JOURNAL OF HAZARDOUS MATERIALS
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2024
·
IF 12.2
Lin Zhang,Wen-Yao Shi,Jia-Ying Xu,Yan Liu,Shi-Jia Wang,Jia-Yang Zheng,Yun-Hong Li,Lin-Xi Yuan,Li-Qiang Qin
Although selenium (Se) and cadmium (Cd) often coexist naturally in the soil of China, the health risks to local residents consuming Se-Cd co-enriched foods are unknown. In the present study, we investigated the effects of chemical-based selenocystine (SeCys 2 ) on cadmium chloride-induced human hepatocarcinoma (HepG2) cell injury and plant ( Cardamine hupingshanensis )-derived SeCys 2 against Cd-induced liver injury in mice. We found that chemical- and plant-based SeCys 2 showed protective effects against Cd-induced HepG2 cell injury and liver damage in mice, respectively. Compared with Cd intervention group, co-treatment with chemical- or plant-based SeCys 2 both alleviated liver toxicity and ferroptosis by decreasing ferrous iron, acyl-CoA synthetase long-chain (ACSL) family member 4, lysophosphatidylcholine acyltransferase 3, reactive oxygen species and lipid peroxide levels, and increasing ACSL3, peroxisome proliferator-activated receptor α, solute carrier family 7 member 11 (SLC7A11) and glutathione and glutathione peroxidase 4 (GPX4) levels. In conclusion, chemical- and plant-based SeCys 2 alleviated Cd-induced hepatotoxicity and ferroptosis by regulating SLC7A11/GPX4 signaling and lipid peroxidation. Our findings indicate that potential Cd toxicity from consuming foods grown in Se- and Cd-rich soils should be re-evaluated. This study offers a new perspective for the development of SeCys 2 -enriched agricultural products.
研究领域:
毒理学
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药理学
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细胞生物学
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植物科学
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DOI
PubMed
高影响因子
ACS Omega
·
2021
·
IF 3.512
Fanzhen Yu,Yingxin Wang,Yilong Teng,Shutong Yang,Yanming He,Zeng Zhang,Hongjie Yang,Chuan-Fan Ding,Ping Zhou
Protein tyrosine phosphatase 1B (PTP1B) is a key negative regulator of insulin and an effective target for the treatment of type 2 diabetes (T2D). A natural hyperbranched proteoglycan extracted from Ganoderma lucidum, namely, Fudan-Yueyang G. Lucidum (FYGL), was demonstrated capable of inhibiting the activity of PTP1B. Here, to identify the effective active components of FYGL, three different components, the polysaccharide FYGL-1, proteoglycans FYGL-2, and FYGL-3, were isolated from FYGL, and then, the protein moiety of FYGL-3 was further separated, namely, FYGL-3-P. Their abilities to enhance the glucose uptake in cells and inhibit the activity of PTP1B were compared. The inhibitory mechanisms were systematically explored by spectroscopic methods and MD simulations. The results showed that FYGL-3 and FYGL-3-P significantly enhanced the insulin-provoked glucose uptake in insulin-resistant HepG2 cells, detected by the glucose oxidase method. Also, the FYGL-3-P protein moiety in FYGL played an essential role in inhibiting the activity of PTP1B. A strong, enthalpy-driven, and multitargeted interaction by electrostatic forces between PTP1B and FYGL-3-P dramatically inhibited the catalytic activity of PTP1B. These results provided deep insights into the molecular mechanisms of FYGL inhibiting the activity of PTP1B and structurally helped researchers seek natural PTP1B inhibitors.
研究领域:
生物化学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
Journal of Oleo Science
·
2022
·
IF 1.628
Runzhou Sun,Ruixin Xiao,Pengfei Lv,Feifei Guo,Yanling Gong,Meixing Yan
Pink lotus essential oil (PLEO) is the volatile components extracted from lotus flowers and there are few relevant research. The purpose of this study was to observe the effect of PLEO on NAFLD in vitro model and its possible mechanism. The ingredients of PLEO were determined by gas chromatography-mass spectrometry (GS-MS) and its lipid-lowering and hepatoprotective activities were investigated. HepG2 cells were treated with free fatty acid (FFA) to establish a cell model of NAFLD. Cell viability was evaluated by 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) method. Total cholesterol (TC), triglyceride (TG), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) were determined by Enzyme-Linked Immune Sorbent Assay (ELISA). Oil red O staining was performed to observe the lipid accumulation in the HepG2 cells. Lipid metabolism enzymes including fatty acid synthase (FAS), acetyl-coA carboxylase (ACC), stearoyl-CoA desaturase 1 (SCD-1), and carnitine palmitoyltransferase-1 (CPT-1), insulin signaling pathways including phosphatidylinositol 3 kinase (PI3K) and protein kinase B Akt, inflammatory signaling pathways such as nuclear factor kappa-B (NF-κB), were determined by Western blotting. There were 46 components determined in PLEO with many terpenoids compounds. PLEO decreased TC and TG contents in the FFA-treated HepG2 cells. Furthermore, PLEO inhibited TNF-α, IL-6 and IL-1β excretion, decreased NF-κB, FAS, ACC and SCD-1 while increased phosphorylation of NF-κB, PI3K, Akt, and CPT-1 expression. It is the first time to reveal that PLEO alleviates FFA-induced steatosis in HepG2 cells by regulating lipid metabolism, inhibiting inflammatory response, and improving insulin sensitivity.
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产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
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2020
·
IF 3.701
Gang Li,Jing Zhou,Mengyu Sun,Juren Cen,Jing Xu
Luteolin derived from Clerodendrum cyrtophyllum Turcz leaves exhibited antioxidant activity. The IC 50 values of luteolin for ABTS· + and DPPH· free radical scavenging was 17.3 ± 0.82 μM and 13.2 ± 0.18 μM, respectively, and the compound showed better antioxidant activities than BHT (Butylated hydroxytoluene) and VC (Vitamin C). Luteolin exhibited neither cytotoxic nor promotional activities and no genotoxic effect toward HepG2 cells. The cell viability was significantly increased in a dose-dependent manner after preincubation of the cells with 1–40 μM luteolin followed by direct exposure to TBHP ( tert -Butyl hydroperoxide). At the concentration of 30 μM, luteolin can reduce intercellular reactive oxygen species accumulation by 43.7 ± 3.98%, lactate dehydrogenase release by 38.7 ± 3.07% malondialdehyde levels by 24.5 ± 1.14% and increased 73.7 ± 6.04% superoxide dismutase activity and 72.3 ± 1.75% glutathione activity. A western blot assay showed that luteolin upregulated procaspase-3 and downregulated cleaved caspase-3 to counteract TBHP-triggered oxidative stress. Our study lays a theoretical foundation for the utilization and further development of luteolin as a promising natural antioxidant.
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DOI
高影响因子
Chemical Science
·
2019
·Vol. 10
·期 35
·8179-8186
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IF 9.556
Xiaohong Pan,Yuehui Zhao,Tingting Cheng,Aishan Zheng,Anbin Ge,Lixin Zang,Kehua Xu,Bo Tang
Reductive stress, the opposite of oxidative stress, represents a disorder in the redox balance state which is harmful to biological systems. For decades, the role of oxidative stress in tumor therapy has been the focus of attention, while the effects of reductive stress have been rarely studied. Here, we report the anti-cancer effects of reductive stress induced by three natural antioxidants (resveratrol, curcumin and celastrol). Considering the fact that the solid tumor microenvironment suffers from hypoxia, we performed cell experiments under hypoxic conditions. In order to observe the reductive stress, we first developed an ultrasensitive fluorescent probe (TCF-MQ) for specifically imaging NAD(P)H which is a marker of reductive stress. TCF-MQ responded to NAD(P)H rapidly and exhibited high sensitivity with a detection limit of 6 nM. With the help of TCF-MQ, we found that upon the treatment of HepG2 cells with pharmacological doses of three natural antioxidants under hypoxic conditions, high levels of NAD(P)H were produced before cell death. The excess NAD(P)H resulted in reductive stress instead of oxidative stress. In contrast, under normoxic conditions, there was no reductive stress involved in the process of cell death induced by three natural antioxidants. Therefore, we hypothesize that the mechanism of cancer cell death induced by natural antioxidants under hypoxia should be attributed to the reductive stress.
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DOI
PubMed
高影响因子
Scientific Reports
·
2017
·Vol. 7
·期 1
·1-10
·
IF 4.259
Chu Qiang,Zhao Yiying,Shi Xuer,Han Wen,Zhang Yanzhen,Zheng Xiaodong,Zhu Jing
To address the need for a high throughput toxicity test in the modern food industry, an in vivo -like 3-D cell model was constructed in this study to provide an alternative to controversial long-term animal models and to improve the sensitivity and accuracy of the traditional monolayer model. The model formed cell cylindroids within polyvinylidene fluoride (PVDF) hollow fibers and therefore mimicked the microenvironment of liver tissue. Microscopy methods were used, and liver-specific functions were measured to demonstrate the superiority of the model compared to the monolayer model, as well as to optimize the model for best cell performances. Later, toxicity tests of sodium nitrite and acrylamide were conducted in both the 3-D model and the monolayer model to study the sensitivity of the 3-D model in toxicity responses. As expected, HepG2 cells within the 3-D model responded at lower concentrations and shorter exposure times compared to cells within the monolayer model. Furthermore, western blot analysis of apoptosis pathways also supported the argument.
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产品关联
DOI
PubMed
高影响因子
Food and Bioprocess Technology
·
2024
·Vol. 17
·期 11
·3693-3703
·
IF 5.3
Xu Chengzhi,Cai Chaonan,Liu Tianyi,Kang Jizhen,Li Sheng,Zhang Juntao,Wei Benmei,Wang Haibo
An important area of focus for developing antioxidant collagen hydrolysates (peptides) involves enhancing the antioxidant properties of collagen hydrolysates. In this study, fish scale collagen hydrolysate (FH) was used as the raw material for plastein reaction. Various enzymes, including papain, alcalase, flavourzyme, and the combination of alcalase and flavourzyme, were employed for this purpose. The plastein reaction significantly improved the thermal stability, chemical antioxidant activity, and capacity to scavenge cellular reactive oxygen species of FH. Notably, the plastein reaction catalyzed by alcalase exhibited the most significant improvement, increasing the hydroxyl radical scavenging rate from 72.3 to 93.4% and restoring the viability of the oxidative stress-induced HepG2 cell model from 50.8 ± 1.7 to 74.9 ± 1.7%. During the plastein reaction, condensation and hydrolysis reactions occurred simultaneously, with condensation being the dominant process. These reactions, along with physical aggregation, facilitated the formation of larger yet more concentrated collagen peptide aggregates, leading to increased exposure of hydrophobic groups. This enhanced the uptake of collagen hydrolysates by the cells and contributed to the enhancement of their antioxidant properties. Thus, the plastein reaction is an effective method for enhancing the antioxidant properties of collagen hydrolysates, with its simplicity of operation and promising application potential.
研究领域:
食品科学
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生物化学
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生物技术
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海洋生物技术
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药学
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DOI
高影响因子
Journal of Functional Foods
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2024
·
IF 3.8
Yunfei Wei,Meiyu Jin,Hao Yu,Xiaoning Hou,Lilei Zhao,Lu Ding,Jiaqi Cheng,Jiazhang Qiu,Haihua Feng
Glycyrrhiza glabra L. is a common heritage herbal medicine rich in antioxidant compounds such as flavonoids and triterpenoids. Non-alcoholic fatty liver disease has been the global prevalent chronic liver disorder. To investigate the curative role and mechanism of the Glycyrrhiza glabra L. crude extract on NAFLD, in vitro , we used oleic acid, palmitic acid, ML-385 and 3-MA to stimulate HepG2 cells. In vivo , we used Tyloxapol to inject mice intraperitoneally to establish an acute model, and high-fat diet to feed wild-type, Nrf2 -/- and ATG5 flox/flox mice to establish a chronic model. We used high performance liquid chromatography to analyse the content of major bioactive components in the Glycyrrhiza glabra L. crude extract. Our study found the Glycyrrhiza glabra L. crude extract could effectively alleviate lipid accumulation in non-alcoholic fatty liver disease, activate Nrf2 and promote autophagy. However, this alleviating effect disappeared when the Nrf2 and autophagy were inhibited separately. Our study demonstrates that crude extraction of active ingredients from traditional herbal medicines may be a potentially inexpensive, rapid and safe approach to alleviate lipid accumulation in non-alcoholic fatty liver disease.
研究领域:
药理学
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肝病学
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分子生物学
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产品关联
DOI
高影响因子
FREE RADICAL BIOLOGY AND MEDICINE
·
2024
·
IF 7.1
Reziyamu Wufuer,Keli Liu,Jing Feng,Meng Wang,Shaofan Hu,Feilong Chen,Shanshan Lin,Yiguo Zhang
Cisplatin ( cis -Dichlorodiamineplatinum[II], CDDP) is generally accepted as a platinum-based alkylating agent type of the DNA-damaging anticancer drug, which is widely administrated in clinical treatment of many solid tumors . The pharmacological effect of CDDP is mainly achieved by replacing the chloride ion ( Cl − ) in its structure with H 2 O to form active substances with the strong electrophilic properties and then react with any nucleophilic molecules, primarily leading to genomic DNA damage and subsequent cell death. In this process, those target genes driven by the consensus electrophilic and/or antioxidant response elements (EpREs/AREs) in their promoter regions are also activated or repressed by CDDP. Thereby, we here examined the expression profiling of such genes regulated by two principal antioxidant transcription factors Nrf1 and Nrf2 (both encoded by Nfe2l1 and Nfe2l2, respectively) in diverse cellular signaling responses to this intervention. The results demonstrated distinct cellular metabolisms, molecular pathways and signaling response mechanisms by which Nrf1 and Nrf2 as the drug targets differentially contribute to the anticancer efficacy of CDDP on hepatoma cells and xenograft tumor mice. Interestingly, the role of Nrf1, rather than Nrf2, is required for the anticancer effect of CDDP, to suppress malignant behavior of HepG2 cells by differentially monitoring multi-hierarchical signaling to gene regulatory networks . To our surprise, it was found there exists a closer relationship of Nrf1α than Nrf2 with DNA repair , but the hyperactive Nrf2 in Nrf1α –∕– cells manifests a strong correlation with its resistance to CDDP, albeit their mechanistic details remain elusive.
研究领域:
肿瘤学
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分子生物学
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药理学
·
细胞生物学
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产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Mingjing Zheng,Huan Ouyang,Zhipeng Li,Tao Hong,Yanbing Zhu,Yuanfan Yang,Xiaoming Guo,Hui Ni,Zedong Jiang
The structure and in vitro hypolipidemic activity of Bangia fusco-purpurea polysaccharide (BFP) assisted extracted with ultra-high pressure (UHP) at 100–600 MPa were studied. Compared to native BFP, UHP assisted extracted BFP had a more loose network structure with higher total sugar and uronic acid contents while less molecular weight ( p < 0.05). Moreover, UHP assisted extraction significantly improved the in vitro hypolipidemic and antioxidant activity of BFP. Especially at 400 MPa UHP, the cholesterol adsorption and antioxidant capacities of BFP were increased by approximately 38.02 % and 11.69 %–32.29 %, respectively. BFP with UHP assisted extraction could alleviate oleic acid-induced lipid accumulation and lipid oxidation in HepG2 cells more effectively by activating the AMPK signaling pathway as well as inhibiting PPARγ expression, which was much related with its reduced molecular weight and loose network structure. The findings indicated that UHP assisted extracted BFP has better potential to develop natural hypolipidemic agent.
研究领域:
食品科学
·
生物化学
·
药理学
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产品关联
DOI
PubMed
高影响因子
ANALYST
·
2024
·
IF 3.6
Jiahuan Zhang,Chaoqun Fei,Shulan Qi,Jiaqi Fu,Shi Zhou,Zhong Wang,Jinlian Li,Yanli Zhao,Dongmei Wu
The electrochemical detection method of cytotoxicity using intracellular purines as biomarkers has shown great potential for in vitro drug toxicity evaluation. However, no electrochemical detection system based on an in vitro drug metabolism mechanism has been devised. In this paper, electrochemical voltammetry was used to investigate the effect of the S9 system on the electrochemical behavior of HepG2 cells, and benzo[a]pyrene, fluoranthene, and pyrene were employed to investigate the sensitivity of electrochemical signals of cells to the cytotoxicity of drugs metabolized by the S9 system. The results showed that, within 8 h of exposure to the S9 system, the electrochemical signal of HepG2 cells at 0.7 V did not alter noticeably. The levels of xanthine, guanine, hypoxanthine, and adenine in the cells were not significantly altered. Compared with the absence of S9 system metabolism, benzo[a]pyrene and fluoranthene processed by the S9 system decreased the electrochemical signal of the cells in a dose-dependent manner, while pyrene did not change it appreciably. HPLC also revealed that benzo[a]pyrene and fluoranthene metabolized by the S9 system decreased the intracellular purine levels, whereas pyrene had no effect on them before and after S9 system metabolism. The cytotoxicity results of the three drugs examined by electrochemical voltammetry and MTT assay showed a strong correlation and good agreement. The S9 system had no effect on the intracellular purine levels or the electrochemical signal of cells. When the drug was metabolized by the S9 system, variations in cytotoxicity could be precisely detected by electrochemical voltammetry.
研究领域:
毒理学
·
药理学
·
分析化学
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产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2024
·
IF 10.7
Hongliang Li,Yingmeng Hou,Shiyu Jia,Mingqian Tan,Haitao Wang
Fucoxanthin (Fx) has garnered significant interest due to its exceptional biological properties. However, its efficacy in enhancing food quality and human health is contingent upon the solubility of the compound in water and its physicochemical stability. Therefore, nanocarriers must be developed to enhance the stability and biocompatibility of Fx. In this study, oxidized paramylon and Fx self-assembled nanoparticles (Fx-OEP) were prepared via the anti-solvent method, with a loading rate of 82.47 % for Fx. The Fx-OEP exhibited robust storage and photostability. In vitro simulated digestion assays demonstrated that Fx-OEP effectively protected Fx from premature gastric release, while achieving a release efficiency of 72.17 % in the intestinal phase. Fx-OEP has the capacity to scavenge a range of reactive oxygen species (ROS) induced by cellular oxidative stress. Treatment with Fx-OEP resulted in a significant reduction in ROS accumulation in insulin-resistant HepG2 cells, which was attributed to the activation of the nuclear factor E2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) pathway. This, in turn, activated insulin receptor substrate 1/glucose transporter type 4 (IRS1/GLUT4), promoting cellular glucose absorption and utilization. These findings indicate the potential of self-assembled nanoparticles based on oxidized paramylon as a new type of nanocarrier for delivering hydrophobic substances.
研究领域:
营养学
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药理学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）