Heliyon
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2019
·
IF 0
Chunli Liu,Chunlong Yuan,Hosahalli S. Ramaswamy,Yamei Ren,Xiaolin Ren
The antioxidant activities in vitro and hepatoprotective effects against carbon tetrachloride (CCl 4 ) induced acute liver injury in vivo of myristic acid acylated derivative of phloridzin (PZM) were investigated. The PZM was obtained by enzymatic acylation of myristic acid and phloridzin (PZ). The antioxidant capability of PZM in vitro was evaluated by the ferric reducing antioxidant power assay (FRAP), 2,2′-Azinobis- 3-ethylbenzthiazoline-6-sulphonate (ABTS + ·) and 2,2-diphenyl-1-picrylhydrazyl (DPPH·) radical scavenging assay. Mice were intragastrically treated with control or PZM (20, 40, and 80 mg/kg) for 5 days and intra-peritoneal injection with CCl 4 . The enzymatic acylated synthesis of myristic acid and phloridzin was region-selective taken place on 6″-OH of phloridzin glycoside moiety and achieved 93% yield. PZM had a significantly higher total antioxidant ability, same scavenging ABTS + · ability and weaker scavenging DPPH· ability when compared to the parent PZ. The of aminotransferase serum activity and malondialdehyde hepatic activity were elevated (P < 0.015) after treatment with CCl 4 , while the related liver enzymatic activities and glutathione concentration were lower. These changes were enhanced by PZM. Further studies showed that PZM reduced the interleukin-6 expression and stimulated liver regeneration caused by CCl 4 . PZM attained good antioxidant capacity in vitro and had excellent hepatoprotective effects in vivo and better bioactivity compared to the parent phloridzin. The significance of hepatoprotective effect of phloridzin derivative against CCl 4 -induced hepatotoxicity in mice is an important and new finding.
研究领域:
药理学
·
生物化学
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PubMed
JOURNAL OF GENERAL VIROLOGY
·
2024
·Vol. 105
·期 5
·001996
·
IF 3.6
Yuting Duan,Haichuan Li,Shuai Huang,Yaoming Li,Shuyi Chen,Lilan Xie
Transmissible gastroenteritis virus (TGEV), an enteropathogenic coronavirus, has caused huge economic losses to the pig industry, with 100% mortality in piglets aged 2 weeks and intestinal injury in pigs of other ages. However, there is still a shortage of safe and effective anti-TGEV drugs in clinics. In this study, phloretin, a naturally occurring dihydrochalcone glycoside, was identified as a potent antagonist of TGEV. Specifically, we found phloretin effectively inhibited TGEV proliferation in PK-15 cells, dose-dependently reducing the expression of TGEV N protein, mRNA, and virus titer. The anti-TGEV activity of phloretin was furthermore refined to target the internalization and replication stages. Moreover, we also found that phloretin could decrease the expression levels of proinflammatory cytokines induced by TGEV infection. In addition, we expanded the potential key targets associated with the anti-TGEV effect of phloretin to AR, CDK2, INS, ESR1, ESR2, EGFR, PGR, PPARG, PRKACA, and MAPK14 with the help of network pharmacology and molecular docking techniques. Furthermore, resistant viruses have been selected by culturing TGEV with increasing concentrations of phloretin. Resistance mutations were reproducibly mapped to the residue (S242) of main protease (Mpro). Molecular docking analysis showed that the mutation (S242F) significantly disrupted phloretin binding to Mpro, suggesting Mpromight be a potent target of phloretin. In summary, our findings indicate that phloretin is a promising drug candidate for combating TGEV, which may be helpful for developing pharmacotherapies for TGEV and other coronavirus infections.
研究领域:
病毒学
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药理学
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分子生物学
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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
PHYTOMEDICINE
·
2026
·
IF 8.3
Chong Gao,Wei Liu,Sai-Hu Liu,Shuang Zheng,Chen-Yu Wang,Xu Dai,Li-Hua Lian,Zhen-Yu Cui,Ji-Xing Nan,Yan-Ling Wu
Background Reprogramming of aerobic glycolysis occurs with HSCs activation and is associated with regression of liver fibrosis. Trigonelline (TRG), a plant alkaloid extracted from Trigonella foenum-graecum L seeds, has a variety of pharmacological effect. Purpose The current study investigated the hepatoprotective effect and mechanism of TRG against hepatic fibrosis by regulating glycolysis. Methods Anti-hepatic fibrosis effects of TRG were detected in thioacetamide (TAA)-induced hepatic fibrosis mice. HSCs or LX-2 were stimulated with TGF-β or conditioned medium (CM) from LPS-stimulated THP-1, then incubated with TRG, phloretin (PHL), rosiglitazone (RGZ), siRNA Glut-1 or plasmid with Glut-1. Results TRG significantly reduced serum transaminase levels, liver histopathological changes, excessive collagen deposition, inflammatory response, and neutrophil recruitment in TAA-induced mice. TAA increased hepatic Glut-1, HIF-1α and key enzymes of glycolysis expressions, while TRG completely reversed this effect. TRG also obviously regulated the combination of Glut-1 and HIF-1α to affect glycolysis in activated HSCs. TRG could inhibit α-SMA, IL-6, IL1R1, and HIF-1α expressions accompanying inhibition of Glut-1, function as PHL (Glut-1 inhibitor). Glut-1 silencing weakened α-SMA, IL-6, IL1R1, and HIF-1α expressions and enhanced the effect of TRG in activated LX-2. TRG inhibited LX-2 activation caused by Glut-1 overexpression, even demonstrated in interaction between LX-2 and macrophages. Further, TRG shown that improved fibrogenesis and inflammatory response by inhibiting Glut-1 compared with PHL in vivo . Conclusion TRG could ameliorate hepatic fibrosis through inhibiting ECM excessive deposition and inflammatory response. Inhibiting Glut-1-HIF-1α axis and glycolysis was a potential therapeutic strategy for TRG ameliorating liver microenvironment, further against hepatic fibrosis.
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高影响因子
MATERIALS & DESIGN
·
2026
·
IF 8.2
Feng Li,Wei Tian,Quan Ma,Weiliang Qian,Binghua Liu,Yanan Zhang,Kailong Zhang,Yongliang Chen,Fan Zhao
A copper-phloretin nanoplatform (Cu-Phl MPN) selectively targets respiration-active prostate cancer cells through cuproptosis vulnerability. • Cu-Phl MPNs block GLUT1-mediated glucose uptake, suppressing copper efflux and chelation to amplify intracellular Cu + accumulation. • The nanoplatform synergistically triggers apoptosis and cuproptosis, achieving potent antitumor efficacy with high biosafety. Prostate cancer (PCa) cells, characterized by sustained high mitochondrial respiratory activity following malignant transformation, possess intrinsic sensitivity to cuproptosis, rendering them suitable candidates for cuproptosis-induced therapies. By exploiting this metabolic vulnerability, tumor microenvironment-responsive copper-based metal-phenolic networks (Cu-Phl MPNs) were developed via self-assembly of Cu 2+ and phloretin to synergistically induce of apoptosis and cuproptosis in respiration-active PCa cells. Following cellular internalization, Cu-Phl MPNs underwent glutathione (GSH) responsive degradation, co-releasing Cu + and Phl. The liberated Phl specifically interrupted GLUT1-mediated intracellular glucose supply, suppressing ATP and NADPH synthesis. ATP depletion downregulated the copper exporter ATP7A and curbed copper efflux, while impaired NADPH production compromised GSH regeneration and diminished copper chelation, collectively facilitating intracellular Cu + accumulation. The accumulated Cu + drove a Fenton-like reaction to generate reactive oxygen species, which disrupted redox homeostasis and triggered mitochondrial apoptosis. Meanwhile, cuproptosis could be efficiently activated under the combination of excess Cu + and inherent sensitivity. Both in vitro and in vivo results demonstrated that Cu-Phl MPNs exerted potent and selective antitumor efficacy against respiration-active LNCaP cells while exhibiting minimal toxicity toward glycolysis-dependent PC3 cells, with favorable biosafety profiles. This work presents a metabolism-directed nanoplatform that aligns therapeutic mechanisms with tumor intrinsic features for precision PCa therapy. Download: Download high-res image (197KB) Download: Download full-size image
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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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JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2025
·
IF 9.7
Runze Wang,Wenting Cheng,Hailong Tian,Mengchao Dong,Weifeng He,Xie Wang,Yingying Zou
Diabetic wounds represent a significant clinical challenge owing to infection, oxidative stress, and immune dysregulation. In this study, a multifunctional photoimmunotherapy nanoplatform (I-P-T NPs) was developed through the self-assembly of the near-infrared photosensitizer IR820, the immunomodulatory agent thymopentin (TP5), and the antioxidant phloretin (Phl) via intermolecular hydrogen bonding and hydrophobic interactions. This nanoplatform integrates photothermal therapy (PTT), immune modulation, and reactive oxygen species scavenging to address the infection–oxidation–immunosuppression triad in diabetic wounds. The I-P-T NPs exhibited robust photothermal conversion under 808 nm irradiation, generating localized hyperthermia with antibacterial effects. In vitro experiments demonstrated that I-P-T NPs promoted M2 macrophage polarization, reduced oxidative stress, enhanced endothelial and keratinocyte migration, and suppressed pro-inflammatory cytokine release. Additionally, the nanoplatform displayed potent antibacterial activity against both Gram-positive and Gram-negative bacteria. In a streptozotocin-induced diabetic mouse model with infected wounds, topical application of I-P-T NPs combined with photothermal treatment accelerated wound closure, enhanced re-epithelialization and collagen deposition, and mitigated inflammation. The self-assembled design improved the solubility of Phl and enabled spatiotemporally controlled delivery of multiple therapeutic components. No significant systemic toxicity was observed, confirming the biocompatibility of I-P-T NPs. This study presents a novel nanoplatform that synergistically combines photothermal sterilization, TP5-mediated immune regulation, and Phl-driven antioxidant effects, offering a promising strategy for managing complex diabetic wounds. This modular design highlights the potential for translating multifunctional nanotherapies into clinical applications for the treatment of chronic wounds.
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高影响因子
FOOD CHEMISTRY
·
2025
·
IF 9.8
Qianqian Liang,Xin Jiang,Dajun Wang,Shumin Zhang,Qifei Hua,Wenzheng Shi
The effects of myofibril-bound serine protease (MBSP) inhibitors screened by molecular docking on the activity of crude MBSP (cMBSP), the thermal degradation of myofibrillar protein (MP), and the surimi gel properties were explored in this study. The results implied that five flavor enhancers screened by molecular docking had certain inhibitory effects on cMBSP activity, and could delay the degradation of MP at 55 °C. Meanwhile, the gel strength, hardness and springiness of flavor enhancers groups were improved. And the flavor enhancer groups showed a more orderly three-dimensional network structure. Moreover, saltiness and umami of surimi gel were enhanced after adding flavor enhancers, and phloretin (PR) significantly reduced the intensity of the odor attributes of surimi gel. These results indicated that all these flavor enhancers could be used as MBSP inhibitors to improve the quality of surimi gels, and the effect of PR was relatively good.
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高影响因子
RSC Advances
·
2026
·Vol. 16
·期 9
·7717-7725
·
IF 6.1
Siyang Chen,Jinhui Jia,Jian Du,Ningbo Qin,Xiaodong Xia
Due to its capacity to form complexes with polyphenols and to self-assemble as nanoparticles, zein could be utilized as an excellent carrier for polyphenols. The objective of this study was to examine the interaction between zein and phloretin (PHL) through multispectral analysis and molecular docking, and to prepare and characterize PHL-loaded zein nanoparticles. Spectral analysis and docking data confirmed that the binding process of the zein-PHL complex is mainly influenced by hydrogen bonding and van der Waals forces, and hydrophobic interaction was auxiliary, with static quenching as the primary fluorescence quenching mechanism. Meanwhile, zein nanoparticles loaded with PHL were successfully prepared using the anti-solvent precipitation method, which was evidenced by the morphology and size characterization. The hydrogen bond and hydrophobic interaction in the nanoparticles were further confirmed by Fourier transform infrared spectroscopy. This study elucidates the noncovalent interaction mechanism between zein and PHL, providing a theoretical foundation for the design of zein-polyphenol nanocarriers. These carriers show promising applications as emulsion stabilizers or delivery systems for lipophilic bioactives, thereby facilitating the development of functional foods with improved stability and enhanced bioavailability.
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高影响因子
PLANT GROWTH REGULATION
·
2023
·Vol. 100
·期 3
·633-646
·
IF 4.2
Wang Jie,Jia Jingyu,Sun Jiaju,Pang Xinyue,Li Bairu,Yuan Jiangfeng,Chen Enyan,Li Xin
Trypsin can significantly improve the storage quality of Cucumis sativus ( C. sativus ) due to its novel superoxide scavenging activity. Based on the results of physiological indices, an integrated analysis of widely targeted metabolomics and transcriptomics was carried out, gene function was further confirmed by VIGS, a potential molecular mechanism of resistance improvement of C. sativus due to flavonoid biosynthesis induced by trypsin was proposed and discussed. Transcriptomic results showed that 1,068 genes highly related to flavonoid biosynthesis gathered in the brown module were obtained by the advanced method WGCNA. An isomeric compound of dihydrochalcone, trilobatin, was likely to be the key metabolite regulated by trypsin. Results of O2PLS and co-expression network illustrated that CsUGT91C1 acted as the hub gene which regulated the biosynthesis of flavonoids, especially trilobatin, in C. sativus . CsUGT91C1 also played as a hub node in the Protein-Protein Interactions network of WGCNA screened genes (WSGs). GO and KEGG analyses of WSGs enriched the transferase activities, especially UDP-glycosyltransferase activity and KEGG pathways of “Phenylpropanoid biosynthesis (map00940)” and “Flavonoid biosynthesis (map00941)”. Results of webtools of the PlantCARE database identified the G-box region of CsUGT91C1 , which can bind to the transcription factor CsMYC2. The expression and biological effects of CsUGT91C1 were significantly impeded by the silencing of CsMYC2 through VIGS. The results of this study might give new insight into the exploration of the postharvest resistance mechanism of C. sativus induced by trypsin and provide useful information for the subsequent mining of resistance genes in C. sativus . Graphical abstract
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Foods
·
2022
·Vol. 11
·期 23
·3793
·
IF 5.561
Yang Liu,Jiali Lin,Tiantian Cheng,Yangjie Liu,Fuliang Han
Anthocyanins are substances with multiple physiological activities widely present in red wine, but the influence of structure (methylation, hydroxylation, acylation, glycosylation) on the transport remains ill-defined. In the present study, Caco-2 monolayers were used as an in vitro model of the absorptive intestinal epithelium to transport different types of anthocyanin samples. Results showed that both methylation and acetylation promote the level of transport. Monoglycoside standard exhibited higher transport amount and rate compared to diglycoside standard while the transport level of the monoglycoside mixture was unexpectedly lower than that of the diglycoside mixture. Caco-2 monolayers appeared to be more capable of transporting the single standard than the mixed standard. Meanwhile, the transport of anthocyanins in Caco-2 cell model showed time- and concentration-dependent trends. Anthocyanin treatment had a greater effect on sodium-dependent glucose transporter 1 (SGLT1) mRNA expression than glucose transporter 2 (GLUT2), and significantly down-regulated the protein expression of SGLT1. Although the low bioavailability of anthocyanins requires much more research, further evidence of the role of structure is provided.Keywords:wine;anthocyanins;Caco-2 cell monolayer;absorption;SGLT1;GLUT2
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Journal of Ocean University of China
·
2022
·Vol. 21
·期 3
·782-788
·
IF 1.179
Zhang Pengpeng,Zhang Miaomiao,Dong Kaiyu,Zhang Yicong,Yang Shuang,Wang Yuanhong,Jiang Tingfu,Yu Mingming,Lv Zhihua
Chito-oligosaccharide (COS) had shown a variety of biological activities and potential biomedical implications. The present study investigated the pharmacokinetics, bioavailability, and in vitro absorption of COS with degrees of polymerization (DPs) 2–7 and explored the influence of DPs on them. From Caco-2 cell permeation studies, COS were low permeability compounds with no directional effects, suggesting a low in vivo absorption mediated by facilitation diffusion and paracellular absorption. After an intragastrical administration to rats, COS2 showed the highest systemic exposure in six oligosaccharides. The bioavailability of COS2–7 was 7.33%, 6.11%, 4.67%, 4.13%, 4.02%, 0.99%, respectively. Differences in bioavailability for each COS correlated to structural variations, with high DPs contributing to a decrease in bioavailability. In conclusion, COS could be absorbed by the intestinal tract both in vitro and in vivo . The very low oral bioavailability of COS could be due to low permeability. DPs can affect absorption and bioavailability of COS2–7. This study provided evidence for the absorption characteristics of COS2–7 to help us better understanding the pharmacological actions.
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高影响因子
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