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NARINGENIN
FOOD CHEMISTRY · 2025 · IF 9.8

Naringenin-loaded Flammulina velutipes chitin-glucan complexes gel system: structural modulation and dual lipid-lowering mechanisms

Simin Feng,Shuqi Liang,Jianyu Yang,Jiahao Yu,Yang Lin,Yizhen Xie,Peilong Sun,Ping Shao

This study developed a synergistic lipid-lowering system using chitin-glucan complex (CGC) from Flammulina velutipes through green preparation and structural optimization. Enzyme-alkali treated CGC3 exhibited superior acetylation (47.85 %), crystallinity (42.29 %), and molecular weight (1.848 × 10 6  Da) through partial glucan removal. The derived hydrogel (gel-CGC3) had a dense porous network (density 2.92 ± 0.09 × 10 −3  g/cm 3 ), excellent mechanical stability, and regular pore structure. Ball milling prolonged naringenin (NAR) release to 900 min (87.5 % longer than block hydrogels) without compromising structural integrity. Meanwhile, the microgel conferred multiple functional advantages to the system (includes CGC gel and NAR loaded), and its porous structuring (powder-to-hydrogel transition) and structural refinement ( via microgel conversion) maximized binding site exposure, enhancing adsorption efficiency for cholesterol micelles (12.42 ± 0.73 mg/g), sodium taurocholate (3.91 ± 0.07 mg/g), and sodium glycopyrrolate (3.51 ± 0.07 mg/g) by exposing more binding sites. The system synergistically combines lipid adsorption and biometabolism, underscoring the significance of structure-function synergy in polysaccharide-based platforms for metabolic disorder intervention.

CAS / MDL: 9014-01-1 9001-61-0
研究领域: 食品科学 · 高分子科学 · 药剂学 · 生物技术 · 营养生物化学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY · 2024 · IF 5.7

Naringenin Inhibits Acid Sphingomyelinase-Mediated Membrane Raft Clustering to Reduce NADPH Oxidase Activation and Vascular Inflammation

Meng Ding,Yuan Zhu,Xiaoting Xu,Hui He,Tianyu Jiang,Xiaochuan Mo,Zhuting Wang,Wenfeng Yu,Hailong Ou

Macrophage inflammation and oxidative stress promote atherosclerosis progression. Naringenin is a naturally occurring flavonoid with antiatherosclerotic properties. Here, we elucidated the effects of naringenin on monocyte/macrophage endothelial infiltration and vascular inflammation. We found naringenin inhibited oxidized low-density lipoprotein (oxLDL)-induced pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α toward an M2 macrophage phenotype and inhibited oxLDL-induced TLR4 (Toll-like receptor 4) membrane translocation and downstream NF-κB transcriptional activity. Results from flow cytometric analysis showed that naringenin reduced monocyte/macrophage infiltration in the aorta of high-fat-diet-treated ApoE-deficient mice. The aortic cytokine levels were also inhibited in naringenin-treated mice. Further, we found that naringenin reduced lipid raft clustering and acid sphingomyelinase (ASMase) membrane gathering and inhibited the TLR4 and NADPH oxidase subunit p47phox membrane recruitment, which reduced the inflammatory response. Recombinant ASMase treatment or overexpression of ASMase abolished the naringenin function and activated macrophage and vascular inflammation. We conclude that naringenin inhibits ASMase-mediated lipid raft redox signaling to attenuate macrophage activation and vascular inflammation.

CAS / MDL: 128446-36-6 1320-06-5
研究领域: 心血管疾病 · 药理学 · 免疫学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES · 2021 · IF 4.384

Preparation and characterization of a naringenin solubilizing glycyrrhizin nanomicelle ophthalmic solution for experimental dry eye disease

Qiqi Li,Xiaoming Wu,Shanshan Xin,Xianggen Wu,Jie Lan

An ophthalmic solution of naringenin (NAR) based on dipotassium glycyrrhizinate (DG) micelle solubilization, called DG-NAR, was prepared, and its effect on dry eye disease (DED) was evaluated. DG-NAR was a clear, colorless aqueous solution with small micelle size (24.75±0.52 nm), narrow size distribution of polydispersity index 0.273±0.160, and a high entrapment efficiency (99.67±0.51%). The solution also revealed good storage stability in a 12-week short-term storage evaluation; it also displayed good vivo ocular tolerance in rabbit eyes investigated via a slit lamp observation and histopathological examination. When observed under fluorescence microscopy, the solution further exhibited improved in vivo corneal permeation profiles in mice eyes. As expected, in a BAC-induced DED mouse model, ocular topical administration of DG-NAR achieved a remarkable efficacy against dry eye symptoms when compared to the DG&NAR physical mixture solution or free NAR solution; this included decreased rose bengal and fluorescein staining, increased tear volume and corneal sensitivities, alleviated histopathological symptoms, and reversed corneal epithelium and endothelium damages. Additionally, performance in some efficacy evaluation parameters were better than in the commercialized 0.1% hyaluronic acid sodium salt eye drops. This therapeutic effect can be attributed to the mechanisms regulating HMGB1 signaling and its related proinflammatory cytokines. Together, these in vitro/in vivo results suggested that this novel phytochemical-based nanoformulation of DG-NAR may be a promising candidate in the efficacious treatment of DED.

研究领域: 药剂学 · 眼科 · 纳米技术 · 药理学
✓ 已验证 DOI PubMed 高影响因子
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ULTRASONICS SONOCHEMISTRY · 2025 · IF 9.7

Ultrasound-driven antisolvent precipitation for engineered naringenin ultrafine crystals with potent xanthine oxidase inhibitory and bacteriostatic effects

Yan Huang,Cuixia Weng,Fajian Zeng,Xiaoxiao Dai,Xiaoying Qiu,Jiachi Lin,Botao Peng,Xiaonan Zhang,Zhiwei Liu

Naringenin is a natural flavonoid with strong antioxidant and antibacterial properties, but its poor solubility and limited bioavailability severely restrict its broader application. Addressing this challenge is the key motivation of the present study. This study employed ultrasonic-assisted antisolvent precipitation to fabricate naringenin ultrafine crystals, and the optimal parameters were ascertained as presented below: a surfactant concentration of 0.54 %, a solution concentration of 14.20 mg/mL, and a anti-solvent to solvent ratio of 10.71. Under these established conditions, naringenin nanocrystals featuring a minimum average particle size of 290.51 ± 0.73 nm were successfully obtained. The introduction of ultrasound during the crystallization process played a crucial role, as the acoustic cavitation and subsequent microjets greatly enhanced solvent–antisolvent mixing, promoted uniform supersaturation, and facilitated the formation of evenly distributed nuclei. These effects not only reduced the tendency for particle agglomeration but also improved the reproducibility of the precipitation process. The experimental results revealed that the half-maximal inhibitory concentration (IC 50 ) value of the ultrafine crystals was 2.61 ± 0.22 μM, representing a significant 9.3 enhancement compared to that of the native naringenin powder. In addition, the antibacterial efficacy of the ultrafine crystals against Staphylococcus aureus was investigated. The ultrafine crystal samples exhibited an inhibition zone diameter of 21.69 mm, corresponding to an inhibition rate of 36.15 %, which clearly outperformed the antibacterial activity of native naringenin. Overall, this study not only demonstrates the efficiency of ultrasonic-assisted crystallization in tailoring particle size and bioactivity, but also highlights its potential as a versatile strategy for expanding the applications of natural flavonoids.

CAS / MDL: 69-89-6
✓ 已验证 产品关联 DOI PubMed 高影响因子
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AAPS PHARMSCITECH · 2016 ·Vol. 18 ·期 3 ·586-594 · IF 1.954

Enhanced Solubility and Bioavailability of Naringenin via Liposomal Nanoformulation: Preparation and In Vitro and In Vivo Evaluations

Wang Yuanwen,Wang Shicheng,Firempong Caleb Kesse,Zhang Huiyun,Wang Miaomiao,Zhang Ya,Zhu Yuan,Yu Jiangnan,Xu Ximing

This study was aimed at preparing orally administered naringenin-loaded liposome for pharmacokinetic and tissue distribution studies in animal models. The liposomal system, consisting of phospholipid, cholesterol, sodium cholate, and isopropyl myristate, was prepared using the thin-film hydration method. Physicochemical characterization of naringenin-loaded liposome such as particle size, zeta potential, and encapsulation efficiency produced 70.53 ± 1.71 nm, −37.4 ± 7.3 mV, and 72.2 ± 0.8%, respectively. The in vitro release profile of naringenin from the formulation in three different media (HCl solution, pH 1.2; acetate buffer solution, pH 4.5; phosphate buffer solution, pH 6.8) was significantly higher than the free drug. The in vivo studies also revealed an increase in AUC of the naringenin-loaded liposome from 16648.48 to 223754.0 ng·mL −1  h as compared with the free naringenin. Thus, approximately 13.44-fold increase in relative bioavailability was observed in mice after oral administration. The tissue distribution further showed that the formulation was very predominant in the liver. These findings therefore indicated that the liposomal formulation significantly improved the solubility and oral bioavailability of naringenin, thus leading to wider clinical applications.

研究领域: 药剂学 · 药物代谢动力学 · 纳米医学
✓ 已验证 DOI 高影响因子
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PROGRESS IN ORGANIC COATINGS · 2024 · IF 6.5

Robust polyurethane networks with flame-retardant, antioxidative, self-healing and reprocessing capabilities from biobased naringenin and vanillin

Chaoying Hu,Fanqi Liu,Zhaoyi Luo,Quanqian Yi,Yanning Zeng,Yunhua Chen,Chaoyang Wang

Biobased reprocessable polyurethane (PU) networks have drawn significant attention due to limited petroleum resources and aggravating environmental issues. However, the preparation of biobased PU networks with simultaneous efficient flame-retardant, antioxidative, self-healing and reprocessing performance is a great challenge due to the complicated structural design required. A novel strategy to fabricate multifunctional PU networks containing dynamic phenol–carbamate bonds from biobased naringenin and vanillin has been developed. First, a vanillin-based diol containing organic phosphorus moieties (VD) was prepared. Then modified diol and naringenin were combined to produce a self-healable, recyclable, antioxidative and flame-retarded PU (NVP-x)s where x represents the molar ratio of n[-OH (VD) ] / n{[-OH (naringenin) ] + [-OH (VD) ] + [-OH (PTMG) ]} possesses excellent flame-retardant, antioxidative, self-healing and reprocessing performance due to the presence of dynamic phenol–carbamate bonds, organophosphorus and phenolic moieties. An effective approach to the manufacture of multifunctional PUs with a potential application in the field of self-healing and flame-retardant coating, wound dressing membranes and fire-control engineering materials has been demonstrated.

CAS / MDL: 77-58-7
研究领域: 材料科学 · 化学工程
✓ 已验证 产品关联 DOI 高影响因子
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BIOCHEMICAL PHARMACOLOGY · 2026 · IF 6.5

Naringenin modulate peroxisome proliferator-activated receptorα (PPARα) to ameliorate hepatic ferroptosis by restoring GPX4 during liver regeneration

HaoranZhong,Lei Sun,Jiajun Yu,Yanrong Wang,Tongjie Xu,Tingfeng Yang,Niangkun Liu,Jiayuan Chen,Jinwu Liu,Haochen,Wenguang Fu

Liver regeneration is essential for recovery after major resection or acute injury, yet early regenerative failure remains common. Ferroptosis, an iron-dependent form of lipid peroxidation-driven cell death, impairs hepatocyte survival and may constrain regeneration. Naringenin (NAR), a citrus flavonoid with hepatoprotective activity, has been reported to modulate oxidative stress; however, whether it supports liver regeneration through ferroptosis modulation and which upstream targets are involved remains unclear. Here, hepatocyte models (AML12, Huh7, HepG2) and a murine 70% partial hepatectomy (PHx) model were used to investigate the involvement of PPARα signaling. Proliferation was assessed by CCK-8, EdU, and cell-cycle proteins. Ferroptosis-associated readouts (Fe 2+ , MDA, ROS, GSH) were measured following RSL3 exposure with or without NAR, ferrostatin-1, fenofibrate, or GW6471. Target identification involved network pharmacology, molecular docking, protease protection assay, and CETSA. In PHx mice, NAR was associated with improved liver regrowth (LW/BW ↑25% at 48 h), reduced ALT/AST (∼30–40%), increased proliferation markers, elevated GSH/CAT, and decreased Fe 2+ /MDA. In vitro, NAR increased GPX4/SLC7A11 expression and attenuated RSL3-induced ferroptosis-associated changes. These effects were mimicked by fenofibrate and attenuated by GW6471. NAR was associated with increased PPARα stability and expression. These findings suggest that NAR is associated with reduced ferroptosis and improved liver regeneration, potentially through modulation of PPARα-related signaling, warranting further validation.

✓ 已验证 DOI PubMed 高影响因子
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BIOORGANIC CHEMISTRY · 2024 · IF 4.5

Enzymatic properties and immobilization of a thermostable prenyltransferase from Aspergillus fumigatiaffinis for the production of prenylated naringenin

Wenbo Li,Xin Yan,Wenli Xia,Linguo Zhao,Jianjun Pei

Prenyltransferases catalyze the synthesis of prenylated flavonoids, providing these with greater lipid solubility, biological activity, and availability. In this study, a thermostable prenyltransferase (AfPT) from Aspergillus fumigatiaffinis was cloned and expressed in Escherichia coli . By optimizing induction conditions, the expression level of AfPT reached 39.3 mU/mL, which was approximately 200 % of that before optimization. Additionally, we determined the enzymatic properties of AfPT. Subsequently, AfPT was immobilized on carboxymethyl cellulose magnetic nanoparticles (CMN) at a maximum load of 0.6 mg/mg. Optimal activity of CMN-AfPT was achieved at pH 8.0 and 55 °C. Thermostability assays showed that the residual activity of CMN-AfPT was greater than 50 % after incubation at 55 °C for 4 h. Km and Vmax of CMN-AfPT for naringenin were 0.082 mM and 5.57 nmol/min/mg, respectively. The Kcat/Km ratio of CMN-AfPT was higher than that of AfPT. Residual prenyltransferase activity of CMN-AfPT remained higher than 70 % even after 30 days of storage. Further, CMN-AfPT retained 68 % of its original activity after 10 cycles of reuse. Compared with free AfPT, CMN-AfPT showed higher catalytic efficiency, thermostability, metal ion tolerance, substrate affinity, storage stability, and reusability. Our study presents a thermostable prenyltransferase and its immobilized form for the production of prenylated flavonoids in vitro .

CAS / MDL: 7705-08-0 7758-94-3
研究领域: 生物化学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Oxidative Medicine and Cellular Longevity · 2019 · IF 4.868

Naringenin Attenuates Myocardial Ischemia-Reperfusion Injury via cGMP-PKGIα Signaling and In Vivo and In Vitro Studies

Li-Ming Yu,Xue Dong,Jian Zhang,Zhi Li,Xiao-Dong Xue,Hong-Jiang Wu,Zhong-Lu Yang,Yang Yang,Hui-Shan Wang

Endoplasmic reticulum (ER) stress and oxidative stress contribute greatly to myocardial ischemia-reperfusion (MI/R) injury. Naringenin, a flavonoid derived from the citrus genus, exerts cardioprotective effects. However, the effects of naringenin on ER stress as well as oxidative stress under MI/R condition and the detailed mechanisms remain poorly defined. This study investigated the protective effect of naringenin on MI/R-injured heart with a focus on cyclic guanosine monophosphate- (cGMP-) dependent protein kinase (PKG) signaling. Sprague-Dawley rats were treated with naringenin (50 mg/kg/d) and subjected to MI/R surgery with or without KT5823 (2 mg/kg, a selective inhibitor of PKG) cotreatment. Cellular experiment was conducted on H9c2 cardiomyoblasts subjected to simulated ischemia-reperfusion treatment. Before the treatment, the cells were incubated with naringenin (80 μmol/L). PKGIα siRNA was employed to inhibit PKG signaling. Our in vivo and in vitro data showed that naringenin effectively improved heart function while it attenuated myocardial apoptosis and infarction. Furthermore, pretreatment with naringenin suppressed MI/R-induced oxidative stress as well as ER stress as evidenced by decreased superoxide generation, myocardial MDA level, gp91phox expression, and phosphorylation of PERK, IRE1α, and EIF2α as well as reduced ATF6 and CHOP. Importantly, naringenin significantly activated myocardial cGMP-PKGIα signaling while inhibition of PKG signaling with KT5823 (in vivo) or siRNA (in vitro) not only abolished these actions but also blunted naringenin’s inhibitory effects against oxidative stress and ER stress. In summary, our study demonstrates that naringenin treatment protects against MI/R injury by reducing oxidative stress and ER stress via cGMP-PKGIα signaling. Its cardioprotective effect deserves further clinical study.

CAS / MDL: 480-41-1 67604-48-2
研究领域: 心脏病学 · 药理学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Analytical Methods · 2015 ·Vol. 7 ·期 20 ·8847-8856 · IF 1.821

Electrochemical behavior of naringenin and its sensitive determination based on a single-walled carbon nanotube modified electrode

Wenjing Wang,Jian Gao,Lu Wang,Baoxian Ye

A stable voltammetric sensor (SWCNTs/GCE), single-walled carbon nanotubes (SWCNTs) cast on a glassy carbon electrode (GCE), was employed in the initial electrochemical determination of naringenin. The complex electrochemical behavior of naringenin on this sensor was investigated in detail, and the dynamic and thermodynamic parameters were calculated. The new electroanalytical method for naringenin was proposed with a low detection limit of 2.0 × 10−8 mol L−1 (S/N = 3) and wide linear ranges from 8 × 10−8 to 5 × 10−6 mol L−1 and 5 × 10−6 to 1.2 × 10−5 mol L−1, respectively. More importantly, this sensor exhibited good reproducibility and long-term stability. Then this sensor was successfully applied for the determination of naringenin in Fructus Aurantii Immaturus with satisfactory results.

CAS / MDL: 480-41-1 67604-48-2
研究领域: 分析化学 · 电化学传感器
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Nutrients · 2023 ·Vol. 15 ·期 6 ·1340 · IF 5.9

Naringenin Attenuates Isoprenaline-Induced Cardiac Hypertrophy by Suppressing Oxidative Stress through the AMPK/NOX2/MAPK Signaling Pathway

Yu Li,Bo He,Chao Zhang,Yanji He,Tianyang Xia,Chunyu Zeng

Cardiac hypertrophy is accompanied by increased myocardial oxidative stress, and whether naringenin, a natural antioxidant, is effective in the therapy of cardiac hypertrophy remains unknown. In the present study, different dosage regimens (25, 50, and 100 mg/kg/d for three weeks) of naringenin (NAR) were orally gavaged in an isoprenaline (ISO) (7.5mg/kg)-induced cardiac hypertrophic C57BL/6J mouse model. The administration of ISO led to significant cardiac hypertrophy, which was alleviated by pretreatment with naringenin in both in vivo and in vitro experiments. Naringenin inhibited ISO-induced oxidative stress, as demonstrated by the increased SOD activity, decreased MDA level and NOX2 expression, and inhibited MAPK signaling. Meanwhile, after the pretreatment with compound C (a selective AMPK inhibitor), the anti-hypertrophic and anti-oxidative stress effects of naringenin were blocked, suggesting the protective effect of naringenin on cardiac hypertrophy. Our present study indicated that naringenin attenuated ISO-induced cardiac hypertrophy by regulating the AMPK/NOX2/MAPK signaling pathway.Keywords:naringenin;cardiac hypertrophy;oxidative stress;AMPK;NOX2

CAS / MDL: 480-41-1 67604-48-2
研究领域: 药理学 · 心脏病学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Materials Today Bio · 2023 · IF 8.2

Electrospun sandwich mesh structures loaded with naringenin and vitamin K2 polycaprolactone/gelatin nanofibers synergistically promote bone regeneration

Jiafeng Wang,Longhui Shao,Xiaoyu Wu,Chun Liu,Su Ni,Ting Dai,Hongwei Liu,Hongbin Zhao

Osteoblasts and osteoclasts play a crucial role in the dynamically coupled balance during bone regeneration and remodeling. They complement and restrict each other in the human body. Decreased osteoblasts lead to insufficient bone formation or excessive formation of osteoclasts, leading to increased bone resorption, which will destroy the structure of the bone tissue. This will greatly increase the risk of diseases such as osteoporosis and nonunions caused by bone defects. Herein, gelatin and polycaprolactone were used as substrates, and biomaterial membranes with mesh and sandwich structures were constructed using the electrospinning technology. Naringenin was loaded into the shell, and vitamin K 2 was loaded into the core layer of the nanofibrous membrane. The biocompatibility and osteogenic capacity of the membranes were assessed in vitro using mouse bone marrow mesenchymal stem cells (BMSCs). During osteoclast induction, the receptor activator of nuclear factor kappa-Β ligand (RANKL) was used to coculture RAW264.7 cells with various materials. The regulatory effect of various membranes on osteoclast growth was evaluated by detecting the expression levels of osteoclast-related genes and proteins in the cells. Subsequently, we constructed a model of a rat skull defect and implanted different membranes into the defect. Then, we evaluated the new bone formation in the defect using histological staining and micro-computed tomography after 4 and 8 weeks. The results of in vitro experiments confirmed that the incorporation of naringenin and vitamin K 2 stimulated the expression of osteogenesis-related genes and the secretion of osteogenesis-related proteins. Simultaneously, the results showed that naringenin and vitamin K 2 inhibited the formation and growth of osteoclasts. Therefore, naringenin and vitamin K 2 have a synergistic effect in promoting bone growth and regulating osteoclast growth.

研究领域: 生物材料 · 组织工程 · 骨再生 · 细胞生物学 · 材料科学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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