Journal of Zhejiang University-SCIENCE B
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2018
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IF 1.815
Yi-ying Zhao,Qiang Chu,Xu-er Shi,Xiao-dong Zheng,Xiao-ting Shen,Yan-zhen Zhang
To address the controversial issue of the toxicity of dental alloys and silver nanoparticles in medical applications, an in vivo-like LO2 3-D model was constructed within polyvinylidene fluoride hollow fiber materials to mimic the microenvironment of liver tissue. The use of microscopy methods and the measurement of liver-specific functions optimized the model for best cell performances and also proved the superiority of the 3-D LO2 model when compared with the traditional monolayer model. Toxicity tests were conducted using the newly constructed model, finding that four dental castings coated with silver nanoparticles were toxic to human hepatocytes after cell viability assays. In general, the toxicity of both the castings and the coated silver nanoparticles aggravated as time increased, yet the nanoparticles attenuated the general toxicity by preventing metal ion release, especially at high concentrations.
研究领域:
材料科学
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毒理学
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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
JOURNAL OF ETHNOPHARMACOLOGY
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2023
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IF 5.4
Tisong Liang,Jiexin Zhou,Pu Jing,Zhengjun He,Shunshan Jiao,Wenji Zhao,Qi Tong,Guofu Jia
Ethnopharmacological relevance Rhodiola crenulata (Rc) is a traditional herb, used in Tibetan medicine, has shown promise efficacy in physical performance improvement, work capacity enhancement, fatigue elimination, and altitude sickness prevention. Also, Rc exhibited therapeutic effects on aging-related diseases. However, relevant researches on Rc and their bioactive components are quite few and needs further investigation. Aim of the study : The objective of this study was to understand the relationship between phytochemical profiles and their activities of Rc extracts. Materials and methods Rc extracts prepared by solvents with various hydrophilicity (i.e. aqueous ethanol (70%, v/v), water, and ethyl acetate), and their chemical compositions and specific compounds were analyzed by chemical analysis method and ultra-performance liquid chromatography quadruple time-of-flight mass spectrometry (UPLC-QTOF-MS). The regulate effects of Rc extracts on senescence and antioxidant activity were evaluated using the models of LO 2 cells and Caenorhabditis elegans . Results The 70% ethanol extracts exhibited better regulating effects on senescence via the assays of senescence -associated β-galactosidase (SAβG) staining and lifespan, which was consistent with the higher antioxidant activities observed based on the results of antioxidant assays. A total of 14 phytochemicals have been identified in 70% ethanol extracts, whereas the other two extracts contained much fewer compounds in varieties. Phytochemical profile of water extract was similar to the first half (polar compounds, running time: 0–6 min) of 70% ethanol extract profile, while those of ethyl acetate extract was consistent with its second half (more nonpolar compounds, running time: 6–12 min). Conclusions The 14 phytochemicals in Rc might exhibit additive or synergistic effects on senescence regulating and antioxidant activities, providing theoretical basis for daily administration of Rc.
研究领域:
药理学
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民族药理学
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老年医学
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生物化学
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产品关联
DOI
PubMed
高影响因子
ACS Food Science & Technology
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2023
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IF 2.3
Yi Wu,Yongtai Wu,Zhenhui Zhang,Jiaxian Cai,Minhua Zong,Lin Li,Xia Zhang,Hong Wu,Bing Li
Advanced glycation end products (AGEs) are widely found in processed foods; their free fractions could significantly affect cellular glucose and lipid metabolism, but this mechanism remains poorly understood. We selected Nε-(carboxymethyl)lysine (CML) as a representative free AGE to study the biochemical processes involved in glucose metabolism, lipid synthesis, and catabolism in human LO2 cells. A combination of biochemical, metabolic flux, and comparative experiments revealed that the mechanism of CML intervention in glucose metabolism mainly involves promoting the dephosphorylation of glucose 6-phosphate and inhibiting the conversion of cis-aconitate to isocitrate in the Krebs cycle. Regarding lipid metabolism, CML combined with high-glucose stimulation synergistically promoted de novo lipogenesis, and CML also promoted fatty acid β-oxidation. These results provide constructive insights into the mechanisms and targets of the imbalance in cellular glucose and lipid metabolism induced by dietary AGEs.
研究领域:
生物化学
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细胞代谢
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营养学
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产品关联
DOI
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2020
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IF 3.69
Liping Wang,Qiangwei Chen,Suqi Zhuang,Yuying Wen,Wanqiu Cheng,Zhijun Zeng,Tao Jiang,Chunping Tang
Ethnopharmacological relevance Anoectochilus roxburghii ( A. roxburghii ) is a popular folk medicine in many Asian countries, which has been used traditionally for treatment of some diseases such as diabetes, tumors, hyperlipemia , and hepatitis. The ethanol extract from A. roxburghii was recently shown to exert better ability to scavenge free radicals in vitro and possess antioxidant on natural aging mice in vivo . Aim of the study This study is to characterize the chemical composition, and investigate the protective effect of the A. roxburghii flavonoids extract (ARF) against hydrogen peroxide (H 2 O 2 )-induced oxidative stress in LO2 cells in vitro and D-galactose (D-gal)-induced aging mice model in vivo , and explore the underlying mechanisms. Materials and methods The chemical components of the flavonoids extract fro m A. roxburghii were detected by ultraperformance lipid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UPLC-QTOF-MS/MS). H 2 O 2 was used to establish an oxidative stress model in LO2 cells. Cytotoxic and protective effects of ARF on the LO2 cells were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Moreover, the levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), and malondialdehyde (MDA) in cell supernatants were measured by commercial reagent kits. Kun-Ming mice were induced to aging with D-gal (400 mg/kg, BW) by subcutaneous injection for 58 days. From the 28th day to the 58th day of D-gal treatment, ARF (122.5, 245 and 490 mg/kg, BW) and vitamin E (100 mg/kg, BW) were orally administrated to aging mice once a day for consecutive 30 days. After 25 days of the treatment with ARF, learning and memory were assessed using Morris Water Maze (MWM). At the end of the test period, the animals were euthanized by cervical dislocation , and the levels of SOD, GSH-PX, and MDA in serum, liver homogenates and brain homogenates were measured. The levels of monoamine oxidase (MAO) and acetylcholinesterase (AchE) were determined in brain homogenates. Skin and liver histopathological morphology were observed by H&E staining. Furthermore, antioxidant-related gene expression levels in the liver were carried out by quantitative real-time polymerase chain reaction (qRT-PCR). Results Nine flavonoids were identified in the extracts of A. roxburghii . In vitro assay, a high concentration of ARF (>612.5 μg/ml) reduced the survival rate and had toxic effects on LO2 cells. In addition, ARF (245 μg/ml, 490 μg/ml) and Vitamin C (200 μg/ml) markedly inhibited generations of MDA and increased activities of SOD, GSH-PX in H 2 O 2 -induced LO2 cells supernatants. In vivo assay, ARF (122.5 mg/kg, 245 mg/kg and 490 mg/kg) and Vitamin E (100 mg/kg) not only ameliorated learning and memory ability but also improved skin and liver pathological alterations. Strikingly, ARF significantly decreased MDA and MAO levels, markedly enhanced antioxidant enzyme (SOD and GSH-PX) activities. Further, compared to the D-gal group, ARF could obviously up-regulate glutathione peroxidase-1 (GPx-1) and glutathione peroxidase-4 (GPx-4) mRNA levels. Conclusions These findings suggested that ARF protects LO2 cells against H 2 O 2 -induced oxidative stress and exerts the potent anti-aging effects in D-gal aging mice model, which may be related to the inhibition of oxidative stress. Flavonoid compounds may contribute to the anti-oxidative capability and modulating aging.
研究领域:
药理学
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生物化学
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细胞生物学
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老年学
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民族药理学
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产品关联
DOI
PubMed
高影响因子
Food Bioscience
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2023
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IF 5.2
Yifei Dong,Na Sun,Qi Ge,Renzhi Lv,Songyi Lin
In this study, SHECN (Ser-His-Glu-Cys-Asn) and SHCMN (Ser-His-Cys-Met-Asn) soybean peptides were used as the research objects to investigate their antioxidant activities and XO (xanthine oxidase) activity reduction effects. The results show that SHECN and SHCMN have strong antioxidant activities, and at the same time protect the oxidative stress damage caused by HUA (hyperuricemia). They can quench XO, change the secondary structure of XO, and reduce its activity, which leads to the reduction of UA (uric acid) levels. Molecular docking demonstrated soybean peptides could bind to XO target proteins, respectively. In this study, SHECN and SHCMN were obtained from soybean peptides. Based on the data, soy peptides may be an attractive natural ingredient for the development of novel functional foods that inhibit XO activity.
研究领域:
食品科学
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生物化学
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药理学
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产品关联
DOI
高影响因子
Food Bioscience
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2022
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IF 5.318
Su Zhou,Jiaying Chen,Shiyan Yang,Yani Pan,Xinyu Feng,Shicheng Ma,Fangyuan Fan,Shuying Gong,Yuefei Wang,Ping Chen,Qiang Chu
Non-alcoholic fatty liver disease (NAFLD) is a clinical syndrome associated with steatosis and excessive deposition in the liver, while safe, green and efficient curative therapy is still lacking. Current researches have shown that plant polyphenols possess superior lipid-lowering and liver protective activities. Pu'er raw tea, a widely consumed tea with increasing fans, has been reported with various healthcare functions, such as blood lipids-lowering, weight loss, anti-microbes and anti-cancer. Therefore, in this study, polyphenols were extracted, purified and identified from Pu'er raw tea. The beneficial effects of Pu'er raw tea extract (PTE) on lipidoses in both LO2 cells and Caenorhabditis elegans were investigated. In vitro , PTE manifested beneficial effects in protecting cells from oxidative stress , alleviating lipid accumulation and expression of metabolic transcription factors such as Pparα, CD36 , Plin2, Scd1, and activating the SIRT1-FOXO pathway to inhibit the expression of SREBP-1c and FAS. In vivo , PTE regulated the abnormal athletic ability of C. elegans and inhibited lipidosis in the whole body induced by oleic acid (OA). Therefore, PTE has exhibited superior bioactivity in alleviating lipid deposition both in vivo and in vitro , and could be regarded as a potential therapeutic strategy for NAFLD in the future.
研究领域:
药理学
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分子生物学
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营养学
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细胞生物学
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DOI
高影响因子
MEDICINAL CHEMISTRY RESEARCH
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2012
·Vol. 22
·期 5
·2524-2530
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IF 1.271
Guo Yibing,Zheng Cheng,Xu Wen,Si Yongxing,Dou Sufeng,Yang Yumin
Abstract Salidroside, a phenylpropanoid glycoside isolated from a traditional Chinese medicinal plant Rhodiola rosea L. displays a broad spectrum of pharmacological properties. It has been found to play a hepatoprotective role in liver diseases through inhibiting apoptosis of hepatocytes and proliferation of hepatic stellate cells, decreasing serum aminotransferase, reversing hepatic fibrosis, and improving liver function. In this study as an ongoing study on the discovery and development of new hepatoprotective agents, about 12 novel glycosides were synthesized, and 2,2-diphenyl-1-picrylhydrazyl radical scavenge activity of each glycoside was evaluated. 2-(3,4,5-trihydroxyphenyl)ethyl β- d -glucopyranoside ( 4g ) and 2-(3,4,5-trihydroxyphenyl)ethyl β- d -galactopyranoside ( 4h ) exhibited significant activity prior to salidroside with an IC 50 value of 38.05 and 35.85 μM, respectively. The hepatoprotective effect of compounds 4g and 4h on CCl 4 -induced cytotoxicity in LO2 cells was assessed for further research. Graphical abstract 2-(3,4,5-Trihydroxyphenyl)ethyl β- d -glucopyranoside ( 4g ) and 2-(3,4,5-trihydroxyphenyl)ethyl β- d -galactopyranoside ( 4h ) exhibited significant hepatoprotective activity prior to salidroside.
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产品关联
DOI
高影响因子
RUSSIAN JOURNAL OF GENERAL CHEMISTRY
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2023
·Vol. 93
·期 6
·1468-1473
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IF 0.9
Wang Jialing,Fu Linlin,Wang Chang,Zhang Xuelian,Wang Zhuo,Zhao Xuemei
Abstract A series of new isatin derivatives was synthesized and evaluated for anti-proliferative activity against SNU-398 and LO2 cells through CCK-8 assay. Among them, 3-{2-[4-(benzyloxy)phenyl]-2-oxoethyl}-3-hydroxy-1-phenethylindolin-2-one exhibited the most inhibitory activity against SNU-398 cells (IC 50 = 6.69 μM), which could be as a lead compound to develop more potent anti-tumor agents.
研究领域:
药理学
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肿瘤学
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DOI
高影响因子
Natural Product Communications
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2022
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IF 1.496
Ruolan Yang,Jingjing Ma,Hui Guo,Qinghua Meng,Yuwei Wang,Hao Yan,Ruyi Jin,Zhi Li,Lingjie Meng
MS, and IR, 1H NMR and 13C NMR spectroscopy were employed to elucidate 4 novel evodiamine (EVO) derivatives with nitro, amino, and methoxy groups, namely 2-NO2-EVO (7a), 10-OCH3-2-NO2-EVO (7b), 2-NH2-EVO (8a), and 10-OCH3-2-NH2-EVO (8b). The amino compounds (8a, 8b) were obtained by the reduction of nitro derivatives (7a, 7b) with SnCl2/HCl. The antiproliferative activities of these compounds were tested by Cell Counting Kit-8 assay for 48 h against the MDA-MB-231 and sw620 cancer cell lines, as well as the normal LO2 cells. The in vitro experiment showed that 8a possesses the most potent inhibitory activities against MDA-MB-231 and SW620 cells, with IC50 values of 0.79 and 1.28 μM, respectively. The cytotoxicity of 8a against the 2 cancer cell lines was higher than that of EVO.
研究领域:
药物化学
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肿瘤学
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有机合成
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产品关联
DOI
高影响因子
CHEMOSPHERE
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2021
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IF 7.086
Yuting Wang,Lei Xu,Lu Peng,Changyu Fang,Qi Qin,Xuying Lv,Zixuan Liu,Bingwei Yang,Erqun Song,Yang Song
Polybrominated diphenyl ethers (PBDEs), a kind of flame retardants , were widely used in the furniture, textile and electronics industries. Because of their lipophilic, persistent and bio-accumulative properties, PBDEs were listed on the Stockholm Convention as typical persistent organic pollutants (POPs). We have previously reported that a highly active, quinone-type metabolite of PBDEs (PBDEQ) causes DNA damage and subsequently triggers apoptosis. However, it is remaining unclear whether PBDEQ provokes protein damage and stimulates corresponding signaling cascade. Using human normal liver (LO2) cells as an in vitro model, we demonstrated that PBDEQ causes oxidative protein damage through excess reactive oxygen species (ROS). Consistently, we found PBDEQ exposure causes the depletion of protein thiol group, the appearance of carbonyl group and the accumulation of protein aggregates. Endoplasmic reticulum (ER) stress was involved in the repair of oxidized proteins. Under the scenario of severe damage, LO2 cells degrade oxidized proteins through ubiquitin-proteasome system (UPS) and autophagy. The blockage of these protein degradation pathways aggravates PBDEQ-induced cytotoxicity in LO2 cells, whilst antioxidant N-acetyl-cysteine (NAC) rescues PBDEQ-induced oxidative protein damage conversely. In summary, our current study first demonstrated PBDEQ-induced protein oxidative damage in LO2 cells, which offer a better understanding of the cytotoxicity of PBDEs and corresponding metabolites.
研究领域:
毒理学
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细胞生物学
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环境科学
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DOI
PubMed
高影响因子
Journal of Diabetes Research
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2024
·Vol. 2024
·期 1
·7146054
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IF 3.6
Liangxiu Wu,Weicheng Lai,Lanlan Li,Sen Yang,Fengjuan Li,Chen Yang,Xiaobing Gong,Liangyan Wu
Background: Diabetic liver injury is a serious complication due to the lack of effective treatments and the unclear pathogenesis. Ferroptosis, a form of cell death involving reactive oxygen species (ROS)-dependent lipid peroxidation (LPO), is closely linked to autophagy and diabetic complications. Therefore, this study is aimed at investigating the role of autophagy in regulating ferroptosis by modulating the degradation of acyl-CoA synthetase long-chain family member 4 (ACSL4) in diabetic hepatocytes and its potential impact on diabetic liver injury. Methods: Initially, ferroptosis and autophagy were assessed in liver tissues from streptozotocin-induced diabetic rats and in palmitic acid (PA)–treated LO2 cells. Subsequently, the study focused on elucidating the regulatory role of autophagy in mediating ferroptosis through the modulation of ACSL4 expression in PA-treated LO2 cells. Results: The results demonstrated that ACSL4-mediated ferroptosis and inhibition of autophagy were observed in diabetic hepatocytes in vivo and in PA-treated LO2 cells. Additionally, the ferroptosis inhibitor was able to mitigate the PA-induced cell death in LO2 cells. Mechanistically, the stability and expression level of the ACSL4 protein were upregulated and primarily degraded via the autophagy-lysosome pathway in PA-treated LO2 cells. The use of the autophagy inhibitor 3-methyladenine (3-MA) and the inducer rapamycin further demonstrated that autophagy regulated ferroptosis by mediating ACSL4 degradation, highlighting its critical role in diabetic liver injury. Conclusions: These results elucidate the roles of ferroptosis, autophagy, and their interactions in the pathogenesis of diabetic liver injury, offering potential therapeutic targets. Furthermore, they shed light on the pathogenesis of ferroptosis and other diabetic complications.
研究领域:
糖尿病
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肝病学
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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
Frontiers in Pharmacology
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2023
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IF 5.6
Chen Lexian,Lv Qianqian,Cai Jianghong,Liang Jiajie,Liang Ziyan,Lin Jiahui,Xiao Ying,Chen Ruiyao,Zhang Zhiling,Hong Yue,Ji Hong
Coumarin derivatives have diverse structures and show various significant biological activities. Aiming to develop more potent coumarin derivatives for cancer treatment, a series of coumarin acrolein hybrids were designed and synthesized by using molecular hybridization approach, and investigated for their antiproliferative activity against A549, KB, Hela and MCF-7 cancer cells as well as HUVEC and LO2 human normal cells. The results indicated that most of the synthesized compounds displayed remarkable inhibitory activity towards cancer cells but low cytotoxicity on normal cells. Among all the compounds, 5d and 6e were the most promising compounds against different cancer cell lines, especially for A549 and KB cells. The preliminary action mechanism studies suggested that compound 6e, the representative compound, was capable of dose-dependently suppressing migration, invasion and inducing significant apoptosis. Furthermore, the combined results of network pharmacology and validation experiments revealed that compound 6e induced mitochondria dependent apoptosis via the PI3K/AKT-mediated Bcl-2 signaling pathway. In summary, our study indicated compound 6e could inhibit cell proliferation, migration, invasion and promote cell apoptosis through inhibition of PI3K/AKT signaling pathway in human oral epidermoid carcinoma cells. These findings demonstrated the potential of 3-(coumarin-3-yl)-acrolein derivatives as novel anticancer chemotherapeutic candidates, providing ideas for further development of drugs for clinical use.
研究领域:
药理学
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肿瘤学
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化学
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细胞生物学
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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）