JOURNAL OF FOOD BIOCHEMISTRY
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2021
·Vol. 45
·期 4
·e13668
·
IF 2.72
Jing-Yu Duan,Yong-Jian Wang,Wei Chen,Yang-Qi Zhao,Zhong-Hui Bai,Liang-Liang He,Chun-Ping Zhang
The fruits of Swietenia macrophylla King have been processed commercially to a variety of health foods and healthcare products and exhibited antidiabetic, anti-inflammatory, antimutagenicity, antitumor activity, and so on. This study was aimed to examine the glucose consumption in human hepatoma HepG2 cells and the expression of PPARγ of limonoids isolated from the fruits of S . macrophylla . The phytochemical investigation of the fruits led to the isolation of ten limonoids which structures were elucidated by spectroscopic analysis as swietenine ( 1 ), khayasin T ( 2 ), 6-deoxyswietenine ( 3 ), 3- O -tigloylswietenolide ( 4 ), swietenolide ( 5 ), 3,6- O,O -diacetylswietenolide ( 6 ), 7-deacetoxy-7-oxogedunin ( 7 ), fissinolide ( 8 ), proceranolide ( 9 ), 7-deacetoxy-7α-hydroxygedunin ( 10 ), and compound 10 was isolated from this plant for the first time. The glucose consumption assay revealed that compounds 1 , 2 , 3 , 5, and 9 could promote glucose consumption significantly in normal hyperglycemia-induced HepG2 cells, furthermore, compounds 1 , 5, and 9 had a better effect on promoting glucose consumption in insulin-resistant HepG2 cells. In addition, compounds 1 and 5 could dramatically enhance the expression of PPARγ protein in insulin-resistant HepG2 cells according to the western blotting analysis result. Practical applications Swietenia macrophylla King belongs to the family Meliaceae and the fruits have been exhibited a wide range of biological activities, such as antidiabetic, anti-inflammatory, antimutagenicity, antitumor activity, and so on. Phytochemical investigations of S . macrophylla have revealed that limonoids and triterpenoids were effective antidiabetic agents. However, the mechanism of these limonoids to antidiabetic activity is unclear. In this study, limonoids were isolated from the fruit of S . macrophylla and their effects on the glucose consumption of insulin-resistant HepG2 cells were studied. The results showed that compounds 1 and 5 could dramatically enhance the expression of PPARγ protein in insulin-resistant HepG2 cells, which will give aid to explore the mechanism of these limonoids in the treatment of type 2 diabetes. Therefore, this research might facilitate further research and development of S . macrophylla .
研究领域:
药理学
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生物化学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
TOXICOLOGY IN VITRO
·
2012
·
IF 2.775
Jing Liu,Erqun Song,Lichao Liu,Xiaoyan Ma,Xingguo Tian,Hui Dong,Yang Song
Parent polychlorinated biphenyls (PCBs) have been shown to induce cellular oxidative stress. However, the effects of PCB active metabolites have not been extensively investigated. Parent PCBs are first converted to hydroquinone metabolites via cytochrome P-450-catalyzed hydroxylation, and the hydroquinone metabolites are then further oxidized into the corresponding quinone metabolites. Quinones are responsible for a wide range of toxic effects because of their high reactivity. Previous studies have suggested that reactive oxygen species (ROS) play important roles in multiple toxic mechanisms. In this context, the present study was undertaken to investigate oxidative stress resulting from treatment with PCB quinones in HepG2 cells. The protective effects resulting from co-administration of dihydrolipoic acid (DH-LA) were also investigated. We have found that exposure to PCB quinones leads to: (1) a decrease in cell viability; (2) an increase in both the total ROS production and superoxide production; (3) only 3Cl-PCBQ caused significant increase in the thiobarbituric acid reactive substances (TBARS) level; (4) an increase in SOD activity and a decrease in catalase activity; and (5) a decrease in GST activity and GSH level. We have also found that quinones possessing a higher number of chlorine atoms on the quinone ring display a greater activity and that DH-LA is an effective protective agent as it diminishes PCB quinone-induced cellular oxidative stress.
研究领域:
毒理学
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细胞生物学
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环境健康
✓ 已验证
DOI
PubMed
高影响因子
Polymer Chemistry
·
2013
·Vol. 4
·期 16
·4442-4449
·
IF 5.231
Tao Xing,Xianzhu Yang,Liyi Fu,Lifeng Yan
Glycopolymer with near infrared fluorescence (NIRF glycopolymer) has been designed and synthesized. The NIRF glycopolymer was prepared by firstly employing a combination of ring opening polymerization and Reversible Addition–Fragmentation Chain Transfer (RAFT) polymerization, followed by post-functionalization with an aminocyanine molecule. The obtained NIRF glycopolymer was characterized by nuclear magnetic resonance (NMR), gel permeation chromatography (GPC), and UV-vis and fluorescence spectrophotometry. The as-prepared copolymer is a potential drug delivery system with a bioimaging probe in the NIR region for tracing the biodistribution of the polymer in cells or the body. The bioactivity of the obtained material was evaluated by incubating the material with HepG2 cells, and the result shows an enhanced and fast endocytosis due to the specific interaction between the HepG2 cells and NIRF glycopolymer, and the process can be traced by fluorescence microscopy.
研究领域:
生物医学工程
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高分子化学
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分子生物学
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细胞生物学
✓ 已验证
产品关联
DOI
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2018
·
IF 3.977
Chunxue Zhao,Yiwei Zhou,Liangliang Liu,Jimin Long,Hongwen Liu,Juan Li,Yi Cao
Nanoparticle (NP) exposure might promote hepatic steatosis , but relatively few studies investigated the influence of multi-walled carbon nanotubes (MWCNTs) on lipid accumulation in hepatocytes in vitro . This study investigated lipid accumulation and the possible role of lipophagy (autophagic degradation of lipid droplets) in MWCNT-exposed HepG2 cells. Pristine (XFM19) and carboxylated MWCNTs (XFM21) were internalized, accompanying cytotoxicity, lysosomal destabilization , and intracellular reactive oxygen species (ROS) production. Compared with XFM21, XFM19 promoted lipid accumulation in HepG2 cells more effectively, which was further enhanced by pre-incubation with autophagy inhibitor NH 4 Cl. In addition, MWCNTs increased the expression of lipophagy genes PLIN2 and BECN1 but decreased that of ATG7 . The expression of endoplasmic reticulum (ER) stress regulators, namely DDIT3 , HSPA5 , and XBP- 1s, was also altered in MWCNT exposed HepG2 cells. Combined, these results suggested that MWCNT exposure might promote lipid accumulation in hepatocytes probably through the modulation of lipophagy pathway.
研究领域:
毒理学
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细胞生物学
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纳米技术
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
MEDICAL SCIENCE MONITOR
·
2018
·
IF 1.894
Youxia Huang,Yingjian Cai,Ronggui Huang,Xingzhong Zheng
Background Hepatic carcinoma is the third leading cause of cancer-related deaths. This study aimed to evaluate the anti-tumor effects of rosmarinic acid (RosA) combined with Adriamycin (ADM) on proliferation and apoptosis of hepatic carcinoma cell lines. Material/Methods Human HepG2 and Bel-7402 cells were treated with RosA and ADM and divided into HepG2 or Bel-7402, 25 μg/ml, 50 μg/m, and 100 μg/ml RosA+0.4 μg/ml ADM groups, respectively. The Cell Counting Kit-8 (CCK-8) assay was used to evaluate cell viability. Immunohistochemistry assay was used to examine B cell lymphoma-2 (Bcl-2) and Bcl-2-associated X (Bax) expression. Cell cycle analysis was used to detect cell cycle distribution. Flow cytometry and terminal deoxynucleotidyl transferase-mediated d-UTP nick-end labeling (TUNEL) assay were utilized to evaluate apoptosis. Results RosA combined with ADM damaged cell morphology and decreased cell viability, and significantly decreased S-phase cell numbers compared to the HepG2 or Bel-7402 group ( p <0.05). Apoptosis rates in the RosA combined with ADM group were significantly increased compared to the HepG2 or Bel-7402 group ( p <0.05). TUNEL assay showed that RosA combined with ADM significantly induced DNA damage (TUNEL-positive staining) in the HepG2 and Bel-7402 groups ( p <0.05). RosA combined with ADM significantly reduced Bcl-2 expression in HepG2 or Bel-7402 cells ( p <0.05). RosA combined with ADM significantly increased Bax expression in HepG2 and Bel-7402 cells ( p <0.05). Cell viability, apoptosis, cell cycle, and Bcl-2 and Bax expression were changed with increased concentrations of RosA. Conclusions RosA combined with ADM damaged tumor cell morphologies, decreased cell viability, and induced apoptosis of HepG2 and Bel-7402 by triggering the mitochondria-mediated signaling pathway.
研究领域:
肿瘤学
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药理学
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细胞生物学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Food & Function
·
2020
·Vol. 11
·期 7
·6487-6495
·
IF 4.171
Dongmei Li,Xiaokang Na,Haitao Wang,Congcong Wang,Zihan Yuan,Bei-Wei Zhu,Mingqian Tan
Endogenous nanoparticles produced during food processing have received considerable attention due to their unique physicochemical properties and potential safety risks. However, the bio-impact of endogenous nanoparticles on cell metabolism has not been fully studied. In this work, the effects of carbon dots (CDs) derived from the Maillard reaction of glucose and lysine on the cellular substance and energy metabolism were assessed using HepG2 cells as a model. When the HepG2 cells were incubated with 10.0 mg mL−1 of CDs, the mitochondrial membrane potential decreased significantly and the mitochondrial function was affected. The extracellular acidification rate and oxygen consumption rate were decreased in comparison to normal cells without CDs. The CDs blocked the glycolysis pathway by reducing the activities of key enzymes including phosphofructokinase and pyruvate kinase. The energy supply pathway of HepG2 cells changed from glycolysis to TCA cycle, but the increase of the TCA cycle flux could not meet the requirements for restoring cell proliferation. The increase of the compensatory flux in the TCA cycle may be the result of up-regulation of the metabolism of glucogenic amino acids and ketogenic amino acids, while lipid metabolism did not seem to be affected in this process.
研究领域:
纳米技术
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细胞生物学
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生物化学
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毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2023
·
IF 8.2
Chunhua Zhu,Mingjing Mou,Leilei Yang,Zedong Jiang,Mingjing Zheng,Zhipeng Li,Tao Hong,Hui Ni,Qingbiao Li,Yuanfan Yang,Yanbing Zhu
κ-Carrageenase can degrade κ-carrageenan to produce bioactive κ-carrageenan oligosaccharides (KCOs) that have potential applications in pharmaceutical, food, agricultural, and cosmetics industries. Immobilized enzymes gain their popularity due to their good reusability, enhanced stability, and tunability. In this study, the previously characterized catalytic domain of Pseudoalteromonas purpurea κ-carrageenase was covalently immobilized on the synthesized amine-modified zeolitic imidazolate framework-8 nanoparticles with the formation of cross-linked enzyme aggregates, and the immobilized κ-carrageenase was further characterized. The immobilized κ-carrageenase demonstrated excellent pH stability and good reusability, and exhibited higher optimal reaction temperature, better thermostability, and extended storage stability compared with the free enzyme. The KCOs produced by the immobilized κ-carrageenase could significantly decrease the TC, TG, and LDL-C levels in HepG2 cells, increase the HDL-C level in HepG2 cells, and reduce the free fatty acids level in Caco-2 cells. Biochemical assays showed that the KCOs could activate AMPK activity, increase the ratios of p-AMPK/AMPK and p-ACC/ACC, and downregulate the expression of the lipid metabolism related proteins including SREBP1 and HMGCR in the hyperlipidemic HepG2 cells. This study provides a novel and effective method for immobilization of κ-carrageenase, and the KCOs produced by the immobilized enzyme could be a potential therapeutic agent to prevent hyperlipidemia.
研究领域:
生物化学
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药学
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生物技术
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF FOOD BIOCHEMISTRY
·
2021
·Vol. 45
·期 9
·e13898
·
IF 2.72
Jing-Yu Duan,Wei Chen,Yang-Qi Zhao,Liang-Liang He,En-Chao Li,Zhong-Hui Bai,Yong-Jian Wang,Chun-Ping Zhang
Hypericum patulum has been used as a folk medicine for its varied therapeutic effects including antifungal, wound-healing, spasmolytic, stimulant, hypotensive activities. The water decoction is drank as tea could treat cold, infantile malnutrition. The present study aims to isolate the constituents of the plant and investigate their effects on the glucose consumption in insulin-resistant HepG2 cells, furthermore, lipid metabolism in oleic acid (OA)-treated HepG2 cells was also studied. The phytochemical investigation of the plant led to the isolation of eleven compounds, and their structures were identified by spectroscopic analysis as n -dotriacontanol ( 1 ), shikimic acid ( 2 ), 1- O -caffeoylquinic acid methyl ester ( 3 ), 5- O -caffeoylquinic acid methyl ester ( 4 ), 5- O -coumaroylquinic acid methyl ester ( 5 ), 5- O -caffeoylquinic acid butyl ester ( 6 ), quercetin-3- O - α - L -rhamnoside ( 7 ), quercetin ( 8 ), quercetin-3- O -(4״-methoxy) -α-L -rahmnopyranosyl ( 9 ), hyperoside ( 10 ), and rutin ( 11 ). The results revealed that compounds 7, 9, and 10 could enhance glucose consumption significantly in hyperglycemia induced HepG2 cells and insulin-resistant HepG2 cells. In addition, the western blotting analysis result exhibited that compounds 7, 9, and 10 in high concentration (5 μM, H) group could dramatically upregulate the expression of PPARγ protein, and even the effect of them had no significant difference compared with that of rosiglitazone. Furthermore, compounds 9 and 10 in middle concentration (2.5 μM, M) group and H group could dramatically promote triglyceride metabolism and decrease TG content in OA-treated HepG2 cells, and even in H group, reactive oxygen species (ROS) level were significantly decreased compared with model group. Practical applications Hypericum patulum is a well-known plant of the genera Hypericum for its varied preventive and therapeutic potential activities. To study the chemical constituents and their effects on glucose and lipid metabolism in vitro, we detected glucose consumption in insulin-resistant HepG2 cells, triglyceride content and reactive oxygen species level in OA-treated HepG2 cells. In addition, PPARγ protein was also detected by western blotting analysis in the study. Compounds 1 , 2 , 3 , 5 , 6 , 9 , 10 , and 11 were isolated from the plant for the first time. Quercetin-3- O -(4"-methoxy)- α - L -rahmnopyranosyl ( 9 ) and hyperoside ( 10 ) had potential therapeutic benefit against glucose and lipid metabolic disease. Therefore, this study might have certain guiding significance for further research and development of H. patulum .
研究领域:
药理学
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生物化学
·
细胞生物学
·
药用植物
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG METABOLISM AND DISPOSITION
·
2025
·
IF 4
Yixuan Wang,Tingting Yu,Xinjie Zhang,Yutong Wang,Lanlan Gui,Wushuang Zeng,Liang Huang,Ke Lan
Sterol 12α-hydroxylase (CYP8B1) is a key regulator of bile acid (BA) homeostasis and an emerging therapeutic target for metabolic disorders. To address the challenge of cellular CYP8B1 inhibition characterization, this work developed a pharmacologically optimized HepG2 cells model using triiodothyronine-dexamethasone-bezafibrate (TDB) induction, which significantly enhances the 12α-hydroxylation activity along the acidic pathway of BA biosynthesis in HepG2 cells. Employing stable isotope tracing with apolipoprotein A1-solubilized 2,3,4- 13 C 3 -cholesterol, we established an LC-MS-based flux analysis platform to track de novo BA synthesis. Combined with recombinant CYP8B1 assay, flux analysis revealed CYP8B1 participates in cholic acid synthesis in HepG2 cells, typically via 12α-hydroxylation of 7α-hydroxy-3-oxo-4-cholestenoic acid and dihydroxycholestanoic acid. In TDB-HepG2 cells, azole antifungals exhibited differentiated inhibition of 12α-hydroxylation activity, generally mirroring the enzymatic data. Econazole acted as a relatively selective CYP8B1 inhibitor with cellular half maximal inhibitory concentration of 0.31-0.45 μM, tioconazole and posaconazole dually inhibited CYP8B1 and sterol 27-hydroxylase (CYP27A1), itraconazole and voriconazole primarily inhibited CYP27A1, and fluconazole showed no activity toward either enzyme. This study provides the first direct evidence that CYP8B1 participates in cholic acid synthesis via acidic pathway and establishes a high-throughput cellular platform for screening CYP8B1 inhibitors, revealing azoles as effective modulators of this pathway.
研究领域:
分子生物学
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药物代谢
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肝脏病学
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代谢组学
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生物化学
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药理学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Pin Gong,Xufeng Wang,Yewen Han,Hui Long,Wenjuan Yang,Fuxin Chen,Mengjiao Cui,Wenjun Zhai,Benzhong Zheng,Xuefeng Chen
This study devised optimal conditions to extract Eucommia ulmoides leaf (EUL) polysaccharides using a cellulase and pectinase composite enzyme system based on one-way experiments and response surface methodology. Crude EUL polysaccharides (EULPs) were extracted and purified using a DEAE chromatography column. The polysaccharides EUL-w, EUL1, EUL2, and EUL3 were obtained by elution with water, 0.1 mol/L NaCl, 0.2 mol/L NaCl, and 0.3 mol/L NaCl, respectively. The EUL-w fraction had the highest hypoglycemic activity based on its α-amylase and α-glucosidase activities. The preliminary structure of purified EUL-w1 was elucidated. In vitro hypoglycemic activity studies and metabolomics analyses suggested that EUL-w1 modulated glucose metabolism by mediating the AMPK/PI3K/Akt signaling pathway. Our findings provide novel insights and data support for the utilization of EULPs as an emerging food resource in functional foods.
研究领域:
药理学
·
生物化学
·
细胞生物学
·
代谢组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
·
2015
·Vol. 36
·期 5
·1282-1290
·
IF 2.088
Bin Gao,Lei Shen,Ke-Wu He,Wei-Hua Xiao
The aim of the present study was to examine the apoptosis of the hepatocellular carcinoma cell line, HepG2, induced by treatment with folic acid-conjugated silica-coated gold nanorods (GNRs@SiO2-FA) in combination with radiotherapy, and to determine the involvement of apoptosis-related proteins. An MTT colorimetric assay was used to assess the biocompatibility of GNRs@SiO2-FA. The distribution of GNRs@SiO2-FA into the cells was observed using transmission electron microscopy (TEM). HepG2 cells cultured in vitro were divided into the following 4 groups: i)the control group (untreated), ii) the GNRs@SiO2-FA group, iii) the radiotherapy group (iodine 125 seeds) and iv) the combination group (treated with GNRs@SiO2-FA and iodine 125 seeds) groups. The apoptosis of the HepG2 cells was detected by flow cytometry. The concentration range of <40 µg/ml GNRs@SiO2-FA was found to be safe for the biological activity of the HepG2 cells. GNRs@SiO2-FA entered the cytoplasm through endocytosis. The apoptotic rates of the HepG2 cells were higher in the GNRs@SiO2-FA and radiotherapy groups than in the control group (P<0.05). The apoptotic rate was also significantly higher in the combination group than the GNRs@SiO2-FA and radiotherapy groups (P<0.05). Taken together, these findings demonstrate that the combination of GNRs@SiO2-FA and radiotherapy more effectively induces the apoptosis of HepG2 cells. These apoptotic effects are achieved by increasing the protein expression of Bax and caspase-3, and inhibiting the protein expression of Bcl-2 and Ki-67. The combination of GNRs@SiO2-FA and radiotherapy may thus prove to be a new approach in the treatment of primary liver cancer.
研究领域:
癌症研究
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纳米技术
·
分子生物学
·
放射生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TOXICOLOGY LETTERS
·
2019
·
IF 3.499
Qiong Shi,Yawen Wang,Wenjing Dong,Erqun Song,Yang Song
Autophagy, which works to remove stress and maintain cellular homeostasis, is usually considered a “pro-survival” signal. Contrarily, apoptosis is programmed “pro-death” machinery. Polychlorinated biphenyls (PCBs) are a group of ubiquitous industrial pollutants. Our previous studies illustrated that a PCB quinone metabolite, PCB29-pQ, elicited both autophagy and apoptosis. However, the signaling underlying the autophagy and apoptosis cross-talk has not been characterized. Here, we found that PCB29-pQ-induced autophagy mainly occurred at a lower concentration (5 μM), while apoptosis mostly arose at a higher concentration (15 μM) in HepG2 cells. Next, we demonstrated the elevation of intracellular calcium levels and calpain activity with PCB29-pQ treatment; however, the unaffected subcellular location of truncated ATG5 and Beclin1 suggested the irrelevance of calpain towards the autophagy-to-apoptosis signaling shift. HMGB1 and p53 both serve as transcription factors that play crucial roles in the regulation of PCB29-pQ-induced autophagy and apoptosis. PCB29-pQ not only enhanced the expression of HMGB1 and p53 but also promoted their binding and cytosolic translocation. Interestingly, HMGB1 rather than p53 plays a primary role in 5 μM of PCB29-pQ-induced autophagy in the nucleus; however, p53 promoted apoptosis to a great extent in the cytosol at the dose of 15 μM PCB29-pQ. Together, HMGB1 and p53 provided a subtle balance between autophagy and apoptosis, thus determining the fate of PCB29-pQ-treated cells.
研究领域:
毒理学
·
细胞生物学
·
分子生物学
✓ 已验证
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）