MOLECULES
·
2023
·Vol. 29
·期 1
·66
·
IF 4.6
Meng Zhang,Xue Zhuang,Siqi Li,Yansong Wang,Xiangyu Zhang,Jinlian Li,Dongmei Wu
Binary ethosome vesicles have been developed as flexible lipid vesicles for the enhanced physicochemical stability and skin delivery of drugs. This work aimed to prepare phloretin-loaded propylene glycol ethosomes (PHL-PGEs) to improve their stability, skin permeability and antioxidant activity. PHL-PGEs were prepared via the ethanol injection method and optimized using different weight ratios of ethanol to propylene glycol (PG). When the ethanol/PG mass ratio changed from 10:0 to 0:10, the encapsulation efficiency and stability of ethosomes increased. At a PHL concentration of 1mg/mL, the EE% was 89.42 ± 2.42 and the DL% was 4.21 ± 0.04, which exhibited their highest values. The encapsulation of the PHL in the PHL-PGEs was strengthened via XRD analysis and FTIR analysis. The results of the in vitro percutaneous permeability test demonstrated that the combined use of ethanol and PG exhibited a notable enhancement in skin permeability, and the skin retention of PHL-PGEs was 1.06 times that of PHL-ethosomes (PHL-Es) and 2.24 times that of the PHL solution. An in vitro antioxidant activity study indicated that solubility and antioxidant activity was potentiated via the nanoencapsulation of phloretin. Therefore, these results confirm the potential of this nanocarrier to enhance physicochemical stability, skin permeability and antioxidant activity.Keywords:binary ethosomes;propylene glycol;skin permeability;antioxidant activity
研究领域:
药剂学
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皮肤科学
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生物化学
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PubMed
高影响因子
RSC Advances
·
2023
·Vol. 13
·期 50
·35429-35434
·
IF 3.9
Liang Li,Mao Qiang Wang,Feng Duan,Jin Long Zhang,Bing Yuan,Bao Cui,Heng Zhang,Jie Yu Yan
Transcatheter arterial embolization is an effective treatment for liver cancer. However, the development of novel embolic agents remains a challenge. In this study, we evaluated polyacrylic acid microspheres loaded with phloretin and tantalum as potential embolic agents for liver cancer treatment. Microspheres were synthesised via emulsion polymerisation and characterised in terms of size, shape, and drug-loading efficiency. Nanosized tantalum powder (0 to 15%) was added to the microspheres as an X-ray blocking agent. The maximum drug-loading capacity of the microspheres was approximately 20 mg g−1. The phloretin-loaded microspheres showed a sustained drug release profile in vitro. The microspheres were also evaluated for their in vivo anticancer efficacy in a rabbit VX2 liver tumour model. In conclusion, polyacrylic acid microspheres loaded with phloretin and tantalum have great potential as novel embolic agents for transcatheter arterial embolization for liver cancer treatment.
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高影响因子
POULTRY SCIENCE
·
2021
·
IF 3.352
Hong Hu,Xi Bai,Kexing Xu,Cheng Zhang,Liang Chen
ABSTRACT The objective of this work was to evaluate the effect of phloretin on growth performance, serum biochemical parameters, antioxidant profile, glutathione ( GSH )-related enzymes, nuclear factor erythroid 2–related 2 ( Nrf2 ) and heat shock protein 70 ( HSP70 ) in heat-stressed broilers. A total of 240, 22-day-old Arbor Acres broilers were divided into 4 groups. The control group was housed at 23.0 ± 0.61°C and fed with basal diet, while the 3 heat-stressed groups (A, B, and C groups) were housed at 30.5 ± 0.69°C and fed with basal diet containing 0, 100, and 200 mg/kg phloretin, respectively. Serum was taken form 42-day-old broilers. Results showed that heat stress decreased ( P < 0.05) the final body weight ( FBW ), body weight gain ( BWG ), feed intake ( FI ), serum total protein ( TP ), triglyceride ( TG ), triiodothyronine (T3), thyroxine ( T4 ), GSH, catalase ( CAT ), and total antioxidant capacity ( T-AOC ) levels, but increased ( P < 0.05) the feed-to-gain ratio ( FGR ) and serum malondialdehyde ( MDA ) levels in broilers compared with that in the control group. Among the heat-stressed groups, supplementary 200 mg/kg phloretin increased ( P < 0.05) the FBW, BWG, FI, serum TP, TG, T4, GSH, CAT, and T-AOC levels, and decreased ( P < 0.05) the FGR and serum MDA in broilers. There were significant decreases ( P < 0.05) in the glutathione peroxidase ( GSH-Px ), γ-glutamylcysteine synthetase ( γ-GCS ), and Nrf2, but significant increases ( P < 0.05) in the HSP70 of the broiler serum after heat stress treatment. Among the heat-stressed groups, supplementary 200 mg/kg phloretin increased ( P < 0.05) the GSH-Px, γ-GCS, and Nrf2 levels, but decreased ( P < 0.05) the serum HSP70 level in the heat-stressed broilers. Under high temperature condition, FBW, BWG, FI, FGR, serum TP, TG, T4, MDA, GSH, CAT, T-AOC, GSH-Px, γ-GCS, Nrf2 and HSP70 were linearly affected by inclusion of phloretin. These results indicated that phloretin may improve growth performance, serum parameters, and antioxidant profiles through regulated GSH-related enzymes, Nrf2 and HSP70 in heat-stressed broilers.
研究领域:
家禽科学
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动物营养
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生理学
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生物化学
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PubMed
高影响因子
PHYTOMEDICINE
·
2026
·
IF 11.3
Renwei Lu,Ruyi Zhao,Panpan Lian,Gang Chen,Ranran Wang,Junaid Wazir,Bojie Ma,Chaode Gu,Wenyuan Pu,Li Li,Zhiqiang Huang,Zhonglan Su,Da Huo,Hongwei Wang
Background Psoriasis is a chronic inflammatory skin disease characterized by keratinocyte hyperproliferation and immune dysregulation. Although the natural flavonoid Phloretin (Phl) shows anti-inflammatory potential, its poor bioavailability limits its therapeutic use. Purpose This study aimed to elucidate the antipsoriatic mechanism of Phl and develop a targeted, thermoresponsive nanodelivery system to enhance its efficacy for topical treatment. Methods The therapeutic effects of Phl were assessed in an imiquimod (IMQ)-induced psoriasis mouse model. Network pharmacology, molecular docking, and molecular dynamics simulations were used to predict and verify the binding stability of Phl with its potential targets. Quantitative proteomics was conducted to provide a global view of the proteomic shifts and affected pathways. These results were validated in vivo and in cytokine-stimulated HaCaT keratinocytes using western blotting, RT-qPCR, and immunofluorescence. Phl-loaded thermoresponsive phase-change material nanoparticles (PCM-Phl) were synthesized, characterized, and evaluated both in vitro and in vivo . Results Phl administration significantly ameliorated erythema, scaling, and epidermal hyperplasia in psoriatic mice. This effect was mediated through the concurrent inhibition of the STAT3 and NF-κB signaling pathways, which suppressed keratinocyte hyperproliferation, aberrant differentiation, and proinflammatory cytokine expression. The PCM-Phl formulation prolonged drug retention at the lesion site, triggered by the inherent hyperthermia of psoriatic lesions and near-infrared irradiation, and demonstrated superior therapeutic outcomes compared to free Phl, achieving a more profound and sustained inhibition of the target pathways. Conclusion This study identified dual inhibition of STAT3 and NF-κB as key mechanisms for the antipsoriatic activity of Phl. Furthermore, it presents a promising thermoresponsive nanodelivery strategy that overcomes the biopharmaceutical barriers of Phl, offering a novel approach for topical treatment of psoriasis.
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高影响因子
Science China-Life Sciences
·
2020
·Vol. 63
·期 11
·1734-1743
·
IF 4.611
Jiang Chunmei,Liu Xiaonan,Chen Xianqing,Cai Yi,Zhuang Yibin,Liu Tian,Zhu Xiaoxi,Wang Hui,Liu Yuwan,Jiang Huifeng,Wang Wen
Phloretin is an important skin-lightening and depigmenting agent from the peel of apples. Although de novo production of phloretin has been realized in microbes using the natural pathway from plants, the efficiency of phloretin production is still not enough for industrial application. Here, we established an artificial pathway in the yeast to produce phloretin via assembling two genes of p -coumaroyl-CoA ligase (4CL) and chalcone synthase (CHS). CHS is a key enzyme which conventionally condenses a CoA-tethered starter with three molecules of malonyl-CoA to form the backbone of flavonoids. However, there was 33% of by-product generated via CHS by condensing two molecules of malonyl-CoA during the fermentation process. Hence, we introduced a more efficient CHS and improved the supply of malonyl-CoA through two pathways; the by-product ratio was decreased from 33% to 17% and the production of phloretin was improved from 48 to 83.2 mg L −1 . Finally, a fed-batch fermentation process was optimized and the production of phloretin reached 619.5 mg L −1 , which was 14-fold higher than that of the previous studies. Our work established a platform for the biosynthesis of phloretin from the low-cost raw material 3-(4-hydroxyphenyl) propanoic acid and also illustrated the potential for industrial scale bio-manufacturing of phloretin.
研究领域:
生物技术
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生物化工
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代谢工程
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PubMed
高影响因子
International Journal of Pharmaceutics-X
·
2025
·
IF 6.4
Teng Xiao,Fanghong Wang,Ye Li,Gaoyang Lin,Xiaochen Wu
Acute kidney injury (AKI) is a severe clinical condition with high morbidity and mortality, often triggered by nephrotoxic drugs like cisplatin. The cGAS/STING pathway, activated by DNA damage, plays a critical role in cisplatin-induced AKI. This study explores the potential of phloretin-loaded selenium nanoparticles (Phl/HS15-Se) as a therapeutic strategy to mitigate cisplatin-induced nephrotoxicity. Phloretin, a natural flavonoid with antioxidant properties, was encapsulated in polyethylene glycol (15)-hydroxy stearate (HS15) micelles and combined with selenium nanoparticles to enhance its renal protective effects. The in vitro and in vivo experiments demonstrated that Phl/HS15-Se significantly reduced oxidative stress, DNA damage, and inflammation by inhibiting the cGAS/STING pathway. In a cisplatin-induced AKI mouse model, Phl/HS15-Se alleviated renal pathological injury, improved renal function, and reduced the expression of inflammatory markers. This study provides a promising nanomedicine approach for the treatment of cisplatin-induced AKI by targeting the cGAS/STING pathway.
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高影响因子
FOOD RESEARCH INTERNATIONAL
·
2026
·
IF 8.8
Hong Li,Haiying Cui,Tariq Aziz,Ashwag Shami,Abdelrahman R. Ahmed,Fakhria A. Al-Joufi,Lin Lin
Inhibitory mechanism of phloretin on the AgrA LytTR- agr complex was revealed. • The AgrA LytTR domain protein was purified successfully. • EMSA confirmed phloretin may disrupt the binding of AgrA LytTR domain and P3 promoter. • MD simulations revealed that phloretin sterically hindered AgrA- agr binding, validated by mixed fluorescence quenching. • Phloretin acts as QSI to inhibit the secretion of enterotoxin and hemolysin in beef. Staphylococcus aureus ( S. aureus ) represents a major foodborne pathogen whose enterotoxin production poses significant challenges to food safety due to its high environmental resistance and limited efficacy of conventional sterilization. Since the expression of enterotoxins is predominantly governed by the agr quorum sensing system, targeting this regulatory pathway has become a strategic choice for virulence control. This study elucidated the mechanism by which phloretin, a potential quorum sensing inhibitor, interferes with the agr system to attenuate virulence. To achieve this, the recombinant AgrA LytTR domain was expressed and purified, and its interaction with phloretin was characterized using thermal shift assays (TSA), electrophoretic mobility shift assays (EMSA), and molecular dynamics (MD) simulations. The results showed that phloretin specifically binds to the AgrA LytTR domain, enhancing its thermal stability and disrupting AgrA LytTR- agr operon binding by reducing the free energy of interaction between them, without causing significant structural rearrangement. Mechanistic analysis indicated that phloretin sterically hinders key β -sheet turn residues (HIS169, ASN201, ARG233), thereby impairing DNA recognition, downregulating RNAIII transcription, and inhibiting agr signaling. In cooked beef, phloretin significantly inhibited the secretion of enterotoxins and α -hemolysin, while delaying lipid oxidation and protein degradation, and maintaining the meat texture. These findings suggested that phloretin is a multifunctional substance with anti-virulence, antioxidant, and preservative properties, demonstrating its potential as a natural food preservative. Download: Download high-res image (118KB) Download: Download full-size image
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高影响因子
FOOD RESEARCH INTERNATIONAL
·
2026
·
IF 8.8
Qianqian Liang,Yan Li,Xuehua Zhang,Xin Jiang,Dajun Wang,Wenzheng Shi
Phloretin acted as a reversible competitive inhibitor of MBSP. • Phloretin interacted with MBSP via hydrogen bonds and van der Waals forces. • The binding affinity of phloretin for MBSP was stronger at 55 °C than at 4 °C. • At least one optimal phloretin binding site was present on the MBSP. This study aims to investigate the inhibitory effect of phloretin on myofibril-bound serine proteinase (MBSP) activity in grass carp and its underlying mechanism. The results showed that phloretin acted as a reversible competitive inhibitor of MBSP. Phloretin exhibited static quenching of MBSP, and it primarily interacted with MBSP through hydrogen bonds and van der Waals forces, with at least one optimal binding site on MBSP. Concurrently, molecular dynamics simulations confirmed the binding affinity was stronger at 55 °C compared to 4 °C. With rising phloretin concentration, the α -helix content of MBSP first increased and then decreased, an effect more pronounced at 55 °C. MBSP surface hydrophobicity decreased initially before increasing, while mean size and PDI value gradually increased, with both trends being more evident at 55 °C. These findings could provide guidance for the use of phloretin as a natural inhibitor of MBSP and for enhancing the quality of heat-processed aquatic products. Download: Download high-res image (304KB) Download: Download full-size image
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高影响因子
FOOD RESEARCH INTERNATIONAL
·
2021
·
IF 6.475
Zheng Hu,Hualin Wang,Linlin Li,Qian Wang,Suwei Jiang,Minmin Chen,Xingjiang Li,Jiang Shaotong
This study demonstrates a pH-responsive antibacterial film based on polyvinyl alcohol/poly (acrylic acid) incorporated with aminoethyl-phloretin (PVA/PAA-AEP) for intelligent food packaging. The thermal, mechanical, barrier and light transmittance properties of PVA/PAA are enhanced by PAA presence of ≤6%. The interactions between PVA and PAA were hydrogen and ester bonds. The pH-responsive characteristic is dependent on the protonation/deprotonation tendency of the carboxylic groups on PAA in acidic/alkaline environment. The PVA/PAA3 is selected for the incorporation of AEP and its pH-responsive swelling follows Ritger-Peppas and Schott second-order models. The AEP is hydrogen bonded with the matrix of PVA/PAA3 and the release of AEP is pH-responsive and a rate-limiting step following the First-order model. With pH decrease, the predominant release control was gradually changing from polymer relaxation to Fick diffusion. The PVA/PAA3-AEP films demonstrate AEP content dependent antioxidant and antimicrobial activities. Furthermore, the antibacterial efficiency against Listeria monocytogenes and Staphylococcus aureus is significantly better than Escherichia coli . The target film PVA/PAA3-AEP3 can effectively prolong the shelf-life of pork (TVB-N < 25 mg/100 g) by 4 days at 25 °C, suggesting its great potential in intelligent food packaging.
研究领域:
食品科学
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材料科学
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DOI
PubMed
高影响因子
Stress Biology
·
2025
·Vol. 5
·期 1
·74
·
IF 5.8
Li Jie,Jiang Enhui,Zhang Mengyang,Pan Chuanying,Lei Chuzhao,Han Lin,Lan Xianyong
Ferroptosis has been increasingly implicated in adipose and muscle dysfunction, systemic metabolic disturbances, and several diseases in livestock, which necessitates effective and side-effect-free inhibition strategies. Phloretin, a dihydrochalcone with excellent antioxidant and anti-inflammatory properties, may have the potential to restrain cell ferroptosis. Herein, phloretin was verified to significantly inhibit (1S,3R)-RSL3-induced ferroptosis by reducing intracellular MDA, Fe 2 ⁺, and ROS levels and restoring cell total antioxidant capacity in bovine and mouse preadipocytes or myoblasts. It also alleviated oxidative stress (OS), a vital inducer of ferroptosis, by restoring antioxidant enzyme activity in the above cells and obese mice. In vivo, phloretin gavage significantly reversed the trend where high-fat diet (HFD)-induced OS promoted the expression of ferroptosis-promoting genes and proteins (e.g., ACSL4 and PTGS2) while inhibiting the expression of ferroptosis-negative regulators (e.g., Fth1 and Gpx4 ). Unlike most flavonoids that exert anti-inflammatory or antioxidant activities by altering the gut microbiota composition, metagenomic sequencing analysis of cecal contents from phloretin-gavaged and HFD mice revealed that phloretin exerts its antioxidative and ferroptosis-inhibitory effects independent of modulating gut microbiota diversity. Further transcriptomic analyses of mouse adipose tissues revealed that phloretin alleviated ferroptosis in adipocytes by modulating the transcription of genes enriched in AMPK and PPAR signaling pathways, such as Camkk2 . Hence, based on multi-omics analysis combined with in vivo and in vitro verification, phloretin effectively alleviated the OS to further inhibit ferroptosis of adipose or muscle cells through the AMPK-PPAR pathway, which can provide new research ideas for ameliorating adipose or myocyte dysfunction induced by ferroptosis in animals. Graphical
研究领域:
细胞生物学
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分子生物学
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动物科学
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营养学
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代谢紊乱
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氧化应激研究
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药理学
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2025
·
IF 8.3
Linlin Ding,Qingjie Li,Kaige Qi,Yonghui Chen,Na Hu,Sangyu Hu,Tianqi Fang,Shuang Guan,Jianfeng Wang,Jiazhang Qiu,Xuming Deng,Lei Xu
Background Salmonella pullorum ( S. pullorum ) is an enteric pathogen that impairs growth performance, leading to substantial economic losses. Evidence demonstrates that the natural flavonoid phloretin can modulate intestinal microbiota functionality, and which underpins its therapeutic efficacy in ameliorating gastrointestinal disorders. However, the protective effects of phloretin against S. pullorum infections and underlying mechanisms remain unelucidated. Purpose This study aimed to elucidate the protective effects and mechanisms of phloretin in improving defense against S. pullorum infection by modulating gut microbiota in chicks. Methods H&E staining, RT-qPCR and ELISA assays were used to assess the protective potentials of phloretin in S. pullorum -infected chicks. Then, 16S rRNA gene sequencing and untargeted metabolomics were employed to identify key microbiota and metabolites regulating the intestinal microenvironment. Moreover, fecal microbiota transplantation (FMT) and dietary metabolite supplementation were conducted to reshape the gut microbiota, elucidate the interaction between the microbiota and S. pullorum infection. Results Phloretin treatment alleviated intestinal injury and enhanced growth performance in S. pullorum -infected chicks via improved intestinal barrier integrity, suppression of inflammatory responses, and restructuring of gut microbial composition. Additionally, these beneficial effects were also observed following FMT from phloretin-treated donors. Subsequent microbial and untargeted metabolomic analysis revealed that phloretin significantly enriched abundance of the functional bacterium Faecalibacterium , and the microbiota-derived phenylalanine metabolites 3-phenylpropionic acid (3-PPA). Importantly, 3-PPA supplementation attenuates S. pullorum -induced intestinal barrier damaged and inflammation in chicks through modulation of the AhR/IL-22/STAT-3 signalling axis. Conclusion These findings provide new insights into the therapeutic potentials of phloretin for S. pullorum -infected chicks.
研究领域:
微生物学
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免疫学
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分子生物学
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兽医学
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代谢组学
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药理学
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PubMed
高影响因子
JOURNAL OF FOOD SCIENCE
·
2024
·Vol. 89
·期 12
·8398-8409
·
IF 3.2
Junguo Wang,Hongyue Wang,Keshuang Guo,Xindi Zhang,Xiangrong Zhang
The purpose of this study was to prepare and evaluate the formulation of nanoemulsions (NEs) to encapsulate phloretin (PT) to improve its stability, antioxidant, and tyrosinase inhibitory competence. The aim of this study was to improve the stability, antioxidant, and tyrosinase inhibitory effects of PT via NEs. The formulations were prepared using low energy emulsification method for PT-VE-NEs, α -tocopherol (Vitamin E) and medium chain triglycerides (MCT) were used as the oil phase, and Tween 60 was used as the emulsifier and PEG-400 as the co-emulsifier. The droplet size and zeta potential of oil-in-water NEs were evaluated using dynamic light scattering. The PT-VE-NEs were also characterized by transmission electron microscopy and Fourier transform infrared spectroscopy. The mean droplet diameter was 14.85 ± 0.14 nm, with a zeta potential of −2.47 ± 0.51 mV. Fourier transform infrared spectroscopy revealed the formation of molecular interactions in the NEs formulations. PT-VE-NEs size was maintained the same during the in vitro digestion study. The particle size of PT-VE-NE remained stable during in vitro digestion. The addition of VE significantly improved the antioxidant, tyrosinase inhibitory effects, as well as thelion and physical stability of PT-VE-NE. The results revealed that NEs is a promising strategy to improve the functionality and stability of PT and VE. PT-VE-NEs will be applied for the preservation of fruits.
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高影响因子
危险品化学品经营许可证（带存储）