Emodin Protects against Diabetic Cardiomyopathy by Regulating the AKT/GSK-3β Signaling Pathway in the Rat Model

Wu, Zhiqin; Chen, Qingwei; Ke, Danxia; Li, Guiqiong; Deng, Wei

doi:10.3390/molecules190914782

Cited by 48 publications

(37 citation statements)

References 45 publications

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“…For example, Wu et al found that emodin protected against diabetic cardiomyopathy by modulating Akt/GSK-3β cascade in rats [27]. Emodin also inhibited acute cardiac ischemic injury through mitigation of local inflammation and apoptosis in mice [28].…”

Section: Discussionmentioning

confidence: 99%

Aloe-Emodin Relieves High-Fat Diet Induced QT Prolongation via MiR-1 Inhibition and IK1 Up-Regulation in Rats

Sun

Zhao

et al. 2017

Cell Physiol Biochem

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Background/Aims: High-fat diet (HFD) causes cardiac electrical remodeling and increases the risk of ventricular arrhythmias. Aloe-emodin (AE) is an anthraquinone component isolated from rhubarb and has a similar chemical structure with emodin. The protective effect of emodin against cardiac diseases has been reported in the literature. However, the cardioprotective property of AE is still unknown. The present study investigated the effect of AE on HFD-induced QT prolongation in rats. Methods: Adult male Wistar rats were randomly divided into three groups: control, HFD, and AE-treatment groups. Normal diet was given to rats in the control group, high-fat diet was given to rats in HFD and AE-treatment groups for a total of 10 weeks. First, HFD rats and AE-treatment rats were fed with high-fat diet for 4 weeks to establish the HFD model. Serum total cholesterol and triglyceride levels were measured to validate the HFD model. Afterward, AE-treatment rats were intragastrically administered with 100 mg/kg AE each day for 6 weeks. Electrocardiogram monitoring and whole-cell patch-clamp technique were applied to examine cardiac electrical activity, action potential and inward rectifier K + current (I K1 ), respectively. Neonatal rat ventricular myocytes (NRVMs) were subjected to cholesterol and/or AE. Protein expression of Kir2.1 was detected by Western blot and miR-1 level was examined by real-time PCR in vivo and in vitro, respectively. Results: In vivo, AE significantly shortened the QT interval, action potential duration at 90% repolarization (APD 90 ) and resting membrane potential (RMP), which were markedly elongated by HFD. AE increased I K1 current and Kir2.1 protein expression which were reduced in HFD rats. Furthermore, AE significantly inhibited pro-arrhythmic miR-1 in the hearts of HFD rats. In vitro, AE decreased miR-1 expression levels resulting in an increase of Kir2.1 protein levels in cholesterol-enriched NRVMs. Conclusions: AE prevents HFD-induced QT prolongation by repressing miR-1 and upregulating its target Kir2.1. These findings suggest a novel pharmacological role of AE in HFD-induced cardiac electrical remodeling.

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Section: Discussionmentioning

confidence: 99%

Aloe-Emodin Relieves High-Fat Diet Induced QT Prolongation via MiR-1 Inhibition and IK1 Up-Regulation in Rats

Sun

Zhao

et al. 2017

Cell Physiol Biochem

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“…Recent studies have demostrated that Emodin protected against cisplatin-induced oxidative stress in cultured HEK 293 cells [8] and attenuated hypoxia and LPS-induced intestinal epithelial barrier dysfunction through inhibition of NF-κB and HIF-1α signaling pathways [9]. Emodin has been reported to protect against diabetic cardiomyopathy by regulating the AKT/GSK-3β signaling pathway in rats [10]. The animal study demonstrated that Emodin ameliorated renal dysfunction through inhibition of activation of p38 MAPK pathway in rats with DKD [11].…”

Section: Introductionmentioning

confidence: 99%

Emodin Ameliorates High Glucose Induced-Podocyte Epithelial-Mesenchymal Transition In-Vitro and In-Vivo

Tingfang

Zheng

Xiao

et al. 2015

Cell Physiol Biochem

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Background: Epithelial-to-mesenchymal transition (EMT) is a potential pathway leading to podocyte depletion and proteinuria in diabetic kidney disease (DKD). Here, we investigated the protective effects of Emodin (EMO) on high glucose (HG) induced-podocyte EMT in-vitro and in-vivo. Methods: Conditionally immortalized mouse podocytes were exposed to HG with 30μg /ml of EMO and 1μmol/ml of integrin-linked kinase (ILK) inhibitor QLT0267 for 24 h. Streptozotocin (STZ)-induced diabetic rats were treated with EMO at 20 mg· kg^-1· d^-1 and QLT0267 at 10 mg· kg^-1· w^-1 p.o., for 12 weeks. Albuminuria and blood glucose level were measured. Immunohistochemistry, immunofluorescence, western blotting and real-time PCR were used to detect expression of ILK, the epithelial marker of nephrin and the mesenchymal marker of desmin in-vitro and in-vivo. Results: HG increased podocyte ILK and desmin expression while decreased nephrin expression. However, EMO significantly inhibited ILK and desmin expression and partially restored nephrin expression in HG-stimulated podocytes. These in-vitro observations were further confirmed in-vivo. Treatment with EMO for 12 weeks attenuated albuminuria, renal histopathology and podocyte foot process effacement in diabetic rats. EMO also repressed renal ILK and desmin expression, preserved nephrin expression, as well as ameliorated albuminuria in STZ-induced diabetic rats. Conclusion: EMO ameliorated glucose-induced EMT and subsequent podocyte dysfunction partly through ILK and desmin inhibition as well as nephrin upregulatiotion, which might provide a potential novel therapeutic option for DKD.

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“…In animal models, emodin has demonstrated blood glucose‐lowering effect and improved insulin resistance. Treatment of emodin (100 mg/kg body weight [bw]) orally for 6 or 8 weeks showed maximum fasting blood glucose (FBG) reduction of 53.6%, attenuated hyperlipidemia and insulin resistance in high‐fat diet KKAy, and C57BL/6J mice and streptozotocin (STZ)‐induced diabetic rats (Abu Eid et al, ; Bing et al, ; Cao et al, ; Song, Fan, Guo, Fan, & Yang, ; Tzeng, Lu, Liou, Chang, & Liu, ; Wu, Chen, Ke, Li, & Deng, ). In contrast, administration of emodin for 7 days at same dose and via the same route reduced FBG by 77.2% in C57BL/6J mice (Feng et al, ).…”

Section: Resultsmentioning

confidence: 99%

“…In addition, the upregulation of peroxisome proliferator activated receptor‐γ by emodin administration may have a crucial role in improving insulin sensitivity via increased glucose transporter 2 expression (Bing et al, ; Chen et al, ). Meanwhile, the high DPP‐4 inhibition and downregulation of glycogen synthase kinase‐3β expression by emodin showed the potential to improve insulin secretion and modulation of hepatic and muscle glycogen contents in vivo (Song et al, ;Wang et al, ; Wu, Chen, et al, ). The amelioration of diabetes‐associated complications and pancreatic β‐cell failure by emodin and catenarin administration are linked to the downregulation of the mitogen‐activated protein kinase p38, c‐Jun N‐terminal Kinases, NF‐kB, integrin‐linked kinase and desmin expression, and the restoration of nephrin expression in diabetic rats model (Bae et al, ; Chen et al, ; Shen et al, ; Heo, Yun, Noh, & Park, ; Wang et al, ).…”

Section: Resultsmentioning

confidence: 99%

“…The available data in the literature indicated that relatively low concentrations of the AQs were detected in the plasma with higher amount of conjugated metabolites at the post‐oral consumption (Wu et al, ; Peng et al, ; Wu, Chen, et al, ; Shia et al, ; ; Lee et al, ; Krumbiegel & Schulz, ). With the exception of rhein, these concentrations were lower compared with the IC 50 values obtained for most of the in vitro and cell‐based studies.…”

Section: Resultsmentioning

confidence: 99%

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Antidiabetic potential of anthraquinones: A review

Mohammed

Ibrahim

Tajuddeen

et al. 2019

Phytotherapy Research

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The present study was designed to review the antidiabetic potential of anthraquinones (AQs) with emphasis on the extent of blood glucose reduction, the half maximal inhibitory concentration values (in vitro studies), the proposed mechanisms of action, and the structure activity relationship studies. We sourced relevant data from the major scientific databases (Pubmed, Science Direct, Medline, and Google Scholar). According to our search, 25 AQs have shown variable antidiabetic potential, whereas one AQ (morindone‐6‐O‐β‐D‐primeveroside) showed no blood glucose‐lowering ability. Emodin and rhein showed the most promising antidiabetic potential in various models. The proposed mechanisms of antidiabetic action include upregulation of insulin receptor substrates‐1, phosphoinositide‐3‐kinase, and Akt‐ser473 expression and elevation of glucagon‐like peptide‐1 level in diabetic animal models linked to the potent protein tyrosine phosphatase 1B and dipeptidyl peptidase‐4 inhibitions. In addition, activation of peroxisome proliferator‐activated receptors gamma and inhibition of α‐glucosidase activity are other possible targets proposed as the mechanism of AQs antidiabetic action. The position and the number of hydroxyl group showed great influence on the overall antidiabetic potential of AQs. AQs hold promising antidiabetic activity despite scanty information. We hope that the present study will serve as a template to further explore the antidiabetic potential of AQs and subsequent antidiabetic drug development.

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Emodin Protects against Diabetic Cardiomyopathy by Regulating the AKT/GSK-3β Signaling Pathway in the Rat Model

Cited by 48 publications

References 45 publications

Aloe-Emodin Relieves High-Fat Diet Induced QT Prolongation via MiR-1 Inhibition and IK1 Up-Regulation in Rats

Aloe-Emodin Relieves High-Fat Diet Induced QT Prolongation via MiR-1 Inhibition and IK1 Up-Regulation in Rats

Emodin Ameliorates High Glucose Induced-Podocyte Epithelial-Mesenchymal Transition In-Vitro and In-Vivo

Antidiabetic potential of anthraquinones: A review

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