with polyphenols (resveratrol, luteolin), aiming to simultaneously enhance the functional properties and antioxidant capacity of PPI. This modification increases the solubility of PPI in the critical acidic pH range (3–5); At low polyphenol levels, the emulsifying activity index increased by 12.4–35.4 %. Importantly, covalent binding of polyphenols provides synergistic antioxidant protection, effectively reducing the levels of protein oxidation markers induced by hydroxyl radicals. This study successfully demonstrated that laccase mediated covalent coupling of polyphenols is an effective means of converting PPI into components with enhanced functionality and strong antioxidant activity, providing an important foundation and promising solution for its application as antioxidants in protein based health food systems.

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Food Bioscience · 2025 · IF 5.9

Novel mechanistic insights into Luteolin and its analogues as potent inhibitors of xanthine oxidase activity: Inhibition thermodynamics, kinetics and docking simulation

Yuanyong Yao,Meng Zhang,Jiarong Chen,Ao Ma,Qi Huang,Jiangzhou Yan,Hai Yang,Shixue Chen

The utilization of potent flavonoid inhibitors for systematically investigating their inhibitory mechanisms on Xanthine oxidase (XOD) offers significant potential for the development of functional foods from a novel perspective. The deprotonation of Luteolin and its analogues into corresponding phenolates has been confirmed as effective inhibitory agents, exhibiting differential effects on superoxide production originating from XOD. However, the Stern-Volmer plots of F 0 / F versus [Q] at various temperatures failed to demonstrate polynomial-linear fitting, instead approaching the X-axis to varying extents, which deviates from the anticipated good linearity. This indicates that the thermodynamics of inhibition may be concentration-dependent. At lower inhibitor concentrations, the formation of the ground-state complex is characterized by static fluorescence quenching within an accessible interaction region, as evidenced by linear-fitting plots. As the concentration increases, inaccessible interactions are observed, indicated by curves in the Stern-Volmer plots that approached the X-axis, suggesting a reduction in fluorescence quenching intensity. Furthermore, in the inhibition kinetics, Luteolin and its analogues exhibit mixed-type inhibition (both non-competitive and competitive) at higher concentrations, contrasting with non-competitive inhibition at lower concentrations. Simultaneously, the binding interaction between the inhibitor and enzyme is validated through synchronous fluorescence analysis and molecular docking simulations. Consequently, this study successfully redefines the novel inhibition mechanism of flavonoids from a new perspective.

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Materials Today Bio · 2025 · IF 10.2

aHSCs-Targeted Bimetallic Nanozymes and Luteolin-Loaded Liposomes: Synergistic Reversal of Liver Fibrosis via Antioxidant, cellular Senescence, and cellular Apoptotic Mechanisms

Zihao Sun,Chuipeng Liang,Yuxin Zhao,Jijiao Wu,Lin Wen,Xiaolian Liu,Mingyi Shi,Xiaofang Li

Liver fibrosis is a prevalent pathological process in the development of a range of chronic liver diseases. Hepatic stellate cells (HSCs) are known to be highly activated in the Liver fbrosis environment, and the proliferation of activated HSCs (aHSCs) and the secretion of associated extracellular matrix are crucial in the process of Liver fibrosis, which in turn promotes the development of Liver fibrosis. Concurrently, the inhibition of HSCs activation and the induction of aHSCs senescence/apoptosis have been identified as a therapeutic strategy that exhibits numerous synergistic mechanisms. In addition, the efficacy of clinical treatment is constrained by a number of factors, including the limited selectivity of pharmaceuticals and the inefficiency of drug delivery mechanisms. Consequently, the present study proposes a Luteolin-loaded liposome (LUT@LIP-BSA) and Ce/Mn bimetallic nanozyme (CMB) dual nanodelivery system, which has been modified by BSA to target aHSCs. The results of both in vitro and in vivo experiments demonstrated that the aHSCs-targeted dual delivery system combining LUT@LIP-BSA with CMB exhibited effective targeting delivery capacity to aHSCs. In vitro, LUT@LIP-BSA effectively induced senescence, apoptosis, and counteracted oxidative stress in aHSCs. These effects were confirmed in vivo. Consequently, this combination reduced extracellular matrix production and deposition, thereby inhibiting liver fibrosis. This combinatorial strategy provides a promising foundation for the construction and clinical application of hybrid delivery systems that synergize metal nanoenzymes with natural drugs as an effective targeted therapeutic approach for liver fibrosis.

研究领域: 纳米医学 · 药理学 · 肝病学 · 生物化学 · 材料科学
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Food & Function · 2022 ·Vol. 13 ·期 6 ·3572-3589 · IF 6.317

6,8-(1,3-Diaminoguanidine) luteolin and its Cr complex show hypoglycemic activities and alter intestinal microbiota composition in type 2 diabetes mice

Xiaodong Ge,Xiaoyu He,Zhenshan Lin,Yuxian Zhu,Xiaoqin Jiang,Liyuan Zhao,Feng Zeng,Ligen Chen,Wei Xu,Tingting Liu,Zhigang Chen,Chao Zhao,Ying Huang,Bin Liu

Flavonoid compounds such as luteolin exhibit hypolipidemic effects, and there are few reports on the hypoglycemic activity of luteolin derivatives. In this research, 6,8-(1,3-diaminoguanidine) luteolin (DAGL) and its Cr complex (DAGL·Cr) were obtained as a result of structural modifications to luteolin, and the hypoglycemic activities and the composition of intestinal microbiota in T2DM mice were investigated. This study found that DAGL and DAGL·Cr could significantly restore body weight, FBG, OGTT, AUC, and GSP in T2DM mice. Moreover, the pancreatic islet function index and the biochemical indicators of serum and the liver were also significantly improved. The histopathological results also showed that DAGL and DAGL·Cr had a stronger repair ability in the liver and the pancreas. It was also revealed that the potential hypoglycemic mechanism of DAGL and DAGL·Cr was involved in the simultaneous regulation of PI3K/AKT-1/GSK-3β/GLUT-4 and PI3K/AKT-1/mTOR/S6K1/IRS-1. Furthermore, DAGL and DAGL·Cr could also regulate the structure of the intestinal microbiota and increase the content of SCFA to relieve the symptoms of hyperglycemia in T2DM mice. This included a significant reduction in the ratio of Firmicutes and Bacteroidetes (F/B), and at the genus level, an increase in the relative abundance of Alistipe and Ruminiclostridium, and improvement in the content of SCFA in the feces of T2DM mice. In conclusion, in this study, DAGL and DAGL·Cr were found to improve hyperglycemia in T2DM mice by improving the pancreatic islet function index, regulating the biochemical indicators of serum and the liver, repairing damaged tissues, and regulating the PI3K/AKT-1 signaling pathway as well as reducing F/B, increasing the relative abundance of intestinal beneficial microbiota, and the content of SCFA in the feces. The hypoglycemic effect of DAGL·Cr on the body weight, serum IL-10, serum IL-6, and pancreatic islet function index was significantly better than that of DAGL.

研究领域: 药理学 · 糖尿病研究 · 微生物学 · 分子生物学
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MICROCHEMICAL JOURNAL · 2021 · IF 4.821

A novel nanozyme comprised of electro-synthesized molecularly imprinted conducting PEDOT nanocomposite with graphene-like MoS2 for electrochemical sensing of luteolin

Xinyu Lu,Yingying Li,Xuemin Duan,Yifu Zhu,Ting Xue,Liangmei Rao,Yangping Wen,Qingyun Tian,Yue Cai,Quan Xu,Jingkun Xu

A novel nanozyme sensor based on the electro-synthesized molecularly imprinted conducting poly(3,4-ethylenedioxythiophene) (PEDOT) nanocomposite with graphene-like two-dimensional layered molybdenum disulfide (MoS 2 ) was successfully prepared for electrochemical detection and analysis of luteolin in Gnaphalium affine. MoS 2 -MIPs were prepared facilely by electrochemical polymerization of monomer 3,4-ethylenedioxythiophene in the presence of both modifier MoS 2 and template molecule luteolin that can change the morphological structure and specific surface area of PEDOT, enhance electronic conductivity of MoS 2 , and improve the recognition capability and electrocatalytic capacity of electrode interface. The morphological structure of MoS 2 -MIPs was characterized by SEM, and its electrochemical performance and sensing parameters were investigated by voltammetry. The electrochemical response of luteolin was recorded by MoS 2 -MIPs in the linear concentration range from 3 × 10 -7 to 3 × 10 -5 Μ with limit of detection of 0.04 μΜ under the optimal conditions, which was successfully employed for electrochemically detecting luteolin in Gnaphalium affine with acceptable recoveries in comparison with high-performance liquid chromatography. This will provide a new nanozyme sensing platform comprised of electro-synthesized molecularly imprinted conducting polymers and graphene-like two-dimensional layered nanomaterials.

研究领域: 分析化学 · 材料科学 · 电化学
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