AQUACULTURE
·
2026
·
IF 4.4
Peng Zhao,Chong-Chao Zhong,Nermeen Abu-Elala,Yu-Chen Zhou,Zhi-Wei Hao,Zhi Luo,Xiao-Ying Tan
This study evaluated the effects of dietary hesperetin (Hes) on growth performance, intestinal lipid deposition, oxidative stress, and inflammatory responses in largemouth bass ( Micropterus salmoides ) fed high-fat diets. A 2 × 3 factorial design was employed, consisting of two dietary lipid levels (9.85% and 17.85%) and each lipid with three hesperetin supplementation (0, 1.25, and 2.5 g/kg). High-purity hesperetin with constant chemical characterization was purchased from Aladdin Industrial Corporation (purity >97%). Six isonitrogenous diets were formulated and fed to juvenile largemouth bass (6.94 ± 0.10 g) for 10 weeks. Significant interactions between dietary lipid and hesperetin levels were observed for final body weight (FBW), weight gain (WG), specific growth rate (SGR), feed intake (FI), feed conversion ratio (FCR), and viscerosomatic index (VSI). Under high-fat condition, hesperetin improved FBW, WG, and SGR, while reducing FCR and VSI; however, opposite trends occurred at the lower lipid level. Dietary lipid and hesperetin interacted to influence intestinal villus, Srebp1 and ER-ApoB48 protein abundance, and expression of lipid metabolism-related genes ( fas , dgat2 , pparγ , abca1 , mttp , apob ). HFD significantly elevated TG content, and hesperetin decreased TG levels at both lipid levels. At both lipid levels, hesperetin downregulated mRNA expression of lipogenic genes ( fas , dgat2 , pparγ , abca1 ) and protein expression of Srebp1, increased villus width, and upregulated mttp and apob mRNA expression, although its ER-ApoB48 protein expression increased only under high-fat condition. Antioxidant enzyme activities (CAT, T-SOD), total antioxidant capacity (T-AOC), and mRNA expression of nrf2 , sod1 , sod2 , cat , gpx1 , and gpx2 were enhanced by hesperetin supplementation. In contrast, MDA content and expression of keap1 and pro-inflammatory cytokines ( tnf-α , stat1 , il-1β , il-6 , il-8 ) decreased, and anti-inflammatory il-10 expression increased at both lipid levels. Overall, hesperetin supplementation effectively mitigated HFD-induced inhibition in growth performance, intestinal lipid metabolism, oxidative status, and inflammatory signaling in largemouth bass. These findings support the application of hesperetin as a functional dietary additive for improving intestinal health in fish species.
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Foods
·
2026
·Vol. 15
·期 13
·2356
·
IF 6
Guangsen Li,Junwei Zhang,Youxiang Wu,Xiang Wang,Xin Lei,Hanyu Wei,Zhiwen Hu,Qibiao Weng,Qinhua Zhang,Chengrong Wen,Yilan Sun,Qian Ning
A KGM/CMC/PVA film loaded with a hydroxypropy-β-cyclodextrin/hesperetin (HP-β-CD/HES) inclusion complex was developed for strawberry preservation. The inclusion complex showed an encapsulation efficiency of 70.41 ± 4.01%. Loading the inclusion complex enhanced the barrier and bioactive properties of the films. At the better loading level (KCP-HH3, 1.5%), the film provided nearly complete UV shielding at 200–350 nm and showed a transmittance of approximately 21% at 800 nm. Relative to KCP, KCP-HH3 exhibited lower water vapor permeability (0.69 ± 0.06 g·mm/(m2·h·kPa)) and oxygen permeability (0.066 ± 0.006 g·mm/(m2·h·kPa)). The cumulative HES release from KCP-HH3 reached 82.43 ± 2.19% after 7 days at 98% relative humidity. KCP-HH3 scavenged 78.19 ± 3.71% of DPPH radicals and 88.89 ± 4.30% of ABTS radicals. It also inhibited Escherichia coli (91.18 ± 2.99%), Staphylococcus aureus (79.21 ± 3.45%), and Aspergillus niger (92.85 ± 2.75%). This highest-loading formulation delivered the best overall strawberry-preservation performance. After 12 days of storage, strawberries packaged with KCP-HH3 showed higher firmness (0.89 ± 0.04 N) and total soluble solids (7.96 ± 0.21%), as well as lower weight loss (14.30 ± 0.40%), than the polyethylene control, which showed a firmness of 0.42 ± 0.05 N, total soluble solids of 6.22 ± 0.20%, and weight loss of 16.36 ± 0.66%. These results support the potential of HP-β-CD/HES-loaded KCP films as biodegradable active packaging for fruit preservation.
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Frontiers in Pharmacology
·
2023
·
IF 5.6
Meng-Fei An,Chang Shen,Shao-Shi Zhang,Ming-Yue Wang,Ze-Rui Sun,Mao-Si Fan,Li-Juan Zhang,Yun-Li Zhao,Jun Sheng,Xuan-Jun Wang
Hesperetin is a natural flavonoid with many biological activities. In view of hyperuricemia treatment, the effects of hesperetin in vivo and in vitro , and the underlying mechanisms, were explored. Hyperuricemia models induced by yeast extract (YE) or potassium oxonate (PO) in mice were created, as were models based on hypoxanthine and xanthine oxidase (XOD) in L-O2 cells and sodium urate in HEK293T cells. Serum level of uric acid (UA), creatinine (CRE), and urea nitrogen (BUN) were reduced significantly after hesperetin treatment in vivo . Hesperetin provided hepatoprotective effects and inhibited xanthine oxidase activity markedly, altered the level of malondialdehyde (MDA), glutathione peroxidase (GSH-PX) and catalase (CAT), downregulated the XOD protein expression, toll-like receptor (TLR)4, nucleotide binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, interleukin-18 (IL-18), upregulated forkhead box O3a (FOXO3a), manganese superoxide dismutase (MnSOD) in a uric acid-synthesis model in mice. Protein expression of organic anion transporter 1 (OAT1), OAT3, organic cationic transporter 1 (OCT1), and OCT2 was upregulated by hesperetin intervention in a uric acid excretion model in mice. Our results proposal that hesperetin exerts a uric acid-lowering effect through inhibiting xanthine oxidase activity and protein expression, intervening in the TLR4-NLRP3 inflammasome signaling pathway, and up-regulating expression of FOXO3a, MnSOD, OAT1, OAT3, OCT1, and OCT2 proteins. Thus, hesperetin could be a promising therapeutic agent against hyperuricemia.
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Journal of Zhejiang University-SCIENCE B
·
2019
·
IF 1.879
Su-fang Gu,Li-ying Wang,Ying-jie Tian,Zhu-xian Zhou,Jian-bin Tang,Xiang-rui Liu,Hai-ping Jiang,You-qing Shen
Hesperetin, an abundant bioactive component of citrus fruits, is poorly water-soluble, resulting in low oral bioavailability. We developed new formulations to improve the water solubility, antioxidant activity, and oral absorption of hesperetin. Two nano-based formulations were developed, namely hesperetin-TPGS ( D -α-tocopheryl polyethylene glycol 1000 succinate) micelles and hesperetin-phosphatidylcholine (PC) complexes. These two formulations were prepared by a simple technique called solvent dispersion, using US Food and Drug Administration (FDA)-approved excipients for drugs. Differential scanning calorimetry (DSC) and dynamic light scattering (DLS) were used to characterize the formulations’ physical properties. Cytotoxicity analysis, cellular antioxidant activity assay, and a pharmacokinetic study were performed to evaluate the biological properties of these two formulations. The final weight ratios of both hesperetin to TPGS and hesperetin to PC were 1:12 based on their water solubility, which increased to 21.5-and 20.7-fold, respectively. The hesperetin-TPGS micelles had a small particle size of 26.19 nm, whereas the hesperetin-PC complexes exhibited a larger particle size of 219.15 nm. In addition, the cellular antioxidant activity assay indicated that both hesperetin-TPGS micelles and hesperetin-PC complexes increased the antioxidant activity of hesperetin to 4.2-and 3.9-fold, respectively. Importantly, the in vivo oral absorption study on rats indicated that the micelles and complexes significantly increased the peak plasma concentration ( C max ) from 2.64 μg/mL to 20.67 and 33.09 μg/mL and also increased the area under the concentration–time curve of hesperetin after oral administration to 16.2-and 18.0-fold, respectively. The micelles and complexes increased the solubility and remarkably improved the in vitro antioxidant activity and in vivo oral absorption of hesperetin, indicating these formulations’ potential applications in drugs and healthcare products.
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JOURNAL OF MOLECULAR LIQUIDS
·
2020
·
IF 5.065
Xingang Lv,Qilei Wang,Lang-Hong Wang,Er-Fang Ren,Deming Gong
In this work, the inhibitory effect of two citrus flavonoids naringenin and hesperetin on human purine nucleoside phosphorylase (hPNP) and their binding mechanism were evaluated. Results from enzymatic kinetics revealed that naringenin and hesperetin reversibly inhibited hPNP via a mixed-type manner with IC 50 values of 4.83 × 10 −4 M and 5.32 × 10 −4 M, respectively. Analysis of molecular modeling revealed that both naringenin and hesperetin bound directly into the active site by generating multiple forces including hydrogen bonding , π–π and π-Alkyl interactions with His64, Glu201, Ser220, His257, Phe200 and Val217 residues of hPNP, which caused the inhibition of hPNP activity. Moreover, conformational analysis by three-dimension fluorescence, circular dichroism and atomic force microscopy revealed that the binding of naringenin and hesperetin to hPNP induced changes in the microenvironment, secondary structure and morphology of hPNP. These results suggested that occupying the active site and enzymatic conformational perturbation induced by naringenin and hesperetin are the main reasons for reducing the inhibition of hPNP activity, which would be helpful in understanding the inhibitory mechanism of naringenin and hesperetin against hPNP.
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2024
·Vol. 25
·期 23
·13148
·
IF 4.9
Run-Jia Wang,Ya-Jing Ni,Yan-Qiang Liu
Hesperetin (Hst) is a common citrus fruit flavonoid with antioxidant, anti-inflammatory, and anti-neurodegenerative effects. To explore the antioxidant and anti-aging effects and mechanisms of Hst, we induced chronic oxidative stress in Caenorhabditis elegans (C. elegans) using low-concentration H 2 O 2 and examined its effects on lifespan, healthy life index, reactive oxygen species (ROS), antioxidant enzymes, and transcriptomic metrics. Hst significantly prolonged lifespan, increased body bending and pharyngeal pumping frequency, decreased ROS accumulation, and increased antioxidant enzyme activity in normal and stressed C. elegans . Hst significantly upregulated daf-18 , daf-16 , gst-2 , gst-3 , gst-4 , gst-39 , hsp-16.11 , sip-1 , clpp-1 , and dve-1 and downregulated ist-1 and kgb-1 mRNAs in stressed C. elegans . These genes are involved in the insulin/insulin-like growth factor-1 signaling (IIS), heat shock protein (HSP), mitochondrial unfolded protein response (mtUPR), and c-Jun N-terminal kinase (JNK) pathways. In summary, Hst increases lifespan and antioxidant ability, correlating with these pathways, during chronic oxidative stress in C. elegans .
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TALANTA
·
2019
·
IF 4.916
Dan-Dan Wang,Die Gao,Yi-Ke Huang,Wan-Jun Xu,Zhi-Ning Xia
A novel restricted access molecularly imprinted polymers (RAMIPs) fiber was developed for solid-phase microextraction (SPME) of hesperetin and its metabolites in livers of live rats in vivo . Hesperetin as the template, N-isopropylacrylamide as the functional monomer , ethylene glycol dimethyl acrylate as the crosslinker, 2,2-azobisisobutyonnitrile as initiator and bovine serum albumin as the restricted access material were applied in the preparation process. Scanning electron microscopy and Fourier transform infrared spectroscopy were applied to characterize the polymers. The adsorption experiments indicated that RAMIPs-SPME fibers performed high selective recognition property to hesperetin. The selectivity experiment indicated that the adsorption capacity and selectivity of RAMIPs-SPME fibers to hesperetin was higher than that of quercetin , luteolin and baicalein . Macromolecules elimination test showed RAMIPs-SPME fibers could eliminate 94.80%–98.96% of macromolecules, which indicated that RAMIPs-SPME fibers can be used to extract analytes directly from complex biological samples. Furthermore, RAMIPs-SPME sampling combined to ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was applied to capture and identify hesperetin and its metabolites in rat livers in vivo . Finally, hesperetin-7- O -glucuronide, hesperetin-3′- O -glucuronide, eriodictyol and homoeriodictyol were identified as the metabolites of hesperetin. In comparison with the MIPs fibers, commercial PDMS and DVB fibers, RAMIPs-SPME fibers possessed better exclusion effect to macromolecules and higher selectivity to hesperetin and its metabolites. The results demonstrated that the prepared RAMIPs-SPME fiber were proven to be effective tool for the selective adsorption and enrichment of hesperetin and its metabolites from the complex biological fluids.
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CHEMOSPHERE
·
2021
·
IF 7.086
Liangmei Rao,Xinyu Lu,Lulu Xu,Yifu Zhu,Ting Xue,Yu Ge,Zhongshu Duan,Xuemin Duan,Yangping Wen,Jingkun Xu
It is an urgent need to exploit a potentially green, cost efficient and eco-friendly strategy for the utilization of waste kudzu vine. We developed a one-step green preparation of kudzu vine biochar (BC) decorated graphene-like molybdenum selenide (MoSe 2 ) with the oxidase-like activity as intelligent nanozyme sensing platform for voltametric detection of hesperetin (HP) in orange peel using the in-situ hydrothermal synthesis method. The structure and properties of MoSe 2 -BC was characterized, and found that BC significantly improved electrochemical cycle stability, electronic conductivity, electrochemical active area, and electrocatalytic activity of MoSe 2 . The oxidase-like activity of MoSe 2 -BC was confirmed by the oxidization of the colorless substrate 3,3′,5,5′-tetramethylbenzidine (TMB) to form blue products and the change of absorbance intensity of UV–vis absorption spectra . The MoSe 2 -BC exhibited excellent electrochemical sensing performance for the detection of HP in wide linear ranges from 10 nM to 9.5 μM with a low limit of detection of 2 nM using differential pulse voltammetric method. An emerging machine learning technique is used to realize the intelligent sensing of HP, and the performance evaluation of regression analysis was selected to evaluate this technique. This work will provide a guidance for the preparation and application of biochar decorated graphene-like nanomaterials with the oxidase-like activity and the development of intelligent nanozyme sensing platform.
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DRUG METABOLISM AND DISPOSITION
·
2015
·Vol. 43
·期 10
·1430-1440
·
IF 3.252
Hua Sun,Xiao Wang,Xiaotong Zhou,Danyi Lu,Zhiguo Ma,Baojian Wu
Sulfonation is an important metabolic pathway for hesperetin. However, the mechanisms for the cellular disposition of hesperetin and its sulfate metabolites are not fully established. In this study, disposition of hesperetin via the sulfonation pathway was investigated using human embryonic kidney (HEK) 293 cells overexpressing sulfotransferase 1A3. Two monosulfates, hesperetin-3′-O-sulfate (H-3′-S) and hesperetin-7-O-sulfate (H-7-S), were rapidly generated and excreted into the extracellular compartment upon incubation of the cells with hesperetin. Regiospecific sulfonation of hesperetin by the cell lysate followed the substrate inhibition kinetics (Vmax = 0.66 nmol/min per mg, Km = 12.9 μM, and Ksi= 58.1 μM for H-3′-S; Vmax = 0.29 nmol/min per mg, Km = 14.8 μM, and Ksi= 49.1 μM for H-7-S). The pan–multidrug resistance-associated protein (MRP) inhibitor MK-571 at 20 μM essentially abolished cellular excretion of both H-3′-S and H-7-S (the excretion activities were only 6% of the control), whereas the breast cancer resistance protein–selective inhibitor Ko143 had no effects on sulfate excretion. In addition, knockdown of MRP4 led to a substantial reduction (>47.1%; P < 0.01) in sulfate excretion. Further, H-3′-S and H-7-S were good substrates for transport by MRP4 according to the vesicular transport assay. Moreover, sulfonation of hesperetin and excretion of its metabolites were well characterized by a two-compartment pharmacokinetic model that integrated drug uptake and sulfonation with MRP4-mediated sulfate excretion. In conclusion, the exporter MRP4 controlled efflux transport of hesperetin sulfates in HEK293 cells. Due to significant expression in various organs/tissues (including the liver and kidney), MRP4 should be a determining factor for the elimination and body distribution of hesperetin sulfates.
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FOOD RESEARCH INTERNATIONAL
·
2026
·
IF 8.8
Guangfan Qu,Jiangling Zhang,Feiyan Yang,Xu Wang,Shuguo Sun
HMP significantly reduced the oil-water interfacial tension of QT particles. • QTH particles shows a high viscoelastic interface film on the O/W interface. • Pickering HIPEs prepared from QTH particles exhibit multi-stimuli responsiveness. • Multi-responsive Pickering HIPEs improve the bioavailability of hesperetin. Protein-polyphenol composite particles are ideal carriers for bioactive substances. However, their tendency to aggregate and precipitate under weakly acidic conditions limits their broader application. This study investigated the effect of interfacial behavior of quinoa protein isolate-tannic acid (QPI-TA) particles regulated by high-methoxyl pectin (HMP) via self-assembly on the properties of Pickering high internal phase emulsions (HIPEs). Multispectral analysis demonstrated that HMP changed the hydrophobic microenvironment in QPI-TA (QT) particles, disrupted hydrogen bond structures, and triggered reassembly to form QPI-TA-HMP (QTH) composite particles. Interfacial adsorption kinetics, dilatational rheology, and quartz crystal microbalance with dissipation (QCM-D) analysis demonstrated that HMP significantly increased the interfacial pressure and adsorption rate of QT particles. The interfacial film formed by QTHs particles showed enhanced compactness, thickness, viscoelasticity, and mechanical strength relative to that of QT particles alone. Moreover, Pickering HIPEs stabilized by QTHs composite particles exhibited excellent stability and intelligent responsive properties under various oil phases, pH, centrifugation, temperature and storage conditions. Simulated in vitro digestion results demonstrated that both the release of free fatty acids and the bioaccessibility of hesperetin in hesperetin-loaded HIPEs were dramatically improved. This study demonstrates that incorporating anionic polysaccharides to optimize interfacial behavior in multi-responsive Pickering HIPEs provides a promising strategy for effective encapsulation and controlled delivery of hesperetin. Download: Download high-res image (407KB) Download: Download full-size image
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INTERNATIONAL IMMUNOPHARMACOLOGY
·
2020
·
IF 3.943
Jingyuan Wan,Ge Kuang,Li Zhang,Rong Jiang,Yongtao Chen,Zhen He,Duyun Ye
Acetaminophen (APAP) is a common antipyretic and analgesic drug, but its overdose can induce acute liver failure with lack of effective therapies. Hesperetin, a dihydrogen flavonoid compound, has been revealed to exert multiple pharmacological activities. Here, we explored the protective effects and mechanism of hesperetin on APAP-induced hepatotoxicity. The results showed that pretreatment with hesperetin dose-dependently attenuated APAP-induced acute liver injury in mice, as measured by alleviated serum enzymes activities, hepatic pathological damage and apoptosis. Moreover, hesperetin mitigated APAP-induced oxidative stress and inflammatory response in mice by inhibiting oxidative molecules but increasing antioxidative molecules production, reducing inflammatory cells infiltration and proinflammatory cytokines production, blocking Toll-like receptor (TLR)-4 signal activation. In vitro experiment indicated that hesperetin dose-dependently inhibited APAP-primed cytotoxicity, apoptosis, and reactive oxygen species (ROS) in murine AML12 hepatocytes. Notably, hesperetin up-regulated expression of heme oxygenase-1 (HO-1) mRNA and protein in the liver of mice and AML12 cells exposed to APAP. Furthermore, knockdown of HO-1 by adenovirus-mediated HO-1 siRNA reverted these beneficial effects of hesperetin on APAP-induced hepatocytotoxicity as well as ROS and inflammatory response in vivo and in vitro . These findings demonstrated that hesperetin exerted a protective prophylaxis on APAP-induced acute liver injury by inhibiting hepatocyte necrosis and apoptosis, oxidative stress and inflammatory response via up-regulating HO-1 expression.
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