Bioresources and Bioprocessing
·
2021
·Vol. 8
·期 1
·1-9
·
IF 4.578
Ma Jun,Zeng Xiankun,Zhou Min,Cheng Le,Ren Difeng
Spirulina platensis protein hydrolysates were prepared by digesting protein extracts with papain, and the hydrolysates were separated into 30, 10, and 3 kDa weights using membrane ultrafiltration. The 0–3 kDa low-molecular-weight Spirulina peptides (LMWSPs) proved the highest chemical antioxidant activity by 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging ability, hydroxyl radical (·OH) scavenging activities and total antioxidant capacity. Cellular antioxidant ability of LMWPs fractions against 2000 μg/mL H2O2 induced oxidative damage of L02 cells were investigated. The MTT assay results displayed that LMWSPs at different concentrations (0–1000 μg/mL) had proliferation effect on the L02 cells and that treatment of the L02 cells with the 1000 μg/mL LMWSPs (0–3 kDa) significantly prevented H2O2-induced oxidative damage compared with control cells. Moreover, the 2′,7′-dichlorofluorescein diacetate (DCFH-DA) fluorescent probe assay showed that the levels of ROS and NO were significantly lower in the experimental group that was treated with the peptides for 24 h than in the control group. Furthermore, using the corresponding kits, the treatment inhibited the reduction of SOD activity and the increase of MDA contents in the L02 cells. Therefore, LMWSPs (0–3 kDa) may have potential applications in antioxidant and liver health products.
研究领域:
营养学
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
FITOTERAPIA
·
2024
·
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
·
肝病学
·
天然产物化学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
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
·
肝病
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产品关联
DOI
PubMed
高影响因子
CHEMISTRY & BIODIVERSITY
·
2022
·Vol. 19
·期 8
·e202200471
·
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
·
分子生物学
·
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
·
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
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
·
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
JOURNAL OF MOLECULAR LIQUIDS
·
2021
·
IF 6.165
Danfeng Wang,Min Liu,Yushu Wu,Yanna Zhao,Qingpeng Wang,Tianxin Weng,Lu Wang,He Liu,Yongfang Ren,Jun Han
Self-assembled DNA nanostructures, as a novel type of nano-biomaterials, are widely used for smart and targeted drug delivery due to their precise structures and versatile functions. The binding affinity of drugs to DNA nanostructures plays an important role in drug loading, release and efficacy. The interaction of mithramycin (MTR) with AS1411-tethered DNA nanotrains (AS1411NTrs) in the presence of different divalent metal ions (Mg 2+ , Zn 2+ , and Mn 2+ ) was studied by fluorescence spectroscopy, differential scanning calorimetry and viscosity measurement. The binding mode between the MTR dimers and AS1411NTrs was determined by viscosity experiment and melting temperature measurement. The thermodynamic parameters of the binding process (binding stoichiometry, binding constant, enthalpy change, entropy change and Gibbs free energy change) were determined by fluorescence spectroscopy and differential scanning calorimetry, and the effect of different metal ions on the binding was compared. The release of the MTR dimers loaded by AS1411NTrs in the absence and presence of DNase I was analyzed. The in vitro cytotoxicity of the MTR dimers to HepG2 cancer cells and L02 normal cells and their intracellular uptake efficiency were evaluated. The binding parameters were correlated with the loading, release and cytotoxicity of the MTR dimers. These studies showed that AS1411NTrs had high drug loading and sustained release effect on (MTR) 2 Mg 2+ , (MTR) 2 Zn 2+ and (MTR) 2 Mn 2+ . This drug loading system improved the lethality to cancer cells and reduced the side effects on normal cells. This study may provide a theoretical basis for the clinical application of MTR loaded by DNA nanostructures.
研究领域:
纳米技术
·
药学
·
生物技术
·
癌症研究
·
分子生物学
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产品关联
DOI
高影响因子
RSC Advances
·
2015
·Vol. 5
·期 50
·40258-40268
·
IF 3.84
Jing Wang,Qingqing Tian,Fang Ding,Yanyan Yu,Fanhong Wu
Functionalized graphene oxide (CGO–cRGDyK/POLO) nanosheets were designed and developed for targeted drug delivery to integrin expression. The anticancer drug cambretastain A4 (CA4) was conjugated onto the CGO–cRGDyK/POLO nanosheets. The tumor targeting ligands, cyclic arginine–glycine–aspartic acid–tyrosine–lysine pentapeptides (cRGDyK), were conjugated to carboxylated graphene oxide (CGO) nanosheets, and poloxamer 188 (POLO) was rendered to make the CGO–cRGDyK nanosheets stable. The CGO–cRGDyK/POLO nanosheets exhibited good cytocompatibility, high CA4-loading capacity (0.6872 ± 0.0121 mg mg−1) via π–π stacking or hydrophobic interactions, and controlled release in vitro. The MTT assays showed that the CGO–cRGDyK nanosheets had greater antitumor effects on Hela cells than CGO/POLO nanosheets but lower cytotoxicity on the L02 cells than free CA4. In addition, the cellular uptake of CGO–cRGDyK/POLO nanosheets was increased significantly in human umbilical vein endothelial cells (the integrins-overexpressed cells) compared to the normal L02 cells. Thus, the CGO–cRGDyK/POLO nanosheets are an appealing platform for cancer chemotherapy.
研究领域:
药学
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纳米技术
·
癌症研究
·
药物递送系统
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产品关联
DOI
高影响因子
ONCOGENE
·
2024
·
IF 6.9
Zhang Tingting,Zhao Faming,Hu Yanxia,Wei Jinlan,Cui Fengzhen,Lin Yahang,Jin Yang,Sheng Xia
Humans are widely exposed to phthalates, a major chemical plasticizer that accumulates in the liver. However, little is known about the impact of chronic phthalate exposure on liver cancer development. In this study, we applied a long-term cell culture model by treating the liver cancer cell HepG2 and normal hepatocyte L02 to environmental dosage of monobutyl phthalate (MBP), the main metabolite of phthalates. Interestingly, we found that long-term MBP exposure significantly accelerated the growth of HepG2 cells in vitro and in vivo, but barely altered the function of L02 cells. MBP exposure triggered reprogramming of lipid metabolism in HepG2 cells, where cholesterol accumulation subsequently activated the IRE1α-XBP1s axis of the unfolded protein response. As a result, the XBP1s-regulated gene sets and pathways contributed to the increased aggressiveness of HepG2 cells. In addition, we also showed that MBP-induced cholesterol accumulation fostered an immunosuppressive microenvironment by promoting tumor-associated macrophage polarization toward the M2 type. Together, these results suggest that environmental phthalates exposure may facilitate liver cancer progression, and alerts phthalates exposure to patients who already harbor liver tumors.
研究领域:
毒理学
·
癌症生物学
·
代谢学
·
免疫学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF INORGANIC BIOCHEMISTRY
·
2022
·
IF 4.336
Hong-shuang Liu,Man-yu Zhou,Xi Zhang,Ya-lan Li,Jing-wei Kong,Xin Gao,Dong-yu Ge,Jia-jing Liu,Pei-guang Ma,Gui-ying Peng,Yan Liao
The hepatic protective role of Sagittaria sagittifolia polysaccharide (SSP) and its possible mechanism were discussed in mice and L02 hepatocytes injured by heavy metals mixture of Cd + Cr (VI) + Pb + Mn + Zn + Cu. After 30-day intervention, blood and liver samples were collected for the relevant assessments. Methyl thiazolyl tetrazolium (MTT) assay showed 24 h was the best protecting point and the SSP protection at 1 mg/mL was strongest in L02 hepatocytes. SSP can alleviated hepatic injury, as evidenced by significantly decreased the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and the malondialdehyde (MDA) content, also increased the superoxide dismutase (SOD) activity and glutathione (GSH), total sulphydryl (T-SH) contents. SSP effectively reduced pathological damage of mice and accumulation of heavy metals in liver, as well as decreased the level of reactive oxygen species (ROS) in L02 hepatocytes. After SSP treatment, the protein expressions or gene transcription of nuclear factor erythroid 2-related factor 2 (Nrf2), NAD( P )H dehydrogenase, quinone 1 (NQO1) and heme oxygenase1 (HO-1) decreased in L02. The protein expression of Nrf2 and NQO1 were increased while HO-1 was decreased in liver. Besides, SSP can attenuates apoptosis through reducing the protein expression of Bcl-2-associated X protein (Bax) and caspase-3, and increasing B-cell lymphoma gene 2 (Bcl-2) and B-cell lymphoma-extra large (Bcl-xl). SSP protects against six-heavy-metal-induced hepatic injury in mice and L02 hepatocytes. Supported by Nrf2 gene silencing, the mechanisms may correlate with activating Nrf2 pathway to mitigate oxidative stress and apoptosis.
研究领域:
药理学
·
毒理学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Analytical Chemistry
·
2022
·
IF 1.698
Lijing Li,Kaixuan Zhou,Qiulu Zhao,Yuejie Wang,Jia Liu,Huiwei Bao
Buyang Huanwu Decoction (BHD) has lipid-lowering and antioxidant effects. In this study, HPLC was used to establish the fingerprint of extracts from different polar parts of BHD. Through the L02 cell lipid deposition model induced by oleic acid, extracts from different polar parts of BHD were administered for treatment. Oil red O staining, TG detection, and MDA detection were used to determine lipid deposition and antioxidant activity. The component-effect relationship is established by using grey relational analysis and PLSR analysis. The results showed that the extracts from different polar parts of BHD could reduce the levels of TG and MDA. The grey relational analysis showed that the peaks that contributed greatly to the reduction of TG and MDA were peaks 3, 16, 14, 10, 1, 15, 2, and 11, respectively. Peaks 1, 4, 9, 10, 14, 16, and 17 could reduce TG and MDA through PLSR analysis. According to the results of grey relational analysis and PLSR analysis, peaks 1, 10, 14, and 16 may have good lipid-lowering and antioxidant effects. This study provides a certain preliminary basis for follow-up research on lipid-lowering drugs.
研究领域:
药理学
·
生物化学
·
中医药
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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）