FOOD AND CHEMICAL TOXICOLOGY
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2016
·
IF 3.584
Chongshan Dai,Bin Li,Yan Zhou,Daowen Li,Shen Zhang,Hui Li,Xilong Xiao,Shusheng Tang
The potential toxicity of quinocetone (QCT) has raised widely concern, but its mechanism is still unclear. This study aimed to investigate the protective effect of curcumin on QCT induced apoptosis and the underlying mechanism in human hepatocyte L02 cells. The results showed that QCT treatment significantly decreased the cell viability of L02 cell and increased the release of lactate dehydrogenase (LDH), which was attenuated by curcumin pre-treatment at 1.25, 2.5 and 5 μM. Compared to the QCT alone group, curcumin pre-treatment significantly attenuated QCT induced oxidative stress , mitochondrial dysfunction and apoptosis. In addition, curcumin pretreatment markedly attenuated QCT-induced increase of iNOS activity and NO production in a dose-dependent manner. Meanwhile, curcumin pretreatment markedly down-regulated the expression of nuclear factor –kB (NF-kB) and iNOS mRNAs, but up-regulated the expressions of Nrf2 and HO-1 mRNAs, compared to the QCT alone group. Zinc protoporphyrin IX , a HO-1 inhibitor, markedly partly abolished the cytoprotective effect of curcumin against QCT-induced caspase activation, NF-kB mRNA expression. These results indicate that curcumin could effectively inhibit QCT induced apoptosis and inflammatory response in L02 cells, which may involve the activation of Nrf2/HO-1 and inhibition of NF-kB pathway.
研究领域:
药理学
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毒理学
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分子生物学
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DOI
PubMed
高影响因子
TOXICOLOGY MECHANISMS AND METHODS
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2015
·
IF 1.517
Chongshan Dai,Shusheng Tang,Daowen Li,Kena Zhao,Xilong Xiao
Quinocetone (QCT), a new quinoxaline 1,4-dioxides, has been used as antimicrobial feed additive in China. Potential genotoxicity of QCT was concerned as a public health problem. This study aimed to investigate the protective effect of curcumin on QCT-induced oxidative stress and genotoxicity in human hepatocyte L02 cells. Cell viability and intracellular reactive oxygen species (ROS), biomarkers of oxidative stress including superoxide dismutase (SOD) activity and glutathione (GSH) level were measured. Meanwhile, comet assay and micronucleus assay were carried out to evaluate genotoxicity. The results showed that, compared to the control group, QCT at the concentration ranges of 2–16 μg/mL significantly decreased L02 cell viability, which was significantly attenuated with curcumin pretreatment (2.5 and 5 μM). In addition, QCT significantly increased cell oxidative stress, characterized by increases of intracellular ROS level, while decreased endogenous antioxidant biomarkers GSH level and SOD activity (all p < 0.05 or 0.01). Curcumin pretreatment significantly attenuated ROS formation, inhibited the decreases of SOD activity and GSH level. Furthermore, curcumin significantly reduced QCT-induced DNA fragments and micronuclei formation. These data suggest that curcumin could attenuate QCT-induced cytotoxicity and genotoxicity in L02 cells, which may be attributed to ROS scavenging and anti-oxidative ability of curcumin. Importantly, consumption of curcumin may be a plausible way to prevent quinoxaline 1,4-dioxides-mediated oxidative stress and genotoxicity in human or animals.
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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DOI
PubMed
高影响因子
Frontiers in Chemistry
·
2022
·
IF 5.545
Zeng Zhijun,Shen Huaxiang,Gao Wei,Guo Qifeng,Chen Mengjie,Yan Xiaojun,Liu Hongning,Ji Yanhua
In this study, we use cytarabine anticancer drug to synthesize a new rare earth complex with Europium ion. The study work is an attempt to investigate luminescence and biological properties of the Eu-based coordination polymers of cytarabine (Eu-CP-Ara) anticancer drug which have been prepared by us. Eu-CP-Ara has luminescence properties with emission centering at about 619 nm excited with 394 nm. We study cytarabine and Eu-CP-Ara in vitro cytotoxicity. Cytotoxicity of Eu-CP-Ara against lung cancer cells (A549) could even be comparable to the inhibitory effect of cytarabine ligands, showing the advantage of antitumor activity. In addition, Eu-CP-Ara showed lower cytotoxicity to normal liver cells (L02). At the same, from the CLSM images, Eu-CP-Ara has successfully entered the A549 cell. Hence, Eu-CP-Ara can be used as a potential anticancer drug. Eu-CP-Ara may be an effective strategy for the tracking cytarabine against tumours and might impart better accurate treatment effect and therapeutic efficiency.
研究领域:
药物化学
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材料科学
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肿瘤学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
TOXICOLOGY MECHANISMS AND METHODS
·
2025
·
IF 2.7
Lan Yang,Yewen Lin,Wenping Xu,Yang Zhang
Reactive oxygen species (ROS)-induced DNA oxidative damage is a significant manifestation of oxidative stress in the body and is closely associated with the onset and progression of various diseases. Although Pyripyropene A (PPPA) exhibits anti-tumor and anti-inflammatory activities, its antioxidant and protective effects against DNA oxidative injury remain unclear. In this study, using a hydrogen peroxide-induced oxidative injury model of L02 cells, it was found that PPPA could significantly reduce intracellular ROS and malondialdehyde (MDA) levels, enhance the activities of catalase (CAT) and reduced glutathione (GSH), and increase the 2,2-Diphenyl-1-picrylhydrazyl (DPPH) clearance rate, confirming its antioxidant effect. Comet assay showed a reduction in DNA breakage, and down-regulation of phosphorylated histone (γ-H2AX) and 8-hydroxydeoxyguanosine (8-oxodG), indicating that it effectively alleviates DNA oxidative injury. Meanwhile, the upregulated expression of poly ADP-ribose polymerase (PARP) suggests that PPPA may promote repair by activating the DNA damage response (DDR). This study systematically clarify for the first time that PPPA exerts a protective effect by synergistically antioxidizing, reducing DNA injury, and potentially activating repair pathways, providing a theoretical basis for its application in neoplasm and oxidative stress-related diseases.
研究领域:
分子生物学
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药理学
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氧化应激
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肿瘤学
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毒理学
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细胞生物学
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药物代谢
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产品关联
DOI
PubMed
高影响因子
FITOTERAPIA
·
2024
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IF 2.5
Yungang Tian,Jingjing Fan,Rongshen Wang,Rui Ding,Chunxue Zhao,Jia Xu,Qingyun Zhang,Tiegui Nan,Xianchan Li,Min Ye
Five previously undescribed protopanaxatriol-type saponins, notoginsenosides Ta-Te ( 1 – 5 ), together with eighteen known triterpenoid saponins ( 6 – 23 ) were isolated from the roots of Panax notoginseng . The structures of new compounds were determined by HRESIMS and NMR spectroscopic analyses and chemical methods. Compounds 1 and 2 were the first examples of ginsenosides featuring a 6-deoxy- β - d -glucose moiety from Panax species. Compounds 1 – 4 , 7 , 10 , 12 , 21 – 22 showed protective effects on L02 cells against the injury of acetaminophen (APAP). Among them, notoginsenoside R1 ( 12 ), ginsenoside Rg1 ( 21 ), and ginsenoside Re ( 22 ) were the most potent ones, with cell viabilities >80%. Moreover, compounds 12 and 22 remarkably alleviated APAP-induced liver injury in mice. These saponins are potential hepatoprotective agents.
研究领域:
药理学
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肝病学
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天然产物化学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2024
·
IF 4.8
Dong-xuan Zheng,Qiang Hou,Tao-tao Xue,Xiang Gao,Ruo-yu Geng,Li-mei Wen,Zhi Wang,Qiang Yin,Hai-long Yin,Jun-ping Hu,Jian-hua Yang
Ethnopharmacological relevance Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease worldwide. Nonalcoholic steatohepatitis (NASH) is a crucial component of this disease spectrum. The Yanxiao Di'naer formula (YXDNE) is an Uyghur medical extract that has been used in folk medicine to treat hepatitis for a long time. However, the role and mechanism of action of YXDNE in NASH treatment remains unclear. Objective The objective of this study was to assess the effectiveness of YXDNE in treating NASH induced by injections of carbon tetrachloride combined with a high-fat high-cholesterol diet (HFHCD), and to clarify the underlying mechanisms. Methods The compounds in the YXDNE extract were analysed for classification and proportions using ultra-performance liquid chromatography-mass spectrometry. The efficacy of YXDNE in treating abnormal lipid metabolism was evaluated in L02 cells in vitro . In addition, a C57BL/6 mouse model of NASH was established to evaluate the therapeutic efficacy of YXDNE in vivo . Metabolomics and RNA sequencing were used to analyse the therapeutic effects of YXDNE on the liver. The corresponding signalling pathways were found to target AMPKα1, PPARα, and NF-κB. The efficacy of YXDNE was validated using inhibitors or silencing RNA (siRNA) against AMPKα1 and PPARα. Results This study confirmed that YXDNE treatment ameliorated NASH in a murine model of this disease. Metabolomics analysis suggested that YXDNE efficacy was associated with fatty acid catabolism and AMPK signalling pathways. RNA sequencing results showed that YXDNE efficacy in treating NASH was highly correlated with the AMPK, PPARα and NF-κB pathways. Both in vitro and in vivo experimental data demonstrated that YXDNE affected the expression of p-AMPKα1, PPARα, p–NF–κB, IκB, and p-IκB. The efficacy of YXDNE in treating NASH in vitro was cancelled when AMPK was inhibited with Compound C or PPARα was modulated via siRNA. Conclusions YXDNE may have a therapeutic effect on abnormal lipid metabolism in L02 cells and in a murine model of NASH by affecting the AMPKα1/PPARα/NF-κB signalling pathway. Therefore, YXDNE has the potential for clinical application in the prevention and treatment of NASH.
研究领域:
药理学
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代谢组学
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分子生物学
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民族药理学
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肝病
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产品关联
DOI
PubMed
高影响因子
TOXICOLOGY MECHANISMS AND METHODS
·
2017
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IF 1.595
Chongshan Dai,Lei Lei,Bin Li,Yang Lin,Xilong Xiao,Shusheng Tang
Furazolidone (FZD) is extensively used as the antiprotozoal and antibacterial drug in clinic. The previous study has shown that curcumin pretreatment could improve FZD induced cytotoxicity by inhibiting oxidative stress and mitochondrial apoptotic pathway. The current study aimed to investigate the potential roles of endoplasmic reticulum (ER) stress, p38 mitogen-activated protein kinases (p38 MAPK) signaling pathway in curcumin against FZD cytotoxicity by using human hepatocyte L02 cells. The results showed that curcumin could markedly attenuate FZD induced cytotoxicity. Compared with FZD alone group, curcumin pretreatment significantly reduced the expression of phospho (p)-p38, cyclin D1, p-checkpoint kinase 1 (ChK1) and breast cancer associated gene 1 (BRCA1) protein, followed to attenuate S phase arrest. Meanwhile, curcumin pretreatment prevented FZD induced ER stress, evidenced by the inhibition of glucose-regulated protein 78 and DNA damage inducible gene 153/C/EBP-homologous protein (GADD153/CHOP) protein expression. Moreover, compared with the control, FZD exposure activated the protein and mRNA expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1), which were further activated by curcumin treatment. These results reveal that curcumin could prevent FZD induced cytotoxicity and S phase arrest, which may involve the activation of Nrf2/HO-1 pathway and the inhibition of p38 MAPK pathway and ER stress.
研究领域:
药理学
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毒理学
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
CHEMISTRY & BIODIVERSITY
·
2022
·Vol. 19
·期 8
·e202200471
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IF 2.745
Qiang-Ming Li,Xiu-Rong Yang,Xue-Qiang Zha,Li-Hua Pan,Dan-Dan Zang,Feng-Yun Zhang,Jian-Ping Luo
Dendrobium huoshanense flowers have been widely used for liver protection in China. This work was aimed to discover the natural products with activity of mitigating alcoholic hepatocyte injury from Dendrobium huoshanense flowers via bioactivity-guided isolation, and to clarify the underlying mechanisms of these natural products. As a result, three flavonoids, 3′- O- methylquercetin-3- O-β -D-galactopyranoside ( 1 ), 3′- O- methylquercetin-3- O-β -D-glucopyranoside ( 2 ) and quercetin-3- O-β -D-glucopyranoside ( 3 ), were firstly isolated from D. huoshanense flowers. Results exhibited that flavonoids 1 – 3 could enhance the cell viability, decrease the expression of ALT and AST, inhibit the cell apoptosis, alleviate the oxidative stress, and mitigate the inflammatory response of alcohol-induced L02 cells. Mechanism study exhibited that flavonoids 1 – 3 could increase the expression of Nrf2 as well as its downstream antioxidation genes of alcohol-induced L02 cells, while ML-385 (Nrf2 inhibitor) could abolish the inhibitory effects of 1 – 3 on alcohol-induced hepatocyte injury. Flavonoids 1 – 3 could also reduce the phosphorylation levels of I κ B α and NF- κ B p65 of alcohol-induced L02 cells, while SC75741 (NF- κ B inhibitor) could not enhance the inhibitory effects of 1 – 3 on alcohol-induced L02 cells injury. The data above indicated that flavonoids 1 – 3 could inhibit alcohol-induced hepatocyte injury, which might be attributed to alleviating oxidative stress and mitigating inflammatory response by activating Nrf2 and inhibiting NF- κ B pathways.
研究领域:
药理学
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分子生物学
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肝病学
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2016
·Vol. 4
·期 7
·1331-1336
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IF 4.872
Shanyue Guan,Ruizheng Liang,Chunyang Li,Dan Yan,Min Wei,David G. Evans,Xue Duan
A layered drug nanovehicle was fabricated via the co-intercalation of doxorubicin (DOX) and folic acid (FA) into the gallery of layered double hydroxides (LDHs). This supermolecular nanovehicle (denoted as DOX–FA/LDH) demonstrates excellent fluorescence imaging and targeted therapy toward cancer cells. The nanovehicle shows a uniform platelet morphology with an average diameter of ∼171 nm. The unique host–guest interactions lead to a high dispersion of DOX, and in vitro tests reveal a legible and strong fluorescence imaging for the DOX–FA/LDH sample. In addition, the DOX–FA/LDH material produces a high anticancer activity toward HepG2 cells but rather low cytotoxicity to the normal cells (L02 cells), as a result of the overexpression of FA towards cancer cells. This work provides a facile approach for the design and preparation of a drug nanovehicle with significantly enhanced biocompatibility, diagnosis and targeted therapy, which can be potentially applied in medical imaging and chemotherapy.
研究领域:
纳米技术
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癌症研究
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药学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
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2024
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IF 8.2
Xin Wang,Bo Peng,Cheng Zhang,Mengqi Wu,Wenping Xu,Jiagao Cheng,Liming Tao,Zhong Li,Yang Zhang
The pesticide acetochlor (ACT) is a chiral isomer commonly detected in the global environment, yet its specific impacts on liver function remain poorly understood. We utilized zebrafish and L02 cells as research models to comprehensively investigate how ACT and its chiral isomers affect the liver. Our investigations unveiled that the R , Rac , and S isomers of ACT disrupt hepatic lipid transport, catabolism, and synthesis, leading to delayed yolk sac absorption and the accumulation of lipids in zebrafish embryos. These isomers induce oxidative stress in the liver of zebrafish embryos, reducing antioxidant levels and enzyme activity . The accumulated lipids in the liver render it susceptible to oxidative stress, further exacerbating hepatocyte damage. Hepatocyte damage manifests as extensive vacuolization of liver cells and alterations in liver morphology, which are induced by R , Rac , and S . Furthermore, we elucidated the molecular mechanisms underpinning the disturbance of hepatic lipid metabolism by R , Rac , and S in L02 cells. These compounds stimulate lipid synthesis through the upregulation of the AMPK/SREBP-1c/FAS pathway while inhibiting lipolysis via downregulation of the PPAR-α/CPT-1a pathway. Remarkably, our results highlight that S exhibits significantly higher hepatotoxicity in comparison to R . This study provides valuable insights into the hepatic effects of ACT chiral isomers.
研究领域:
环境毒理学
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分子生物学
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细胞生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2023
·
IF 5.8
Ziyun Hu,Di Xu,Huihui Meng,Wenya Liu,Qi Zheng,Junsong Wang
4-octyl itaconate (4-OI) is a cell-permeable itaconate derivative with anti-inflammatory and antioxidant properties. However, its therapeutic potential for oxidative stress-induced liver injury remains unknown. This study investigated the hepatoprotective effects and mechanisms of 4-OI against oxidative damage in in vitro and in vivo models. 4-OI attenuated H 2 O 2 -induced cytotoxicity, oxidative stress, and mitochondrial dysfunction in L02 and HepG2 cells. Untargeted metabolomics profiling and pathway analysis identified the PI3K/AKT/mTOR and MAPK pathways as key regulators of 4-OI's protective effects. Specifically, 4-OI induced phosphorylation of AKT and ERK1/2, leading to activation of the Nrf2 signaling pathway. Nrf2 upregulated expression of the mitochondrial deacetylase Sirt3, which subsequently alleviated H 2 O 2 -induced cell injury. In mice, 4-OI reduced acetaminophen (APAP)-induced liver injury as evidenced by attenuated hepatocellular necrosis and decreased serum liver enzymes . It also elevated hepatic expression of Nrf2, Sirt3, p-AKT and p-ERK1/2. Inhibition of AKT, ERK1/2 or Nrf2 blocked the protective effects of 4-OI in vitro, suggesting its antioxidant activity is mediated by activating the Nrf2/Sirt3 pathway via AKT and ERK1/2 phosphorylation. In summary, 4-OI exerted antioxidant and hepatoprotective effects by activating the Nrf2/Sirt3 signaling pathway through AKT and ERK1/2 phosphorylation, which were elucidated using in vitro and in vivo oxidative stress models. This provides novel insights into the mechanisms of 4-OI against oxidative stress-related liver diseases.
研究领域:
药理学
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毒理学
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2023
·
IF 8.2
Muguli Muhaxi,Fang Liu,Tzi Bun Ng
In the present study, three novel antioxidant polysaccharides (G-1, AG-1, and AG-2) were isolated and purified from Pleurotus ferulae using mouse erythrocyte hemolysis inhibitory activity as an indicator. These components showed antioxidant activity at the chemical and cellular levels. Given that G-1 displayed superior performance in protecting the human hepatocyte L02 cells against oxidative damage caused by H 2 O 2 compared to AG-1 and AG-2 and had a higher yield and purification rate, the detailed structure of G-1 was further characterized. G-1 mainly contains six kinds of linkage type units as A: →4,6)-α- d -Glcp-(1→, B: →3)-β- d -Glcp-(1→, C: →2,6)-β- d -Glcp-(1→, d : β- d -Manp(1→, E: →6)-β- d -Galp-(1→, F: →4)-β- d -Glcp-(1→. Finally, the potential in vitro hepatoprotective mechanism of G-1 was discussed and elucidated. Results suggested that G-1 can protect L02 cells from H 2 O 2 -induced damage by reducing the leakage of AST and ALT from the cytoplasm, enhancing the activities of SOD and CAT, and suppressing lipid peroxidation and production of LDH. G-1 could further reduce the production of ROS, stabilize mitochondrial membrane potential and maintain cell morphology. Hence, G-1 could be a valuable functional food with antioxidant and hepatoprotective activities.
研究领域:
真菌学
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药理学
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生物化学
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DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）