ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2024
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IF 6.2
Yingying Zhang,Yun Pan,Xiangyu Bai,Wen Sun,Xingfan Zhou,Qing Dong,Hui Wang,Yuanbao Zhang,Wenlin Bai,Wenping Zhang
Epidemiological evidence on the health effects of pesticide exposure among greenhouse workers is limited, and the mechanisms are lacking. Building upon our team’s previous population study, we selected two pesticides, CPF and EB, with high detection rates, based on the theoretical foundation that the liver serves as a detoxifying organ, we constructed a toxicity model using HepG2 cells to investigate the impact of individual or combined pesticide exposure on the hepatic metabolism profile, attempting to identify targeted biomarkers. Our results showed that CPF and EB could significantly affect the survival rate of HepG2 cells and disrupt their metabolic profile. There were 117 metabolites interfered by CPF exposure, which mainly affected ABC transporter, biosynthesis of amino acids, center carbon metabolism in cancer, fatty acid biosynthesis and other pathways, 95 metabolites interfered by EB exposure, which mainly affected center carbon metabolism in cancer, HIF-1 signaling pathway, valine, leucine and isoleucine biosynthesis, fatty acid biosynthesis and other pathways. The cross analysis and further biological experiments confirmed that CPF and EB pesticide exposure may affect the HIF-1 signaling pathway and valine, leucine and isoleucine biosynthesis in HepG2 cells, providing reliable experimental evidence for the prevention and treatment of liver damage in greenhouse workers.
研究领域:
毒理学
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细胞生物学
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代谢组学
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环境健康
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产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
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2023
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IF 5.6
Kun Hu,Yongjin Sun,Jie Wang,Shaojun Wu,Jie Ren,Dan Su,Lidan Tang,Jinhong Gong,Hufeng Fang,Shan Xu,Hao Yang
Hepatocyte lipid accumulation in type 2 diabetes mellitus (T2DM) promotes the development of metabolic dysfunction-associated steatosis liver disease (MASLD), whereas no specific drug treatment is available. Pinocembrin assists in the treatment of many diseases, however, little is known about its protective effect on hepatic lipid metabolism disorders induced by T2DM. In this study, the ameliorative effects of pinocembrin on T2DM-induced hepatocyte lipid accumulation were investigated by in vitro experiments combined with a comprehensive analysis strategy of network pharmacology and molecular docking. High glucose and free fatty acid co-cultured HepG2 cell line was used. The results indicated that pinocembrin reduced lipid deposition by modulating the release of Cyclooxygenase-2 (COX-2)-mediated inflammatory factors and improving insulin resistance (IR) in HepG2 cells. Overall, the findings of this study suggested that pinocembrin ameliorated lipid accumulation and IR in vitro , and thus may be a potential therapeutic agent for the treatment of T2DM-induced hepatic steatosis.
研究领域:
药理学
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细胞生物学
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代谢学
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糖尿病研究
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产品关联
DOI
高影响因子
Foods
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2024
·Vol. 13
·期 21
·3520
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IF 4.7
Yangchen Mao,Ruyi Sha,Yuhao Sun,Zhenzhen Wang,Jun Huang
Rosa Roxburghii(RR), a traditional Chinese medicinal fruit, is rich in bioactive substances that make it a potential natural antioxidant resource. This research aimed to study the antioxidant properties of RR by in vitro experiments and through intracellular assessment in H2O2-induced HepG2 cells. A non-targeted metabolic analysis was conducted to indicate changes in intracellular and extracellular metabolites. Differential metabolites and metabolic pathways were explored using PCA, PLS-DA, and KEGG pathway analysis. The results showed that RR rich in bioactive substances exhibited a significant antioxidative property in vitro and intracellularly. This property may be achieved by scavenging free radicals, increasing the activity of catalase (CAT), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and the levels of bicinchoninic acid (BCA) while reducing the reactive oxygen species (ROS) generation. This study identified 13 differential metabolites intracellularly and 7 extracellularly, among which the key differential metabolites included D-glucopyranose, D-mannose, fructose, citric acid, malic acid, cholesterol, and cholestenone. These key metabolites primarily regulated glucose-related metabolism, the citrate cycle, and the primary bile acid biosynthesis pathway in H2O2-induced HepG2 cells. These findings provide potential application evidence of RR in the development of natural resources for functional foods.
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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代谢组学
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产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
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2020
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IF 3.701
Gang Li,Jing Zhou,Mengyu Sun,Juren Cen,Jing Xu
Luteolin derived from Clerodendrum cyrtophyllum Turcz leaves exhibited antioxidant activity. The IC 50 values of luteolin for ABTS· + and DPPH· free radical scavenging was 17.3 ± 0.82 μM and 13.2 ± 0.18 μM, respectively, and the compound showed better antioxidant activities than BHT (Butylated hydroxytoluene) and VC (Vitamin C). Luteolin exhibited neither cytotoxic nor promotional activities and no genotoxic effect toward HepG2 cells. The cell viability was significantly increased in a dose-dependent manner after preincubation of the cells with 1–40 μM luteolin followed by direct exposure to TBHP ( tert -Butyl hydroperoxide). At the concentration of 30 μM, luteolin can reduce intercellular reactive oxygen species accumulation by 43.7 ± 3.98%, lactate dehydrogenase release by 38.7 ± 3.07% malondialdehyde levels by 24.5 ± 1.14% and increased 73.7 ± 6.04% superoxide dismutase activity and 72.3 ± 1.75% glutathione activity. A western blot assay showed that luteolin upregulated procaspase-3 and downregulated cleaved caspase-3 to counteract TBHP-triggered oxidative stress. Our study lays a theoretical foundation for the utilization and further development of luteolin as a promising natural antioxidant.
研究领域:
药理学
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细胞生物学
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毒理学
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产品关联
DOI
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2018
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IF 3.412
Fuqiang Liang,Yajing Fang,Weiwei Cao,Zhuo Zhang,Siyi Pan,Xiaoyun Xu
The current study evaluates the protective effects of tangeretin, a representative polymethoxyflavone (PMF) mainly isolated from the peels of citrus fruits, against tert-butyl hydroperoxide (t-BHP)-induced oxidative damage in HepG2 cells and the potential mechanisms of this protection. Tangeretin suppressed t-BHP-induced oxidative damage, as evaluated by cell viability, reactive-oxygen-species (ROS) levels, lactate dehydrogenase (LDH) leakage and glutathione (GSH) levels. Further mechanistic studies showed that tangeretin up-regulated the expression of heme oxygenase 1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1). Moreover, tangeretin induced antioxidant-responsive-element (ARE)-dependent luciferase activation, nuclear factor (erythroid-derived 2)-like 2 (Nrf2) nuclear translocation, and mitogen-activated-protein-kinase (MAPK) phosphorylation. Results in the study indicate that the protective effects of tangeretin may be at least partly due to its capacity to up-regulate the antioxidant enzymes NQO1 and HO-1 via the MAPK–Nrf2–ARE signaling pathway. Tangeretin may play an effective protective role in liver injury.
研究领域:
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 AGRICULTURAL AND FOOD CHEMISTRY
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2017
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IF 3.154
Jiarui Nie,Yaning Chang,Yujia Li,Yingjun Zhou,Jiawen Qin,Zhen Sun,Haibin Li
Caffeic acid phenethyl ester (CAPE), extracted from propolis, was evaluated for the ameliorative effects on insulin resistance and the mechanisms were identified, using non-insulin-dependent diabetes mellitus (NIDDM) model mice and insulin resistance (IR) model cells. After 5 weeks of CAPE supplementation, insulin sensitivity, hyperlipidemia, and peroxisome proliferator-activated receptor-α (PPAR-α) levels were improved in mice. Proinflammatory cytokines in serum and the expressions of tumor necrosis factor-alpha (TNF-α) mRNA in tissues were markedly downregulated from CAPE-treated mice. In vitro, CAPE supplement significantly improved glucose consumption, glucose uptake, glycogen content, and oxidative stress and decreased expression of glucose-6-phosphatase (G6Pase) mRNA in cells. Both in vivo and in vitro, CAPE enhanced p-Akt (Ser473) and p-insulin receptor substrate (IRS)-1 (Tyr612), but inhibited p-JNK (Thr183/Tyr185), p-NF-κB p65 (Ser536), and nuclear translocation of p-NF-κB p65 (Ser536). In summary, CAPE can ameliorate insulin resistance through modulation of JNK and NF-κB signaling pathway in mice and HepG2 cells.
研究领域:
药理学
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内分泌学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
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2016
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IF 3.973
Yu Zhang,Shiguo Chen,Chaoyang Wei,Jianchu Chen,Xingqian Ye
The increasing rate of hyperlipidemia has drawn great attention and natural products may play a potential role in prevention of these disorders. Chinese bayberry leaves proanthocyanidin (BLPs) with epigallocatechin-3- O -gallate (EGCG) as its terminal and major extension units is unusual in the plant kingdom. Crude, purified and ultrasound depolymerized BLPs (CBLPs, SPBLPs and UDBLPs) were prepared with the aim to investigate their hypolipidemic mechanisms. BLPs inhibited the lipase activity in vitro and reduced the accumulation of total triacylglycerols (TAG) and cholesterol induced by oleic acid in HepG2 cells. SPBLPs and UDBLPS significantly increased the phosphorylation of AMP-activated protein kinase (AMPK) and thus reduced TAG and sterols biosynthesis by inhibiting its downstream proteins, such as acetyl-CoA carboxylase, 3-hydroxy-3-methylglutaryl-CoA reductase and sterol regulatory element-binding protein. BLPs also promoted glucose consumption in oleic acid induced HepG2 cells. Overall, this study suggests the hypolipidemic property and promotion of glucose consumption of BLPs via AMPK pathway.
研究领域:
药理学
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营养学
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分子生物学
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细胞生物学
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产品关联
DOI
高影响因子
Antioxidants
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2022
·Vol. 11
·期 9
·1837
·
IF 7.675
Yanling Lin,Qinzhi Zhang,Baofu Xie,Haiyang Jiang,Jianzhong Shen,Shusheng Tang,Chongshan Dai
Chelerythrine (CHE) is a majorly harmful isoquinoline alkaloid ingredient inChelidonium majusthat could trigger potential hepatotoxicity, but the pivotal molecular mechanisms remain largely unknown. In the present study, CHE-induced cytotoxicity and the underlying toxic mechanisms were investigated using human HepG2 cells in vitro. Data showed that CHE treatment (at 1.25–10 μM)-induced cytotoxicity in HepG2 cells is dose-dependent. CHE treatment increased the production of ROS and induced oxidative stress in HepG2 cells. Additionally, CHE treatment triggered the loss of mitochondrial membrane potential, decreased the expression of mitochondrial complexes, upregulated the expression of Bax, CytC, and cleaved-PARP1 proteins and the activities of caspase-9 and caspase-3, and downregulated the expression of Bcl-XL, and HO-1 proteins, finally resulting in cell apoptosis. N-acetylcysteine supplementation significantly inhibited CHE-induced ROS production and apoptosis. Furthermore, CHE treatment significantly downregulated the expression of phosphorylation (p)-Akt (Ser473), p-mTOR (Ser2448), and p-AMPK (Thr172) proteins in HepG2 cells. Pharmacology inhibition of Akt promoted CHE-induced the downregulation of HO-1 protein, caspase activation, and apoptosis. In conclusion, CHE-induced cytotoxicity may involve the inhibition of Akt pathway and the activation of oxidative stress-mediated mitochondrial apoptotic pathway in HepG2 cells. This study sheds new insights into understanding the toxic mechanisms and health risks of CHE.Keywords:chelerythrine;oxidative stress;apoptosis;mitochondrial apoptotic pathway;Akt pathway
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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DOI
PubMed
高影响因子
CHINESE JOURNAL OF ANALYTICAL CHEMISTRY
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2017
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IF 0.795
Ze-Jie ZHANG,Xi SU,Yi XU,Li CHEN
A multifunctional microfluidic chip integrated with multi-orifice flow fractionation (MOFF) and magnetic capture technique was developed to specifically separate and capture HepG2 cells in artificial samples. The chip contained a glass substrate and a polydimethylsiloxane (PDMS) micro-channel cover plate. The PDMS cover plate consisted of three 10-mm-long injection channels, a MOFF separation zone and a hexagonal cavity cell enrichment detection zone. The MOFF separation zone, with a total length of 20 mm, was consisted of 80 semi-rhombic shrinkage and expansion units with a length of 0.18 mm, a depth of 50 μm, a shrinkage area width of 0.06 mm, and an expansion area of 0.20 mm. The angle between each group of shrinkage and expansion units was 103.0°. In this work, HepG2-blood cell suspension was used as the sample. Based on the principle that the magnetic beads surface modified c-Met antibody could specifically bind to HepG2 cells, an immune-magnetic beads (anti-MNCs) suspension at a concentration of 50 μg mL −1 was prepared by surface carboxylated beads, EDC (1 mg mL −1 ), NHS (1 mg mL −1 ) and c-Met antibody. At the optimized flow rate of 50 μL min −1 , HepG2 in suspension samples was efficiently captured at the detection zone of chip via a magnetic field. The carbon quantum dots were prepared by microwave heating with citric acid and thiourea to label HepG2 cells which made it possible that the captured HepG2 could be visualized in-situ. The captured cells in the chip detection area were counted by microscope. It was shown that the capture rate of HepG2 cells was 88.5% ± 6.7% (500 μL volume contained 10 6 blood cells and 10 HepG2 cells). The results demonstrated the developed multifunctional microfluidic chip may serve as a promising tool for separation and capture of tumour cells.
研究领域:
生物医学工程
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细胞生物学
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癌症研究
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DOI
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2022
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IF 5.195
Xu-guang Zhang,Ai-xia Liu,Yu-xin Zhang,Ming-yan Zhou,Xiang-yi Li,Ming-hai Fu,Yi-peng Pan,Jian Xu,Jun-qing Zhang
Ethnopharmacological relevance Alpinia officinarum Hance, a perennial natural medicine-food herb, has been traditionally used to treat colds, stomachache, and diabetes for thousands of years. 1,7-Diphenyl-4E-en-3-heptanone (DPH5), a diarylheptanoid isolated from the rhizome of A. officinarum has been reported to be safe and to have antioxidant and hypoglycemic effects, suggesting its potential in the treatment of insulin resistance (IR). Aim of the study : Aim of to investigate the protective effect of DPH5 on IR and elucidate its underlying mechanism of action. Materials and methods HepG2 cells were used as the research objects. Glucose uptake and reactive oxygen species (ROS) levels in high glucose–induced insulin-resistant HepG2 cells were assessed using flow cytometry. Glucose consumption and the levels of malondialdehyde (MDA) and superoxide dismutase (SOD) were analyzed using the corresponding assay kits. The expression of mRNA and proteins related to insulin signaling, glucose metabolism, and antioxidant factor, including insulin receptor substrate-1 (IRS1), phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), translocation of glucose transporter-4, glycogen synthase kinase-3β (GSK3β), glucokinase (GCK), pyruvate kinase (PK), phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G6Pase), nuclear factor-erythroid 2 related factor 2 (Nrf2), heme oxygenase-1 (HO-1), NADPH quinoneoxidoreductase (NQO1), and glutathione peroxidase (GSH-Px) was determined using real-time quantitative polymerase chain reaction and western blotting . Furthermore, molecular docking was performed to determine the spatial mechanism of DPH5 on the key targets PI3K, AKT, Nrf2 , and GSK3β. Results DPH5 could improve IR that manifested as increased glucose uptake and glucose consumption in insulin-resistant HepG2 cells. Moreover, DPH5 could enhance antioxidant capacity by activating Nrf2/HO-1 elements, including increasing Nrf2, HO-1, SOD, NQO1, and GSH-Px expression and reducing MDA, ROS, and JNK levels, thereby improving oxidative stress and ultimately alleviating IR. Additionally, DPH5 could promote the expression of IRS1, PI3K, AKT, GSK3β, GCK, and PK, and downregulate the expression of PEPCK and G6pase, thereby accelerating glucose utilization and enhancing insulin sensitivity. The mechanism underlying the effect of DPH5 in alleviating IR was related to the PI3K/AKT- and Nrf2/HO-1-mediated regulation of the GSK3β signaling pathway, and the results were further confirmed using the specific inhibitors LY294002 and ML385. Results from molecular docking indicated that there were different regulatory sites and interacting forces between DPH5 and PI3K, AKT, Nrf2, and GSK3β; however, the binding force was relatively strong. Conclusions DPH5 improved oxidative stress and glucose metabolism via modulating the PI3K/AKT-Nrf2-GSK3β pathway, thereby ameliorating IR. Overall, our findings suggest the potential of DPH5 as a natural medicine to treat type-2 diabetes mellitus.
研究领域:
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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内分泌学
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糖尿病
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DOI
PubMed
高影响因子
Molecular Medicine Reports
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2016
·Vol. 13
·期 5
·4506-4512
·
IF 1.559
Guoqiang Liang,Fei Wang,Xiudao Song,Lurong Zhang,Zhen Qian,Guorong Jiang
3-Deoxyglucosone (3DG), a highly reactive dicarbonyl intermediate generated during glycation, has been confirmed to be markedly elevated in the plasma of patients with diabetes. Our previous study found that there is an association between increasing accumulation of plasma 3DG and impaired glucose regulation in non-diabetic seniors (females, >50 years old; males, >55 years old). It was also found that 3DG led to impaired plasma glucose homeostasis in healthy mice, however, the mechanisms underlying the deleterious effect of 3DG in diabetes remain to be fully elucidated. The present study aimed to investigate the ability of 3DG to cause hepatic insulin resistance in a cell model by assessing glucose uptake and glycogen content. In addition, the molecular signaling events, including the phosphoinositide 3‑kinase (PI3K)/AKT/glucose transporter 2 (GLUT2) and PI3K/AKT/glycogen synthase kinase‑3 (GSK‑3) pathways, which affect hepatic insulin resistance, were further investigated using Western blot analysis. The results showed that 3DG (10‑300 ng/ml) had no significant effect on HepG2 cell viability, however, the viability of the HepG2 cells decreased with exposure to concentrations of 500 and 1,000 ng/ml. Treatment with non‑cytotoxic 3DG concentrations resulted in decreased uptake of glucose and glycogen content with insulin stimulation, but not under basal conditions. The insulin‑induced expression of GLUT2 and p‑GSK‑3 were eliminated by 3DG (80 and 300 ng/ml), in addition to inhibiting the phosphorylation of downstream effectors of the insulin signaling pathway, including insulin receptor substrate 1, PI3K and AKT. In conclusion, the findings of the present study indicated that the addition of exogenous 3DG directly contributed to the induction of insulin resistance by impairing insulin signaling in the HepG2 cells, which suggested that 3DG may be involved in worsening of the diabetic condition.
研究领域:
内分泌学
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分子生物学
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细胞生物学
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糖尿病研究
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DOI
PubMed
高影响因子
Natural Product Communications
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2026
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IF 1.5
Dongyuan Liu,Jianyu Zheng,Dongrong Zhu
PurposeAlkaloids, the characteristic components of areca nut, are both active ingredients and a source of safety concerns. This study combined chemical methods with cytotoxic activity screening to balance safety and efficacy, providing experimental evidence for the safety-oriented optimization of areca nut products.MethodsAcid-water extraction combined with macroporous resin adsorption was employed to compare the changes in the major components of areca nut extract before and after purification. The purified product was uniformly mixed with maltodextrin in proportions corresponding to the yields of the crude extract and the raw herb material. The chemical compositions of the crude extract and purified product were characterized by UPLC-Q-Orbitrap, and the major alkaloids (arecoline and guvacoline) were quantified by HPLC-DAD. The effects of different concentrations of areca nut extract on HepG2 cells were compared by the MTT assay and microscopic observation.ResultsA complex composition of major constituents, including phenols, fatty acids, sugars, and alkaloids, was found in the crude concentrated extract. Arecoline was identified as the primary component that was isolated and purified, with a content of over 84% and a yield of more than 89% being achieved. A concentration-dependent inhibitory effect was observed for the crude concentrated extract, which promoted cell proliferation at low concentrations (0.2–0.78 mg/mL) but reduced cell viability at higher concentrations (1.56–100 mg/mL). In contrast, the purified product displayed only weak cytotoxicity at higher concentrations, which was significantly lower than that of the crude concentrated extract at equivalent doses over the toxic concentration range. Microscopic morphological observation revealed that at 50-100 mg/mL, the crude concentrated extract caused extensive cell death with numerous cell fragments floating in the culture medium, whereas the purified product maintained approximately half of the cells viable.ConclusionThe established method effectively produces high-purity arecoline with a yield over 89%. The crude concentrated extract showed significant hepatotoxicity to HepG2 cells at 1.56-100 mg/mL, whereas the purified product exhibited significantly lower hepatotoxicity. These findings suggest that the hepatotoxicity of areca nut is not solely attributable to arecoline but may be synergistically associated with other coexisting components, providing critical experimental evidence for the safety evaluation of areca nut products.
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DOI
高影响因子
危险品化学品经营许可证（带存储）