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JOURNAL OF FOOD BIOCHEMISTRY · 2020 ·Vol. 44 ·期 9 ·e13361 · IF 1.662

Three common caffeoylquinic acids as potential hypoglycemic nutraceuticals: Evaluation of α-glucosidase inhibitory activity and glucose consumption in HepG2 cells

Yongsheng Chen,Sheng Geng,Benguo Liu

The demand for plant-derived antidiabetic nutraceuticals is increasing. In this study, the effects of three common caffeoylquinic acids (CQAs) (chlorogenic acid, isochlorogenic acid A, and cynarin) on α-glucosidase activity and glucose consumption in HepG2 cells were systematically compared. Their α-glucosidase inhibitory activities followed the order of isochlorogenic acid A > chlorogenic acid > cynarin. The fluorescence analysis indicated that they exerted the inhibitory role by forming the complex with α-glucosidase at the molar ratio of 1:1. Isochlorogenic acid A possessed the highest binding capacity, followed by chlorogenic acid and cynarin. The effect of caffeoyl group distribution on the α-glucosidase inhibitory activity was clarified by the molecular docking results. In the HepG2 cells, isochlorogenic acid A also showed the best glucose consumption with negligible cytotoxicity, which might be related to its reactive oxygen species scavenging capacity in cells. Our results confirm its potential application as the antidiabetic nutraceutical. Practical applications The hypoglycemic activities of three common CQAs (chlorogenic acid, isochlorogenic acid A, and cynarin) were systemically evaluated in this study. Isochlorogenic acid A exhibited the strongest α-glucosidase inhibitory activity and highest glucose consumption in HepG2 cells with low cytotoxicity. The results suggest that isochlorogenic acid A can be used as the potential hypoglycemic nutraceutical in functional foods.

研究领域: 营养学 · 药理学 · 代谢生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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INTERNATIONAL JOURNAL OF FOOD SCIENCE AND TECHNOLOGY · 2020 ·Vol. 55 ·期 6 ·2509-2516 · IF 2.773

Yogurt and Streptococcus thermophilus metabolites ameliorated telomere attrition in D-galactose-induced ageing mice and t-BHP-challenged HepG2 cells

Shufang Shan,Tianli Zheng,Chaoxiong Zhang,Xuejiao Song,Jiayi Chen,Ying Shi,Jia You,Guo Cheng,Jingyuan Xiong

Summary Antioxidant-rich diets affect telomere length, an integrative marker associated with age-related diseases. Yogurt exerts antioxidative capacity and is speculated to support healthy ageing. However, direct experimental evidence is missing. Here, the effects of yogurt and dairy-fermenting bacteria on D-galactose-induced ageing mice and chemically challenged HepG2 cells were evaluated. Relative telomere length (RTL) in leucocyte and liver were significantly longer in yogurt (1.21 ± 0.07; 1.23 ± 0.11) and Streptococcus thermophilus group (1.18 ± 0.15; 1.13 ± 0.12). When t -BHP-challenged HepG2 cells were treated with digested yogurt and S. thermophilus , the senescence index (13.67 ± 3.30; 19.67 ± 2.87) were lower and RTL (1.25 ± 0.11; 1.18 ± 0.10) were longer than the model. Antioxidative effects were observed for yogurt and S. thermophilus metabolites, whereas milk and Lactobacillus rhamnosus metabolites showed minimal influence on RTL and oxidative stress. In conclusion, this study showed that yogurt and S. thermophilus metabolites ameliorated telomere attrition in ageing mice and t -BHP-challenged HepG2 cells, possibly by reducing oxidative stress.

CAS / MDL: 3646-73-9
研究领域: 营养学 · 衰老 · 分子生物学 · 细胞生物学
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Biochemistry and Biophysics Reports · 2023 · IF 2.7

Silibinin ameliorates deoxycholic acid-induced pyroptosis in steatotic HepG2 cells by inhibiting NLRP3 inflammasome activation

Meiqing Mai,Ya Wang,Mengliu Luo,Zhongxia Li,Di Wang,Yongdui Ruan,Honghui Guo

Nonalcoholic steatohepatitis (NASH) represents an inflammatory subtype of nonalcoholic fatty liver disease (NAFLD). The activation of the NOD-like receptor protein 3 (NLRP3) inflammasome triggers pyroptosis, thus propelling the progression from simple steatosis to NASH. Silibinin, a hepatoprotective compound derived from milk thistle, exerts diverse hepatoprotective effects. However, the direct impact of silibinin on NLRP3 inflammasome activation and its ability to mitigate pyroptosis remain uncertain. To address this, we utilized an in vitro model of NASH, employing HepG2 cells treated with deoxycholic acid (DCA) and free fatty acids. Subsequently, we treated these model cells with silibinin for 24 h. Our findings demonstrated that, although there were no significant changes in cellular lipid content, silibinin effectively ameliorated hepatocyte injuries. Silibinin treatment inhibited the activation of the NLRP3 inflammasome and suppressed DCA-induced pyroptosis. Additionally, molecular docking analysis revealed that silibinin exhibited a binding affinity to components of the NLRP3 inflammasome similar to that of MCC950, a selective NLRP3 inhibitor. These results suggest that silibinin may alleviate inflammation in DCA-exposed HepG2 cells by mitigating pyroptosis, possibly through its binding affinity and inhibition of the NLRP3 inflammasome. Overall, our study indicates that silibinin holds promise as a therapeutic agent for NASH by modulating pyroptosis and inhibiting NLRP3 inflammasome activation.

CAS / MDL: 112-80-1 7664-38-2
研究领域: 药理学 · 细胞生物学 · 肝病学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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WATER RESEARCH · 2022 · IF 13.4

Metabonomic and transcriptomic modulations of HepG2 cells induced by the CuO-catalyzed formation of disinfection byproducts from biofilm extracellular polymeric substances in copper pipes

Jun Hu,Jiajia Qu,Lin Deng,Huiyu Dong,Liying Jiang,Jianming Yu,Siqing Yue,Haifeng Qian,Qizhou Dai,Zhimin Qiang

Cupric oxide (CuO) is able to catalyze the reactions among disinfectant, extracellular polymeric substances (EPS) and bromide (Br − ) in copper pipes, which may deteriorate the water quality. This study aimed to investigate the metabonomic and transcriptomic modulations of HepG2 cells caused by the CuO-catalyzed formation of disinfection byproducts (DBPs) from EPS. The presence of CuO favored the substitution reactions of chlorine and bromine with EPS, inducing a higher content of total organic halogen (TOX). In addition, DBPs were shifted from chlorinated species to brominated species. A total of 182 differential metabolites (DMs) and 437 differentially expressed genes (DEGs) were identified, which were jointly involved in 38 KEGG pathways. Topology analysis indicates that glycerophospholipid and purine metabolism were disturbed most obviously. During glycerophospholipid metabolism, the differential expression of genes GPATs, AGPATs, LPINs and DGKs impacted the conversion of glycerol-3-phosphate to 2-diacyl- sn -glycerol, which further affected the conversion among phosphatidylcholine, phosphatidylserine and phosphocholines. During purine metabolism, it was mainly the differential expression of genes POLRs, RPAs, RPBs, RPCs, ENTPDs and CDs that impacted the transformation of RNA into guanine-, xanthosine-, inosine- and adenosine monophosphate, which were further successively transformed into their corresponding nucleosides and purines. The study provides an omics perspective to assess the potential adverse effects of overall DBPs formed in copper pipes on human.

研究领域: 环境科学 · 毒理学 · 分子生物学
✓ 已验证 DOI PubMed 高影响因子
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Foods · 2024 ·Vol. 13 ·期 3 ·470 · IF 4.7

Studies on the Changes of Fermentation Metabolites and the Protective Effect of Fermented Edible Grass on Stress Injury Induced by Acetaminophen in HepG2 Cells

Tao He,Xianxiu Li,Zhenzhen Wang,Jianwei Mao,Yangchen Mao,Ruyi Sha

In this study, gas chromatography-mass spectrometry (GC-MS) based untargeted metabolomics was used to describe the changes of metabolites in edible grass withLactobacillus plantarum(Lp) fermentation durations of 0 and 7 days, and subsequently to investigate the protective effect of fermented edible grass on acetaminophen-induced stress injury in HepG2 cells. Results showed that 53 differential metabolites were identified, including 31 significantly increased and 22 significantly decreased metabolites in fermented edible grass. Fermented edible grass protected HepG2 cells against acetaminophen-induced stress injury, which profited from the reduction in lactate dehydrogenase (LDH) and malondialdehyde (MDA) levels and the enhancement in superoxide dismutase (SOD) activity. Cell metabolomics analysis revealed that a total of 13 intracellular and 20 extracellular differential metabolites were detected. Fermented edible grass could regulate multiple cell metabolic pathways to exhibit protective effects on HepG2 cells. These findings provided theoretical guidance for the formation and regulation of bioactive metabolites in fermented edible grass and preliminarily confirmed the protective effects of fermented edible grass on drug-induced liver damage.Keywords:edible grass;fermentation;metabolomics;HepG2 cells;acetaminophen-induced stress injury

CAS / MDL: 103-90-2 103616-89-3
研究领域: 食品科学 · 药理学 · 细胞生物学 · 代谢组学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF APPLIED POLYMER SCIENCE · 2021 ·Vol. 138 ·期 48 ·51537 · IF 3.125

Construction of gold nanoparticles by tubular polysaccharide from black fungus and their apoptosis-inducing activities in HepG2 cells

Haoying Song,Na Hu,Ziwei Gao,Baohui Zhang,Junjie Hu,Zhenpeng Qiu,Guohua Zheng,Cong Chang,Yan Meng

Gold nanoparticles (AuNPs) with size of 12 ~ 25 nm were loaded on the dendritic nanotubes (DNTs), which were self-assembled by the triple-helix polysaccharides from black fungus (AF1). The characterization results proved that the AuNPs were dispersed on the surface of DNTs without affecting their tubular structure. Due to the dendritic structure, the loading content of AuNPs could arrived at 46.4%. Moreover, the potential anticancer activities of the complex (DNT-Au) were evaluated by the induction of apoptosis in HepG2 cells. It was found DNT-Au could be taken up by cells and enter into lysosomes, further inducing apoptosis in HepG2 cells by ROS-mediated mitochondrial dysfunction. This work was benefit for the development of natural polysaccharide as a substrate to stabilize nanoparticles in biomedical fields.

CAS / MDL: 23491-52-3 38215-36-0
研究领域: 纳米技术 · 癌症生物学 · 生物医学工程 · 药学
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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY · 2023 · IF 6.8

Protective effect of vitamin C against tetrachlorobenzoquinone-induced 5-hydroxymethylation-dependent apoptosis in HepG2 cells mainly via the mitochondrial apoptosis pathway

Cuiping Li,Mengfan Pang,Yaping Li,Lirong Han,Yajiao Fan,Xuelian Xin,Xian Zhang,Ning Zhang,Yan Qin

Tetrachlorobenzoquinone (TCBQ) is an active metabolite of pentachlorophenol, and stimulates the accumulation of ROS to trigger apoptosis. The preventive effect of vitamin C (Vc) against TCBQ-induced apoptosis in HepG2 cells is unknown. And there is little known about TCBQ-triggered 5-hydromethylcytosine (5hmC)-dependent apoptosis. Here, we confirmed that Vc alleviated TCBQ-induced apoptosis. Through investigating the underlying mechanism, we found TCBQ downregulated 5hmC levels of genomic DNA in a Tet-dependent manner, with a particularly pronounced decrease in the promoter region, using UHPLC-MS-MS analysis and hydroxymethylated DNA immunoprecipitation sequencing. Notably, TCBQ exposure resulted in alterations of 5hmC abundance to ∼91% of key genes at promoters in the mitochondrial apoptosis pathway, along with changes of mRNA expression in 87% of genes. By contrast, 5hmC abundance of genes only exhibited slight changes in the death receptor/ligand pathway. Interestingly, the pretreatment with Vc, a positive stimulator of 5hmC generation, restored 5hmC in the genomic DNA to near-normal levels. More notably, Vc pretreatment further counter-regulated TCBQ-induced alteration of 5hmC abundance in the promoter with 100% of genes, accompanying the reverse modulation of mRNA expressions in 89% of genes. These data from Vc pretreatment supported the relationship between TCBQ-induced apoptosis and the altered 5hmC abundance. Additionally, Vc also suppressed TCBQ-stimulated generation of ROS, and further increased the stability of mitochondria. Our study illuminates a new mechanism of TCBQ-induced 5hmC-dependent apoptosis, and the dual mechanisms of Vc against TCBQ-stimulated apoptosis via reversely regulating 5hmC levels and scavenging ROS. The work also provided a possible strategy for the detoxification of TCBQ.

CAS / MDL: 118-75-2 50-81-7
研究领域: 毒理学 · 分子生物学 · 细胞生物学 · 药理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE · 2023 · IF 4.1

Identification of novel antioxidant collagen-peptides for preventing and treating H2O2-induced oxidative stress in HepG2 cells through in vitro and in silico approaches

Bowei Du,Chao Zhang,Guiya Deng,Shuai Zhang,Shiqi Wang,Yuepeng Guan,Yaqin Huang

Background Nowadays, the prevalence of oxidative stress-related chronic diseases is increasing. The identification of novel antioxidant collagen-peptides to counteract oxidative stress for individuals’ health have gained significant intention. Results In this study, the collagen-peptides with antioxidant activities were separated and identified by ion chromatography (IEC), reversed-phase high-performance liquid chromatography (RP-HPLC), and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The identified antioxidant collagen-peptides were further screened by molecular docking for Keap1-targeted peptide inhibitors and their theoretical interaction mechanisms were investigated. Four novel antioxidant collagen-peptides, GPAGPIGPVG, GPAGPpGPIG, ISGPpGPpGPA and IDGRPGPIGPA with high binding affinity to Keap1 were selected. Molecular docking results demonstrated that the putative antioxidant mechanism of four antioxidant collagen-peptides contributed to their blockage of Keap1-Nrf2 interactions. The results of antioxidant activity of four antioxidant collagen-peptides proved that IDGRPGPIGPA exerted a high scavenging capacity to DPPH and ABTS free radicals, while GPAGPpGPIG improved the resistance of cells to hydrogen peroxide (H 2 O 2 ) induced oxidative damage by promoting the activation of intracellular antioxidant enzymes and the production of reduced glutathione in human hepatoma (HepG2) cells. Conclusion The antioxidant collagen-peptides (GPAGPIGPVG, GPAGPpGPIG, ISGPpGPpGPA and IDGRPGPIGPA) will be developed as the novel functional food for human health in the near future. This article is protected by copyright. All rights reserved.

CAS / MDL: 1898-66-4 28752-68-3
研究领域: 药理学 · 生物化学 · 分子生物学 · 细胞生物学 · 食品科学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ENVIRONMENTAL POLLUTION · 2022 · IF 9.988

Aryl-, halogenated- and alkyl- organophosphate esters induced oxidative stress, endoplasmic reticulum stress and NLRP3 inflammasome activation in HepG2 cells

Yuanyuan Zhou,Hanyu Liao,Shanshan Yin,Pengqiao Wang,Xiaoqing Ye,Jianyun Zhang

Organophosphate esters (OPEs) are a group of extensively used man-made chemicals with diverse substituents that are ubiquitously detected in human-related samples including serum, breastmilk, food and house dust. The understanding of their toxicological effects and potential mechanisms on hepatocytes is still limited. In this study, nine most frequently detected OPEs were selected and divided into three subgroups (aryl-, halogenated- and alkyl-OPEs) based on their substituents. The cytotoxicity, apoptosis, oxidative stress, endoplasmic reticulum (ER) stress and NLRP3 inflammasome activation induced by OPEs were evaluated in human hepatocellular carcinomas HepG2 cells. All OPEs induced apoptosis likely through a caspase-dependent apoptotic pathway. The activities of anti-oxidative enzyme SOD and CAT exhibited sensitive responses after OPEs treatment for 6 h. The OPEs induced ROS overproduction, DNA damage, endoplasmic reticulum (ER) stress and NLRP3 inflammasome activation varied among aryl-, halogenated- and alkyl-OPEs. Halogenated- and alkyl- OPEs induced overproduction of ROS and DNA damage, and elevated ER stress and NLRP3 inflammasome activation are observed aryl-OPEs induced cytotoxicity.

CAS / MDL: 67-68-5
研究领域: 毒理学 · 细胞生物学 · 环境科学 · 药理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Journal of Functional Foods · 2020 · IF 3.701

Phenolic profile of bayberry followed by simulated gastrointestinal digestion and gut microbiota fermentation and its antioxidant potential in HepG2 cells

Vemana Gowd,Lianghua Xie,Chongde Sun,Wei Chen

Bayberry (BB) fruits contain high levels of polyphenols and possess good bioactivities. However, there are no specific studies to illustrate the impact of human gut microbiota fermentation (HGMF) on BB polyphenols subjected to gastrointestinal digestion (GID). Therefore, in this study, BB was subjected to simulated GID and HGMF (0–48 h) in order to study the fate of BB bioactive components. Phenolic gut metabolites were identified and quantified by relevant standards using HPLC. Cyanidin-3- O -glucoside was the only anthocyanin in BB and could be detected in its free form even after gut fermentation for 24 h. Gut metabolites of BB showed better hypoglycemic activity by improving hepatic glucose consumption and glycogen content. Furthermore, gut metabolites significantly ameliorated glucolipotoxicity induced oxidative stress. Since BB gut metabolites showed good hypoglycemic and antioxidant activities, BB can be considered as a functional food and dietary supplementation of BB could help in maintenance of good health.

CAS / MDL: 75-05-8 67-56-1
研究领域: 食品科学 · 营养学 · 药理学 · 微生物学
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Evidence-based Complementary and Alternative Medicine · 2016 · IF 1.931

Diosgenin and 5-Methoxypsoralen Ameliorate Insulin Resistance through ER-α/PI3K/Akt-Signaling Pathways in HepG2 Cells

Ke Fang,Hui Dong,Shujun Jiang,Fen Li,Dingkun Wang,Desen Yang,Jing Gong,Wenya Huang,Fuer Lu

To determine the effects and the underlying mechanism of diosgenin (DSG) and 5-methoxypsoralen (5-MOP), two main active components in the classical Chinese prescription Hu-Lu-Ba-Wan (HLBW), on insulin resistance, HepG2 cells were incubated in medium containing insulin. Treatments with DSG, 5-MOP, and their combination were performed, respectively. The result showed that the incubation of HepG2 cells with high concentration insulin markedly decreased glucose consumption and glycogen synthesis. However, treatment with DSG, 5-MOP, or their combination significantly reversed the condition and increased the phosphorylated expression of estrogen receptor-α (ERα), sarcoma (Src), Akt/protein kinase B, glycogen synthase kinase-3β (GSK-3β), and the p85 regulatory subunit of phosphatidylinositol 3-kinase p85 (PI3Kp85). At the transcriptional level, expression of the genes mentioned above also increased except for the negative regulation of GSK-3β mRNA. The increased expression of glucose transport-4 (GLUT-4) was meanwhile observed through immunofluorescence. Nevertheless, the synergistic effect of DSG and 5-MOP on improving glycometabolism was not obvious in the present study. These results suggested that DSG and 5-MOP may improve insulin resistance through an ER-mediated PI3K/Akt activation pathway which may be a new strategy for type 2 diabetes mellitus, especially for women in an estrogen-deficient condition.

CAS / MDL: 50-28-2
研究领域: 药理学 · 内分泌学 · 细胞生物学 · 中医
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Scientific Reports · 2017 ·Vol. 7 ·期 1 ·1-10 · IF 4.259

In vivo-like 3-D model for sodium nitrite- and acrylamide-induced hepatotoxicity tests utilizing HepG2 cells entrapped in micro-hollow fibers

Chu Qiang,Zhao Yiying,Shi Xuer,Han Wen,Zhang Yanzhen,Zheng Xiaodong,Zhu Jing

To address the need for a high throughput toxicity test in the modern food industry, an in vivo -like 3-D cell model was constructed in this study to provide an alternative to controversial long-term animal models and to improve the sensitivity and accuracy of the traditional monolayer model. The model formed cell cylindroids within polyvinylidene fluoride (PVDF) hollow fibers and therefore mimicked the microenvironment of liver tissue. Microscopy methods were used, and liver-specific functions were measured to demonstrate the superiority of the model compared to the monolayer model, as well as to optimize the model for best cell performances. Later, toxicity tests of sodium nitrite and acrylamide were conducted in both the 3-D model and the monolayer model to study the sensitivity of the 3-D model in toxicity responses. As expected, HepG2 cells within the 3-D model responded at lower concentrations and shorter exposure times compared to cells within the monolayer model. Furthermore, western blot analysis of apoptosis pathways also supported the argument.

CAS / MDL: 79-06-1 7632-00-0
研究领域: 毒理学 · 细胞生物学 · 食品科学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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