JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE
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2023
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IF 4.1
Bowei Du,Chao Zhang,Guiya Deng,Shuai Zhang,Shiqi Wang,Yuepeng Guan,Yaqin Huang
Background Nowadays, the prevalence of oxidative stress-related chronic diseases is increasing. The identification of novel antioxidant collagen-peptides to counteract oxidative stress for individuals’ health have gained significant intention. Results In this study, the collagen-peptides with antioxidant activities were separated and identified by ion chromatography (IEC), reversed-phase high-performance liquid chromatography (RP-HPLC), and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The identified antioxidant collagen-peptides were further screened by molecular docking for Keap1-targeted peptide inhibitors and their theoretical interaction mechanisms were investigated. Four novel antioxidant collagen-peptides, GPAGPIGPVG, GPAGPpGPIG, ISGPpGPpGPA and IDGRPGPIGPA with high binding affinity to Keap1 were selected. Molecular docking results demonstrated that the putative antioxidant mechanism of four antioxidant collagen-peptides contributed to their blockage of Keap1-Nrf2 interactions. The results of antioxidant activity of four antioxidant collagen-peptides proved that IDGRPGPIGPA exerted a high scavenging capacity to DPPH and ABTS free radicals, while GPAGPpGPIG improved the resistance of cells to hydrogen peroxide (H 2 O 2 ) induced oxidative damage by promoting the activation of intracellular antioxidant enzymes and the production of reduced glutathione in human hepatoma (HepG2) cells. Conclusion The antioxidant collagen-peptides (GPAGPIGPVG, GPAGPpGPIG, ISGPpGPpGPA and IDGRPGPIGPA) will be developed as the novel functional food for human health in the near future. This article is protected by copyright. All rights reserved.
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高影响因子
Journal of Functional Foods
·
2023
·
IF 5.6
Ritian Jin,Jude Juventus Aweya,Rong Lin,Wuyin Weng,Jiaqi Shang,Dangfeng Wang,Yiling Fan,Shen Yang
VLATSGPG (VLA) was a DPP-IV inhibitory peptide isolated from salmon ( Salmo Salar ) skin. Here, we demonstrated that VLA inhibited the activation of PERK through the AKT signaling pathway. Furthermore, we investigated the effect of VLA on free fatty acid (FFA)-induced lipid accumulation disorder and inflammation in HepG2 cells, elucidating the potential regulatory mechanism in this nonalcoholic fatty liver disease cell model. VLA reduced the mRNA expression of adipogenic factors FAS, ACC, and SCD-1 through the PERK/eIF2α pathway and the level of apolipoprotein B-100 secretion. These may contribute to the reducing FFA-induced lipid accumulation in cells and reducing intracellular lipid levels. In addition, VLA increased IκBα mRNA expression via the PERK/IκBα pathway, inhibited the NF-κB p65 activation, and thus inhibited cell inflammation.
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Antioxidants
·
2022
·Vol. 11
·期 9
·1837
·
IF 7.675
Yanling Lin,Qinzhi Zhang,Baofu Xie,Haiyang Jiang,Jianzhong Shen,Shusheng Tang,Chongshan Dai
Chelerythrine (CHE) is a majorly harmful isoquinoline alkaloid ingredient inChelidonium majusthat could trigger potential hepatotoxicity, but the pivotal molecular mechanisms remain largely unknown. In the present study, CHE-induced cytotoxicity and the underlying toxic mechanisms were investigated using human HepG2 cells in vitro. Data showed that CHE treatment (at 1.25–10 μM)-induced cytotoxicity in HepG2 cells is dose-dependent. CHE treatment increased the production of ROS and induced oxidative stress in HepG2 cells. Additionally, CHE treatment triggered the loss of mitochondrial membrane potential, decreased the expression of mitochondrial complexes, upregulated the expression of Bax, CytC, and cleaved-PARP1 proteins and the activities of caspase-9 and caspase-3, and downregulated the expression of Bcl-XL, and HO-1 proteins, finally resulting in cell apoptosis. N-acetylcysteine supplementation significantly inhibited CHE-induced ROS production and apoptosis. Furthermore, CHE treatment significantly downregulated the expression of phosphorylation (p)-Akt (Ser473), p-mTOR (Ser2448), and p-AMPK (Thr172) proteins in HepG2 cells. Pharmacology inhibition of Akt promoted CHE-induced the downregulation of HO-1 protein, caspase activation, and apoptosis. In conclusion, CHE-induced cytotoxicity may involve the inhibition of Akt pathway and the activation of oxidative stress-mediated mitochondrial apoptotic pathway in HepG2 cells. This study sheds new insights into understanding the toxic mechanisms and health risks of CHE.Keywords:chelerythrine;oxidative stress;apoptosis;mitochondrial apoptotic pathway;Akt pathway
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高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2022
·
IF 5.195
Xu-guang Zhang,Ai-xia Liu,Yu-xin Zhang,Ming-yan Zhou,Xiang-yi Li,Ming-hai Fu,Yi-peng Pan,Jian Xu,Jun-qing Zhang
Ethnopharmacological relevance Alpinia officinarum Hance, a perennial natural medicine-food herb, has been traditionally used to treat colds, stomachache, and diabetes for thousands of years. 1,7-Diphenyl-4E-en-3-heptanone (DPH5), a diarylheptanoid isolated from the rhizome of A. officinarum has been reported to be safe and to have antioxidant and hypoglycemic effects, suggesting its potential in the treatment of insulin resistance (IR). Aim of the study : Aim of to investigate the protective effect of DPH5 on IR and elucidate its underlying mechanism of action. Materials and methods HepG2 cells were used as the research objects. Glucose uptake and reactive oxygen species (ROS) levels in high glucose–induced insulin-resistant HepG2 cells were assessed using flow cytometry. Glucose consumption and the levels of malondialdehyde (MDA) and superoxide dismutase (SOD) were analyzed using the corresponding assay kits. The expression of mRNA and proteins related to insulin signaling, glucose metabolism, and antioxidant factor, including insulin receptor substrate-1 (IRS1), phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), translocation of glucose transporter-4, glycogen synthase kinase-3β (GSK3β), glucokinase (GCK), pyruvate kinase (PK), phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G6Pase), nuclear factor-erythroid 2 related factor 2 (Nrf2), heme oxygenase-1 (HO-1), NADPH quinoneoxidoreductase (NQO1), and glutathione peroxidase (GSH-Px) was determined using real-time quantitative polymerase chain reaction and western blotting . Furthermore, molecular docking was performed to determine the spatial mechanism of DPH5 on the key targets PI3K, AKT, Nrf2 , and GSK3β. Results DPH5 could improve IR that manifested as increased glucose uptake and glucose consumption in insulin-resistant HepG2 cells. Moreover, DPH5 could enhance antioxidant capacity by activating Nrf2/HO-1 elements, including increasing Nrf2, HO-1, SOD, NQO1, and GSH-Px expression and reducing MDA, ROS, and JNK levels, thereby improving oxidative stress and ultimately alleviating IR. Additionally, DPH5 could promote the expression of IRS1, PI3K, AKT, GSK3β, GCK, and PK, and downregulate the expression of PEPCK and G6pase, thereby accelerating glucose utilization and enhancing insulin sensitivity. The mechanism underlying the effect of DPH5 in alleviating IR was related to the PI3K/AKT- and Nrf2/HO-1-mediated regulation of the GSK3β signaling pathway, and the results were further confirmed using the specific inhibitors LY294002 and ML385. Results from molecular docking indicated that there were different regulatory sites and interacting forces between DPH5 and PI3K, AKT, Nrf2, and GSK3β; however, the binding force was relatively strong. Conclusions DPH5 improved oxidative stress and glucose metabolism via modulating the PI3K/AKT-Nrf2-GSK3β pathway, thereby ameliorating IR. Overall, our findings suggest the potential of DPH5 as a natural medicine to treat type-2 diabetes mellitus.
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2018
·
IF 3.412
Fuqiang Liang,Yajing Fang,Weiwei Cao,Zhuo Zhang,Siyi Pan,Xiaoyun Xu
The current study evaluates the protective effects of tangeretin, a representative polymethoxyflavone (PMF) mainly isolated from the peels of citrus fruits, against tert-butyl hydroperoxide (t-BHP)-induced oxidative damage in HepG2 cells and the potential mechanisms of this protection. Tangeretin suppressed t-BHP-induced oxidative damage, as evaluated by cell viability, reactive-oxygen-species (ROS) levels, lactate dehydrogenase (LDH) leakage and glutathione (GSH) levels. Further mechanistic studies showed that tangeretin up-regulated the expression of heme oxygenase 1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1). Moreover, tangeretin induced antioxidant-responsive-element (ARE)-dependent luciferase activation, nuclear factor (erythroid-derived 2)-like 2 (Nrf2) nuclear translocation, and mitogen-activated-protein-kinase (MAPK) phosphorylation. Results in the study indicate that the protective effects of tangeretin may be at least partly due to its capacity to up-regulate the antioxidant enzymes NQO1 and HO-1 via the MAPK–Nrf2–ARE signaling pathway. Tangeretin may play an effective protective role in liver injury.
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Applied Materials Today
·
2024
·
IF 7.2
Rui Deng,Jibin Wu,Baokang Zhu,Gaoqing Song,Tao Zhou,Musheng Yang,Lingling Pan,Jian Wang,Xuan Zou,Ziquan Lv,Xiaobao Jin,Yinghua Xu,Xuemei Lu,Shuiqing Gui
Hepatocellular carcinoma (HCC) has emerged as one of the most prevalent and highly malignant tumor malignancies worldwide and is characterized by poor prognosis and high mortality. Therefore, effective medications are urgently needed to improve therapeutic effects with HCC. Exosomes are nanoscale vesicles that can transfer cellular information. Owing to their excellent biocompatibility, exosomes are frequently utilized as drug carriers for cancer treatment. Targeted drug delivery systems that modify exosomes to increase targeting have emerged as promising therapeutic platforms in response to the lack of precise targeting by natural exosomes. In this study, HTPP-Exo was successfully constructed by modifying the exosome membrane by connecting sulfhydryl group of HTPP with maleimide in DSPE-PEG2000-Mal, and the antimicrobial peptide M1–8 was included for the first time through co-incubation, thus successfully establishing the HTPP-Exo-M1–8 targeted drug delivery system. The targeting ability of HTPP-Exo-M1–8 was verified by evaluating its in vitro and in vivo targeting of HepG2 cells, and its therapeutic ability was evaluated by its inhibitory effect on HepG2 cells and in situ liver cancer in mice. The results showed that HTPP-Exo-M1–8 targeted drug delivery system could target HepG2 cells in vivo and in vitro , and the survival rate of HepG2 cells was 45 % after HTPP-Exo-M1–8 treatment for 48 h. After in vivo treatment, the volume of HCC in HTPP-Exo-M1–8 group (270.4 mm 3 ) was much smaller than that in control group (969.5 mm 3 ), which achieved the expected purpose of HCC treatment. Further research showed that the targeted drug delivery system HTPP-Exo-M1–8 could be used to treat HCC by inhibiting the lysosome–autophagosome fusion in HepG2 cells. Additionally, there was no obvious toxicity to healthy cells or tissues when HTPP-Exo-M1–8 was used. Overall, the exosome-based targeted drug delivery system HTPP-Exo-M1–8 can treat HCC by targeting and penetrating tumor cells, which provides a new strategy for the treatment of HCC.
研究领域:
肿瘤学
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药学
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生物技术
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高影响因子
International Journal of Nanomedicine
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2023
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IF 8
Chun-ge Zhang,Qiao-ling Zhu,Yi Zhou,Yang Liu,Wei-liang Chen,Zhi-Qiang Yuan,Shu-di Yang,Xiao-feng Zhou,Ai-jun Zhu,Xue-nong Zhang,Yong Jin
N-Succinyl-chitosan (NSC) was synthesized and NSC nanoparticles (NPs) with loaded osthole (Ost) (Ost/NSC-NPs) were prepared by emulsion solvent diffusion. Subsequently, low-density lipoprotein (LDL)-mediated NSC-NPs with loaded Ost (Ost/LDL-NSC-NPs) were obtained by coupling LDL with Ost/NSC-NPs through amide linkage. The average particle size of Ost/NSC-NPs was approximately 145 nm, the entrapment efficiency was 78.28%±2.06%, and the drug-loading amount was 18.09%±0.17%. The release of Ost from Ost/NSC-NPs in vitro showed a more evident sustained effect than the native material. The half maximal inhibitory concentration of Ost/LDL-NSC-NPs was only 16.23% that of the free Ost at 24 hours in HepG2 cells. Ost inhibited HepG2 cell proliferation by arresting cells in the synthesis phase of the cell cycle and by triggering apoptosis. Cellular uptake and subcellular localization in vitro and near-infrared fluorescence real-time imaging in vivo showed that Ost/LDL-NSC-NPs had high targeting efficacy. Therefore, LDL-NSC-NPs are a promising system for targeted Ost delivery to liver tumor.
研究领域:
药理学
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药物递送
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癌症研究
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分子生物学
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高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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2019
·Vol. 20
·期 20
·5074
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IF 4.183
Mingzhuo Cao,Yong Gao,Mengling Zhan,Nasha Qiu,Ying Piao,Zhuxian Zhou,Youqing Shen
In the last 2–3 decades, gene therapy represented a promising option for hepatocellular carcinoma (HCC) treatment. However, the design of safe and efficient gene delivery systems is still one of the major challenges that require solutions. In this study, we demonstrate a versatile method for covalent conjugation of glycyrrhizin acid (GL) or glycyrrhetinic acid (GA) to increase the transfection efficiency of Polyethyleneimine (PEI, Mw 1.8K) and improve their targeting abilities of hepatoma carcinoma cells. GA and GL targeting ligands were grafted to PEI via N-acylation, and we systematically investigated their biophysical properties, cytotoxicity, liver targeting and transfection efficiency, and endocytosis pathway trafficking. PEI-GA0.75, PEI-GL10.62and PEI-GL20.65conjugates caused significant increases in gene transfection efficiency and superior selectivity for HepG2 cells, with all three conjugates showing specific recognition of HepG2 cells by the free GA competition assay. The endocytosis inhibition and intracellular trafficking results indicated that PEI-GA0.75and GL10.62conjugates behaved similarly to SV40 virus, by proceeding via the caveolae- and clathrin-independent mediated endocytosis pathway and bypassing entry into lysosomes, with an energy independent manner, achieving their high transfection efficiencies. In the HepG2 intraperitoneal tumor model, PEI-GA0.75and PEI-GL10.62carrying the luciferase reporter gene gained high gene expression, suggesting potential use for in vivo application.Keywords:gene therapy;glycyrrhizin acid;glycyrrhetinic acid;hepatic tumor targeting;caveolae- and clathrin-independent pathway;HepG2 intraperitoneal tumor model
研究领域:
药理学
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分子生物学
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基因治疗
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癌症研究
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高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2015
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IF 4.152
Man Li,Min Gao,Yunlan Fu,Chao Chen,Xuan Meng,Aiping Fan,Deling Kong,Zheng Wang,Yanjun Zhao
On-demand curcumin delivery via stimuli-responsive micellar nanocarriers holds promise for addressing its solubility and stability problem. Polymer-curcumin prodrug conjugate micelle is one of such nanosystems. The diversity of linker and conjugation chemistry enabled the generation and optimization of different curcumin micelles with tunable stimuli-responsiveness and delivery efficiency. The aim of the current work was to generate and assess acetal-linked polymeric micelles to enrich the pH-responsive curcumin delivery platforms. Curcumin was slightly modified prior to conjugating to amphiphilic methoxy poly(ethylene glycol)-poly(lactic acid) (mPEG-PLA) copolymer via an acetal bond, whereas an ester bond-linked conjugate was used as the control. The acetal-containing micelles showed a hydrodynamic diameter of 91.1 ± 2.9 (nm) and the accompanying core size of 63.5 ± 7.1 (nm) with a zeta potential of −10.9 ± 0.7 (mV). Both control and pH-labile micelles displayed similar critical micelle concentration at 1.6 μM. The acetal-containing nanocarriers exhibited a pH-dependent drug release behavior, which was faster at lower pH values. The cytotoxicity study in HepG2 cells revealed a significantly lower IC 50 at 51.7 ± 9.0 (μM) for acetal-linked micelles in contrast to the control at 103.0 ± 17.8 (μM), but the polymer residue showed no cytotoxicity upon drug release. The acetal-linked micellar nanocarrier could be a useful addition to the spectrum of currently available stimuli-responsive curcumin nano-formulations.
研究领域:
药学
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纳米技术
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药物递送系统
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PubMed
高影响因子
BMC Pregnancy and Childbirth
·
2026
·Vol. 26
·期 1
·363
·
IF 3.1
Xie Xinping,Yan Jianying,Chen Xiaoyun,He Lidan,Wu Jianbo,Lu Lin
Background Insulin resistance (IR) is a pivotal determinant in the pathophysiological processes underlying gestational diabetes mellitus (GDM). Angiopoietin-like protein 8 (ANGPTL8) exhibits an ambiguous influence on glucose metabolism in the onset and progression of GDM. However, the functions of ANGPTL8 in the metabolic profiles of insulin-resistant (IR) HepG2 cells, glucose tolerance in GDM mice, and the possible underlying mechanisms require further exploration. Methods ANGPTL8 knockout and over-expressing HepG2 cell lines were established. Glucose uptake capacity in three clones (wild-type, ANGPTL8 knockout, and over-expressing) of insulin-resistant HepG2 cells was detected. Proteomic analysis of the IR HepG2 cells identified a cluster of relevant signaling pathways, and the effect of ANGPTL8 on metabolomic changes was evaluated. The GDM model was induced by a high-fat diet (HFD) and intraperitoneal injection of Streptozotocin (STZ) in pregnant mice. An oral glucose tolerance test (OGTT) was performed in both GDM mice and ANGPTL8 over-expressing GDM mice. Results The PI3K/Akt signaling cascade was stimulated by insulin resistance, and this activation could be effectively suppressed by inhibitors targeting PI3K, Akt, and GSK-3β. HepG2 cells over-expressing ANGPTL8 and exposed to high insulin concentrations demonstrated a marked enhancement in glucose uptake capacity, as opposed to their wild-type counterparts or ANGPTL8 knockout cells under IR conditions. The most substantial down-regulation was observed in lactate and branched-chain amino acids (BCAAs), which exhibited a positive correlation with IR. Promoted translation of ANGPTL8 was found in the liver, pancreas, and placental tissues of GDM mice. Significantly better glucose tolerance was observed in GDM mice transfected with m-ANGPTL8 compared with those that were not. Furthermore, the activation of Akt was observed in the primary hepatocytes of ANGPTL8 over-expressing GDM mice. Conclusion Over-expression of ANGPTL8 may increase glucose uptake capacity and influence the metabolic profiles in IR HepG2 cells, enhancing the insulin-mediated activation of the PI3K/Akt/GSK-3β pathway. ANGPTL8 may improve glucose tolerance in GDM mice. These findings might contribute to a new understanding of the roles of ANGPTL8 in glucose metabolism during the onset and progression of insulin resistance, providing novel insights for the clinical therapy of GDM.
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RSC Advances
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2016
·Vol. 6
·期 10
·8336-8345
·
IF 3.289
Yu-Feng Chen,Jin Hong,Dong-Yan Wu,Ying-Ying Zhou,Mathew D'Ortenzio,Ya Ding,Xing-Hua Xia
To improve current cancer treatment efficacy, a method for early and accurate detection is of great importance, especially for cancer biomarkers with a specific theranostic target. Matrix metalloproteases (MMPs) are a family of endopeptidases that are highly expressed in various types of cancers and play an important role inmetastasis. To detect and locate over-expressed MMPs in vitro and in vivo, a fluorescent “off–on” nanoswitch (GNP-p-FITC/mPEG) has been developed by engineering the fluorescein isothiocyanate-labeled peptide (p-FITC) and thiolated polyethyleneglycol monomethyl ether (HS-mPEG, molecular weight 2000 Da) on the surface of gold nanoparticles (GNPs). The p-FITC contains a MMP preferential cleavage site and HS-mPEG is used to improve the stability and biocompatibility of the nanoswitch in vivo. The nanoswitch has a very low background signal and displays sensitive response to compound enzymes (containing MMP-2, MMP-4, and MMP-9 that may contribute to MMPs activity) either in vitro or in vivo. As a result of using GNPs, the nanoswitch has enhanced cellular internalization with HepG2 cells due to the endocytosis process as well as improved tumor penetration performance due to its small-size-induced enhanced permeability and retention (EPR). Furthermore, the biocompatibility and tumor targeting ability of the nanoswitch are established by its cytotoxicity with HepG2 cells and distributions in normal organs and tumor tissues. The simple preparation process, the complete fluorescence quenching, and the effective fluorescence recovery (about 50-fold intensity) makes the present MMP-responsive nanoswitch an accurate diagnosis probe for mapping MMPs and evaluating the tumor development both in vitro and in vivo.
研究领域:
肿瘤学
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生物医学工程
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分子生物学
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高影响因子
Journal of Analysis and Testing
·
2024
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IF 5.5
Zhang Hui,Chen Guilin,Zhang Yongli,Muema Felix Wambua,Ding Jun,Guo Mingquan
With the growing prevalence of diabetes and obesity worldwide, the role of α -glucosidase and lipase inhibitors has gained increasing concentration. Mulberry, a functional medicinal and edible plant, has been reported extensively in alleviating both diabetes and obesity. However, there is still a lack of refined research on its active ingredients and mechanisms. In our study, the inhibitory activities of mulberry leaf against α -glucosidase and pancreatic lipase reached 191.37 ± 14.46 and 775 ± 68.60 μg/mL, respectively. Meanwhile, it also promoted glucose consumption in the HepG2 cells model. Subsequently, four α -glucosidase ligands and four pancreatic lipase ligands were identified through bio-affinity ultrafiltration combined with liquid-chromatography-mass spectrometry (UF-HPLC–MS/MS). In vitro inhibition assays confirmed the inhibitory potential of these representative ligands. Molecular docking suggested that these possible ligands could be inserted into the active pocket of the target enzyme through multiple intermolecular forces. Our findings indicated that the polyphenols in mulberry leaves may contribute significantly to their hypoglycemic and hypolipidemic properties. Furthermore, our study provides valuable insights for the screening of active ingredients in other medicinal and edible plants, which could help in the development of new therapies for diabetes and obesity.
研究领域:
药理学
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生物化学
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药物化学
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植物科学
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高影响因子
危险品化学品经营许可证（带存储）