Pharmaceutics
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2026
·Vol. 18
·期 1
·98
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IF 5.5
Jingjing Wang,Rui Ni,Ziwei Li,Jianhong Chen,Yao Liu
Background/Objectives:Wound healing represents a pervasive and urgent clinical challenge. Hard-to-heal chronic wounds are frequently complicated by infections, inflammatory responses, and oxidative stress. Currently, wound dressings are broadly categorized into dry and moist types, with moist wound dressings for chronic wounds accounting for approximately 70% of market revenue. Recently, adipose-derived stem cells (ADSCs), which possess self-renewal and multi-lineage differentiation capabilities, have emerged as a promising strategy for promoting tissue regeneration and wound repair.Methods:In this study, we developed a novel luteolin nanoparticle–ADSCs composite hydrogel (GelCA@LUT@ADSCs). This system was constructed by first encapsulating ADSCs within a chitosan/alginate hydrogel (GelCA), followed by coating the hydrogel with luteolin-loaded nanoparticles (LUT@NPs).Results:The sustained release of LUT@NPs from the hydrogel modulates the wound microenvironment, enhancing the pro-healing functions of ADSCs at the wound site. The GelCA hydrogel exhibited excellent biocompatibility. Both in vitro and in vivo results demonstrated that GelCA@LUT@ADSCs treatment effectively reduced inflammation, promoted angiogenesis and collagen deposition, stimulated cell proliferation and migration, and polarized macrophages toward an anti-inflammatory, pro-healing M2phenotype, thereby accelerating wound healing.Conclusions:Overall, this innovative therapeutic approach provides a novel strategy for wound management through a synergistic division of labor between pharmaceutical agents and stem cells.
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BIOORGANIC CHEMISTRY
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2026
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IF 5.1
Xianying Fang,Wenhui Zhu,Lanxin Lu,Lulu Wu,Yufeng Zhang,Suxiang Liu,Wuyang Huang,Linguo Zhao
With the increasing popularity of olive oil, the cultivation area of Olea europaea L. (olive) trees has been expanding, and the processing and utilization of olive leaves are gaining more attention. Besides oleuropein, the main active compounds in olive leaves include luteolin and its glycosides. Through fractionation, a component rich in key active substances, designated OLE, was prepared from olive leaves. Our activity analysis showed that luteolin exhibits excellent DPPH radical scavenging and higher anti-inflammatory activities compared to its glycosides. To enhance the activity of OLE, a glycosidase Bbxyl was screened, identified and used to catalyze OLE. Luteolin-5- O -glucoside, luteolin-7- O -glucoside, luteolin-4’- O -glucoside, and luteolin-3’- O -glucoside in OLE were hydrolyzed into luteolin with a conversion rate of 94%. OLE hydrolyzed by Bbxyl (OLEB), with a luteolin content of approximately 5.93 mg/g, was obtained through macroporous resin purification. The anti-inflammatory activity mediated by macrophages and T cells of OLEB was increased by 51% and 39%, respectively. In a DSS-induced mouse colitis model, OLEB significantly alleviated intestinal inflammation symptoms, promoted weight recovery, reduced spleen swelling, restored colon length, repaired the intestinal epithelial barrier, decreased the oxidative and inflammatory levels, outperforming both the positive control drug 5-ASA and OLE. The primary mechanism of action likely involves components such as luteolin in OLEB inhibiting the release of inflammatory factors by blocking the TLR4-NF-κB/AHR pathway, thereby mitigating pathological damage in the colon. This study provides an innovative processing approach for the development of high-value olive leaf products with enhanced anti-inflammatory activity and intestinal health-protective functions.
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AQUACULTURE
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2026
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IF 4.4
Songlin Luo,Fansheng Zeng,Guohao Chen,Shunqiang Wei,Chushun Yi,Xuemin Wei,Yinghui Wang,Aiguo Huang
White Spot Syndrome Virus (WSSV) is a major viral pathogen severely threatening crustacean aquaculture. Although natural products possess antiviral potential, their application remains limited due to stability and utilization constraints. This study employed a self-assembly strategy to construct a natural product-based metal-organic nanostructure of luteolin-loaded magnesium-gallic acid (Mg-GA) metal-organic framework (LM), to enhance the anti-WSSV efficacy of luteolin. Results indicate that the prepared LM exhibits a regular prismatic nanostructure with uniform particle size distribution, stable coordination structure, and good biocompatibility. In vivo experiments demonstrated that compared to single luteolin or Mg-GA treatment groups, LM significantly reduced WSSV viral copy numbers in infected crayfish Procambarus clarkii and markedly improved host survival rates. Gene expression analysis revealed that this self-assembled nanomaterial significantly downregulated expression of key viral genes IE1 , DNApol , and VP28 , while upregulating host antioxidant-related genes CAT and SOD , apoptosis-regulating genes BI-1 , and downregulating apoptosis-regulating genes BAX , inflammation-related genes COX1 and COX2 . This indicates its ability to synergistically inhibit viral replication and enhance host defense capabilities. Histopathological results further confirmed that LM effectively alleviated pathological damage caused by WSSV to gill and intestinal tissues, with no apparent toxicity observed in healthy individuals. In summary, the self-assembled natural product metal-organic nanostructure significantly enhances the anti-WSSV efficacy of single compounds, offering a novel nanostrategy for controlling viral diseases in aquaculture.
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Journal of Translational Medicine
·
2026
·Vol. 24
·期 1
·335
·
IF 9.7
Li Tong,Li Yifei,Gao Jiaxiang,Ma Ruichen,Peng Yue,Zhang Qidong,Chen Yingzhi,Wang Weiguo
Background Steroid-induced osteonecrosis of the femoral head (SONFH) lacks effective early-stage interventions, and its systemic drivers remain incompletely defined. Luteolin (Lut) is reported to be protective, but the in vivo mechanism is unclear. We investigated whether Lut acts through a gut microbiota–metabolite–innate immunity axis in SONFH. Methods Male Sprague–Dawley rats underwent SONFH induction using lipopolysaccharide plus methylprednisolone and received oral Lut or L-Carnitine; gut microbiota dependence was examined using a four-antibiotic depletion regimen. Femoral heads were evaluated by histology and micro-computed tomography. Mechanisms were interrogated by integrated 16S rRNA profiling, untargeted serum Liquid Chromatography–Mass Spectrometry metabolomics, and femoral-head transcriptomics. Dexamethasone (Dex)-injuried ROS17/2.8 osteoblasts and HMEC-1 endothelial cells were used for functional validation, and IFIH1 was silenced by shRNA to test pathway necessity. Results Lut preserved trabecular microarchitecture and reduced empty osteocyte lacunae in vivo, yet minimally rescued Dex-injured osteoblasts and endothelial cells, indicating an indirect mechanism mediated by gut microbiota-derived metabolic changes. Microbiota depletion abolished Lut’s in vivo benefit, establishing microbiota dependence. Metabolomics identified an increase in circulating L-Carnitine that correlated with four bacterial genera. Exogenous L-Carnitine restored cell proliferation, reduced apoptosis, and improved endothelial tube formation, and in vivo improved trabecular indices while lowering inflammatory cytokines (IL-1β, IL-6, TNF-α). Integrated multi-omics highlighted an interferon-stimulated gene module (OAS1A, HERC6, IFIH1, IFI44), with IFIH1 most strongly associated with disease severity. L-Carnitine attenuated Dex-induced IFIH1 expression, and IFIH1 knockdown mimicked L-Carnitine and eliminated its additional anti-inflammatory effect. Conclusions Lut alleviates SONFH via gut microbiota-driven elevation of L-Carnitine, which constrains IFIH1 expression and inflammation to preserve femoral-head trabecular microarchitecture. Targeting the microbiota–L-Carnitine–IFIH1 axis may enable mechanism-based early intervention strategies for SONFH.
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Food Bioscience
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2025
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IF 5.9
Siting Wei,Youdan Ning,Deming Gong,Peng Zhang,Guowen Zhang,Xing Hu
Excessive inflammatory response is an important cause of various diseases. Toll-like receptor 4 (TLR4), a central innate immune receptor, represents a promising target for treating inflammatory diseases. Therefore, the search for natural inhibitors of TLR4 is essential for the prevention and treatment of inflammatory diseases. Luteolin (Lut), a dietary flavonoid with significant anti-inflammatory effects, is a highly promising functional food ingredient. Through integrated spectroscopic characterization and computational simulations, the molecular interaction dynamics between Lut and TLR4 were elucidated in this work. It was found that Lut exhibited concentration-dependent TLR4 fluorescence quenching through static quenching, forming a stable complex spontaneously, speculating that it may bind to the amino acid residues Arg264, Tyr292, Asp294 and Thr319 in TLR4 mainly through electrostatic and hydrogen-bonding interactions. Lut decreased the content of α-helix of TLR4, increased the content of random coil, and decreased its protein compactness and structural instability, thereby inhibiting TLR4 activation. The binding constant between the mutant protein and Lut was significantly decreased by alanine mutagenesis, confirming that Arg264 and Tyr292 are critical residues for the interaction between Lut and TLR4. These findings revealed the molecular mechanism by which Lut regulated the conformational changes of TLR4 and inhibited its activation, providing an important theoretical foundation for exploiting Lut as a natural TLR4-targeted therapeutic agent.
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INDUSTRIAL CROPS AND PRODUCTS
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2025
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IF 6.2
Siwen Zhang,Liwei Niu,Xiaoyu Si,Lulu Li,Zunlai Sheng
Peanut shells, a byproduct of peanut cultivation, have limited uses but contain bioactive compounds like luteolin, a flavonoid with antioxidant, antibacterial, and anti-inflammatory properties. This study employed microwave-assisted extraction (MAE) technology combined with Natural Deep Eutectic Solvents (NADESs) to enhance the extraction process and clarify the underlying mechanisms. The most effective NADES, composed of choline chloride and ethylene glycol, was employed. Single-factor experiments assessed the effects of microwave time, power, and liquid-solid ratio on luteolin extraction. Following this, response surface methodology (RSM) and artificial neural network-genetic algorithm (ANN-GA) were applied for further optimization. The optimal extraction conditions were identified as 92 s of microwave time, 601 W of power, and a liquid-solid ratio of 32 mL/g, yielding a maximum luteolin extraction of 2.90 ± 0.02 mg/g. The ANN-GA and RSM models showed strong agreement with experimental values, with correlation percentages of 99.66 % and 98.95 %, respectively, indicating their reliability for optimizing extraction. Additionally, using the Conductor-like Screening Model for Real Solvents (COSMO-RS), quantum chemical calculations revealed that luteolin had the lowest logarithm of the infinite dilution activity coefficient (-16.43) and the most negative intermolecular interaction energy (-87.82 kJ/mol) in the NADES. These findings were consistent with validation test results, confirming the effectiveness of the NADES-MAE technology for luteolin extraction.
研究领域:
食品科学
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化学工程
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JOURNAL OF HAZARDOUS MATERIALS
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2025
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IF 11.3
Cheng Tan,Chunyang Kang,Pan Liu,Yajuan Sun,Hui Jin
The neurotoxicological consequences of chronic exposure to polystyrene nanoplastics (PSNPs) at environmentally relevant concentrations remain poorly understood, particularly their impact on hippocampal neurons dysfunction. In this study, a mouse model co-exposed to PSNPs and/or luteolin (LUT) was replicated by intraperitoneal injection to investigate the mechanism and effective treatment of PSNPs induced striatal neurodegeneration. Here, we elucidated that PSNPs exposure induced striatal injury characterized by neuronal disorganization and mitochondrial dysfunction in vivo and in vitro. Notably, PSNPs triggered oxidative dysregulation and iron accumulation by enhancing antioxidant enzyme activity and suppressing lipid peroxidation, leading to ferroptosis and neuroinflammation. Additionally, PSNPs exposure induced a decrease in glycolysis and tricarboxylic acid (TCA) cycle imbalance by disrupting G6PD/glutathione-dependent pathway, leading to an imbalance in cellular energy metabolism. Our findings highlighted the role of the Piezo1/CaN/NFAT1 axis in PSNPs-induced ER Ca 2 + homeostasis imbalance, which was effectively inhibited by LUT. Notably, LUT alleviated the susceptibility to striatal ferroptosis induced by PSNPs via the G6PD/glutathione axis. Collectively, our study provides critical insights into the neurotoxic mechanisms of PSNPs and establishes LUT as a agent against PSNPs-induced neurodegeneration. These findings underscore the urgent need for environmental regulation of nanoplastics and offer potential strategies for combating their health effects.
研究领域:
神经毒理学
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环境科学
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药理学
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CHEMICAL ENGINEERING JOURNAL
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2025
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IF 13.2
Wenli Shi,Ruimin Ran,Xin Guo,Linjing He,Guoying Li
Despite its important role in reducing food waste and global hunger, preservation films exhibit poor environmental sustainability, mechanical protection and freshness-preserving capabilities. Herein, we proposed a sustainable in-situ rapid gelation strategy for fruit preservation. The core strategy involves sequentially encapsulating the natural antimicrobial and antioxidant luteolin (Lut) within liposome (Lip) and chitosan (CS) outer shell to construct core-double-shell structured nanoparticles. The outer shell confers excellent interfacial compatibility between Lut@Lip (LUL) and the CS substrate. Finally, rapid deprotonation cross-linking (70 s) forms a dense, porous gel structure. Lut was stably incorporated into the phospholipid bilayer of Lip through hydrophobic and hydrogen bonding interactions. This complex retained Lut's biological activity and the carrier advantages of Lip, demonstrating excellent physical stability, controlled release, antioxidant capacity (DPPH scavenging rate: 92.5 %; ABTS scavenging rate: 96.2 %), and favorable antibacterial properties. Density functional theory studies revealed that Lut achieved highly efficient electron transfer through the lowest HOMO-LUMO gap (ΔE = 2.6136 eV), playing a key role in antioxidant activity. Benefiting from the symbiotic reinforcement of LUL and CS, the gel coating demonstrated excellent water vapor and UV barrier properties, antifungal activity ( Botrytis cinerea inhibition rate: 86.9 %), and mechanical protection (reducing impact damage to cherries by 48.3 %). Cherries preservation experiment further validated the effectiveness of this gel coating. Under room temperature conditions (26–28 °C), the gel coating extended cherry shelf life by two-fold through reducing weight loss, preventing nutrient depletion, and inhibiting microbial growth. Additionally, compared to PE film, it reduced spoilage rates, carbon emissions, and costs by 63.6 %, 63.9 %, and 63.1 %, respectively, and achieved soil degradation within 21 days. This low-cost in-situ gelation technology offers a consumer-safe and scalable solution to reduce food waste, advance sustainable packaging, and alleviate plastic pollution.
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APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY
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2025
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IF 3.3
Gahlot Himanshi,Kang Sun Chul
Synergistic therapy is unwaveringly developing as a potential approach to enhance the effectiveness of anticancer medications in chemotherapy. Incorporating adjuvants alongside conventional anticancer medications has demonstrated selective cytotoxicity toward cancer cells while mitigating adverse effects such as DNA damage and systemic toxicity in normal cells. The extended use of 5-FU, a synthetic medicine used in chemotherapy, has many adverse effects, which limit its long-term use in clinical settings. Numerous investigations have demonstrated that luteolin exhibits anticancer effects and alleviates inflammation in mammalian cells. In this study, we provide the first experimental evidence of the synergistic interaction between luteolin and 5-FU in murine melanoma (B16F10) cells, compared to monotherapies (luteolin and 5-FU alone). Using MTT assay for cell viability, flow cytometry for cell cycle analysis, and Western blotting for apoptosis markers, we demonstrate that simultaneous exposure to luteolin and 5-FU speeds up oxidative stress and enhances the production of endogenous ROS. The combination therapy induced the G1-phase cell cycle arrest (65.39%) and decreased the cell viability of B16F10 cells to 34.6%. This, in turn, activates the DNA damage response and initiates the apoptotic pathway by suppressing autophagy and the DNA repair system. Further, the co-treatment of luteolin and 5-FU significantly decreases the mitochondrial membrane potential and reduces ATP production. The results indicate that the combination of luteolin and 5-FU may improve treatment efficacy while potentially decreasing the necessary dosage of 5-FU, therefore reducing its toxicity in clinical settings.
研究领域:
肿瘤学
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药理学
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生物化学
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细胞生物学
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分子生物学
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Frontiers in Pharmacology
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2025
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IF 4.8
Jihong Bi,Yan Li,Lin Lu,Tingting Yin,Shaohua Mao,Run Zhang,Juan He,Xing Ni,Kai Wang,Jirui Bi
Objective: To investigate the protective effects of luteolin on ALI induced by lipopolysaccharide (LPS) in male mice and to explore the underlying mechanisms.Methods: A two-sample Mendelian randomization (MR) analysis was conducted to assess the causal relationship between hepatocyte growth factor (HGF) and acute respiratory distress syndrome (ARDS). Network pharmacology analysis was employed to identify herbs that mitigate inflammation and apoptosis by upregulating HGF expression and to determine the hub active ingredients. These findings were subsequently validated through in vivo experiments using an LPS-induced ALI mouse model. Lung histopathological examination, enzyme-linked immunosorbent assay, and Western blot analysis were performed to evaluate relevant biomarkers of inflammation and apoptosis.Results: The MR analysis demonstrated a causal effect of HGF on ARDS (IVW: β = −1.120, OR = 0.326, 95% CI = 0.116–0.916, P = 0.033). Among herbs associated with upregulating HGF expression, Salvia miltiorrhiza Bunge is involved in the negative regulation of apoptotic process and positive regulation of cell population proliferation. Luteolin was identified as the hub active ingredient extracted from S. miltiorrhiza Bunge. In LPS-induced ALI mice, luteolin significantly alleviated histopatholocial damage, inflammation, and apoptosis in the lungs. However, these protective effects were abrogated by c-Met inhibition.Conclusion: Luteolin attenuates inflammation and apoptosis in the lungs of LPS-induced ALI mice via activation of the HGF/c-Met pathway.
研究领域:
免疫学
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分子生物学
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药理学
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呼吸病学
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转化医学
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LWT-FOOD SCIENCE AND TECHNOLOGY
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2024
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IF 6
Zihao Chen,Min Fu,Jun Chen,Guowen Zhang,Ti Li,Qin Geng,Taotao Dai
Molecular docking simulations and multispectral approaches were used to study the non-covalent interactions between β-lactoglobulin (β-LG) and chosen luteolin (Lu), isoorientin (Iso), and cynaroside (Cyn). The fluorescence quenching results demonstrated that Lu, Iso, and Cyn spontaneously formed stable complexes with β-LG through static quenching. Thermodynamic parameters and molecular docking simulations demonstrated that hydrogen bonds were the primary forces driving the interactions between the protein and flavonoids. The binding constants followed the order: β-LG-Lu (2.87 × 10⁴ L/mol) > β-LG-Iso (1.83 × 10⁴ L/mol) > β-LG-Cyn (1.52 × 10⁴ L/mol). Additionally, the C-glycosylated flavonoid (Iso) showed a higher propensity to form hydrogen bonds with β-LG compared to the O-glycosylated flavonoid (Cyn). The results of circular dichroism indicated that the β-LG structure became looser with the introduction of Lu, Iso, and Cyn. Furthermore, the assembly of β-LG-flavonoid complexes decreased the surface hydrophobicity and oil-water interfacial tension of β-LG, improved its foaming and emulsifying capabilities, and protected the antioxidant properties of the flavonoids to a certain extent. This study investigated the interaction mechanisms between flavonoids with different glycosyl types and β-LG, providing insights for the incorporation of suitable flavonoids into dairy products, and offering theoretical perspectives on preserving the antioxidant properties of flavonoids.
研究领域:
食品科学
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分子生物学
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Journal of Integrative Medicine-JIM
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2024
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IF 4.2
Pan Zhai,Xiao-hu Ouyang,Meng-ling Yang,Lan Lin,Jun-yi Li,Yi-ming Li,Xiang Cheng,Rui Zhu,De-sheng Hu
Objective Myocardial ischemia/reperfusion injury (MIRI) is an obstacle to the success of cardiac reperfusion therapy. This study explores whether luteolin can mitigate MIRI by regulating the p53 signaling pathway. Methods Model mice were subjected to a temporary surgical ligation of the left anterior descending coronary artery, and administered luteolin. The myocardial infarct size, myocardial enzyme levels, and cardiac function were measured. Latent targets and signaling pathways were screened using network pharmacology and molecular docking. Then, proteins related to the p53 signaling pathway, apoptosis and oxidative stress were measured. Hypoxia/reoxygenation (HR)-incubated HL1 cells were used to validate the effects of luteolin in vitro. In addition, a p53 agonist and an inhibitor were used to investigate the mechanism. Results Luteolin reduced the myocardial infarcted size and myocardial enzymes, and restored cardiac function in MIRI mice. Network pharmacology identified p53 as a hub target. The bioinformatic analyses showed that luteolin had anti-apoptotic and anti-oxidative properties. Additionally, luteolin halted the activation of p53, and prevented both apoptosis and oxidative stress in myocardial tissue in vivo. Furthermore, luteolin inhibited cell apoptosis, JC-1 monomer formation, and reactive oxygen species elevation in HR-incubated HL1 cells in vitro. Finally, the p53 agonist NSC319726 downregulated the protective attributes of luteolin in the MIRI mouse model, and both luteolin and the p53 inhibitor pifithrin‐α demonstrated a similar therapeutic effect in the MIRI mice. Conclusion Luteolin effectively treats MIRI and may ameliorate myocardial damage by regulating apoptosis and oxidative stress through its targeting of the p53 signaling pathway.
研究领域:
药理学
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心脏病学
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分子生物学
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生物信息学
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