scholarly journals Inhibitory effect of oleanolic acid on non-enzymatic glycation and glycometabolism in insulin resistant HepG2 cells

2021 ◽  
Vol 50 (1) ◽  
pp. 112-124
Author(s):  
Z.K. Xie ◽  
S.Y. Yu ◽  
M. He ◽  
S.X. Yu ◽  
H.F. Xiao ◽  
...  
Keyword(s):  
Oleanolic Acid ◽  
Hepg2 Cells ◽  
Glycogen Content ◽  
Glucose Production ◽  
Inhibitory Effect ◽  
Food Industries ◽  
Insulin Resistant ◽  
Significant Inhibitory Effect ◽  
Glycation End Products ◽  
Enzymatic Glycosylation

AbstractIn this paper, we studied the inhibitory effect of oleanolic acid (OA) on non-enzymatic glycosylation and the improvement of glycometabolism in insulin resistant (IR) human liver tumour (HepG2) cells. The anti-glycosylation activity of OA was determined by bovine serum albumin (BSA) fructose model. The results showed that OA moderately inhibited the formation of the intermediates of non-enzymatic glycosylation, fructosamine and α-dicarbonyl compounds, and strongly inhibited the formation of advanced glycation end products (AGEs). In addition, we analysed the effect of OA on glycometabolism induced by palmitic acid (PA) in HepG2 cells. The results showed that OA had almost no impact on HepG2 cell viability at concentrations lower than 30 µM. With the increase of OA concentration, glucose production in IR HepG2 cells decreased, while glycogen content increased. Meanwhile, OA has a significant inhibitory effect on reactive oxygen species (ROS) levels in IR-HepG2 cells. Those results suggested that OA could be a promising natural blood glucose decreasing substance in the pharmaceutical and functional food industries.

scholarly journals Carpachromene Ameliorates Insulin Resistance in HepG2 Cells via Modulating IR/IRS1/PI3k/Akt/GSK3/FoxO1 Pathway

Molecules ◽  
2021 ◽  
Vol 26 (24) ◽  
pp. 7629
Author(s):  
Rania Alaaeldin ◽  
Iman A. M. Abdel-Rahman ◽  
Heba Ali Hassan ◽  
Nancy Youssef ◽  
Ahmed E. Allam ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Enzyme Activity ◽  
Insulin Receptor ◽  
Glucose Concentration ◽  
Hepg2 Cells ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Glycogen Content ◽  
Insulin Signalling ◽  
Antidiabetic Activity ◽  
Insulin Resistant

Insulin resistance contributes to several disorders including type 2 diabetes and cardiovascular diseases. Carpachromene is a natural active compound that inhibits α-glucosidase enzyme. The aim of the present study is to investigate the potential activity of carpachromene on glucose consumption, metabolism and insulin signalling in a HepG2 cells insulin resistant model. A HepG2 insulin resistant cell model (HepG2/IRM) was established. Cell viability assay of HepG2/IRM cells was performed after carpachromene/metformin treatment. Glucose concentration and glycogen content were determined. Western blot analysis of insulin receptor, IRS1, IRS2, PI3k, Akt, GSK3, FoxO1 proteins after carpachromene treatment was performed. Phosphoenolpyruvate carboxykinase (PEPCK) and hexokinase (HK) enzymes activity was also estimated. Viability of HepG2/IRM cells was over 90% after carpachromene treatment at concentrations 6.3, 10, and 20 µg/mL. Treatment of HepG2/IRM cells with carpachromene decreased glucose concentration in a concentration- and time-dependant manner. In addition, carpachromene increased glycogen content of HepG2/IRM cells. Moreover, carpachromene treatment of HepG2/IRM cells significantly increased the expression of phosphorylated/total ratios of IR, IRS1, PI3K, Akt, GSK3, and FoxO1 proteins. Furthermore, PEPCK enzyme activity was significantly decreased, and HK enzyme activity was significantly increased after carpachromene treatment. The present study examined, for the first time, the potential antidiabetic activity of carpachromene on a biochemical and molecular basis. It increased the expression ratio of insulin receptor and IRS1 which further phosphorylated/activated PI3K/Akt pathway and phosphorylated/inhibited GSK3 and FoxO1 proteins. Our findings revealed that carpachromene showed central molecular regulation of glucose metabolism and insulin signalling via IR/IRS1/ PI3K/Akt/GSK3/FoxO1 pathway.

scholarly journals Oleanolic Acid Attenuates Insulin Resistance via NF-κB to Regulate the IRS1-GLUT4 Pathway in HepG2 Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Ming Li ◽  
Zongyu Han ◽  
Weijian Bei ◽  
Xianglu Rong ◽  
Jiao Guo ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Protein Expression ◽  
Oleanolic Acid ◽  
Hepg2 Cells ◽  
Glucose Transporter ◽  
Underlying Mechanism ◽  
Pyrrolidine Dithiocarbamate ◽  
Glucose Content ◽  
Insulin Resistant

The aim of our study is to elucidate the mechanisms of oleanolic acid (OA) on insulin resistance (IR) in HepG2 cells. HepG2 cells were induced with FFA as the insulin resistance model and were treated with OA. Then the glucose content and the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were analyzed. Moreover, protein expression of nuclear factor kappa B (NF-κB), insulin receptor substrate 1(IRS1), and glucose transporter 4 (GLUT4) in cells treated with OA were measured by Western blot analysis. Additionally, IRS1 protein expression exposed to OA was detected after using pyrrolidine dithiocarbamate (PDTC).Our results revealed that OA decreased the glucose content in HepG2 cells in vitro. Moreover, OA reduced the levels of TNF-α and IL-6 and upregulated IRS1 and GLUT4 protein expression. Furthermore, OA also reduced NF-κB protein expression in insulin-resistant HepG2 cells. After blocking NF-κB, the expression of IRS1 protein had no obvious changes when treated with OA. OA attenuated insulin resistance and decreased the levels of TNF-α and IL-6. Meanwhile, OA decreased NF-κB protein expression and upregulated IRS1 and GLUT4 protein expression. Therefore, regulating the IRS1-GLUT4 pathway via NF-κB was the underlying mechanism of OA on insulin resistance.

Potential antidiarrheal agents: 1-(11-Cyano-6,11-dihydrodibenzo[b,e]thiepin-11-yl-alkyl)- and 1-(10-cyano-10,11-dihydrodibenzo[b,f]thiepin-10-yl-alkyl)-4-substituted piperidines

1985 ◽  
Vol 50 (5) ◽  
pp. 1089-1096 ◽  
Author(s):  
Karel Šindelář ◽  
Jan Metyš ◽  
Miroslav Protiva
Keyword(s):  
Inhibitory Effect ◽  
Substitution Reactions ◽  
Significant Inhibitory Effect

Substitution reactions of 11-(2-bromoethyl)- and 11-(3-bromopropyl)-6,11-dihydrodibenzo[b,e]thiepin-11-carbonitrile and further of 10-(2-bromoethyl)- and 10-(3-bromopropyl)-10,11-dihydrodibenzo[b,f]thiepin-10-carbonitrile with ethyl 4-phenylpiperidine-4-carboxylate, 4-phenylpiperidin-4-ol, 4-(2-tolyl)piperidin-4-ol, 4-(4-fluorophenyl)piperidin-4-ol, 4-(2-oxobenzimidazolin-1-yl)-piperidine and 1-phenyl-1,3,8-triazaspiro[4,5]decan-4-one afforded the tricyclic piperidinoalkyl nitriles IV-XIII which are cyclic analogues of the antidiarrheal agents diphenoxylate (I) and loperamide (III). Out of the compounds prepared only IV and XI showed a significant inhibitory effect towards diarrhea elicited by intravenously administered serotonin in mice.

scholarly journals A novel BRD4 inhibitor suppresses osteoclastogenesis and ovariectomized osteoporosis by blocking RANKL-mediated MAPK and NF-κB pathways

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Ying Liu ◽  
Wenjie Liu ◽  
Ziqiang Yu ◽  
Yan Zhang ◽  
Yinghua Li ◽  
...  
Keyword(s):  
Bone Loss ◽  
Osteoporosis Treatment ◽  
Inhibitory Effect ◽  
Specific Gene ◽  
Actin Ring ◽  
Treatment Target ◽  
Significant Inhibitory Effect ◽  
Promising Treatment

AbstractBromodomain-containing protein 4 (BRD4) has emerged as a promising treatment target for bone-related disorders. (+)-JQ1, a thienotriazolodiazepine compound, has been shown to inhibit pro-osteoclastic activity in a BRD4-dependent approach and impede bone loss caused by ovariectomy (OVX) in vivo. However, clinical trials of (+)-JQ1 are limited because of its poor druggability. In this study, we synthesized a new (+)-JQ1 derivative differing in structure and chirality. One such derivative, (+)-ND, exhibited higher solubility and excellent inhibitory activity against BRD4 compared with its analogue (+)-JQ1. Interestingly, (-)-JQ1 and (-)-ND exhibited low anti-proliferative activity and had no significant inhibitory effect on RANKL-induced osteoclastogenesis as compared with (+)-JQ1 and (+)-ND, suggesting the importance of chirality in the biological activity of compounds. Among these compounds, (+)-ND displayed the most prominent inhibitory effect on RANKL-induced osteoclastogenesis. Moreover, (+)-ND could inhibit osteoclast-specific gene expression, F‐actin ring generation, and bone resorption in vitro and prevent bone loss in OVX mice. Collectively, these findings indicated that (+)-ND represses RANKL‐stimulated osteoclastogenesis and averts OVX-triggered osteoporosis by suppressing MAPK and NF-κB signalling cascades, suggesting that it may be a prospective candidate for osteoporosis treatment.

scholarly journals Polysaccharide Derived from Nelumbo nucifera Lotus Plumule Shows Potential Prebiotic Activity and Ameliorates Insulin Resistance in HepG2 Cells

Polymers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1780
Author(s):  
Bao Le ◽  
Pham-Thi-Ngoc Anh ◽  
Seung-Hwan Yang
Keyword(s):  
Insulin Resistance ◽  
Hepg2 Cells ◽  
Structural Characteristics ◽  
Physicochemical Characterization ◽  
Deae Cellulose ◽  
Hot Water ◽  
Nelumbo Nucifera ◽  
Molar Ratio ◽  
Prebiotic Activity ◽  
Insulin Resistant

Polysaccharides are key bioactive compounds in lotus plumule tea, but their anti-diabetes activities remain unclear. The purpose of this study was to investigate the prebiotic activities of a novel polysaccharide fraction from the Nelumbo nucifera lotus plumule, and to examine its regulation of glucose metabolism in insulin-resistant HepG2 cells. The N. nucifera polysaccharide (NNP) was purified after discoloration, hot water extraction, ethanol precipitation, and DEAE-cellulose chromatography to obtain purified polysaccharide fractions (NNP-2). Fourier transform infrared spectroscopy was used to analyze the main structural characteristics and functional group of NNP-2. Physicochemical characterization indicated that NNP-2 had a molecular weight of 110.47 kDa and consisted of xylose, glucose, fructose, galactose, and fucose in a molar ratio of 33.4:25.7:22.0:10.5:8.1. The prebiotic activity of NNP-2 was demonstrated in vitro using Lactobacillus and Bifidobacterium. Furthermore, NNP-2 showed bioactivity against α-glucosidase (IC50 = 97.32 µg/mL). High glucose-induced insulin-resistant HepG2 cells were used to study the effect of NNP-2 on glucose consumption, and the molecular mechanism of the insulin transduction pathway was studied using RT-qPCR. NNP-2 could improve insulin resistance by modulating the IRS1/PI3K/Akt pathway in insulin-resistant HepG2 cells. Our data demonstrated that the Nelumbo nucifera polysaccharides are potential sources for nutraceuticals, and we propose functional food developments from the bioactive polysaccharides of N. nucifera for the management of diabetes.

scholarly journals Geniposide Suppresses Hepatic Glucose Production via AMPK in HepG2 Cells

2016 ◽  
Vol 39 (4) ◽  
pp. 484-491 ◽  
Author(s):  
Lixia Guo ◽  
Xuxu Zheng ◽  
Jianhui Liu ◽  
Zhongyi Yin
Keyword(s):  
Hepg2 Cells ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Hepatic Glucose

scholarly journals Decreased sensitivity of very-low-density lipoprotein secretion to the inhibitory effect of insulin in cultured hepatocytes from lactating rats

1996 ◽  
Vol 316 (3) ◽  
pp. 737-741 ◽  
Author(s):  
Catherine S. BOURGEOIS ◽  
Geoffrey F. GIBBONS
Keyword(s):  
Milk Fat ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Inhibitory Effect ◽  
Defined Medium ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Inhibitory Effects ◽  
Insulin Resistant ◽  
Lactating Mammary Gland

Hepatocytes were prepared from 10–11-day lactating rat dams and from lactating dams which had been weaned for periods of either 1–2 days or 7 days. Hepatocytes from each group were cultured for periods of up to 48 h in a chemically defined medium. Compared with those from the 7-day weaned animals, hepatocytes from the lactating rats were resistant to the inhibitory effects of insulin on the secretion of very-low-density lipoprotein (VLDL) triacylglycerol (TAG). These differences persisted for up to 48 h in culture. Hepatocytes from the 1–2-day weaned animals remained relatively insulin-resistant in this respect. Similar differences in the response to insulin were not observed for the secretion of VLDL apolipoprotein B. TAG production increased and ketogenesis decreased in the hepatocytes from the lactating compared with those from the 7-day weaned rats. Insensitivity of the liver to the normal effects of insulin on the secretion of VLDL TAG may arise from a need to maintain an adequate flux of hepatic lipids to the lactating mammary gland in order to meet the large demand for milk-fat production.

Inhibitory effect of FSLLRY-NH2 on inflammatory responses induced by hydrogen peroxide in HepG2 cells

2017 ◽  
Vol 40 (7) ◽  
pp. 854-863 ◽  
Author(s):  
Yeon Joo Lee ◽  
Su Jin Kim ◽  
Kyoung Wan Kwon ◽  
Won Mo Lee ◽  
Wi Joon Im ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Hepg2 Cells ◽  
Inflammatory Responses ◽  
Inhibitory Effect
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