Novel Insights Into the Pathogenesis of Diabetic Cardiomyopathy and Pharmacological Strategies

Muñoz-Cordova, Felipe; Hernández‐Fuentes, Carolina; López-Crisosto, Camila; Troncoso, Mayarling Francisca; Calle, Ximena; Guerrero-Moncayo, Alejandra; Gabrielli, Luigi; Chiong, Mario; Castro, Pablo; Lavandero, Sergio

doi:10.3389/fcvm.2021.707336

Cited by 8 publications

(5 citation statements)

References 143 publications

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“…Oxidative stress and other risk factors may promote cardiomyocyte death, interstitial fibrosis, and cardiac stiffness, leading to diastolic and systolic dysfunction, and eventually heart failure. Therefore, pharmacological strategies for reducing ROS burden or increasing antioxidant mechanisms may provide a successful strategy for the treatment of DCM ( 24 ). Here, the GO analysis revealed that the target genes of YNJ on DCM were numerous and complex, mainly focusing on biological processes such as response to regulation to protein stability and response to oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

YuNü-Jian attenuates diabetes-induced cardiomyopathy: integrating network pharmacology and experimental validation

Wang¹,

Liu²,

Zhu³

et al. 2023

Front. Endocrinol.

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IntroductionDiabetic cardiomyopathy (DCM) is one of the most prevalent complications of diabetes with complex pathogenesis. YuNü-Jian (YNJ) is a traditional Chinese medicinal formula widely used for diabetes with hypoglycemic and cardioprotective effects. This study aims to investigate the actions and mechanisms of YNJ against DCM which has never been reported.MethodsNetwork pharmacology approach was used to predict the potential pathways and targets of YNJ on DCM. Molecular docking between hub targets and active components of YNJ was performed and visualized by AutoDock Vina and PyMOL. Then type 2 diabetic model was employed and intervened with YNJ for 10 weeks to further validate these critical targets.ResultsFirst, a total of 32 main ingredients of YNJ were identified and 700 potential targets were screened to construct herb-compound-target network. Then 94 differentially expressed genes of DCM were identified from GEO database. After that, PPI network of DCM and YNJ were generated from which hub genes (SIRT1, Nrf2, NQO1, MYC and APP) were assessed by topology analysis. Next, functional and pathway analysis indicated that the candidate targets were enriched in response to oxidative stress and Nrf2 signaling pathway. Furthermore, molecular docking revealed strong affinity between core targets and active components of YNJ. Finally, in rats with type 2 diabetes, YNJ obviously attenuated cardiac collagen accumulation and degree of fibrosis. Meanwhile, YNJ significantly upregulated protein expression of SIRT1, Nrf2 and NQO1 in diabetic myocardium.DiscussionCollectively, our findings suggested that YNJ could effectively ameliorate cardiomyopathy induced by diabetes possibly through SIRT1/Nrf2/NQO1 signaling.

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Section: Discussionmentioning

confidence: 99%

YuNü-Jian attenuates diabetes-induced cardiomyopathy: integrating network pharmacology and experimental validation

Wang¹,

Liu²,

Zhu³

et al. 2023

Front. Endocrinol.

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“…DCM, a consequence of dysregulated glucose and lipid metabolism in diabetes mellitus, remains a major challenge, because of the complexity of its pathogenesis and the difficulty in developing targeted interventions [1,17]. BBR, a naturally occurring isoquinoline alkaloid, has been demonstrated to have substantial cardioprotective potential, by markedly decreasing myocardial infarct size and mitigating ventricular arrhythmia, according to animal studies [18].…”

Section: Discussionmentioning

confidence: 99%

Berberine Ameliorates Diabetic Cardiomyopathy in Mice by Decreasing Cardiomyocyte Apoptosis and Oxidative Stress

Sun,

Li,

Wang

et al. 2023

CVIA

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Background: Diabetic cardiomyopathy is a multifaceted complication of diabetes that lacks effective treatments. Berberine (BBR), a bioactive compound from Rhizoma coptidis, has potential therapeutic implications, but its precise role in diabetic cardiomyopathy remains to be defined. Methods: In this study, a diabetic cardiomyopathy model was established by administration of a high-fat diet and streptozotocin injection to C57BL/6J mice. Concurrently, the mice received BBR treatment daily for a duration of 8 weeks. After the treatment period, myocardial injury, cardiac function, and the levels of oxidative stress and apoptosis were assessed. Results: BBR significantly ameliorated cardiac dysfunction and histopathological damage caused by diabetic cardiomyopathy. This treatment also elevated serum superoxide dismutase levels while decreasing malondialdehyde levels. The anti-apoptotic activity of BBR was evidenced by a decrease in TUNEL-positive cells and the percentage of apoptotic cells, as determined by flow cytometry, in conjunction with diminished levels of BCL2-associated X protein/B cell lymphoma 2 (BAX/BCL2) in heart tissues. Mechanistically, BBR was found to ameliorate diabetic cardiomyopathy by upregulating the expression of myocardial methionine sulfoxide reductase A (MsrA) and concurrently suppressing cardiac CaMKII oxidation. Conclusions: BBR alleviates diabetic cardiomyopathy by inhibiting myocardial apoptosis and oxidative stress through the MsrA and CaMKII signaling pathways.

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“…Blood glucose, glycosylated hemoglobin, and INS levels were measured following the manufacturer's instructions. Muñoz-Córdova et al, 2021;Tang et al, 2022). Previous research has demonstrated that the nucleotide-binding oligomerization domain-like-receptor family pyrin domain-containing 3 (NLRP3) deficiency enhanced insulin (INS) sensitivity in obese mice, suggesting that NLRP3 plays a crucial role in metabolism (Li et al, 2022).…”

Section: Detection Of Blood Glucose-related Indicatorsmentioning

confidence: 99%

Polygonatum polysaccharide attenuates inflammation through inhibiting NLRP3 inflammasome in diabetic cardiomyopathy rats

et al. 2023

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Polygonatum polysaccharide (PP) has good myocardial protection. This study aims to find whether PP can relieve inflammation and play a protective role in diabetic cardiomyopathy (DCM). Intraperitoneal injection of streptozotocin was used to induce DCM in rats, which were then separated into four groups: model group, PP-200 group (200 mg/kg PP), PP-400 group (400 mg/kg PP), and Met group (120 mg/kg metformin). Both control (NC) and model groups of rats were administered normal saline. According to the kit instructions mentioned on the kit, the levels of blood glucose, glycosylated hemoglobin, insulin (INS), and myocardial enzymes (creatinine kinase, B-type natriuretic peptide, and cardiac troponin I) were measured after 8 weeks. Cardiac function was detected by echocardiography. Hematoxylin and eosin (HE) and Masson staining were used to observe pathological changes. Myocardial RNA and protein levels of NLR family pyrin domain containing 3 (NLRP3), caspase-1, and Gasdermin D (GSDMD) were quantified through reverse transcription-polymerase chain reaction and Western blotting analysis. The in vivo findings showed that PP could reduce blood glucose, glycosylated hemoglobin, and INS levels, enhance heart functioning, restore histological alterations and myocardial enzymes, and relieve myocardial fibrosis. Furthermore, PP suppressed the expressions of NLRP3, caspase-1, and GSDMD. PP could reduce inflammation in DCM rats by suppressing NLRP3 inflammasome.

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Novel Insights Into the Pathogenesis of Diabetic Cardiomyopathy and Pharmacological Strategies

Cited by 8 publications

References 143 publications

YuNü-Jian attenuates diabetes-induced cardiomyopathy: integrating network pharmacology and experimental validation

YuNü-Jian attenuates diabetes-induced cardiomyopathy: integrating network pharmacology and experimental validation

Berberine Ameliorates Diabetic Cardiomyopathy in Mice by Decreasing Cardiomyocyte Apoptosis and Oxidative Stress

Polygonatum polysaccharide attenuates inflammation through inhibiting NLRP3 inflammasome in diabetic cardiomyopathy rats

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