CHEMOSPHERE
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2024
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IF 8.1
Chunyan Shao,Tongwang Luo,Shujie Wang,Zhuoyue Li,Xiaoqiang Yu,Ya Wu,Sheng Jiang,Bin Zhou,Quanjiang Song,Shengzhe Song,Xiaodu Wang,Houhui Song
Cadmium (Cd) is an important environmental toxicant that could cause serious damage to various organs including severe hepatotoxicity in intoxicated animals. Selenium has been reported to possess the protective effects against Cd toxicity, but the specific mechanism is still unclear. The purpose of this study was to explore the effects and mechanism of chitosan coated selenium nanoparticles (CS-SeNPs) against Cd-induced hepatotoxicity in animal and cellular models. ICR mice and rat hepatocyte BRL-3A cells were exposed to cadmium chloride (CdCl 2 ) to evaluate the therapeutic efficiency of CS-SeNPs. Analysis of histopathological images, mitochondrial membrane potential (MMP) and ultramicrostructure, serum liver enzyme activities, ferroptosis-related indicators contents, and further molecular biology experiments were performed to investigate the underlying mechanisms. In vivo experiment results showed that CdCl 2 caused significant pathological damage involving significant increase of liver index, contents of tissue MDA and serum ALT and AST, and significant decrease of serum GSH-Px activity. Moreover, CdCl 2 exposure upregulated ACSL4 and HO-1 protein levels, downregulated GPX4, TfR1, ferritin protein levels in the liver. Notably, CS-SeNPs increased the expression level of GPX4 and ameliorated CdCl 2 -induced changes in above-mentioned indicators. In vitro experimental results showed that treatment with CS-SeNPs significantly elevated GSH-Px activity and GPX4 protein level, reversed CdCl 2 -induced expression of several ferroptosis-related proteins TfR1, FTH1 and HO-1, and repressed ROS production and increased MMP of the cells exposed to CdCl 2 . Our research indicated that CdCl 2 induced hepatocyte injury by inducing ferroptosis, while CS-SeNPs can inhibit ferroptosis and reduce the degree of hepatocyte injury. This study is of great significance for further revealing the mechanism of Cd hepatotoxicity and expanding the clinical application of SeNPs.
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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分子生物学
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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
Haotian Zhang,Ziyun Wei,Yichen Tong,Xiuping Song,Siyue Li,Yuanfang Sun,Chun Liu,Fei Han,Jia Yu
Ethnopharmacological relevance Alcoholic liver disease (ALD) is the most serious and irreversible liver damage associated with alcohol consumption. Flos Puerariae and Semen Hoveniae are traditional Chinese medicines (TCM) for dispelling the effects of alcohol. Many studies have shown that the combination of two medicinal materials has the enhanced effect of treating ALD. Aim of the study The aim of this study is to assess the pharmacological effects of Flos Puerariae-Semen Hoveniae medicine pair, to elucidate its action mechanism in the treatment of alcohol-induced BRL-3A cells, and to reveal the active ingredients in the medicine pair that exerted pharmacological effects by spectrum-effect relationship study. Materials and methods Firstly, MTT assays, ELISA, fluorescence probe analysis, and Western blot were employed to study the underlying mechanisms of the medicine pair in alcohol-induced BRL-3A cells by examining pharmacodynamic indexes and related protein expression. Secondly, HPLC method was established for chemical chromatograms of the medicine pair with different ratios and the sample extracted by different solvents. Then, principal component analysis, pearson bivariate correlation analysis and grey relational analysis were applied for development of the spectrum-effect correlation between pharmacodynamic indexes and HPLC chromatograms. Moreover, prototype components and their metabolites in vivo were identified by the HPLC-MS method. Results Flos Puerariae-Semen Hoveniae medicine pair remarkably increased cell viability, decreased the activity of ALT, AST, TC and TG, reduced the generation of TNF-α, IL-1β, IL-6, MDA and ROS, increased the activity of SOD and GSH-Px, reduced protein expression of CYP2E1, compared with alcohol-induced BRL-3A cells. The medicine pair modulated the PI3K/AKT/mTOR signaling pathways by up-regulating the levels of phospho-PI3K, phospho-AKT and phospho-mTOR. Also, the results of the spectrum-effect relationship study showed that P1 (chlorogenic acid), P3 (daidzin), P4 (6″-O-xylosyl-glycitin), P5 (glycitin), P6 (unknown), P7 (unknown), P9 (unknown), P10 (6″-O-xylosyl-tectoridin), P12 (tectoridin) and P23 (unknown) can be considered as the main components of the medicine pair in the treatment of ALD. Furthermore, 6″-O-xylosyl-tectoridin, tectoridin, daidzin, 6″-O-xylosyl-glycitin and glycitin can be absorbed into the blood and showed clear metabolic and excretion behaviors in rats. Conclusion In this study, the hepatoprotective effects and the pharmacology mechanism of Flos Puerariae-Semen Hoveniae medicine pair in alcohol-induced BRL-3A cells were initially investigated and revealed. Through the spectrum-effect relationship study, the potential pharmacodynamic constituents such as daidzin, 6″-O-xylosyl-glycitin, 6″-O-xylosyl-tectoridin, glycitin, and tectoridin exert pharmacological effects on alcohol-induced oxidative stress and inflammation by modulating the PI3K/AKT/mTOR signaling pathways. This study provided experimental basis and data support for revealing the pharmacodynamic substance basis and pharmacology mechanism in the treatment of ALD. Moreover, it provides a robust mean of exploring the primary effective components responsible for the bioactivity of complicated TCM.
研究领域:
药理学
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民族药理学
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细胞生物学
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分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2019
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IF 4.527
Yuezhu Zhang,Shuyue Wang,Tianyang Zhao,Liwei Yang,Shuangyu Guo,Yanbin Shi,Xueting Zhang,Liting Zhou,Lin Ye
Mono-2-ethylhexyl phthalate (MEHP), as the major metabolite of Di-(2-ethylhexyl) phthalate (DEHP), can induce lipid accumulation in hepatocytes and further leads to non-alcoholic fatty liver disease (NAFLD), while the underlying mechanism is unclear. We aim to clarify the effects of JAK2/STAT5 pathway on lipid accumulation induced by MEHP and the role of oxidation stress in NAFLD. BRL-3A hepatocytes were exposed to MEHP (0, 10, 50, 100 and 200 μM) for 24 h and 48 h. Then the lipid droplets in cells were observed by Oil-Red-O staining and quantified by isopropyl alcohol . The levels of TG, SOD, TBARS, AST and ALT were all detected by commercial kits. RT-PCR was used to detect mRNA expression, and western blotting was used to detect the expression of proteins encoded by JAK2/STAT5 pathway genes and lipid metabolism-related genes. As a result, MEHP promoted the lipid synthesis and accumulation in BRL-3A cells. MEHP down-regulated the expression and inhibited the activation of JAK2/STAT5. Moreover, the lipid metabolism-related kinases levels were elevated after MEHP exposure. In addition, the SOD levels were gradually decreased and the TBARS levels were increased in MEHP-treated groups. The lipid metabolism-related proteins levels were correlated with the oxidation stress levels. Furthermore, the ALT and AST levels were elevated after MEHP exposure. Therefore, we concluded that MEHP led to lipid accumulation through inhibiting JAK2/STAT5 pathway, resulted in damaging liver parenchyma and NAFLD by aggravating oxidation stress.
研究领域:
毒理学
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细胞生物学
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肝病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Food Science & Technology
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2025
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IF 2.8
Zhen-Xing Wang,Li-Li Zhang,Xin-Huai Zhao
Yam (Dioscorea opposita Thunb.) is cultivated as one of the staple food crops, and its edible tubers are found to contain various bioactive substances, especially the so-called soluble and nondigestible yam polysaccharides (YPs). However, whether covalent Se-grafting of YP could lead to changed antioxidant and hypoglycemic activities remains unknown. YPs were thus separated from fresh Chinese yam tubers using water extraction and enzymatic treatment and then chemically selenized to yield two products, namely, YPSe-I and YPSe-II. These products acquired covalent Se-grafting in the form of selenite and had different Se contents (0.795 and 1.48 versus 0.035 g/kg) or selenization extents. The results obtained from the determination of antioxidant capacity indicated that the two Se-grafted products possessed a higher antioxidant activity compared to YP because they were more effective in scavenging both OH and ABTS radicals or reducing Fe3+ to Fe2+. Meanwhile, the two Se-grafted products, especially YPSe-II, had a higher capacity than YP to inhibit the activities of two digestive enzymes, namely, α-amylase and α-glucosidase. The results derived from cell experiments indicated that YP, YPSe-I, and YPSe-II were not cytotoxic to the normal BRL-3A liver cells and established insulin-resistant BRL-3A cells. However, YPSe-I and particularly YPSe-II exhibited a hypoglycemic effect in the model cells that was higher than that of YP, resulting in increased glucose consumption and enhanced oxidase activities in superoxide dismutase, catalase, and glutathione peroxidase. Data comparison results also manifested that YPSe-II consistently demonstrated higher antioxidant and hypoglycemic activities than YPSe-I. It was thus concluded that the covalent Se-grafting and high selenization extent endowed the Se-grafted YP products with enhanced beneficial functions, such as antioxidant and hypoglycemic effect. Meanwhile, this covalent Se-grafting could potentially serve as a suitable chemical approach to modify the two beneficial functions of natural polysaccharides.
研究领域:
食品科学
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营养学
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生物化学
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药理学
✓ 已验证
产品关联
DOI
高影响因子
Frontiers in Pharmacology
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2021
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IF 5.811
An Jing,Cheng Lijun,Yang Liping,Song Nali,Zhang Ju,Ma Kejian,Ma Ji
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, and it has gradually become the main disease burden in the world. However, the pathogenesis of NAFLD is complex, involving such things as dyslipidemia, oxidative stress, inflammation, etc. This brings to the table a significant challenge for drug development, and there is still no drug approved by the FDA on the market to treat the disease. GAS and HBA are active ingredients of the orchidaceae plant gastrodia elata and have exhibit effects in ameliorating nervous system diseases caused by oxidative stress. HBA is a metabolite of GAS that could perform lipid regulation and improve oxidative stress on HCD-induced NAFLD larval zebrafish, as reported by previous studies; we therefore explored the role of HBA in lipid regulation and oxidative stress on HCD-induced NAFLD larval zebrafish in vivo and FFA-induced BRL-3A hepatocyte in vitro. The gene expression of lipogenesis, inflammation, and oxidative stress were measured to investigate the underlying mechanism of HBA, and the potential protein target of HBA was explored by immunofluorescence. Altogether, our data highlight the role of HBA in improving NAFLD by use of its lipid-lowering and anti-oxidative properties via the Nrf2/HO-1 signaling pathway, providing a potential therapeutic compound for NAFLD treatment.
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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细胞生物学
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斑马鱼模型
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药物开发
✓ 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）