Artesunate protects pancreatic beta cells against cytokine-induced damage via SIRT1 inhibiting NF-κB activation

Yu, Liu; Chen, J. F.; Shuai, Xuanyu; Xu, Yiming; Ding, Ye; Zhang, J.; Yang, Wenjie; Liang, Xiaowen; Su, Dongming; Yan, Caifeng

doi:10.1007/s40618-015-0328-1

Cited by 34 publications

(30 citation statements)

References 32 publications

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“…This was probably due to differences in mechanisms by which each ferroptosis inducer contributes to the various metabolic derangements that lead ultimately to ER stress. Since DFO has pleiotropic effects (inhibition of iron-mediated lipid peroxidation, inhibition of NF-κB activation, and involvement in several peroxidative systems [ 48 , 49 ]), DFO may affect ART-induced ER stress and its activation of NF-κB by preventing IκBα degradation [ 48 , 50 , 51 ]. Obviously, further studies are necessary to understand the molecular mechanism of differences between each ferroptosis inducer-induced ER stress.…”

Section: Discussionmentioning

confidence: 99%

Molecular crosstalk between ferroptosis and apoptosis: emerging role of ER stress-induced p53-independent PUMA expression

et al. 2017

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Ferroptosis is a type of programmed cell death that depends on iron and is characterized by the accumulation of lipid peroxides. In the present study, we investigated the nature of the interplay between ferroptosis and other forms of cell death such as apoptosis. Human pancreatic cancer PANC-1 and BxPC-3 and human colorectal cancer HCT116 cells were treated with ferroptotic agents such as erastin and artesunate (ART) in combination with the apoptotic agent tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). We observed synergistic interaction of erastin or ART with TRAIL as determined by cell death assay, caspase activation, poly [ADP-ribose] polymerase 1 (PARP-1) cleavage, flow cytometry analysis, and lipid peroxidation assay. Moreover, erastin and ART induced endoplasmic reticulum (ER) stress and promoted p53 upregulated modulator of apoptosis (PUMA) expression via C/EBP-homologous protein (CHOP). Synergy of erastin/ART and TRAIL was abolished in PUMA-deficient HCT116 cells and CHOP-deficient mouse embryonic fibroblasts, but not in p53-deficient HCT116 cells. The results suggest the involvement of the p53-independent CHOP/PUMA axis in response to ferroptosis inducers, which may play a key role in ferroptotic agent-mediated sensitization to TRAIL-induced apoptosis.

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Section: Discussionmentioning

confidence: 99%

Molecular crosstalk between ferroptosis and apoptosis: emerging role of ER stress-induced p53-independent PUMA expression

et al. 2017

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“…We also confirmed that artemether protected beta cells function by reducing the apoptosis of pancreatic beta cells and increasing insulin secretion in db/db mice. In cell experiments, artesunate was proved to protect pancreatic beta cells against cytokine-induced damage via SIRT1 inhibiting NF- κ B activation [ 22 ]. And in type 1 diabetic rat artemisinins as approved drugs were identified that can confer β cell characteristics to α cell.…”

Section: Discussionmentioning

confidence: 99%

Antidiabetic and Antiobesity Effects of Artemether in db/db Mice

Guo

Xin

et al. 2018

BioMed Research International

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This study is designed to investigate the effect of artemether on type 2 diabetic db/db mice. The experiments consisted of three groups: normal control (NC, db/+, 1% methylcellulose, intragastric administration), diabetic control (DM, db/db, 1% methylcellulose, intragastric administration), and artemether treated (artemether, db/db, 200 mg/kg of artemether, intragastric administration). The treatment lasted for two weeks. The food intake, body weight, and fasting blood glucose of mice were measured every three days. At the start and end of the experiment, the intraperitoneal glucose tolerance test (IPGTT) and insulin tolerance test (IPITT) were performed. We determined the serum insulin and glucagon levels by ELISA kits and calculated insulin resistance index (HOME-IR). HE staining was used to observe the morphologies of pancreas and liver in mice. The damage of pancreatic beta cells was evaluated by TUNEL staining and immunofluorescence. We found the following: (1) compared with the DM group, the food intake and weight increase rate of artemether group significantly reduced (P < 0.05); (2) compared with pretreatment, artemether significantly reduced the fasting blood glucose levels, and the areas under the curves (AUCs) of IPGTT were decreased significantly, increasing the tolerance to glucose of db/db mice. (P < 0.05); (3) artemether improved hyperinsulinemia and decreased the AUCs of IPITT and HOME-IR, increasing the insulin sensitivity of db/db mice. (4) Artemether significantly ameliorated islet vacuolar degeneration and hepatic steatosis in db/db mice. (5) Artemether reduced the apoptosis of pancreatic beta cells and increased insulin secretion in db/db mice compared with DM group (P < 0.05). Our results indicated that artemether significantly improved glucose homeostasis and insulin resistance and had the potential activity to prevent obesity, reduced the severity of fatty liver, and protected pancreatic beta cells, promising to treat type 2 diabetes.

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“…Patients with diabetes have more than double the risk of ICD after correction for other risk factors, relative to individuals without diabetes [68]. Yu et al newly found that artesunate could elicit a protective effect on pancreatic beta-cells exposed to IL-1 β by stimulating SIRT1 expression, which resulted in the decrease of NF-kB activity, iNOS expression, and NO production [69]. Hence, ART might be an effective drug for diabetes after ICD.…”

Section: Effect Of Artesunate On Central Nervous System Diseasesmentioning

confidence: 99%

The Potential Therapeutic Effects of Artesunate on Stroke and Other Central Nervous System Diseases

Zuo

Liu

et al. 2016

BioMed Research International

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Artesunate is an important agent for cerebral malaria and all kinds of other severe malaria because it is highly efficient, lowly toxic, and well-tolerated. Loads of research pointed out that it had widespread pharmacological activities such as antiparasites, antitumor, anti-inflammation, antimicrobes activities. As we know, the occurrence and development of neurological disorders usually refer to intricate pathophysiologic mechanisms and multiple etiopathogenesis. Recent progress has also demonstrated that drugs with single mechanism and serious side-effects are not likely the candidates for treatment of the neurological disorders. Therefore, the pluripotent action of artesunate may result in it playing an important role in the prevention and treatment of these neurological disorders. This review provides an overview of primary pharmacological mechanism of artesunate and its potential therapeutic effects on neurological disorders. Meanwhile, we also briefly summarize the primary mechanisms of artemisinin and its derivatives. We hope that, with the evidence presented in this review, the effect of artesunate in prevention and curing for neurological disorders can be further explored and studied in the foreseeable future.

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Artesunate protects pancreatic beta cells against cytokine-induced damage via SIRT1 inhibiting NF-κB activation

Abstract: ART can elicit a protective effect on beta-cells exposed to IL-1β by stimulating SIRT1 expression, which resulted in the decrease of NF-κB activity, iNOS expression, and NO production. Hence, ART might be an effective drug for diabetes.

Cited by 34 publications

References 32 publications

Molecular crosstalk between ferroptosis and apoptosis: emerging role of ER stress-induced p53-independent PUMA expression

Molecular crosstalk between ferroptosis and apoptosis: emerging role of ER stress-induced p53-independent PUMA expression

Antidiabetic and Antiobesity Effects of Artemether in db/db Mice

The Potential Therapeutic Effects of Artesunate on Stroke and Other Central Nervous System Diseases

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