Curcumin augments the cardioprotective effect of metformin in an experimental model of type I diabetes mellitus; Impact of Nrf2/HO-1 and JAK/STAT pathways

Abdelsamia, Eman M.; Khaleel, Sahar A.; Balah, Amany; Baky, Nayira A. Abdel

doi:10.1016/j.biopha.2018.11.064

Cited by 56 publications

(33 citation statements)

References 58 publications

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“…We first detected the effect of metformin on fasting blood glucose in diabetic mice after the 4-week treatment. As shown in Figure S1, there was no difference between the metformin group and DM group, which was consistent with a previous report (Abdelsamia et al, 2019). Given the evidence suggesting that HbA1c had little relevance with QTd (Syed et al), the protective effect of metformin on LQT would not likely be dependent on a hypoglycemic effect.…”

Section: Metformin Provides Protection Against a Prolonged Qt Intervasupporting

confidence: 89%

Metformin Shortens Prolonged QT Interval in Diabetic Mice by Inhibiting L-Type Calcium Current: A Possible Therapeutic Approach

Wang

Lü

et al. 2020

Front. Pharmacol.

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The incidence and mortality of cardiovascular disease in diabetic patients are 2-3 times higher than those in non-diabetic patients. Abnormal function of the L-type calcium channel in myocardial tissue might result in multiple cardiac disorders such as a prolonged QT interval. Therefore, QT prolongation is an independent risk factor of cardiovascular disease in patients with diabetes mellitus. Metformin, a hypoglycemic agent, is widely known to effectively reduce the occurrence of macrovascular diseases. The aim of the present study was to evaluate the effect of metformin on prolonged QT interval and to explore potential ionic mechanisms induced by diabetes. Diabetic mouse models were established with streptozotocin and an electrocardiogram was used to monitor the QT interval after 4 weeks of metformin treatment in each group. Action potential duration (APD) and L-type calcium current (I Ca-L) were detected by patch-clamp in isolated mice ventricular cardiomyocytes and neonatal cardiomyocytes of mice. The expression levels of CACNA1C mRNA and Cav1.2 were measured by real-time PCR, western blot and immunofluorescence. A shortened QT interval was observed after 4 weeks of metformin treatment in diabetic mice. Patch-clamp results revealed that both APD and I Ca-L were shortened in mouse cardiomyocytes. Furthermore, the expression levels of CACNA1C mRNA and Cav1.2 were decreased in the metformin group. The same results were also obtained in cultured neonatal mice cardiomyocytes. Overall, these results verify that metformin could shorten a prolonged QT interval by inhibiting the calcium current, suggesting that metformin may play a role in the electrophysiology underlying diabetic cardiopathy.

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Section: Metformin Provides Protection Against a Prolonged Qt Intervasupporting

confidence: 89%

Metformin Shortens Prolonged QT Interval in Diabetic Mice by Inhibiting L-Type Calcium Current: A Possible Therapeutic Approach

Wang

Lü

et al. 2020

Front. Pharmacol.

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“…Oxidative stress in the diabetic rat-induced by STZ could be attenuated by CUR through activation of the Keap1-Nrf2-ARE signaling pathway [ 29 ]. In addition, CUR augments the cardioprotective effect of metformin in an experimental model of type I diabetes mellitus via the Nrf2/HO-1 pathway which is also reported in previous study [ 30 ]. However, the detailed mechanism underlying the antidepressant effects of CUR as related to Nrf2 in the brain remains seldom studied.…”

Section: Introductionsupporting

confidence: 79%

Curcumin Attenuates Chronic Unpredictable Mild Stress-Induced Depressive-Like Behaviors via Restoring Changes in Oxidative Stress and the Activation of Nrf2 Signaling Pathway in Rats

Liao

Cao

et al. 2020

Oxidative Medicine and Cellular Longevity

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Accumulating evidence has demonstrated that oxidative stress is associated with depression. Our present study aimed at investigating the antidepressant effect and the possible mechanisms of curcumin (CUR) in chronic unpredictable mild stress- (CUMS-) induced depression model in rats. After exposure to CUMS for four weeks, the rats showed depressive-like behavior, and the depressive-like behaviors in CUMS-treated rats were successfully corrected after administration of CUR. In addition, CUR could effectively decrease protein expression of oxidative stress markers (Nox2, 4-HNE, and MDA) and increase the activity of CAT. CUR treatment also reversed CUMS-induced inhibition of Nrf2-ARE signaling pathway, along with increasing the mRNA expression of NQO-1 and HO-1. Furthermore, the supplementation of CUR also increased the ratio of pCREB/CREB and synaptic-related protein (BDNF, PSD-95, and synaptophysin). In addition, CUR could effectively reverse CUMS-induced reduction of spine density and total dendritic length. In conclusion, the study revealed that CUR relieves depressive-like state through the mitigation of oxidative stress and the activation of Nrf2-ARE signaling pathway.

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“…As an antioxidant, Cur is able to eliminate ROS and RNS by increasing the expression of antioxidant proteins via induction of upstream coding genes such as nuclear factor erythroid 2-related factor 2 (Nrf2), kelch-like ECH-associated protein 1 (Keap1), and antioxidant response element (ARE) ( Abdelsamia et al, 2019 ). Nrf2 is a transcription factor involved in cellular stress response.…”

Section: Natural Compounds Enhancing Sirt1 Expression and Activitymentioning

confidence: 99%

SIRT1 Activation by Natural Phytochemicals: An Overview

et al. 2020

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Sirtuins are class III histone deacetylases, whose enzymatic activity is dependent on NAD + as a cofactor. Sirtuins are reported to modulate numerous activities by controlling gene expression, DNA repair, metabolism, oxidative stress response, mitochondrial function, and biogenesis. Deregulation of their expression and/or action may lead to tissue-specific degenerative events involved in the development of several human pathologies, including cancer, neurodegeneration, and cardiovascular disease. The most studied member of this class of enzymes is sirtuin 1 (SIRT1), whose expression is associated with increasing insulin sensitivity. SIRT1 has been implicated in both tumorigenic and anticancer processes, and is reported to regulate essential metabolic pathways, suggesting that its activation might be beneficial against disorders of the metabolism. Via regulation of p53 deacetylation and modulation of autophagy, SIRT1 is implicated in cellular response to caloric restriction and lifespan extension. In recent years, scientific interest focusing on the identification of SIRT1 modulators has led to the discovery of novel small molecules targeting SIRT1 activity. This review will examine compounds of natural origin recently found to upregulate SIRT1 activity, such as polyphenolic products in fruits, vegetables, and plants including resveratrol, fisetin, quercetin, and curcumin. We will also discuss the potential therapeutic effects of these natural compounds in the prevention and treatment of human disorders, with particular emphasis on their metabolic impact.

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Curcumin augments the cardioprotective effect of metformin in an experimental model of type I diabetes mellitus; Impact of Nrf2/HO-1 and JAK/STAT pathways

Cited by 56 publications

References 58 publications

Metformin Shortens Prolonged QT Interval in Diabetic Mice by Inhibiting L-Type Calcium Current: A Possible Therapeutic Approach

Metformin Shortens Prolonged QT Interval in Diabetic Mice by Inhibiting L-Type Calcium Current: A Possible Therapeutic Approach

Curcumin Attenuates Chronic Unpredictable Mild Stress-Induced Depressive-Like Behaviors via Restoring Changes in Oxidative Stress and the Activation of Nrf2 Signaling Pathway in Rats

SIRT1 Activation by Natural Phytochemicals: An Overview

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