Diabetic cardiomyopathy: molecular mechanisms, detrimental effects of conventional treatment, and beneficial effects of natural therapy

Parim, Brahmanaidu; Uddandrao, V. V. Sathibabu; Saravanan, G.

doi:10.1007/s10741-018-9749-1

Cited by 122 publications

(103 citation statements)

References 128 publications

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“…The metabolic environments related to T2DM are hyperglycemia, which can increase the levels of circulating fatty acids and triglycerides and cause abnormal glucose and lipid metabolism and lipid accumulation in myocardial cells, and hyperinsulinemia, which can enhance the expression of inflammatory cytokines, change the molecular signaling pathways in multiple myocardial cells, and damage the contraction of the heart. The signaling pathways related to these factors play an important role in DCM, such as the cardiac ubiquitin proteasome system, the FoxO transcription factor signaling pathway, the hexosamine biosynthetic pathway, the polyol pathway, protein kinase C signaling, NF- κ B signaling, peroxisome proliferator-activated receptor signaling, Nrf2 pathways, the mitogen-activated protein kinase pathways, and microRNAs, especially the AMPK signaling pathway [ 82 ]. Since blood glucose levels, fatty acid oxidation, and glycogen metabolism are regulated by AMPK, AMPK plays a vital role in the formation of DCM.…”

Section: Discussionmentioning

confidence: 99%

Network Pharmacology-Based Strategy Reveals the Effects of Hedysarum multijugum Maxim.-Radix Salviae Compound on Oxidative Capacity and Cardiomyocyte Apoptosis in Rats with Diabetic Cardiomyopathy

Zhang

Yuan

et al. 2020

BioMed Research International

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Objective. To explore the effects of the Hedysarum multijugum Maxim.-Radix Salviae compound (Huangqi-Danshen Compound (HDC)) on oxidative capacity and cardiomyocyte apoptosis in rats with diabetic cardiomyopathy by a network pharmacology-based strategy. Methods. Traditional Chinese Medicine (TCM)@Taiwan, TCM Systems Pharmacology Database and Analysis Platform (TCMSP), TCM Integrated Database (TCMID), and High-Performance Liquid Chromatography (HPLC) technology were used to obtain and screen HDC’s active components, and the PharmMapper database was used to predict HDC human target protein targets. The DCM genes were collected from the GeneCards and OMIM databases, and the network was constructed and analyzed by Cytoscape 3.7.1 and the Database for Annotation, Visualization, and Integrated Discovery (DAVID). Finally, HDC was used to intervene in diabetic cardiomyopathy (DCM) model rats, and important biological processes and signaling pathways were verified using techniques such as immunohistochemistry. Results. A total of 176 of HDC’s active components and 442 potential targets were obtained. The results of network analysis show that HDC can regulate DCM-related biological processes (such as negative regulation of the apoptotic process, response to hypoxia, the steroid hormone-mediated signaling pathway, cellular iron ion homeostasis, and positive regulation of phosphatidylinositol 3-kinase signaling) and signaling pathways (such as the HIF-1 signaling pathway, the estrogen signaling pathway, insulin resistance, the PPAR signaling pathway, the VEGF signaling pathway, and the PI3K-Akt signaling pathway). Animal experiments show that HDC can reduce fasting plasma glucose (FPG), HbA1c, and malondialdehyde (MDA) and increase superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) ( P < 0.05 ). The results of immunohistochemistry showed that HDC can regulate the protein expression of apoptosis-related signaling pathways in DCM rats ( P < 0.05 ). Conclusion. It was initially revealed that HDC improves DCM through its antiapoptotic and anti-inflammatory effects. HDC may play a therapeutic role by improving cardiomyocyte apoptosis in DCM rats.

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Section: Discussionmentioning

confidence: 99%

Network Pharmacology-Based Strategy Reveals the Effects of Hedysarum multijugum Maxim.-Radix Salviae Compound on Oxidative Capacity and Cardiomyocyte Apoptosis in Rats with Diabetic Cardiomyopathy

Zhang

Yuan

et al. 2020

BioMed Research International

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“…Ruscogenin is derived from traditional Chinese medicine, Ophiopogon japonicus,it can anti-in ammatory [49] , anti-thrombosis and protective barrier function [19] . It also can prevent the occurrence of hemorrhagic events.Due to the lack of effective interventions for the bleeding side effects caused by Dasatinib, we considered that Ruscogenin has the function of protecting the endothelial barrier, and there are no clear side effects reported, so we assumed that Ruscogenin can improve the side effects caused by Dasatinib through protects barrier.The use of traditional Chinese medicine to regulate the side effects of other drugs has been initially recognized as a new treatment strategy [50] .…”

Section: Discussionmentioning

confidence: 99%

Ruscogenin Alleviates Intestinal Bleeding and Blood Flow Induced by Dasatinib through ROCK/MLC Pathway

Liu

Dai

Han³

et al. 2020

Preprint

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BackgroundAs a second-generation broad-spectrum tyrosine kinase inhibitor, Dasatinib has the antitumor effect of inhibiting tyrosine kinases such as BCR-ABL and SRC. It is mainly used to treat chronic and acute patients with chronic myelogenous leukemia. However, Dasatinib has many side effects, including gastrointestinal bleeding, respiratory infections, and renal failure, and effective means to improve the side effects of drugs are lacking.MethodsC57BL/6 mice and HUVECs were used to evaluate the side effects caused by dasatinib, RUS was administered in advance to prevent, protein expression and phosphorylation were measured by western blot, and monitored the intestinal bleeding with Laser Doppler Blood Flow Monitor. ResultsWe found that Ruscogenin (RUS) can improve Side effects caused by Dasatinib. Through the Laser Doppler Blood Flow Monitor, it was found that after Dasatinib was administered, blood flow in mice are decreased, and intestinal Evans blue leakage increased. Western blot results showed that connexin (ZO-1, VE-cadherin, Occludin) is destroyed, the activation of ROCK increases, and the phosphorylation of MLC increases. Ruscogenin can reverse the above phenomenon and improve the side effects of gastrointestinal bleeding caused by Dasatinib. In vitro, giving Ruscogenin in advance can protect the endothelial barrier damage caused by Dasatinib, reduce the remodeling of F-actin, and restore the expression of connexin (ZO-1, VE-cadherin), inhibit the activation of ROCK, and reduce Phosphorylation of MLC. ConclusionsThis study provides a new direction for improving the side effects caused by clinical drugs and confirm that Ruscogenin could improve the side effect from Dasatinib by ROCK/MLC pathway.

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“…Related findings suggest that exercise protects pancreatic beta cells by inducing the expression of insulin-sensitive adenosine monophosphate-activated protein kinase (AMPK) and preventing energy metabolism dysfunction in insulin-deficient diabetes mellitus [52]. Furthermore, exercise has been shown to reduce Forkhead box protein O1 (FOXO1) and FOXO1-related factors in pancreatic beta cells and in the myocardium of obese rats; it also activates insulin signaling pathways [53]. Additionally, exercise enhances the function of insulin-regulated glucose transporters via upregulating the expression of protein kinase C [54].…”

Section: Cardiac Cell Metabolismmentioning

confidence: 99%

Exercise as A Potential Therapeutic Target for Diabetic Cardiomyopathy: Insight into the Underlying Mechanisms

Seo

Jang

et al. 2019

IJMS

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Diabetes mellitus is associated with cardiovascular, ophthalmic, and renal comorbidities. Among these, diabetic cardiomyopathy (DCM) causes the most severe symptoms and is considered to be a major health problem worldwide. Exercise is widely known as an effective strategy for the prevention and treatment of many chronic diseases. Importantly, the onset of complications arising due to diabetes can be delayed or even prevented by exercise. Regular exercise is reported to have positive effects on diabetes mellitus and the development of DCM. The protective effects of exercise include prevention of cardiac apoptosis, fibrosis, oxidative stress, and microvascular diseases, as well as improvement in cardiac mitochondrial function and calcium regulation. This review summarizes the recent scientific findings to describe the potential mechanisms by which exercise may prevent DCM and heart failure.

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Diabetic cardiomyopathy: molecular mechanisms, detrimental effects of conventional treatment, and beneficial effects of natural therapy

Cited by 122 publications

References 128 publications

Network Pharmacology-Based Strategy Reveals the Effects of Hedysarum multijugum Maxim.-Radix Salviae Compound on Oxidative Capacity and Cardiomyocyte Apoptosis in Rats with Diabetic Cardiomyopathy

Network Pharmacology-Based Strategy Reveals the Effects of Hedysarum multijugum Maxim.-Radix Salviae Compound on Oxidative Capacity and Cardiomyocyte Apoptosis in Rats with Diabetic Cardiomyopathy

Ruscogenin Alleviates Intestinal Bleeding and Blood Flow Induced by Dasatinib through ROCK/MLC Pathway

Exercise as A Potential Therapeutic Target for Diabetic Cardiomyopathy: Insight into the Underlying Mechanisms

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Diabetic cardiomyopathy: molecular mechanisms, detrimental effects of conventional treatment, and beneficial effects of natural therapy

Cited by 122 publications

References 128 publications

Network Pharmacology-Based Strategy Reveals the Effects of Hedysarum multijugum Maxim.-Radix Salviae Compound on Oxidative Capacity and Cardiomyocyte Apoptosis in Rats with Diabetic Cardiomyopathy

Network Pharmacology-Based Strategy Reveals the Effects of Hedysarum multijugum Maxim.-Radix Salviae Compound on Oxidative Capacity and Cardiomyocyte Apoptosis in Rats with Diabetic Cardiomyopathy

Ruscogenin Alleviates Intestinal Bleeding and Blood Flow Induced by Dasatinib&nbsp;through ROCK/MLC Pathway

Exercise as A Potential Therapeutic Target for Diabetic Cardiomyopathy: Insight into the Underlying Mechanisms

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Ruscogenin Alleviates Intestinal Bleeding and Blood Flow Induced by Dasatinib through ROCK/MLC Pathway