ENVIRONMENTAL TOXICOLOGY
·
2022
·Vol. 37
·期 8
·1840-1852
·
IF 4.109
Huijie Chen,Yue Zhang,Mengmeng Zou,Xiaowei Sun,Xiaodan Huang,Shiwen Xu
Dibutyl phthalate (DBP) is a phthalic acid ester (PAE) that has posed a health hazard to the organisms. Naringenin (NRG) is a flavanone compound that has shown protection against several environmental chemicals through suppression of oxidative stress and activation of phosphatidylinositol 3-kinase/threonine kinase (PI3K/AKT) signaling pathway. Herein, swine testis (ST) cells were treated with 1.8 μM of DBP or/and 25.39 nM of NRG for 24 h, we described the discovery path of NRG inhibition on apoptosis in DBP-exposed ST cells through targeting phosphatase and tensin homologue deleted on chromosome 10 (PTEN). We first found that the anti-apoptosis effect of NRG is dependent on mitochondrial pathway through flow cytometry and related gene/protein expression, and then we detected PI3K/AKT pathway-related gene/protein expression, and established a computational docking assay between NRG and PTEN. We found that NRG specifically binds to three basic residues (His93, Lys125, Lys128) of P loop in PTEN, as well as phosphatase domains (Asp92, His93, Cys124, Lys125, Ala126, Lys128, and Arg130) in active dephosphorylation pockets, thereby reducing PTEN level and activating PI3K/AKT signaling pathway, and further inhibiting oxidative stress and mitochondrial pathway apoptosis. Taken together, our results push forward that NRG deserves further attention as a potential antagonistic therapy against DBP through targeting PTEN to inhibit oxidative stress and activate PI3K/AKT signaling pathway.
✓ 已验证
DOI
PubMed
高影响因子
BMC PLANT BIOLOGY
·
2026
·
IF 4.8
Zhang Zeyu,Chen Bingyan,Zhang Yinghe,Mo Xiaohui,Lu Xing,Wang Tianqi,Liang Cuiyue,Tian Jiang
Background Flavonoids play a crucial role as secondary metabolites in plant growth and development. Naringenin is a central intermediate in flavonoid biosynthesis. It is also a pivotal branching point that gives rise to metabolites such as flavonols, anthocyanins, and isoflavonoids. However, the mechanisms underlying plant root development regulated by flavonoids remain fragmentary, especially in crops. Results In this study, we observed a significant inhibition of soybean (Glycine max) root growth after exposure to 75 μM naringenin. The treated roots showed reduced auxin content and increased reactive oxygen species (ROS) levels in root tips. Through RNA-sequencing and nanoElute high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) analyses, we further investigated molecular responses of soybean roots to naringenin treatment. A total of 6,390 differentially expressed genes (DEGs) were identified. Among them, 3,910 genes were up-regulated and 2,480 were down-regulated. These DEGs notably included genes related to ROS metabolism and the auxin signaling pathway. We also detected 806 differential accumulation proteins (DAPs), including 481 up-regulated and 325 down-regulated proteins. The integration of transcriptomic and proteomic data showed a close association between DEGs and DAPs in roots, especially in pathways related to glutathione metabolism. Conclusion Taken together, this comprehensive analysis highlights the intricate and specific responses of soybean roots to naringenin exposure, mainly affecting the levels of auxin and ROS. It provides valuable insights and candidate genes for further investigating root growth regulated by flavonoids.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH PART A-TOXIC/HAZARDOUS SUBSTANCES & ENVIRONMENTAL ENGINEERING
·
2026
·
IF 2
Jing Zhu,Mengmeng Gao,Hao Ling,Phar Ku Ngwe,Chengxiang Guo,Yinan Hu,Jicang Wang
This study investigated the protective effects of naringenin (Nar) against lead (Pb)-induced testicular injury in rats, focusing on the Nrf2/Keap1 antioxidant pathway and PINK1/Parkin-mediated mitophagy. To this end, male SD rats were exposed to Pb (60 mg/kg) and co-treated with Nar (50 mg/kg) for 8 consecutive weeks, followed by assessments via biochemical detection, oxidative stress (OS) evaluation, hematological examination, histopathological observation, qPCR, WB, and IHC analyses. Pb exposure caused hematological disturbances, reduced serum LH and T levels, and OS imbalance (lower GSH, SOD, CAT; higher MDA), aggravating testicular damage. Meanwhile, it suppressed the Nrf2/NQO1 pathway, elevated Keap1, impaired autophagy (elevated p62, declined LC3‑II/LC3‑I ratio), and induced aberrant accumulation of PINK1/Parkin. Co-treatment with Nar mitigated these alterations, ameliorating testicular injury, restoring redox homeostasis and serum reproductive hormone levels, and normalizing key molecular expressions in both pathways. In conclusion, Nar alleviates Pb-induced rat testicular damage by reactivating the Nrf2/Keap1 axis to suppress OS, and by restoring autophagic flux to facilitate PINK1/Parkin-mediated clearance of damaged mitochondria.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF FISH DISEASES
·
2021
·Vol. 44
·期 10
·1503-1513
·
IF 2.767
Zhong-Chen Sun,Cheng Chen,Fei-Fan Xu,Bing-Ke Li,Jing-Lei Shen,Tao Wang,Hai-Feng Jiang,Gao-Xue Wang
White spot syndrome virus (WSSV) is a serious pathogen threatening global crustacean aquaculture with no commercially available drugs. Herbal medicines widely used in antiviral research offer a rich reserve for drug discovery. Here, we investigated the inhibitory activity of 13 herbal medicines against WSSV in crayfish Procambarus clarkii and discovered that naringenin (NAR) has potent anti-WSSV activity. In the preliminary screening, the extracts of Typha angustifolia displayed the highest inhibitory activity on WSSV replication (84.62%, 100 mg/kg). Further, NAR, the main active compound of T. angustifolia, showed a much higher inhibition rate (92.85%, 50 mg/kg). NAR repressed WSSV proliferation followed a dose-dependent manner and significantly improved the survival of WSSV-challenged crayfish. Moreover, pre- or post-treatment of NAR displayed a comparable inhibition on the viral loads. NAR decreased the transcriptional levels of vital genes in viral life cycle, particularly for the immediately early-stage gene ie1 . Further results showed that NAR could decrease the STAT gene expression to block ie1 transcription. Besides, NAR modulated immune-related gene Hsp70 , antioxidant ( cMnSOD, mMnSOD, CAT, GST ), anti-inflammatory ( COX-1 , COX-2 ) and pro-apoptosis-related factors (Bax and BI-1) to inhibit WSSV replication. Overall, these results suggest that NAR may have the potential to be developed as preventive or therapeutic agent against WSSV.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2020
·Vol. 10
·期 43
·25629-25638
·
IF 3.119
Boran Hao,Rui Yang,Kan Zhang
Epoxy resins are constantly attracting attention from industrial applications due to their excellent comprehensive properties. However, the traditional curing agents for liquid epoxy resins react with epoxides even at room temperature, which causes difficulties in processing since such mixtures cannot be directly used as single-component materials. In order to improve the shelf life of the mixtures, we have designed an intramolecular hydrogen bond-containing benzoxazine monomer as a smart thermal latent polymerization agent for epoxy resins. The newly obtained benzoxazine, NAR-a, has been synthesized from the Mannich condensation of naringenin, aniline and paraformaldehyde. In addition to playing the role of a curing agent, NAR-a has also performed as an excellent property modifier for epoxy thermosetting systems. The resulting thermoset based on the NAR-a/epoxy thermosetting system exhibits high thermal stability and good intrinsic flame retardance, with a Tg temperature of 201 °C, a Td5 temperature of 349 °C, a low CET value (32.4 ppm per °C) and low heat release capacity (HRC of 159.1 J g−1 K−1). The combined long-term storage stability and versatility of the intramolecular hydrogen bond-containing benzoxazine/epoxy system provide a new strategy for the development of one-component epoxy-related thermosetting resins for application in high-performance areas.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
·
2017
·
IF 3.498
Lang-Hong Wang,Xin-An Zeng,Man-Sheng Wang,Charles S. Brennan,Deming Gong
In this work, modifications of cell membrane fluidity, fatty acid composition and fatty acid biosynthesis-associated genes of Escherichia coli ATCC 25922 ( E. coli ) and Staphylococcus aureus ATCC 6538 ( S. aureus ), during growth in the presence of naringenin (NAR), one of the natural antibacterial components in citrus plants, was investigated. Compared to E. coli , the growth of S. aureus was significantly inhibited by NAR in low concentrations. Combination of gas chromatography–mass spectrometry with fluorescence polarization analysis revealed that E. coli and S. aureus cells increased membrane fluidity by altering the composition of membrane fatty acids after exposure to NAR. For example, E. coli cells produced more unsaturated fatty acids (from 18.5% to 43.3%) at the expense of both cyclopropane and saturated fatty acids after growth in the concentrations of NAR from 0 to 2.20 mM. For S. aureus grown with NAR at 0 to 1.47 mM, the relative proportions of anteiso-branched chain fatty acids increased from 37.2% to 54.4%, whereas iso-branched and straight chain fatty acids decreased from 30.0% and 33.1% to 21.6% and 23.7%, respectively. Real time q-PCR analysis showed that NAR at higher concentrations induced a significant down-regulation of fatty acid biosynthesis-associated genes in the bacteria, with the exception of an increased expression of fabA gene. The minimum inhibitory concentration (MIC) of NAR against these two bacteria was determined, and both of bacteria underwent morphological changes after exposure to 1.0 and 2.0 MIC.
✓ 已验证
DOI
PubMed
高影响因子
CYTOTECHNOLOGY
·
2026
·Vol. 78
·期 4
·156
·
IF 2.2
Zhang Yougen,Gu Li,Zhang Xiaoyang,Ran Wei,Yan Yanfeng,Gu Hongwei
Pulmonary inflammation is a key feature of chronic obstructive pulmonary disease (COPD), contributing to disease progression and morbidity. However, the molecular mechanisms underlying therapeutic interventions remain to be fully elucidated. This study aimed to investigate the mechanisms of naringenin in modulating COPD-related pulmonary inflammation. Using an integrated approach combining network pharmacology, molecular docking, and in vitro/in vivo models, we systematically explored the effects of naringenin. Network pharmacology analysis identified NF-κB as a central target, which was validated through molecular docking and dynamics simulations showing stable binding between naringenin and NF-κB. In vitro, cigarette smoke extract-challenged lung epithelial cells treated with naringenin exhibited reduced cytotoxicity, downregulated TNF-α, phospho-NF-κB p65, and NLRP3 expression, inhibited Caspase-1 activation, and attenuated IL-1β maturation, and suppressed Gasdermin D cleavage. In vivo, naringenin-treated COPD mice displayed diminished pulmonary inflammatory cell infiltration, milder histopathological lung damage, decreased serum TNF-α/IL-1β levels, and inhibited activation of the NF-κB/NLRP3/Caspase-1 axis in lung tissue. Collectively, these findings reveal that naringenin alleviates COPD pulmonary inflammation and pyroptosis by targeting the NF-κB/NLRP3/Caspase-1 signaling cascade, providing mechanistic insights for traditional Chinese medicine-based COPD therapies. Graphical abstract
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Jiayu Zhang,Tianfu Cheng,Mengya Sun,Yang Li,Guofang Zhang,Zhaodong Hu,Daoying Wang,Zengwang Guo,Zhongjiang Wang
In this study, changes in the structural and functional properties of soybean protein isolate (SPI)-naringenin (NG) complexes under different amounts of naringenin treatments were explored, elucidating the effect of the complexes as fat replacers at the 15 % substitution level on the properties of low-fat cream. Finally, the correlation between the structure and function of the complex and the properties of low-fat cream was further analyzed. The addition of NG promotes the increase of SPI aggregation and particle size, and reduces the interfacial tension of the complex. Meanwhile, at the mass ratio of 48:3, NG and SPI formed a dendritic network structure suitable for stabilizing cream. The fat properties of cream indicate that low-fat creams stabilized by appropriate proportions of SPI-NG complexes displayed small and dense fat crystal network structures. In addition, low-fat cream stabilized by the SPI-NG complexes have improved whipping time, overrun, firmness, storage stability and rheological properties compared to natural SPI. It is worth noting that the overall quality of the cream stabilized by the SPI-NG complex with a mass ratio of 48:3 was almost close to that of full-fat cream. Therefore, this study promotes the potential applications of protein-polyphenol complexes as fat replacers in the food industry.
✓ 已验证
DOI
PubMed
高影响因子
BIOLOGICAL TRACE ELEMENT RESEARCH
·
2026
·
IF 4.3
Ngwe Phar Ku,Zhu Jing,Ling Hao,Gao Mengmeng,Guo Chengxiang,Hu Yinan,Wang Jicang
Lead (Pb), a persistent and highly toxic environmental contaminant, induces severe multi-organ toxicity, with the liver as a primary target. Naringenin (Nar), a natural flavonoid with established antioxidant properties, shows potential in mitigating chemical-induced liver injury; however, its protective mechanism against Pb hepatotoxicity remains unclear. This study investigated the hepatoprotective effects and underlying mechanisms of Nar in Pb-exposed rats. Thirty-six five-week-old male Sprague-Dawley rats were randomly assigned to six groups ( n = 6): control, three Pb-treated groups (15, 30, and 60 mg/kg), co-treatment group (60 mg/kg Pb + 50 mg/kg Nar), and Nar-alone group (50 mg/kg). After 8 weeks, Pb exposure induced significant liver injury, evidenced by histopathological lesions (e.g., central venous congestion and inflammation), elevated serum levels of ALT, AST, and LDH, and oxidative stress (increased MDA; decreased CAT, T-SOD, and GSH). At the molecular level, Pb exposure suppressed the Nrf2/NQO1 pathway, upregulated Keap1, and impaired autophagic flux, as indicated by a decreased LC3-II/LC3-I ratio, accumulated p62, and a disrupted PINK1/Parkin pathway. Corroborating the impaired flux, transmission electron microscopy (TEM) revealed an accumulation of autophagic vacuoles, indicative of blocked autophagic degradation. Crucially, Nar co-treatment effectively mitigated these Pb-induced disturbances by activating the Nrf2/NQO1 pathway to counteract oxidative stress and restored autophagic flux, which was supported by the reversal of p62 accumulation and normalization of the LC3-II/LC3-I ratio. In conclusion, Nar protects against Pb-induced hepatotoxicity by concurrently alleviating oxidative stress and restoring autophagic function, supporting its potential as a therapeutic agent. Graphical
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY A
·
2016
·
IF 3.926
Shanshan Wang,Chao Han,Sisi Wang,Lijuan Bai,Shanshan Li,Jianguang Luo,Lingyi Kong
Cu(II) complexed amino acid ionic liquid , Cu(II)-[1-butyl-3-methylimidazolium][L-Pro] (Cu(II)-[BMIm][L-Pro]), was successfully adopted as chiral ligand to improve the enantioseparation efficiency in high speed counter-current chromatography (HSCCC). For the enantioseparation of intractable naringenin (NRG) racemic mixtures, Cu(II)-[BMIm][L-Pro] coupled with hydroxypropyl-β-cyclodextrin (HP-β-CD) was successfully applied as dual chiral selectors in HSCCC. The influence of important parameters, including the concentration of the chiral selectors, the pH value, and the temperature were investigated. Under optimal conditions, 4.5 mg of (+)-NRG and 4.1 mg of (−)-NRG were successfully separated from 10 mg NRG racemic mixtures with the purity of 98%. The chiral recognition mechanism of dual chiral selectors was illuminated by the UV–vis and NMR spectra, suggesting that the enantioseparation was upon the difference of the thermodynamic stability of the quaternary complexes of Cu(II), [BMIm][L-Pro], HP-β-CD, and NRG. The results illustrated that the developed HSCCC system, based on the synergistic mechanism of Cu(II)-[BMIm][L-Pro] and HP-β-CD, exhibited better performance on enantioseparation and had great application potential in preparative chiral separation of natural products.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioengineered
·
2021
·
IF 3.269
Shujun Xu,Bingxin Wu,Biying Zhong,Luoqi Lin,Yining Ding,Xiao Jin,Zhiwei Huang,Miaoyang Lin,Huanlin Wu,Danping Xu
Ferroptosis is an important form of myocardial cell death in myocardial ischemia-reperfusion injury (MIRI). Naringenin (NAR), as a flavonoid, has a significant advantage in improving MIRI. But the regulatory effect and mechanism of NAR on ferroptosis in MIRI have not been reported. After the rats were given NAR and induced to form myocardial ischemia-reperfusion (MI/R) injury, Tetrazolium chloride (TTC) staining was used to detect the myocardial infarction area of rats, and Hematoxylin-eosin (H&E) staining was used to detect myocardial injury. The markers of tissue inflammation were detected by ELISA. Serum creatine kinase Serum creatin kinase (CPK), Lactate dehydrogenase (LDH), and lipid peroxide (LPO) and oxidative stress related levels were measured. In addition, iron detection kits were used to detect total iron and Fe2+ levels in cardiac tissues, and western blot was used to detect the expression of ferroptosis-related proteins and the expression of nuclear factor-erythroid factor 2-related factor 2 (Nrf2) and glutathione peroxidase 4 (GPX4). At the cellular level, H9C2 cardiomyocytes were induced by hypoxia/reoxygenation (H/R), and ferroptosis inducer Erastin was administered to detect cell viability, ferroptosis-related indicators, oxidative stress related indicators, and expressions of Nrf2 and GPX4, to explore the mechanisms involved. NAR alleviated MI/R-induced pathological damage, inflammation and lipid peroxidation in myocardial tissue of rats. NAR adjusted the NRF2 /System xc – /GPX4 axis and improved ferroptosis. At the cellular level, ferroptosis inducer Erastin reversed the protective effect of NAR on H/R-induced H9C2 cardiomyocytes. In conclusion, NAR can alleviate MIRI by regulating the Nrf2/System xc-/GPX4 axis to inhibit ferroptosis.
✓ 已验证
DOI
PubMed
高影响因子