Ellagic acid ameliorates oxidative stress and insulin resistance in high glucose-treated HepG2 cells via miR-223/keap1-Nrf2 pathway

Ding, Xiaoqin; Jian, Tunyu; Wu, Yaohong; Zuo, Ya‐Gang; Li, Jiawei; Han, Li; Ma, Li; Ren, Bingru; Zhao, Lei; Li, Weilin; Chen, Jian

doi:10.1016/j.biopha.2018.11.018

Cited by 175 publications

(104 citation statements)

References 45 publications

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“…In conclusion, by means of miR-802, HFD may cause IR via activating the JNK and p38MAPK pathways and also suppressing antioxidative enzymes to induce hepatic OxS [214]. HG-promoted OxS along with IR in HepG2 cells was mediated by decreased levels of miR-233, thus preventing miR-233-dependent direct regulation of Keap1 and reducing levels of Nrf2, HO-1 and SOD1 [215]. OxS in the liver of diabetic mice was ameliorated upon transplantation of brown AT (BAT) from healthy donor mice, as indicated by upregulation of Nrf2 and downregulation of NOX2 and NOX4, along with improvement of glucose and lipid metabolism.…”

Section: Mirnas In Mets-a Link With Obesity and Insulin Resistance/hymentioning

confidence: 86%

“…OxS in the liver of diabetic mice was ameliorated upon transplantation of brown AT (BAT) from healthy donor mice, as indicated by upregulation of Nrf2 and downregulation of NOX2 and NOX4, along with improvement of glucose and lipid metabolism. Detailed studies suggested that circulating miR-99a, whose expression raised, might directly repress the expression of NOX4, thus mitigating OxS in the liver [215,216].…”

Section: Mirnas In Mets-a Link With Obesity and Insulin Resistance/hymentioning

confidence: 99%

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The Role of microRNAs in Metabolic Syndrome-Related Oxidative Stress

Włodarski

Strycharz

Wróblewski

et al. 2020

IJMS

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Oxidative stress (OxS) is the cause and the consequence of metabolic syndrome (MetS), the incidence and economic burden of which is increasing each year. OxS triggers the dysregulation of signaling pathways associated with metabolism and epigenetics, including microRNAs, which are biomarkers of metabolic disorders. In this review, we aimed to summarize the current knowledge regarding the interplay between microRNAs and OxS in MetS and its components. We searched PubMed and Google Scholar to summarize the most relevant studies. Collected data suggested that different sources of OxS (e.g., hyperglycemia, insulin resistance (IR), hyperlipidemia, obesity, proinflammatory cytokines) change the expression of numerous microRNAs in organs involved in the regulation of glucose and lipid metabolism and endothelium. Dysregulated microRNAs either directly or indirectly affect the expression and/or activity of molecules of antioxidative signaling pathways (SIRT1, FOXOs, Keap1/Nrf2) along with effector enzymes (e.g., GPx-1, SOD1/2, HO-1), ROS producers (e.g., NOX4/5), as well as genes of numerous signaling pathways connected with inflammation, insulin sensitivity, and lipid metabolism, thus promoting the progression of metabolic imbalance. MicroRNAs appear to be important epigenetic modifiers in managing the delicate redox balance, mediating either pro- or antioxidant biological impacts. Summarizing, microRNAs may be promising therapeutic targets in ameliorating the repercussions of OxS in MetS.

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Section: Mirnas In Mets-a Link With Obesity and Insulin Resistance/hymentioning

confidence: 86%

Section: Mirnas In Mets-a Link With Obesity and Insulin Resistance/hymentioning

confidence: 99%

The Role of microRNAs in Metabolic Syndrome-Related Oxidative Stress

Włodarski

Strycharz

Wróblewski

et al. 2020

IJMS

View full text Add to dashboard Cite

show abstract

“…In particular, their efficacies and selectivities in vivo need to be more rigorously verified. Up to now, only a few disease models related to the Keap1–Nrf2 PPI have been evaluated in lab and clinical research, such as mouse renal inflammation [88,89], Huntington’s disease [90], drug-induced liver injury [84,91], and many cancer models [92,93,94,95,96,97,98]. Other disease models, such as diabetes [99], neurodegenerative disease [5,46,100,101,102], and cardiovascular diseases [50] may be considered in future studies.…”

Section: Discussionmentioning

confidence: 99%

Emerging Screening Approaches in the Development of Nrf2–Keap1 Protein–Protein Interaction Inhibitors

Leung

Zhang

Yang

et al. 2019

IJMS

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Due to role of the Keap1–Nrf2 protein–protein interaction (PPI) in protecting cells from oxidative stress, the development of small molecule inhibitors that inhibit this interaction has arisen as a viable approach to combat maladies caused by oxidative stress, such as cancers, neurodegenerative disease and diabetes. To obtain specific and genuine Keap1–Nrf2 inhibitors, many efforts have been made towards developing new screening approaches. However, there is no inhibitor for this target entering the clinic for the treatment of human diseases. New strategies to identify novel bioactive compounds from large molecular databases and accelerate the developmental process of the clinical application of Keap1–Nrf2 protein–protein interaction inhibitors are greatly needed. In this review, we have summarized virtual screening and other methods for discovering new lead compounds against the Keap1–Nrf2 protein–protein interaction. We also discuss the advantages and limitations of different strategies, and the potential of this PPI as a drug target in disease therapy.

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“…T2DM is a chronic metabolic disorder syndrome characterized by hyperglycemia and dyslipidemia [29]. T2DM afflicts about 383 million adults, emerging as a serious health burden [30,31]. Oxidative stress is closely associated with the pathogenesis of T2DM.…”

Section: Discussionmentioning

confidence: 99%

Oral DhHP-6 for the Treatment of Type 2 Diabetes Mellitus

Wang

Liang

et al. 2019

IJMS

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Type 2 diabetes mellitus (T2DM) is associated with pancreatic β-cell dysfunction which can be induced by oxidative stress. Deuterohemin-βAla-His-Thr-Val-Glu-Lys (DhHP-6) is a microperoxidase mimetic that can scavenge reactive oxygen species (ROS) in vivo. In our previous studies, we demonstrated an increased stability of linear peptides upon their covalent attachment to porphyrins. In this study, we assessed the utility of DhHP-6 as an oral anti-diabetic drug in vitro and in vivo. DhHP-6 showed high resistance to proteolytic degradation in vitro and in vivo. The degraded DhHP-6 product in gastrointestinal (GI) fluid retained the enzymatic activity of DhHP-6, but displayed a higher permeability coefficient. DhHP-6 protected against the cell damage induced by H2O2 and promoted insulin secretion in INS-1 cells. In the T2DM model, DhHP-6 reduced blood glucose levels and facilitated the recovery of blood lipid disorders. DhHP-6 also mitigated both insulin resistance and glucose tolerance. Most importantly, DhHP-6 promoted the recovery of damaged pancreas islets. These findings suggest that DhHP-6 in physiological environments has high stability against enzymatic degradation and maintains enzymatic activity. As DhHP-6 lowered the fasting blood glucose levels of T2DM mice, it thus represents a promising candidate for oral administration and clinical therapy.

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Ellagic acid ameliorates oxidative stress and insulin resistance in high glucose-treated HepG2 cells via miR-223/keap1-Nrf2 pathway

Cited by 175 publications

References 45 publications

The Role of microRNAs in Metabolic Syndrome-Related Oxidative Stress

The Role of microRNAs in Metabolic Syndrome-Related Oxidative Stress

Emerging Screening Approaches in the Development of Nrf2–Keap1 Protein–Protein Interaction Inhibitors

Oral DhHP-6 for the Treatment of Type 2 Diabetes Mellitus

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