JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2025
·
IF 6.2
Weikang Sun,Renjie Luo,Qingwei Qu,Jie Yang,Guang Yang,Lihua Song,Peng Cao,Erguang Li
Plant-based phenolic components and their metabolites, such as ellagic acid (EA) and urolithin A (UA), possess a variety of biological activities. Here, we investigated the antiviral effect of EA and UA against HSV-1 infection, a virus that causes peripheral infection as well as brain inflammation. Both compounds demonstrated potent antiviral activity. Network pharmacology and molecular docking analyses identified protein kinase CK2 as a common target for their action. We showed that both EA and UA were direct CK2 inhibitors using an enzymatic assay, an observation substantiated in cell culture studies. The effect of EA and UA on HSV-1 infection through CK2 was confirmed in CK2 (CSNK2B) knockout cells. Finally, we demonstrated an antiviral effect using a murine model of herpetic stromal keratitis. EA or UA treatment reduced HSV-1 shedding and prevented viral neuroinvasion. CK2 is a critical enzyme involved in cell proliferation and the proinflammatory response. In addition to identifying CK2 as a putative target of EA and UA antiviral activities, this study also demonstrates that EA and its metabolite UA have the potential to reduce infection-associated neurodegenerative inflammation.
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FOOD CHEMISTRY
·
2026
·
IF 9.8
Zhihao Liu,Fu Zhao,Qihao Li,Qixiang Shang,Daozheng Fang,Xinyue Li,Haimeng Li,Quanrun He,Dapeng Zhang,Juanjuan Cheng,Yong Zhu,Zhongxia Li,Ana Sanches Silva,Jihang Chen
Ellagic acid (EA) is a dietary polyphenol with limited systemic bioavailability, resulting in substantial intestinal exposure. However, the biochemical mechanisms by which EA modulates gut microbiota and metabolism remain unclear. Here, EA improved glucose tolerance and enhanced insulin sensitivity, with histology confirming reduced lipid accumulation and restored tissue architecture in liver, skeletal muscle, brown adipose tissue, and mesenteric fat. Consistently, metagenomic analysis showed that EA enriched Akkermansia muciniphila , Muribaculum intestinale , and Duncaniella dubosii , while reducing Lachnoclostridium phocaeense . These microbial shifts were accompanied by elevated levels of tryptophan-derived metabolites—indole-3-propionic acid, indole, and indole-3-acrylic acid—known to enhance insulin sensitivity. Lipidomic revealed EA decreased triacylglycerols and ceramides, along with restored phosphatidylcholine, phosphatidylethanolamine and phosphatidylserine levels. Transcriptomic revealed EA suppressed hepatic lipogenesis, inhibited MAPK signaling in skeletal muscle, activated thermogenic and oxidative phosphorylation in adipose tissues. Our findings highlight EA as a food-derived polyphenol that alleviates insulin resistance through a gut microbiota–indole metabolite–multi-tissue axis.
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ACS Applied Materials & Interfaces
·
2023
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IF 9.5
Tingyue Zhang,Liwei Guo,Ruolan Li,Jiang Shao,Lei Lu,Ping Yang,Ansha Zhao,Yanqiu Liu
Hydrogel dressings not only have basic functions such as swelling, water retention, gas permeability, and good biocompatibility but also can be endowed with advanced functions such as antibacterial, antioxidant, adhesion, hemostasis, and anti-inflammation, which make hydrogels have great application potential in clinical trauma. However, the complexity of the wound healing process makes the development of multifunctional wound dressings a great challenge. In this work, based on the thiol–ene photoclickable PEG hydrogel, the inclusion complex of the hydrophobic drug ellagic acid (EA) with mono-(6-mercapto-6-deoxy)-β-cyclodextrin (SH-β-CD) participated in the formation of a hydrogel as a crosslinker. The drug EA with antioxidant, antibacterial, and anti-inflammatory activities was introduced into the hydrogel. This strategy increases the loading capacity of the hydrogel for EA and endows the hydrogel with multifunctional properties. Then, dithiothreitol was added to adjust the mechanical stiffness of the hydrogel to meet the requirements of the wound dressing. Our results demonstrated that this wound dressing has excellent cytocompatibility, antioxidant, antibacterial, and anti-inflammatory activities. Furthermore, the results of the infected wound healing model experiment in rats confirmed that the hydrogel has the ability to rapidly shrink the wound area, prevent wound infection, and promote angiogenesis and collagen deposition. All these results suggest that this hydrogel could be a candidate for the treatment of infected wounds and shed new light on the development of multifunctional wound dressings.
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MOLECULES
·
2023
·Vol. 28
·期 22
·7646
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IF 4.6
Qiwei Cheng,Yuzhou Wang,Qi Zhou,Shaobo Duan,Beibei Zhang,Yaqiong Li,Lianzhong Zhang
There is an urgent need to realize precise clinical ultrasound with ultrasound contrast agents that provide high echo intensity and mechanical index tolerance. Graphene derivatives possess exceptional characteristics, exhibiting great potential in fabricating ideal ultrasound contrast agents. Herein, we reported a facile and green approach to synthesizing reduced graphene oxide with ellagic acid (rGO-EA). To investigate the application of a graphene derivative in ultrasound contrast agents, rGO-EA was dispersed in saline solution and mixed with SonoVue (SV) to fabricate SV@rGO-EA microbubbles. To determine the properties of the product, analyses were performed, including ultraviolet–visible spectroscopy (UV–vis), Fourier-transform infrared spectroscopy (FTIR), Raman spectroscopy, transmission electron microscopy (TEM), thermal gravimetric analysis (TGA), X-ray photoelectron spectrum (XPS), X-ray diffraction analysis (XRD) and zeta potential analysis. Additionally, cell viability measurements and a hemolysis assay were conducted for a biosafety evaluation. SV@rGO-EA microbubbles were scanned at various mechanical index values to obtain the B-mode and contrast-enhanced ultrasound (CEUS) mode images in vitro. SV@rGO-EA microbubbles were administered to SD rats, and their livers and kidneys were imaged in CEUS and B-mode. The absorption of rGO-EA resulted in an enhanced echo intensity and mechanical index tolerance of SV@rGO-EA, surpassing the performance of SV microbubbles both in vitro and in vivo. This work exhibited the application potential of graphene derivatives in the field of ultrasound precision medicine.
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MICROCHEMICAL JOURNAL
·
2020
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IF 3.594
Juan-Yan An,Li-Tao Wang,Mu-Jie Lv,Jian-Dong Wang,Zi-Hui Cai,Yan-Qiu Wang,Su Zhang,Qing Yang,Yu-Jie Fu
Chestnut shells in large amounts are significantly underutilized agricultural and forestry waste that can be exploited as a resource for the production of high-valued nature active compounds. In this study, an efficient and green approach was established to extract and recover the highly valued phenolic compound, ellagic acid, from waste chestnut shells with choline chloride-based deep eutectic solvents (DESs). By utilizing optimized ultrasonic-assisted extraction conditions with choline chloride/n-propanol DES, solid–liquid ratio of 40 mg/mL, extraction time of 70 min and extraction power of 200 W, highly efficient extraction value for ellagic acid of 4.64 mg/g was obtained. Meanwhile, ellagic acid was recovered easily with a recovery percentage of 94.9% by anti-solvent precipitation method through the denaturation of DES with water. The purity of ellagic acid in the extracts reached 85.6%, which is more than two times to that via ethanol extraction methods (36.4%). In addition, the recovered ellagic acid exhibited strong antioxidant activity with IC 50 (0.309 mg/mL) and significant antibacterial activity with Minimal inhibitory concentration (MIC) (250 mm) and diameter of inhibition zone (DIZ) (17.60 μg/mL). The anti-solvent precipitation method could denature DES, led to higher extraction and recovery efficiency and high-purity ellagic acid simultaneously in one step. The novel method is of great significance to the whole chestnut production process for the utilization of waste chestnut shells. Furthermore, this method can also be used as a green, pollution-free alternative method for the extraction and recovery of phenolic components from natural resources for pharmaceutical and biochemical applications.
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Separations
·
2021
·Vol. 8
·期 10
·186
·
IF 2.777
Zili Guo,Shuting Xiong,Yuanyuan Xie,Xianrui Liang
Ellagic acid is a phenolic compound that exhibits both antimutagenic and anticarcinogenic activity in a wide range of assays in vitro and in vivo. It occurs naturally in some foods such as raspberries, strawberries, grapes, and black currants. In this study, a valid and reliable method based on mechanochemical-assisted extraction (MCAE) and macroporous adsorption resin was developed to extract and prepare ellagic acid fromPhyllanthus urinariaL. (PUL). The MCAE parameters, acidolysis, and macroporous adsorption resin conditions were investigated. The key MCAE parameters were optimized as follows: the milling time was 5 min, the ball mill speed was 100 rpm, and the ball mill filling rate was 20.9%. Sulfuric acid with a concentration of 0.552 mol/L was applied for the acidolysis with the optimized acidolysis time of 30 min and acidolysis temperature of 40 °C. Additionally, the XDA-8D macroporous resin was chosen for the purification work. Both the static and dynamic adsorption tests were carried out. Under the optimized conditions, the yield of ellagic acid was 10.2 mg/g, and the content was over 97%. This research provided a rapid and efficient method for the preparation of ellagic acid from the cheaply and easily obtained PUL. Meanwhile, it is relatively low-cost work that can provide a technical basis for the comprehensive utilization of PUL.Keywords:Phyllanthus urinariaL.;ellagic acid;mechanochemical-assisted extraction;macroporous adsorption resin
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MICROBIAL PATHOGENESIS
·
2025
·
IF 3.5
Kai Liu,Hong Sun,Hong Wang,Junbo Zheng,Xiuzhen Wang,Xin Wang,Yeting Hou,Qian Ye,Ji Li
Sepsis is a systemic inflammatory response syndrome triggered by infection. Severe sepsis is associated with dysbiosis of the intestinal flora and impaired intestinal function. Ellagic acid (EA) is a natural compound known for its ability to inhibit bacteria and viruses, thereby preventing infections. However, it remains unclear whether EA mitigates intestinal barrier dysfunction. In this work, BALB/c mice were administered doses of EA via gavage, followed by an injection of lipopolysaccharide (LPS) to induce sepsis. Fecal samples, serum, and ileum tissues were collected for molecular or pathological analysis. The intestinal contents underwent 16S rRNA sequencing and targeted metabolomics for short-chain fatty acids (SCFAs) detection. Additionally, an in vitro injury model was established using IEC6 cells treated with LPS; subsequent changes in inflammation and oxidative stress were assessed following EA treatment. The results indicated that EA reduced inflammation and oxidative stress as well as ameliorated intestinal lesions and enhanced intestinal barrier function in both mouse and cell models. Moreover, EA inhibited the signaling of nuclear factor kappa-light-chain-enhancer of activated B cells/myosin light chain kinase/myosin light chain (NF-κB/MLCK/MLC) pathway. Besides, EA also rectified genomic and metabolomic disturbances within the gut microbiota caused by sepsis. In conclusion, EA mitigates sepsis-induced intestinal injury through modulation of gut microbiota composition and inhibition of NF-κB-mediated MLCK/MLC signaling pathway. Thus, EA might represent a promising therapeutic agent for addressing intestinal injuries associated with sepsis.
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Frontiers in Aging
·
2026
·
IF 4.9
Lipeng Xu,Jinze Li,Anran Li,Jixian Chen,Liping Wang,Yaming Shan,Xianbin Cheng
Introduction Ellagic acid (EA) is a naturally occurring polyphenolic antioxidant speculated to influence aging, but its precise biological mechanisms remain poorly understood. Methods Using Caenorhabditis elegans as a model system, we investigated the anti-aging properties of EA. Lifespan assays were performed at multiple concentrations, and healthspan parameters including locomotor activity, lipofuscin accumulation, and reactive oxygen species (ROS) levels were assessed under thermal and oxidative stress. Genetic requirement was examined using loss-of-function mutants of daf-16, hsf-1, hlh-30, and skn-1. Gene expression was analyzed by qRT-PCR and reporter strains, and global transcriptional changes were mapped by RNA-sequencing. Results EA extended lifespan and preserved key healthspan features, including improved locomotor activity, reduced intestinal lipofuscin accumulation, and decreased ROS levels under stress conditions. The lifespan-extending effects of EA required daf-16, hsf-1, hlh-30, and skn-1, as EA failed to extend lifespan in these mutants. EA also enhanced the expression of downstream cytoprotective genes. Complementary RNA-sequencing revealed broader transcriptional remodeling, including metabolic pathways. Discussion These findings position EA as a modulator of a coordinated transcriptional network—rather than a single pathway—involving the insulin/IGF-1 signaling pathway and interconnected stress-response networks to promote longevity and stress resistance.
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Food Bioscience
·
2026
·
IF 6.2
Rui-Bo Jia,Weipei Li,Pengru Yan,Chunxia Zhou,Zirui Huang,Mouming Zhao
This study evaluated dietary ellagic acid (EA) as a food-derived polyphenol for improving glucose and lipid metabolic abnormalities using complementary in vitro , C. elegans , starch-loading, and db/db mouse models. EA inhibited alpha-glucosidase activity and attenuated starch-induced postprandial hyperglycemia. In C. elegans , EA reduced lipid accumulation and glucose storage while preserving feeding-related physiological indicators. In db/db mice, 8-week EA administration improved fasting blood glucose, dyslipidemia, insulin-related indices, and serum GLP-1 compared with diabetic controls. Cecal 16S rRNA gene sequencing and untargeted serum metabolomics further showed that EA intervention was accompanied by shifts in microbial composition and broad remodeling of amino acid, lipid, and glycerophospholipid-related metabolic features. Correlation analysis linked selected bacterial genera and lipid-related metabolites, including several lysophosphatidylcholine species, with GLP-1, fasting blood glucose, and insulin resistance-related markers. These findings support EA as a functional-food candidate associated with coordinated host-microbial metabolic remodeling in diabetic mice. Because the study did not include receptor blockade, microbial-dependence experiments, targeted lysophosphatidylcholine quantification, or urolithin profiling, the microbiota-metabolite-GLP-1 relationship should be interpreted as a candidate mechanism requiring further validation.
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Current Research in Microbial Sciences
·
2025
·
IF 5.8
Yang Yang,Ke Wang,Jia-Chi Chiou,Danyue Zhao
Mounting evidence suggests that dietary polyphenols exert health benefits partly through their favorable interactions with gut bacteria. However, little is known about polyphenol’s metabolic regulatory effects towards individual bacteria at the molecular level. Ellagic acid (EA), a polyphenol abundantly present in plant-based foods, was found to exhibit prebiotic properties through differential interactions with probiotic-like bacteria, including the EA-to-urolithin converting species such as Gordonibacter urolithinfaciens ( G. uro ). This study aimed to investigate the crosstalk between EA and EA-responsive beneficial bacteria, including both conventional and next-generation probiotics originating from the human gut, and to understand the underlying mechanism by which EA exerts prebiotic activities in vitro . The influence of EA and urolithins on probiotic bacteria was investigated at the levels of fecal microbiota and individual strains via anaerobic culturomics and metabolomics approaches. Results indicate that dietary-level EA favorably regulated gut microbial composition through the enrichment of probiotic genera (e.g., Bifidobacterium and Akkermansia ) in vitro . Regarding individual bacteria, EA supplementation promoted the growth of Lacticaseibacillus rhamnosus GG and Bifidobacterium infantis . Integrated targeted and untargeted metabolomic analyses of intracellular and extracellular metabolites revealed that EA/urolithins modulated metabolic pathways associated with amino acid metabolism, energy production and oxidative stress. Furthermore, G. uro exhibited strong EA uptake ability, facilitating the urolithin bioconversion and cellular accumulation in a dose-dependent manner. Overall, this study provides in-depth understanding on how dietary polyphenols with prebiotic properties regulate the growth and metabolic functions of probiotic-like bacteria.
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Theranostics
·
2020
·
IF 8.579
Qingqing Tian,Lu An,Qiwei Tian,Jiaomin Lin,Shiping Yang
Rationale : Chemodynamic therapy (CDT) based on the Fe(II)-mediated Fenton reaction is an emerging tumor treatment strategy. However, the catalytic efficiency in tumors is crucially limited by Fe(II). Herein, an endogenous hydrogen sulfide (H 2 S) accelerated Fe(III)/Fe(II) transformation and photothermal synergistically enhanced CDT strategy based on ellagic acid-Fe-bovine serum albumin (EA-Fe@BSA) nanoparticles (NPs) was developed for colon tumor inhibition. On the one hand, the Fe(III) with low catalytic activity in the EA-Fe@BSA NPs could be rapidly reduced to the highly active Fe(II) by the abundant H 2 S in colon cancer tissues. Thus, a rapid Fe(III)/Fe(II) conversion system was established, wherein highly active Fe(II) ions were continuously regenerated to improve the CDT efficiency. On the other hand, the photothermal effect of EA-Fe@BSA NPs also accelerated the production of hydroxyl radicals (•OH), thereby synergistically enhancing the CDT performance and improving the therapeutic efficacy. Methods : The endogenous H 2 S accelerated Fe(III)/Fe(II) conversion and PTT enhanced CDT were investigated by characterization of the Fe valence state and detection of •OH. T 1 -weighted magnetic resonance imaging (MRI) was tested both in vitro and in vivo . The biocompatibility of NPs were examined via MTT assay, hemolysis analysis and routine blood measurements. The enhanced CDT was investigated in HCT116 colon cancer cells by Calcein-AM/PI staining and MTT assay, and tumor inhibition was demonstrated in HCT116 tumor bearing mice. Results : In this work, EA-Fe@BSA NPs were constructed as a CDT theranostic reagent. The H 2 S accelerated Fe(III)/Fe(II) conversion was confirmed, more degradation of MB and generation of •OH demonstrated the enhanced CDT in vitro . EA-Fe@BSA NPs exhibited good T 1 -weighted MRI performance. More importantly, it displayed strong near-infrared (NIR) absorption and excellent photothermal efficiency, further promotes the production of •OH. Hence, the efficacy of CDT was enhanced, and the tumor growth was inhibited efficiently. Conclusion : All results demonstrate that this strategy based on endogenous H 2 S promoted Fe(III)/Fe(II) transformation together with PTT acceleration permits efficient Fenton-reaction- mediated CDT both in vitro and in vivo , which holds great potential for effective colon cancer theranostics.
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Scientific Reports
·
2018
·Vol. 8
·期 1
·1-10
·
IF 4.122
Chen Peng,Chen Fuchao,Zhou Benhong
Accumulating evidence has suggested that oxidative stress and apoptosis are involved in the ageing process. D-galactose (gal) has been reported to cause symptoms of ageing in rats, accompanied by liver and brain injuries. Our study aimed to investigate the potential antioxidative, anti-inflammatory and anti-apoptotic effects of ellagic acid and to explore how these effects act on rats in a D-gal-induced ageing model. Ageing was induced by subcutaneous injection of D-gal (100 mg/kg/d for 8 weeks). Ellagic acid was simultaneously administered to the D-gal-induced ageing rats once daily by intragastric gavage. Finally, the mental condition, body weight, organ index, levels of inflammatory cytokines, antioxidative enzymes, and liver function, as well as the expression of pro- and anti-apoptotic proteins, were monitored. Our results showed that ellagic acid could improve the mental condition, body weight, organ index and significantly decrease the levels of inflammatory cytokines, normalize the activities of antioxidative enzymes, and modulate the expression of apoptotic protein in ageing rats. In conclusion, the results of this study illustrate that ellagic acid was suitable for the treatment of some ageing-associated problems, such as oxidative stress, and had beneficial effects for age-associated diseases.
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