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In this work, the rapid and efficient preparation of isolated galloyl glucoside tautomer free radical inhibitors was investigated using Saxifraga tangutica as a raw material. Four highly polar galloyl glucoside tautomers, 3-O-galloyl-α-d-glucose ⇌ 3-O-galloyl-β-d-glucose (Fr2-1-1), 2-O-galloyl-α-d-glucose ⇌ 2-O-galloyl-β-d-glucose (Fr2-1-2/2-1-3), 1-O-galloyl-β-d-glucose (Fr2-2-1), and 6-O-galloyl-α-d-glucose ⇌ 6-O-galloyl-β-d-glucose (Fr2-3-1/Fr2-3-2), were obtained via two-step medium-pressure liquid chromatography (with solid loading instead of conventional liquid injection) and one-step high-performance chromatography coupled with on-line RPLC-DPPH techniques for targeted isolation. This separation integration technique not only increases sample intake and reduces time cost but also visualizes each step of targeted separation. All four compounds were isolated from the plant for the first time. In vitro antioxidant activity assays by DPPH (1,1‑diphenyl-2-picrylhydrazyl) revealed that Fr2-1-2/Fr2-1-3 (IC50: 5.52 ± 0.32 μM), Fr2-2-1 (IC50: 7.22 ± 0.57 μM), and Fr2-3–1/Fr2-3-2 (IC50: 7.36 ± 0.25 μM) had superior free radical scavenging abilities and that both were superior to that of quercetin (IC50: 18.61 ± 3.55 μM). Oxidative stress assays revealed that Fr2-1-2/Fr2-1-3 significantly inhibited oxidative stress damage in H2O2-induced HepG2 cells, decreased the level of ROS (P < 0.01) and protected hepatocytes. Combined with the current results, gallic acid showed greater antioxidant activity when H atoms were replaced at d-glucose –OH (C-2) than at the other three sites [–OH (C-1), –OH (C-6) and –OH (C-3)]. [ABSTRACT FROM AUTHOR]

This study was to evaluate the effect of fermented Gardenia jasminoides Ellis by a mixture of Bacillus sp. DU-106 and Lactobacillus plantarum on alcoholic oxidative damage in HepG2 cells. The CCK-8 method was used to explore the optimal alcoholic oxidative damage modelling concentration and the intervention concentration of Gardenia jasminoides Ellis extract. The effect of fermented Gardenia jasminoides Ellis extract on antioxidant capacity indicators such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) activity, malondialdehyde (MDA), glutathione (GSH) content, as well as the release of transaminase-like enzymes such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH), and indicators of evaluation of hepatic injury, such as pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α), were detected. The results showed that Gardenia jasminoides Ellis extract (GE) and fermented Gardenia jasminoides Ellis extract (FGE) significantly increased the viability of ethanol- induced HepG2 cells (P<0.05), and compared with the model group (MN), GE and FGE significantly increased the cellular antioxidative stress, attenuated lipid peroxidation, reduced GSH depletion, lowered cytokine levels (P<0.01), reduced the release of AST, ALT and LDH in the cells, and improved ethanol-induced damage to HepG2 cell membranes. Among them, FEG had significant antioxidant and anti-inflammatory properties, which were potentially valuable for protecting HepG2 cells from alcoholic oxidative damage, and the present study provided useful clues for the development of food products with hepatoprotective function. [ABSTRACT FROM AUTHOR]

AbstractHelicobacter pylori infection has been associated with the development of insulin resistance (IR). This study aimed to examine the effect of H. pylori-derived extracellular vesicles (EVs) on IR induction. EVs were derived from two H. pylori strains, and characterised by transmission electron microscopy and dynamic light scattering. Different concentrations of insulin were added to HepG2 cells to induce IR model. HepG2 cells were exposed to various concentrations of H. pylori-derived EVs to assess IR development. The gene expression of IRS1, AKT2, GLUT2, IL-6, SOCS3, c-Jun and miR-140 was examined using RT-qPCR. Glucose uptake analysis revealed insulin at 5 × 10 −7 mol/l and EVs at 50 µg/ml induced IR model in HepG2 cells. H. pylori-derived EVs downregulated the expression level of IRS1, AKT2, and GLUT2, and upregulated IL-6, SOCS3, c-Jun, and miR-140 expression in HepG2 cells. In conclusion, our findings propose a novel mechanism by which H. pylori-derived EVs could potentially induce IR. [ABSTRACT FROM AUTHOR]

Background/Objectives: Diabetes often goes undiagnosed, with 60% of people in Africa unaware of their condition. Type 2 diabetes mellitus (T2DM) is associated with insulin resistance and is treated with metformin, despite the undesirable side effects. Medicinal plants with therapeutic potential, such as Carica papaya, have shown promising anti-diabetic properties. This study explored the role of C. papaya leaf and root extracts compared to metformin in reducing hyperglycaemia-induced oxidative stress and their impact on liver function using HepG2 as a reference. Methods: The cytotoxicity was assessed through the MTT assay. At the same time, glucose uptake and metabolism (ATP and ∆Ψm) in HepG2 cells treated with C. papaya aqueous leaf and root extract were evaluated using a luminometry assay. Additionally, antioxidant properties (SOD2, GPx1, GSH, and Nrf2) were measured using qPCR and Western blot following the detection of MDA, NO, and iNOS, indicators of free radicals. Results: The MTT assay showed that C. papaya extracts did not exhibit toxicity in HepG2 cells and enhanced glucose uptake compared to the hyperglycaemic control (HGC) and metformin. The glucose levels in C. papaya-treated cells increased ATP production (p < 0.05), while the ∆Ψm was significantly increased in HGR1000-treated cells (p < 0.05). Furthermore, C. papaya leaf extract upregulated GPx1 (p < 0.05), GSH, and Nrf2 gene (p < 0.05), while SOD2 and Nrf2 proteins were reduced (p > 0.05), ultimately lowering ROS (p > 0.05). Contrarily, the root extract stimulated SOD2 (p > 0.05), GPx1 (p < 0.05), and GSH levels (p < 0.05), reducing Nrf2 gene and protein expression (p < 0.05) and resulting in high MDA levels (p < 0.05). Additionally, the extracts elevated NO levels and iNOS expression (p < 0.05), suggesting potential RNS activation. Conclusion: Taken together, the leaf extract stimulated glucose metabolism and triggered ROS production, producing a strong antioxidant response that was more effective than the root extract and metformin. However, the root extract, particularly at high concentrations, was less effective at neutralising free radicals as it did not stimulate Nrf2 production, but it did maintain elevated levels of SOD2, GSH, and GPx1 antioxidants. [ABSTRACT FROM AUTHOR]

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Rationale: MG53’s known function in facilitating tissue repair and anti- inflammation has broad applications to regenerative medicine. There is controversy regarding MG53’s role in the development of type 2 diabetes mellitus. Objective: This study aims to address this controversy – whether MG53’s myokine function contributes to inhibition of insulin signaling in muscle, heart, and liver tissues. Study design: We determined the binding affinity of the recombinant human MG53 (rhMG53) to the insulin receptor extracellular domain (IR-ECD) and found low affinity of interaction with Kd (>480 nM). Using cultured C2C12 myotubes and HepG2 cells, we found no effect of rhMG53 on insulin-stimulated Akt phosphorylation (p-Akt). We performed in vivo assay with C57BL/6J mice subjected to insulin stimulation (1 U/kg, intraperitoneal injection) and observed no effect of rhMG53 on insulin-stimulated p-Akt in muscle, heart and liver tissues. Conclusion: Overall, our data suggest that rhMG53 can bind to the IR-ECD, however has a low likelihood of a physiologic role, as the Kd for binding is ~10,000 higher than the physiologic level of MG53 present in the serum of rodents and humans (~10 pM). Our findings question the notion proposed by Xiao and colleagues – whether targeting circulating MG53 opens a new therapeutic avenue for type 2 diabetes mellitus and its complications. [ABSTRACT FROM AUTHOR]

Three 12, 8-guaianolide sesquiterpene lactones, including a new compound intybusin F (1), and a new natural product cichoriolide I (2), along with six known 12, 6-guaianolide compounds (4–9) were isolated from the roots of Cichorium intybus L. Their structures were determined by extensive spectroscopic analysis. The absolute configurations of new compounds were elucidated based on analysis of the experimental and calculated electronic circular dichroism spectra. Compounds 1, 2, 4, 7, 8 showed significant effects on facilitating the glucose uptake in oleic acid plus high glucose-stimulated HepG2 cells at 50 μM. In addition, compounds 1, 2, 3, 6, 7 exhibited obvious inhibitory effects against NO production, of them, compounds 1, 2, 7 can significantly decrease the secretion of inflammatory cytokines (TNF-α, IL-6 and COX-2) levels in this hyperglycemic HepG2 cell model. [ABSTRACT FROM AUTHOR]

Various strategies have been employed to improve the reliability of 2D, 3D, and co-culture in vitro models of nonalcoholic fatty liver disease, including using extracellular matrix proteins such as collagen I to promote cell adhesion. While studies have demonstrated the significant benefits of culturing cells on collagen I, its effects on the HepG2 cell line after exposure to palmitate (PA) have not been investigated. Therefore, this study aimed to assess the effects of PA-induced lipotoxicity in HepG2 cultured in the absence or presence of collagen I. HepG2 cultured in the absence or presence of collagen I was exposed to PA, followed by analyses that assessed cell proliferation, viability, adhesion, cell death, mitochondrial respiration, reactive oxygen species production, gene and protein expression, and triacylglycerol accumulation. Culturing HepG2 on collagen I was associated with increased cell proliferation, adhesion, and expression of integrin receptors, and improved cellular spreading compared to culturing them in the absence of collagen I. However, PA-induced lipotoxicity was greater in collagen I-cultured HepG2 than in those cultured in the absence of collagen I and was associated with increased α2β1 receptors. In summary, the present study demonstrated for the first time that collagen I-cultured HepG2 exhibited exacerbated cell death following exposure to PA through integrin-mediated death. The findings from this study may serve as a caution to those using 2D models or 3D scaffold-based models of HepG2 in the presence of collagen I. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is a rising global burden, affecting one in four adults. Despite the increasing prevalence of NAFLD, the exact cellular and molecular mechanisms remain unclear, and effective therapeutic strategies are still limited. In vitro models of NAFLD are critical to understanding the pathogenesis and searching for effective therapies; thus, we evaluated the effects of free fatty acids (FFAs) on NAFLD hallmarks and their association with the modulation of Annexin A2 (ANXA2) and Keratin 17 (KRT17) in HepG2 cells. Our results show that oleic and palmitic acids can differentially induce intracellular lipid accumulation, cell death, and promote oxidative stress by increasing lipid peroxidation, protein carbonylation, and antioxidant defense depletion. Moreover, a markedly increased expression of inflammatory cytokines demonstrated the activation of inflammation pathways associated with lipotoxicity and oxidative stress. ANXA2 overexpression and KRT17 nuclear translocation were also observed, supporting the role of both molecules in the progression of liver disease. Taken together, these data provide insights into the interplay between ANXA2 and KRT17 in NAFLD, paving the way for understanding molecular mechanisms involved with the disease and developing new therapeutic strategies. [ABSTRACT FROM AUTHOR]

Abstract In this work, the rapid and efficient preparation of isolated galloyl glucoside tautomer free radical inhibitors was investigated using Saxifraga tangutica as a raw material. Four highly polar galloyl glucoside tautomers, 3-O-galloyl-α-d-glucose ⇌ 3-O-galloyl-β-d-glucose (Fr2-1-1), 2-O-galloyl-α-d-glucose ⇌ 2-O-galloyl-β-d-glucose (Fr2-1-2/2-1-3), 1-O-galloyl-β-d-glucose (Fr2-2-1), and 6-O-galloyl-α-d-glucose ⇌ 6-O-galloyl-β-d-glucose (Fr2-3-1/Fr2-3-2), were obtained via two-step medium-pressure liquid chromatography (with solid loading instead of conventional liquid injection) and one-step high-performance chromatography coupled with on-line RPLC-DPPH techniques for targeted isolation. This separation integration technique not only increases sample intake and reduces time cost but also visualizes each step of targeted separation. All four compounds were isolated from the plant for the first time. In vitro antioxidant activity assays by DPPH (1,1‑diphenyl-2-picrylhydrazyl) revealed that Fr2-1-2/Fr2-1-3 (IC50: 5.52 ± 0.32 μM), Fr2-2-1 (IC50: 7.22 ± 0.57 μM), and Fr2-3–1/Fr2-3-2 (IC50: 7.36 ± 0.25 μM) had superior free radical scavenging abilities and that both were superior to that of quercetin (IC50: 18.61 ± 3.55 μM). Oxidative stress assays revealed that Fr2-1-2/Fr2-1-3 significantly inhibited oxidative stress damage in H2O2-induced HepG2 cells, decreased the level of ROS (P

Abstract The purpose of this study evaluated effects of gelatinized brown rice extract (GBE) on type 2 diabetes mellitus by analyzing antioxidant activity, polysaccharide-degrading enzymes activity, and regulation of insulin secretion and glucose transport-related factors in human liver cells (HepG2). Quantified polyphenols and flavonoids in extract showed 6.7 mg gallic acid equivalent/g dry matter (DM) and 5.3 mg quercetin equivalent/g DM, respectively, with DPPH and ABTS radical scavenging activities confirmed to 67.1 ~ 77.7%. Additionally, extract inhibited alpha-glucosidase activity by 81.9%, thereby demonstrating potential for improving blood glucose regulation. To demonstrate alleviation of type 2 diabetes through mitigation of insulin resistance and promotion of glucose transport, expression of genes related to insulin receptor genes (Insulin Receptor Substrate-1, Protein Kinase B) increased by 18.5 ~ 28.3%, while expression of counterregulatory hormone genes (Insulin-like Growth Factor-1) decreased by 33.3%. Additionally, expression of glucose transporter proteins (Glucose Transporter Type-4, 2) increased by 30.9 ~ 42.0%, and expression of proteins that reduce insulin sensitivity (Insulin Receptor Substrate-2) decreased by 34.6%. These results indicated that insulin resistance in hepatocytes alleviated, and glucose transport promoted, leading to decreased blood glucose levels.

This study was to evaluate the effect of fermented Gardenia jasminoides Ellis by a mixture of Bacillus sp. DU-106 and Lactobacillus plantarum on alcoholic oxidative damage in HepG2 cells. The CCK-8 method was used to explore the optimal alcoholic oxidative damage modelling concentration and the intervention concentration of Gardenia jasminoides Ellis extract. The effect of fermented Gardenia jasminoides Ellis extract on antioxidant capacity indicators such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) activity, malondialdehyde (MDA), glutathione (GSH) content, as well as the release of transaminase-like enzymes such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH), and indicators of evaluation of hepatic injury, such as pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α), were detected. The results showed that Gardenia jasminoides Ellis extract (GE) and fermented Gardenia jasminoides Ellis extract (FGE) significantly increased the viability of ethanol-induced HepG2 cells (P

Objective: To explore the protective effects of 20-Hydroxyecdysone (20-HE) on high glucose induced HepG2 cells and its related molecular mechanism. Methods: In this study, high glucose (50 mmol/L glucose) was used to establish the oxidative damage model in HepG2 cells. The CCK-8 assay, caspase-3 assay, fluorescent probe method, and colorimetric method were used to assess the levels of cell viability, apoptosis, oxygen species (ROS), superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA), respectively. The signaling pathways involved in the regulation of 20-HE were predicted using bioinformatics analysis. The phosphorylation level of Akt protein was detected by Western blot to evaluate the activation level of the PI3K/Akt signaling pathway. The involvement of the PI3K/Akt signaling pathway in the regulatory effects of 20-HE was verified using the inhibitor LY294002. Results: Treatment with 20-HE had no significant toxic effect on HepG2 cells at concentrations lower than 20 μmol/L. In the injured cells, 20-HE could significantly improve the viability (P

Background: Hepatocellular carcinoma (HCC) is a deadly form of liver cancer with limited treatment options. Natural compounds, such as venom-derived peptides, have emerged as potential sources of anticancer agents. 3D cell models, which closely resemble the architectural characteristics of natural tumors, serve as an appropriate system for investigating the cytotoxic and apoptotic effects of scorpion venom on cancer cells. In this study, we investigated the apoptotic effects of low molecular weight peptides isolated from the venom of Odontobuthus bidentatus on HepG2 cells in a 3D cell culture model. Methods and Results: The O. bidentatus venom was subjected to high-performance liquid chromatography (HPLC) for fractionation and purification of the low molecular weight peptides. Subsequently, the isolated peptides were evaluated for their impact on cell viability and apoptosis induction in HepG2 cells within a 3D cell culture system and were compared to crude venom. To create a 3D cell culture, HepG2 cells were enclosed within alginate hydrogel. Subsequently, the cytotoxic effects of scorpion venom were evaluated using MTT and neutral red uptake assays. Changes in the redox potential of HepG2 cells were assessed by measuring accumulated nitric oxide (NO) in the cell culture media, as well as levels of glutathione (GSH) and catalase activity. To determine the induction of apoptosis in cells treated with scorpion venom, various assays including alkaline comet assay, caspase-3 enzyme activity, and cytochrome c release were employed. Additionally, the expression of the pro-apoptotic gene BAX and the anti-apoptotic gene BCL-2 was evaluated using qRT-PCR. The results obtained from the MTT and neutral red uptake assays demonstrated that O. bidentatus crude venom and isolated fractions (Gomes et al. in Anticancer potential of animal venoms and toxins, 2010; Ding et al. in Experimental Biology Med 239(4):387–393, 2014; and Ortiz et al. in Toxicon 93:125–135, 2015) had cytotoxic effects on HepG2 cells in the 3D cell culture. The concentration of NO released into the culture media increased, while the levels of reduced glutathione and catalase decreased in a dose-dependent manner within the 3D culture. The findings from the caspase-3 enzyme activity, cytochrome c release assay, comet assay, and Bax/Bcl-2 gene expression ratio supported the conclusion that O. bidentatus scorpion venom induces apoptosis through the mitochondrial pathway. Conclusion: This finding highlights the potential of scorpion venom-derived peptides as novel therapeutic agents for hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

Zhiliang Li,1,2,&ast; Jiali Yang,1,3,&ast; Yang Sun,1 Shuo Han,1 Jietao Gong,1 Yi Zhang,1,3 Zhiyuan Feng,1 Hong Yao,4 Peiying Shi1,5 1College of Bee Science and Biomedicine, Fujian Agriculture and Forestry University, Fuzhou, 350002, People’s Republic of China; 2College of Food Science, Fujian Agriculture and Forestry University, Fuzhou, 350002, People’s Republic of China; 3College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou, 350002, People’s Republic of China; 4Department of Pharmaceutical Analysis, School of Pharmacy, Fujian Medical University, Fuzhou, 350122, People’s Republic of China; 5State and Local Joint Engineering Laboratory of Natural Biotoxins, Fujian Agriculture and Forestry University, Fuzhou, 350002, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hong Yao, Department of Pharmaceutical Analysis, School of Pharmacy, Fujian Medical University, Fuzhou, 350122, People’s Republic of China, Email hongyao@mail.fjmu.edu.cn Peiying Shi, College of Bee Science and Biomedicine, Fujian Agriculture and Forestry University, Fuzhou, 350002, People’s Republic of China, Email peiyshi@126.comPurpose: Bee pollen possesses favorable anticancer activities. As a medicinal plant source, Schisandra chinensis bee pollen (SCBP) possesses potential pharmacological properties, such as reducing cisplatin-induced liver injury, but its anti–liver cancer effect is still rarely reported. This paper aims to investigate the effect and mechanism of SCBP extract (SCBPE) on hepatocellular carcinoma HepG2 cells.Methods: The effect of SCBPE on cell proliferation and migration of HepG2 cells was evaluated based on MTT assay, morphology observation, or scratching assay. Furthermore, tandem mass tag-based quantitative proteomics was used to study the effect mechanisms. The mRNA expression levels of identified proteins were verified by RT-qPCR.Results: Tandem mass tag-based quantitative proteomics showed that 61 differentially expressed proteins were obtained in the SCBPE group compared with the negative-control group: 18 significantly downregulated and 43 significantly upregulated proteins. Bioinformatic analysis showed the significantly enriched KEGG pathways were predominantly ferroptosis-, Wnt-, and hepatocellular carcinoma-signaling ones. Protein–protein interaction network analysis and RT-qPCR validation revealed SCBPE also downregulated the focal adhesion–signaling pathway, which is abrogated by PF-562271, a well-known inhibitor of FAK.Conclusion: This study confirmed SCBPE suppressed the cell proliferation and migration of hepatocellular carcinoma HepG2 cells, mainly through modulation of ferroptosis-, Wnt-, hepatocellular carcinoma-, and focal adhesion–signaling pathways, providing scientific data supporting adjuvant treatment of hepatocellular carcinoma using SCBP. Keywords: Schisandra chinensis bee pollen extract, HepG2 cells, proteomics, ferroptosis, Wnt-signaling pathway, focal adhesion–signaling pathway

The aim of this study was to investigate the impact of Lycium barbarum leaves flavonoids (LBLF) on lipid accumulation in normal and oleic acid-induced HepG2 cells. The experiment was divided into six groups as follows: blank, model, positive control, low-, medium-, and high-dose LBLF. Oil red O staining was performed to assess the aggregation of lipid droplets in each group, and lipid levels and oxidative stress indicators were measured. Finally, real-time polymerase chain reaction (real-time PCR) and Western blot were used to detect the expression of mRNAs and proteins associated with lipid synthesis. The results indicated that LBLF could decrease the increase in the levels of triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), malondialdehyde (MDA) and reactive oxygen species (ROS) induced by oleic acid in HepG2 cells. It also could increase high-density lipoprotein cholesterol (HDL-C), superoxide dismutase (SOD), glutathione, and catalase levels. Additionally, Western blot results suggested that LBLF intervention could up-regulate phosphorylated adenosine 5’-monophosphate (AMP)-activated protein kinase (p-AMPK) and AMPK levels, and down-regulate the protein expression of sterol regulatory element-binding protein 1c(SREBP-1c), peroxisome proliferator-activated receptor γ (PPARγ), and CCAAT enhancer binding protein alpha (CEBPα). Real-time PCR results indicated that LBLF intervention down-regulated the expression of genes such as ACC, FAS, SREBP-1c, SCD-1, PPARγ, and CEBPα. In conclusion, LBLF could partially alleviate lipid metabolism disorder in oleic acid-induced HepG2 cells by regulating the expression levels of lipid synthesis and oxidation-related genes.

Objective To observe the effects of luteolin on the proliferation, apoptosis, migration and glycolysis of human hepatocellular carcinoma cell lines and to explore their mechanism. Methods HepG2 and Huh7 cells cultured in vitro were divided into two groups. Cells in the control group were treated with DMEM medium, and cells in the experimental groups were treated with 20，40，60，80 and 100 µmol/L luteolin, respectively. Cell proliferation rate was measured by CCK-8 assay. The number of cell clones formed was detected by the cell clone formation experiment to evaluate the cell proliferation ability. The relative expression levels of apoptosis-related proteins (Bax, Bcl-2, and Caspase-3 proteins) were measured by Western blotting to evaluate the apoptosis ability. The cell migration rate was measured by the cell scratch test to evaluate the cell migration ability. The glucose consumption and lactic acid production levels were determined by the kit. Glycolysis-related proteins (GLUT4, PDK1, HK2, PKM2, and LDHA proteins) were detected by Western blotting to evaluate the cell glycolysis ability. Western blotting was used to detect the LKB1/AMPK signaling pathway-related proteins (LKB1/P-LKB1 and AMPK/P-AMPK protein ratios). Results Compared with the control group, the proliferation rates of HepG2 and Huh7 cells in the experimental group decreased in a time- and dose-dependent manner； the number of colony-forming cell colonies of HepG2 and Huh7 cells in the experimental group decreased in a dose-dependent manner (all P<0. 05). Compared with the control group, the relative expression levels of Bax and Caspase-3 proteins in HepG2 and Huh7 cells in the experimental group increased, and the relative expression of Bcl-2 protein decreased in a dose-dependent manner (all P<0. 05). Compared with the control group, the migration rates of HepG2 and Huh7 cells in the experimental group decreased in a time- and dose-dependent manner (both P<0. 05). Compared with the control group, the glucose consumption of HepG2 and Huh7 cells in the experimental group (except for the dose of 20 µmol/L) decreased, and the lactate production increased in a dose-dependent manner； the relative expression levels of GLUT4, PDK1, HK2, PKM2 and LDHA proteins in HepG2 and Huh7 cells in the experimental group decreased in a dose-dependent manner (all P<0. 05). Compared with the control group, the protein expression ratios of LKB1/P-LKB1 and AMPK/ P-AMPK in the experimental group increased in a dose-dependent manner (both P<0. 05). Conclusions Luteolin inhibits the glycolysis process of human hepatocellular carcinoma cell lines, further inhibits cell proliferation, migration and promotes apoptosis in a dose- or time-dependent manner, and the mechanism may be related to the activation of intracellular LKB1/AMPK signaling pathway. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and poses a severe threat to human health. Ginkgo biloba leaf polysaccharide (GBLP) is a bioactive component, and its sulphated derivative (sulfated GBLP, SGBLP) may exhibit high antitumor activity in certain types of cancers. However, the precise mechanisms of the SGBLP antitumor activity, particularly in HCC, remain unclear. Here, we assessed the effect of SGBLP on HepG2 hepatocellular carcinoma cells. SGBLP was shown to inhibit cellular proliferation and promote apoptosis through the regulation of pro- as well as anti-apoptosis markers, and to induce autophagy by supressing the PI3K/AKT/mTOR pathway. In addition, the autophagy inhibitor 3-melyladenine (3-MA) enhanced the antiproliferative and proapoptotic effects of SGBLP in HepG2 cells. Thus, SGBLP exhibits antitumor activity, and its combination with an autophagy inhibitor may represent a promising anticancer strategy in the treatment of HCC. [ABSTRACT FROM AUTHOR]

With its annually increasing prevalence, non‐alcoholic fatty liver disease (NAFLD) has become a serious threat to people's life and health. After a preliminary research, we found that Lactucopicrin has pharmacological effects, such as lowering blood lipids and protecting the liver. Further research showed its significant activation for fatty acid β‐oxidase hydroxyacyl‐coenzyme A (CoA) dehydrogenase trifunctional multienzyme complex subunit alpha (HADHA), so we hypothesized that Lactucopicrin could ameliorate lipid accumulation in hepatocytes by promoting fatty acid β‐oxidation. In this study, free fatty acid (FFA)‐induced human hepatoblastoma cancer cells (HepG2) were used to establish an in vitro NAFLD model to investigate the molecular basis of Lactucopicrin in regulating lipid metabolism. Staining with Oil red O and measurements of triglyceride (TG) content, fatty acid β‐oxidase (FaβO) activity, reactive oxygen species (ROS) content, mitochondrial membrane potential, and adenosine triphosphate (ATP) content were used to assess the extent to which Lactucopicrin ameliorates lipid accumulation and promotes fatty acid β‐oxidation. Quantitative real‐time polymerase chain reaction (qRT‐PCR) and Western blot methods were used to explore the regulatory effects of Lactucopicrin on factors related to fatty acid β‐oxidation. Results showed that Lactucopicrin downregulated phosphorylated mammalian target of rapamycin (P‐mTOR) by activating the adenosine monophosphate‐activated protein kinase (AMPK) pathway and upregulated the messenger RNA (mRNA) and protein expression levels of coactivators (peroxisome proliferator‐activated receptor gamma coactivator 1‐alpha (PGC1α)), transcription factors (peroxisome proliferator‐activated receptor α (PPARα) and peroxisome proliferator‐activated receptor γ (PPARγ)), and oxidative factors (carnitine palmitoyltransferase 1A (CPT1A) and HADHA). This phenomenon resulted in a significant increase in FaβO activity, ATP content, and JC‐1 and a significant decrease in ROS level, TG content, and intracellular lipid droplets. With the addition of Dorsomorphin, all the effects of Lactucopicrin intervention were suppressed. In summary, Lactucopicrin promotes fatty acid β‐oxidation by activating the AMPK pathway, thereby ameliorating FFA‐induced intracellular lipid accumulation in HepG2 cells. [ABSTRACT FROM AUTHOR]

Zinc oxide nanoparticles (ZnONPs) are enormously popular semi-conductor metal oxides with diverse applications in every field of science. Many physical and chemical methods applied for the synthesis of ZnONPs are being rejected due to their environmental hazards. Therefore, ZnONPs synthesized from plant extracts are steered as eco-friendly showing more biocompatibility and biodegradability. Additionally, various synthesis conditions such as the type of precursor salt also play a role in influencing the physicochemical and biological properties of ZnONPs. In this study, green synthesis of ZnONPs from Acacia nilotica was carried out using zinc acetate (ZA-AN-ZNPs), zinc nitrate (ZN-AN-ZNPs), and zinc sulfate (ZS-AN-ZNPs) precursor salts. Surprisingly, characterization of ZnONPs using UV–visible spectroscopy, TEM, XRD, and EDX revealed the important role precursor salts played in influencing the size and shape of ZnONPs, i.e., 20–23 nm spherical (ZA-AN-ZNPs), 55–59 nm triangular (ZN-AN-ZNPs), and 94–97 nm nano-flowers (ZS-AN-ZNPs). FTIR analysis showed the involvement of alkaloids, alcohols, carboxylic acid, and phenolic compounds present in Acacia nilotica extract during the synthesis process. Since different precursor salts showed different morphology of ZnONPs, their biological activities were also variable. ZN-AN-ZNPs showed the highest cytotoxicity towards HepG2 cells with the lowest cell viability (28.92 ± 0.99%), highest ROS/RNS production (3425.3 ± 184.58 relative DHR123 fluorescence), and loss of mitochondrial membrane potential (1645.2 ± 32.12 relative fluorescence unit) as well as induced significant caspase-3 gene expression. In addition to this, studying the zone of inhibitions and minimum bactericidal and inhibitory concentrations of ZnONPs showed their exceptional potential as antibacterial agents. At MIC as low as 8 µg/mL, ZA-AN-ZNPs and ZN-AN-ZNPs exhibited significant bactericidal activities against human pathogens Klebsiella pneumoniae and Listeria monocytogenes, respectively. Furthermore, alkaline phosphatase, DNA/RNA leakage, and phosphate ion leakage studies revealed that a damage to the bacterial cell membrane and cell wall is involved in mediating the antibacterial effects of ZnONPs. [ABSTRACT FROM AUTHOR]

We propose a nucleic acids dilution-induced assembly (NADIA) method for the preparation of lipid nanoparticles. In the conventional method, water-soluble polymers such as nucleic acids and proteins are mixed in the aqueous phase. In contrast, the NADIA method, in which self-assembly is triggered upon dilution, requires dispersion in an alcohol phase without precipitation. We then investigated several alcohols and discovered that propylene glycol combined with sodium chloride enabled the dispersion of plasmid DNA and protamine sulfate in the alcohol phase. The streamlined characteristics of the NADIA method enable the preparation of extracellular vesicles-mimicking lipid nanoparticles (ELNPs). Among the mixing methods using a micropipette, a syringe pump, and a microfluidic device, the lattermost was the best for decreasing batch-to-batch differences in size, polydispersity index, and transfection efficiency in HepG2 cells. Although ELNPs possessed negative ζ-potentials and did not have surface antigens, their transfection efficiency was comparable to that of cationic lipoplexes. We observed that lipid raft-mediated endocytosis and macropinocytosis contributed to the transfection of ELNPs. Our strategy may overcome the hurdles linked to supply and quality owing to the low abundance and heterogeneity in cell-based extracellular vesicles production, making it a reliable and scalable method for the pharmaceutical manufacture of such complex formulations. [ABSTRACT FROM AUTHOR]

Dihydropyrazines (DHPs) are formed by non-enzymatic glycation reactions in vivo and in food. We recently reported that 3-hydro-2,2,5,6-tetramethylpyrazine (DHP-3), which is a methyl-substituted DHP, caused severe oxidative stress and cytotoxicity. However, the molecular mechanisms underlying the cytotoxic pathways of the DHP response remain elusive. Because oxidative stress induces endoplasmic reticulum (ER) stress and autophagy, we investigated the ability of DHP-3 to modulate the ER stress and autophagy pathways. DHP-3 activated the ER stress pathway by increasing inositol-requiring enzyme 1 (IRE1) and PKR-like ER kinase (PERK) phosphorylation and transcription factor 6 (ATF6) expression. Moreover, DHP-3 increased the expression of activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP), which are downstream targets of PERK. In addition, DHP-3 inhibited the autophagy pathway by increasing the accumulation of microtubule-associated protein 1 light chain 3 alpha-phosphatidylethanolamine conjugate (LC3-II) and p62/sequestosome 1 (p62), while decreasing autophagic flux. Taken together, these results indicate that DHP-3 activates the ER stress pathway and inhibits the autophagy pathway, suggesting that the resulting removal of damaged organelles is inadequate. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is the most common liver malignancy and is characterized by increasing incidence and high mortality rates. Current methods for the screening and diagnosis of HCC exhibit inherent limitations, highlighting the ever-growing need for the development of new methods for the early diagnosis of HCC. The aim of this work was to develop a novel electrochemical aptasensor for the detection of HepG2 cells, a type of circulating tumor cells that can be used as biomarkers for the early detection of HCC. A carbon screen-printed electrode was functionalized with a composite suspension containing graphene oxide, chitosan, and polyaniline nanoparticles to increase the electrode surface and provide anchoring sites for the HepG2 cell-specific aptamer. The aptamer was immobilized on the surface of the functionalized electrode using multipulse amperometry, an innovative technique that significantly reduces the time required for aptamer immobilization. The innovative platform was successfully employed for the first time for the amplification-free detection of HepG2 cells in a linear range from 10 to 200,000 cells/mL, with a limit of detection of 10 cells/mL. The platform demonstrated high selectivity and stability and was successfully used for the detection of HepG2 cells in spiked human serum samples with excellent recoveries. [ABSTRACT FROM AUTHOR]

This study examined the saponin extracted from the roots of Andrographis paniculata for the phytochemical content and antimicrobial and anticancer effects. The phytochemicals present in the methanol and aqueous root extracts included alkaloids, tannins, flavonoids, phenolic compounds, saponins, glycosides, steroids, triterpenoids, tannins, proteins, steroids, chlorogenics and carbohydrates. A. paniculata root saponin expressed antibacterial properties against four Gram-negative bacteria (Escherichia coli, Salmonella typhi, Proteus vulgaris, and Klebsiella pneumoniae), four Gram-positive bacteria (Staphylococcus aureus, Bacillus subtilis, Enterococcus faecalis, and Micrococcus luteus), and two fungi (Aspergillus niger and Candida albicans); the saponin also inhibited the proliferation of HePG2 cells, with an IC50 value of 125 µg mL−1. [ABSTRACT FROM AUTHOR]

Chemotherapy has already proven widely effective in treating cancer. Chemotherapeutic agents usually include DNA damaging agents and non-DNA damaging agents. Assessing genotoxic effect is significant during chemotherapy drug development, since the ability to attack DNA is the major concern for DNA damaging agents which relates to the therapeutic effect, meanwhile genotoxicity should also be evaluated for chemotherapy agents' safety especially for non-DNA damaging agents. However, currently applicability of in vitro genotoxicity assays is hampered by the fact that genotoxicity results have comparatively high false positive rates. γ-H2AX has been shown to be a bifunctional biomarker reflecting both DNA damage response and repair. Previously, we developed an in vitro genotoxicity assay based on γ-H2AX quantification using mass spectrometry. Here, we employed the assay to quantitatively assess the genotoxic effects of 34 classic chemotherapy agents in HepG2 cells. Results demonstrated that the evaluation of cellular γ-H2AX could be an effective approach to screen and distinguish types of action of different classes of chemotherapy agents. In addition, two crucial indexes of DNA repair kinetic curve, i.e., k (speed of γ-H2AX descending) and t50 (time required for γ-H2AX to drop to half of the maximum value) estimated by our developed online tools were employed to further evaluate nine representative chemotherapy agents, which showed a close association with therapeutic index or carcinogenic level. The present study demonstrated that mass spectrometric quantification of γ-H2AX may be an appropriate tool to preliminarily evaluate genotoxic effects of chemotherapy agents. [ABSTRACT FROM AUTHOR]

The interaction between herbal remedies and drugs is a fascinating phenomenon that might cause therapeutic complications in patients. Warfarin is an anticoagulant drug that provides anti-blood-clotting effects by inhibiting the formation of vitamin K-dependent coagulation factors, and warfarin interacts with the nuclear receptor PXR, subsequently modulating cytochrome P450 during the metabolism process. St. John's wort, an herbal medicine with antidepressant effects, can alter the pharmacokinetics of warfarin. Thymoquinone is one of the active compounds in N. sativa and has pharmacological activities such as anticoagulant, antidiabetic, diuretic, antidepressant, and anti-inflammatory effects. In this study, we investigated the compounds in Nigella sativa ( N. sativa) against pregnane X receptor (PXR) and evaluated the impact of thymoquinone (TQ) administration on PXR expression in HepG2 cells. The molecular docking analysis was conducted utilizing the Molecular Operating Environment (MOE) with the PXR (PDB ID: 7AXJ). At the same time, the PXR gene expression was measured using RT-PCR instruments. The RMSD value in docking represents the deviation criteria between the native ligand position and the redocking position result, indicating the capability of MOE and PDB qualification for performing molecular docking. The docking analysis showed that warfarin had the strongest binding energy (7AXJ -6.0507) by forming hydrogen binding type on Arg410. Despite TQ being the major component, it also displayed a high affinity for the two PDB IDs (7AXJ -4.5962). Furthermore, the concurrent administration of warfarin and TQ (19.27 μM) in HepG2 cells showed a significant reduction in the relative mRNA expression of the PXR gene. Given the above-mentioned findings, our study adequately enables us to predict the mechanism behind herb-drug interactions (HDIs) implicating N. sativa, specifically the TQ compound to warfarin metabolism via the activation of the PXR receptor. [ABSTRACT FROM AUTHOR]

Citrate, which is obtained from oxaloacetate and acetyl-CoA by citrate synthase in mitochondria, plays a key role in both normal and cancer cell metabolism. In this work, we investigated the effect of 10 mM extracellular citrate supplementation on HepG2 cells. Gene expression reprogramming was evaluated by whole transcriptome analysis using gene set enrichment analysis (GSEA). The transcriptomic data were validated through analyzing changes in the mRNA levels of selected genes by qRT-PCR. Citrate-treated cells exhibited the statistically significant dysregulation of 3551 genes; 851 genes were upregulated and 822 genes were downregulated. GSEA identified 40 pathways affected by differentially expressed mRNAs. The most affected biological processes were related to lipid and RNA metabolism. Several genes of the cytochrome P450 family were upregulated in treated cells compared to controls, including the CYP3A5 gene, a tumor suppressor in hepatocellular carcinoma (HCC) that plays an important protective role in HCC metastasis. The citrate-induced dysregulation of cytochromes could both improve the effectiveness of chemotherapeutics used in combination and reduce the aggressiveness of tumors by diminishing cell migration and invasion. [ABSTRACT FROM AUTHOR]

The present study was to examine the antibacterial and anticancer potential of titanium dioxide mediated (TiO2) nanoparticles using Hypsizygus ulmarius. The nanoparticles were characterized using UV, XRD, FTIR, SEM, EDX, HR-TEM, PSA, and zeta potential. The UV–visible spectroscopy results exhibited a sharp absorbance peak range at 264 nm. The X-ray diffraction analysis reflected the presence of diffraction major peak range at (101), (103), (004), (200), (112), (200), (105), (211), (213), (314), (602), and (215) planes of face centered cubic TiO2NPs. The HR-TEM absorption was expressed the presence of spherical structure particles with a normal size of 80 nm. The EDX results of mycosynthesized TiO2NPs recorded the strong major intense signal which confirms the presence of pure Ti (85%). Mycosynthesized TiO2NPs have a zeta potential value of − 18.4 mV, it shows that they are stable in water. For antibacterial assay, the mycosynthesized TiO2NPs have broad spectrum of growth inhibition against tested human pathogenic bacteria viz., S. aureus (8.4 ± 0.3), B. cereus (7.1 ± 0.5), E. coli (6.2 ± 0.3), and K. pneumoniae (4.0 ± 0.1 mm). The anticancer activity results of green synthesized TiO2NPs proved as highly toxic for the HepG2 cell line and show a reduced cell viability (85%) and L50 value of 83.3 µg/ml after 24 h treatment. Finally, outcome of the present investigation shows that the mycosynthesized titanium dioxide nanoparticles using mushroom extract served as an alternative and eco-friendly nano drugs in the near future. [ABSTRACT FROM AUTHOR]

Globally, hepatocellular carcinoma poses significant health challenges due to its higher incidence and mortality rates. Further adverse effects of synthetic drugs prompted research into herbal plants as safer, more effective and alternative treatments. Mukia maderaspatana (L.) M. Roem. is a traditional medicinal renowned for its therapeutic properties. This study explores the anticancer property of hydroalcoholic leaf extract of M. maderaspatana (HLEMM) against liver carcinoma (HepG2) cells and further unveils the active phytoconstituents. Purification and characterization of HLEMM through spectroscopic analysis (HPLC, UV-Vis, MS, FT-IR, NMR) evidenced 3,3′,4′,5,5′,7–Hexahydroxyflavone (Myricetin) as the active phytoconstituent. Cytotoxicity of HLEMM on HepG2 cells showed a significantly dose-dependent reduction in cell viability with an IC 50 of 128.6 ± 0.4 μg/ml. Cell cycle analysis revealed that HLEMM effectively inhibited HepG2 cells at the G2/M phase. Results of the Annexin-V/PI staining study inferred HLEMM-induced apoptosis in the early and late phases of HepG2 cells. Flow cytometry results confirmed the up-regulation of caspase-3 and caspase-9 along with the simultaneous down regulation of Bcl-2, substantiating the activation of apoptosis, a controlled process of programmed cell death due to cellular stress or damage. Depolarization of the mitochondrial membrane in HepG2 cells was confirmed by a decrease in JC-1 fluorescence, as observed under a confocal fluorescent microscope. This tends to indicate the alteration in membrane potential and interference in energy metabolites. In silico biodegradability pattern of Myricetin by BIOWINTM models showed its rapid biodegradation under aerobic conditions and further emphasized its environmental sustainability. In conclusion, this is the first report spotlighting Myricetin as the active compound from M. maderaspatana and further suggests that it could serve as a potential anti-cancer agent for treating liver cancer. [Display omitted] • A bioactive compound 3,3′,4′,5,5′,7–Hexahydroxyflavone (Myricetin) was isolated from M. maderaspatana. • Cytotoxic potential of HLEMM on HepG2 cell was affirmed by MTT assay. • Results of flow cytometry validated the effect HLEMM on cell cycle arrest, induction of apoptosis, and gene expression. • HLEMM showed promising mitochondrial-mediated intrinsic apoptosis in HepG2 cells. • In silico BIOWINTM models authenticated the biodegradability and environmental suitability of Myricetin. [ABSTRACT FROM AUTHOR]

Oxidative stress significantly contributes to ageing and disease, with antioxidants holding promise in mitigating its effects. Functional foods rich in flavonoids offer a potential strategy to mitigate oxidative damage by free radicals. We investigated the protective effects of mulberry leaf flavonoids (MLF) against H2O2-induced oxidative damage in HepG2 cells. It assessed the inhibitory effect of MLF (62.5–500 μg/mL) on H2O2-induced oxidative damage by analyzing cellular morphology and oxidative stress markers, including ROS production, mitochondrial membrane potential, antioxidant enzyme levels, MDA, and apoptosis-related proteins. The results demonstrated that MLF prevented spiny cell formation triggered by 750 μM H2O2 and significantly reduced ROS levels, restored mitochondrial membrane potential, decreased lactate dehydrogenase and alanine transaminase leakage, and reduced MDA content induced by H2O2. MLF also modulated antioxidant enzymes and attenuated oxidative damage to HepG2 cell DNA, as confirmed by staining techniques. These findings indicate the potential of MLF as a hepatoprotective agent against oxidative damage in HepG2 cells. [ABSTRACT FROM AUTHOR]

Marine natural products constitute a great source of potential new antidiabetic drugs. The aim of this study was to evaluate the role of phosphoeleganin (PE), a polyketide purified from the Mediterranean ascidian Sidnyum elegans, and its derivatives PE/2 and PE/3 on insulin sensitivity in human hepatocellular carcinoma (HepG2) cells. In our experiments, insulin stimulates the phosphorylation of its receptor (INSR) and AKT by 1.5- and 3.5-fold, respectively, whereas in the presence of PE, PE/2, and PE/3, the insulin induced INSR phosphorylation is increased by 2.1-, 2-, and 1.5-fold and AKT phosphorylation by 7.1-, 6.0-, and 5.1-fold, respectively. Interestingly, PE and PE/2 have an additive effect on insulin-mediated reduction of phosphoenolpyruvate carboxykinase (PEPCK) expression. Finally, PE and PE/2, but not PE/3, decrease interleukin 6 (IL6) secretion and expression before and after palmitic acid incubation, while in the presence of high glucose (HG), only PE reduces IL6. Levels of other cytokines are not significantly affected by PE and its derivates. All these data suggest that PE and its synthetic-derived compound, PE/2, significantly decrease IL6 and improve hepatic insulin signaling. As IL6 impairs insulin action, it could be hypothesized that PE and PE/2, by inhibiting IL6, may improve the hepatic insulin pathway. [ABSTRACT FROM AUTHOR]

The Fusarium fungi is found in cereals and feedstuffs and may produce mycotoxins, which are secondary metabolites, such as the T-2 toxin (T-2). In this work, we explored the hepatotoxicity of T-2 using microfluidic 3D hepatic cultures. The objectives were: (i) exploring the benefits of microfluidic 3D cultures compared to conventional 3D cultures available commercially (Aggrewell plates), (ii) establishing 3D co-cultures of hepatic cells (HepG2) and stellate cells (LX2) and assessing T-2 exposure in this model, (iii) characterizing the induction of metabolizing enzymes, and (iv) evaluating inflammatory markers upon T-2 exposure in microfluidic hepatic cultures. Our results demonstrated that, in comparison to commercial (large-volume) 3D cultures, spheroids formed faster and were more functional in microfluidic devices. The viability and hepatic function decreased with increasing T-2 concentrations in both monoculture and co-cultures. The RT-PCR analysis revealed that exposure to T-2 upregulates the expression of multiple Phase I and Phase II hepatic enzymes. In addition, several pro- and anti-inflammatory proteins were increased in co-cultures after exposure to T-2. [ABSTRACT FROM AUTHOR]

Copyright of Shipin Kexue/ Food Science is the property of Food Science Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Microplastics (MPs) are usually co-exposed with a variety of plastic-related products. This co-exposed is harmful to human health. Mono-2-ethylhexyl phthalate (MEHP) is a primary metabolite of di-2-ethylhexyl phthalate (DEHP), a common plasticizer. Once entering into the body, MPs and MEHP accumulate in the liver. Therefore, it is important to study the toxic effects of the co-exposed of MPs and MEHP on the liver and explore the potential mechanisms. In this study, HepG2 cells were treated with polystyrene microplastics (PS-MPs), MEHP, or PS-MPs combined with MEHP. The cell viability, reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and protein expression of COXI, COXIII, SIRT3 and SOD2 were measured. The results showed that PS-MPs or MEHP exposure increased ROS generation and decreased MMP. PS-MPs exposure alone reduced protein expression of COXI and COXIII. These harmful effects were more pronounced when combined exposure, indicated a synergistic effect. Further molecular mechanism study exhibited that PS-MPs treatment down-regulated the protein expression of SIRT3 and SOD2. MEHP treatment down-regulated the protein expression of SIRT3. The combined exposure of PS-MPs and MEHP synergistically down-regulated the protein expression of SIRT3 and SOD2. In summary, the combined exposure of PS-MPs and MEHP resulted in oxidative stress and mitochondrial damage in HepG2 cells, and the underlying molecular mechanism is related to the inhibition of the SIRT3/SOD2 signaling pathway. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease is a complex disease involving abnormal liver metabolism. Its strong association with metabolic dysfunction has led to a change in nomenclature to metabolism dysfunction-associated fatty liver disease (MAFLD). MAFLD pathogenesis involves abnormal accumulation of hepatic lipids that lead to the production of excess free fatty acids (FFAs), which in turn cause an imbalance in hepatic mitochondrial function. Lactucin, a natural compound extracted from Cichorium glandulosum Boiss. et Huet, regulates liver metabolism and protects the liver. However, the potential mechanisms underlying the lactucin-mediated effects in MAFLD require further investigation. In the present study, HepG2 cells were treated with FFAs to establish an in vitro model of MAFLD. Parameters related to lipid accumulation and mitochondrial function, including triglycerides (TG), oil red O-stained lipid droplets, reactive oxygen species (ROS), mitochondrial membrane potential (JC-1), adenine triphosphate (ATP), and complex III were analysed. Morphology of the mitochondria were evaluated by transmission electron microscopy. Furthermore, key proteins in the sirtuin 1 (SIRT1)/peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) signalling axis and mitochondrial quality control were analysed. The SIRT1 inhibitor EX-527 was used to verify the key role of the SIRT1 signalling pathway. Western blotting showed that lactucin upregulated the expression of SIRT-1, PGC-1α, Nrf1, Tfam, Mfn2, and Opa1, and promoted mitochondrial biosynthesis and kinetics. The results suggest that lactucin restores mitochondrial dynamic homeostasis by upregulating the SIRT1/PGC-1α signalling axis, thereby reducing FFA-induced lipid accumulation in HepG2 cells.

Chickpea (Cicer arietinum L.) is a significant dietary source of flavonoids and the hypoglycemic activity were investigated in this study. Firstly, total twenty nine chickpea flavonoids were identified by UPLC-MS/MS with ononin, cyanidin-3-O-glucoside, astragalin, cynaroside, kaempferol-3-O-rutinoside, biochanin A, and daidzin being the most abundant among them. Our results demonstrated that chickpea flavonoids regulated glucose metabolism and lipid metabolism, and reduced oxidative stress in insulin resistance HepG2 cells. Furthermore, insulin resistance was ameliorated by chickpea flavonoids through the activation of insulin receptor substrate1 (IRS1), phosphoinositide 3-kinase (PI3K), and phosphorylated protein kinase B (Akt) in HepG2 cells. More importantly, key differential metabolites include L-tryptophan, L-tyrosine, l-glutamine and linoleic acid were reserved by chickpea flavonoids and correlated with glucolipid metabolism and oxidative stress in IR-HepG2 cells. In conclusion, these results indicated that chickpea flavonoids might act as potential natural products regulating insulin resistance in HepG2 cells.

RationaleMG53’s known function in facilitating tissue repair and anti-inflammation has broad applications to regenerative medicine. There is controversy regarding MG53’s role in the development of type 2 diabetes mellitus.ObjectiveThis study aims to address this controversy – whether MG53’s myokine function contributes to inhibition of insulin signaling in muscle, heart, and liver tissues.Study designWe determined the binding affinity of the recombinant human MG53 (rhMG53) to the insulin receptor extracellular domain (IR-ECD) and found low affinity of interaction with Kd (>480 nM). Using cultured C2C12 myotubes and HepG2 cells, we found no effect of rhMG53 on insulin-stimulated Akt phosphorylation (p-Akt). We performed in vivo assay with C57BL/6J mice subjected to insulin stimulation (1 U/kg, intraperitoneal injection) and observed no effect of rhMG53 on insulin-stimulated p-Akt in muscle, heart and liver tissues.ConclusionOverall, our data suggest that rhMG53 can bind to the IR-ECD, however has a low likelihood of a physiologic role, as the Kd for binding is ~10,000 higher than the physiologic level of MG53 present in the serum of rodents and humans (~10 pM). Our findings question the notion proposed by Xiao and colleagues – whether targeting circulating MG53 opens a new therapeutic avenue for type 2 diabetes mellitus and its complications.

Background: Phytochemicals and their derivatives are promising target drugs for various ailments and have served as therapeutic agents for several decades. Using in vivo and in vitro models and molecular docking, this study investigated the pharmacological potential of a flavonoid-rich fraction of the ethanolic extract of Sesbania grandiflora (SG). Objectives: This research aimed to determine whether flavonoid-rich whole-plant extracts of SGs have any cytoprotective or in vivo hepatoprotective effects. Additionally, the study was intended to elucidate the molecular connections between the discovered flavonoid flavonols and PPARα target proteins linked to liver problems, for which an in silico molecular docking investigation was performed. Materials and methods: To separate the flavonoid components, the entire Sesbania grandiflora plant was first extracted using ethanol as a solvent by soxhlet extraction. The resulting ethanolic extract was then fractionated. The cytoprotective and hepatoprotective properties were evaluated via in vitro and in vivo experiments. SGOT, SGPT, triglyceride, bilirubin, and total protein levels were used to evaluate hepatotoxicity in animal models. In vitro studies on Hepatocellular Carcinoma G2 (HepG2) cell lines have examined their cytotoxic effects and antioxidant activity. The most promising flavonoid-flavanol compounds were identified by conducting molecular docking studies against PPARα target protein (PDB ID: 3VI8) using MOE software. Results: In vivo, the serum levels of SGOT, SGPT, total triglyceride and total bilirubin were measured in experimental animals treated with the flavonoid-rich ethanolic extract of SG. Significant reductions in the levels of these hepatic injury markers were observed, indicating the hepatoprotective potential of the extract. Elevated levels of liver biomarkers in the untreated group indicated liver injury or dysfunction. The treated groups showed significant restoration of these biomarkers, suggesting the hepatoprotective potential of SG. The IC50 value for the total flavonoid content of SG was 190.28 μg/ml, indicating its safety in inhibiting HepG2 cell growth. Flavonoid treatment decreased cell viability but did not affect antioxidant parameters in hepatocytes. In addition, SG restored the damaged hepatocyte architecture. Molecular docking studies revealed the binding affinities of flavonoids for PPARα. These findings suggest that a promising lead candidate for the development of therapeutic medicines against anti-TB drug-induced hepatotoxicity has been identified. Conclusion: Our findings demonstrate the hepatoprotective potential of the flavonoid-rich fraction of Sesbania grandiflora both in vivo and in vitro. This study provides valuable insights into its mechanism of action, highlighting its promising therapeutic application in the management of liver disorders. This study highlights the hepatoprotective and cytoprotective potential of the total flavonoid-rich fraction of SG.

The accumulation of advanced glycosylation end products (AGEs) from food in the body disrupts normal physiological insulin activity and causes insulin resistance. This study compared the effects of ten types of polyphenols on AGEs production in both chemical and food models. It also investigated the impact of polyphenols on AGEs-induced insulin resistance in HepG2 cell models. Results showed that luteolin had the strongest inhibitory effect on fluorescent AGEs in the three chemical models. Rutin exhibited the most potent capacity to inhibit AGEs in biscuit models. Moreover, rutin alleviated the glucose metabolism disorders induced by representative AGEs (methylglyoxal-modified bovine serum albumin, MGO-BSA) in HepG2 cells. Mechanistic studies revealed that rutin could inhibit the phosphorylation of insulin receptor substrate 1 (IRS1) and the activity of suppressor of cytokine signaling 3 (SOCS3), while activating the phosphorylation of phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) to alleviate the MGO-BSA-induced insulin resistance in HepG2 cells.

The objective of this study was to investigate the molecular mechanism behind the regulatory effect of capsaicin combined with quercitrin on liver lipid metabolism. The effects of capsaicin alone or in combination with quercitrin on the survival rate of HepG2 cells with oleic acid-induced lipid accumulation were investigated. Oil red O staining was used to observe lipid accumulation in HepG2 cells. Meanwhile, the levels of total triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and total bile acid (TBA) were determined. Moreover, the expression levels of epidermal growth factor receptor (EGFR), phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), farnesoid X receptor 1 (FXR1), cholesterol 7α-hydroxylase (CYP7A1) and fibroblast growth factor 19 (FGF19) were determined by Western blotting. The results showed that the proliferation rate of HepG2 cells in each treatment group was greater than 75%, demonstrating no significant cytotoxicity. The results of oil red O staining showed a reduction in lipid accumulation in both single and combined treatment groups. The application of capsaicin alone or combined with quercitrin reduced the contents of TG, TC and LDL-C, increased the contents of HDL-C and TBA, and up-regulated the protein expression levels of EGFR, PI3K, Akt, FXR1 and FGF19. In summary, capsaicin combined with quercitrin exerted a synergistic regulatory effect on lipid metabolism in HepG2 cells, with the most pronounced effect being observed at a 3:1 ratio.

Objective： Based on transcriptome sequencing analysis, the effect of grape seed procyanidins on HepG2 cell genes and related functions was identified. The key genes and metabolic pathways involved in the treatment of HepG2 cells with procyanidins were confirmed. Methods: Through transcriptome sequencing, screening differential genes, gene functional annotation and enrichment analysis of the KEGG pathway, transcriptome studies were conducted on grape proanthocyanidin-treated cells. Results: After treating HepG2 cells with grape anthocyanins, the main biological processes enriched are cellular processes, metabolic processes, biological regulatory processes, immune system processes, reproductive regulation, and growth regulation. Research has found that 12 key differentially expressed genes in cell apoptosis are associated with TNF, p53, MAPK, PI3K-Akt and NF-κB signaling pathway is closely related. Conclusion: Cell apoptosis is closely related to the TNF signaling pathway, p53 signaling pathway, PI3K/Akt signaling pathway, NF-κB signaling pathway and MAPK signaling pathway.

Extraction and purification of polysaccharides from the seed kernel of Acer truncatum Bungeto investigate their physicochemical properties and hypoglycemic activity. In the study, the polysaccharide was obtained by water extraction and ethanol precipitation from seed kernel of Acer truncatum Bunge, and the extraction process was optimized by response surface method. The polysaccharide was purified by Sevage deproteinization and column chromatography. The composition and structure of the purified polysaccharide were characterized by infrared spectroscopy, thermogravimetric analysis and ion chromatography, and its hypoglycemic activity was further investigated by the insulin resistance model of liver cancer cell (IR-HepG2). The results showed that the yield of crude polysaccharide (PATM) was 18.17% under the conditions of extraction times 1, liquid-solid ratio 30:1 mL/g, extraction temperature 80 ℃ and extraction time 3.5 h. The purified polysaccharide (PATM-3-1) obtained by the Sevage deproteinization, DEAE-DE cellulose 52 column and SephadexG-100 gel column had the characteristic peak of infrared spectrum of polysaccharide component, and was composed of D-galacturonic acid, L-arabinose, D-galactose, L-rhamnose, D-glucose, D-xylose, D-mannose, D-glucuronic acid, L-fucose, D-ribose and D-glucosamine. The results of hypoglycemic activity experiment in vitro showed that PATM-3-1 had strong α-amylase inhibitory activity, and could significantly (P

Abstract Background The Convolvulus genus is distributed all over the world and has a long history in traditional medicine. As nanotechnology expands its reach into areas like drug delivery and biomedicine, this study intends to assess the potential of Convolvulus arvensis L. extracts as anti-bacterial, anti-inflammatory and anti-cancer agents, along with chemical profiling of the methanolic (MeOH) extract active ingredients. Methods The chemical composition of an 85% MeOH extract was investigated by liquid chromatography with an electrospray source connected to mass spectrometry (LC-ESI-MS). Both the 85% MeOH extract and n-butanol fraction of C. arvensis were loaded for the first time on alginate/chitosan nanoparticles. The 85% MeOH extract, n-butanol fraction and their loaded nanoparticles were tested for their cytotoxicity, anticancer, anti-inflammatory and antibacterial activity (against pathogenic bacteria, E. coli and S. aureus). Results The chemical investigation of 85% MeOH extract of C. arvensis underwent LC-ESI-MS analysis, revealing twenty-six phenolic substances, of which 16 were phenolic acids, 6 were flavonoids, 1 glycolipid, 1 sesquiterpene and 2 unknown compounds. The FT-IR spectra confirmed the encapsulation of the 85% MeOH extract and n-butanol fraction onto alginate/chitosan nanoparticles and small size obtained by TEM maintained them nontoxic and enhanced their anti-inflammatory activity (the IC50 was decreased from 1050 to 175 µg/ml). The anti-cancer activity against HepG2 was increased and the cell viability was decreased from 28.59 ± 0.52 to 20.80 ± 0.27 at a maximum concentration of 1000 µg/ml. In addition, the MIC of encapsulated extracts was decreased from 31.25 to7.78 µg/ml in E. coli (Gm-ve) and from 15.56 to 7.78 µg/ml in S. aureus (Gm + ve) bacteria. Conclusion Both alginate and chitosan are excellent natural polymers for the encapsulation process, which affects positively on the bioactive constituents of C. arvensis extracts and improves their biological properties.

In order to investigate the antioxidant effect of the extract of Euphorbia helioscopia in vitro and its effect on lipid accumulation in HepG2 cells induced by oleic acid. In this study, 25%, 50%, 75% methanol and ethanol were used to extract the powder by immersion method. The antioxidant activities of the different extracts were assessed, and the levels of total phenols and total flavonoids were measured. To establish a model of lipid accumulation in HepG2 cells, the cells were treated with 50% ethanol extract (at concentrations of 20, 40, and 60 µg/mL) for 24 h to observe the formation of lipid droplets. The triglyceride (TG) content, total glutathione (GSH), superoxide dismutase (SOD) activity, and total antioxidant capacity (T-AOC) in the cells were determined. The findings demonstrated that all extracts exhibited concentration-dependent antioxidant activity. Among them, the 50% ethanol extract exhibited the most potent antioxidant effect in a certain concentration range (P

Copyright of Shipin Kexue/ Food Science is the property of Food Science Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Phellinus igniarius (PI) has various kinds of biological activities, such as antitumour activities, and polysaccharides are one of its main components. In this study, polysaccharides from PI (PIP) were prepared, purified, analysed for their structure and investigated for their antitumour activity and mechanism in vitro. PIP consists of 12138 kDa of carbohydrates containing 90.5 ± 1.6% neutral carbohydrates. PIP consists of glucose, galactose, mannose, xylose, D-fructose, L-guluronic acid, glucosamine hydrochloride, rhamnose, arabinose and D-mannoturonic acid. PIP can significantly inhibit HepG2 cell proliferation, induce cell apoptosis and also inhibited migration and invasion in a concentration-dependent manner. PIP increased reactive oxygen species (ROS), increased the expression of p53, and induced cytochrome c release into the cytoplasm to activate caspase-3. PIP is a promising potential candidate for the therapeutic treatment of hepatic carcinoma via the ROS-mediated mitochondrial apoptosis pathway. [ABSTRACT FROM AUTHOR]

AbstractIntroductionMethodsResultsConclusionSirtuin1 (SIRT1) plays a crucial role in the pathophysiology of non-alcoholic fatty liver disease. We investigated the mechanistic role of galbanic acid (Gal) as a regulator of SIRT1 in silico and in vitro.HepG2 cells were treated with Gal in the presence or absence of EX-527, a SIRT1-specific inhibitor, for 24 h. Sirtuin1 gene and protein expression were measured by RT-PCR and Western blotting, respectively. It has been docked to the allosteric reign of SIRT1 (PDB ID: 4ZZJ) to study the effect of Gal on SIRT1, and then the protein and complex molecular dynamic (MD) simulations had been studied in 100 ns.The semi-quantitative results of Oil red (p < .03) and TG level (p < .009) showed a significant reduction in lipid accumulation by treatment with Gal. Also, a significant increase was observed in the gene and protein expression of SIRT1 (p < .05). MD studies have shown that the average root mean square deviation (RMSD) was about 0.51 Å for protein structure and 0.66 Å for the complex. The average of radius of gyration (Rg) is 2.33 and 2.32 Å for protein and complex, respectively, and the pattern of root mean square fluctuation (RMSF) was almost similar.Computational studies show that Gal can be a great candidate to use as a SIRT1 ligand because it does not interfere with the structure of the protein, and other experimental studies showed that Gal treatment with SIRT1 inhibitor increases fat accumulation in HepG2 cells. [ABSTRACT FROM AUTHOR]

In the human living environment, heavy metals and chlorpyrifos can have harmful consequences due to their complex combination. In this study, binary, ternary, and quaternary combinations of three heavy metals and chlorpyrifos in different concentrations were evaluated for their combined toxic effects using an electrochemical method, and the MTT method was used to contrast the outcomes. The combined toxic effectiveness assessed by the electrochemical CI method revealed that, except for the binary combination of cadmium chloride and chlorpyrifos, which exhibited an antagonistic effect when mixed at an equal molar ratio, lead nitrate and chlorpyrifos showed an additive effect when combined, the quaternary combination exhibited a complex transition from synergistic to additive to antagonistic effects, the other mixtures showed consistent synergistic effects. When the ratio of heavy metals in the mixture was reduced, all of them displayed synergistic effects, except for the binary mixture of cadmium chloride and chlorpyrifos, which consistently maintained an antagonistic effect, and the ternary mixture of cadmium chloride, lead nitrate, and chlorpyrifos displayed additive effects. The complex toxicity mechanisms of the mixtures do not impact the response of cellular electrochemical signals coming from the intracellular purine bases on cytotoxicity. The electrochemical approach successfully captured the various combined toxic effects of the mixture, and the outcomes were consistent with the MTT method. This method is expected to emerge as a novel approach for detecting combined toxicity. [ABSTRACT FROM AUTHOR]

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