Quercetin prevents myocardial infarction adverse remodeling in rats by attenuating TGF-β1/Smad3 signaling: Different mechanisms of action

Albadrani, Ghadeer M.; BinMowyna, Mona N.; Bin-Jumah, May; El–Akabawy, Gehan; Aldera, Hussain; Al‐Farga, Ammar

doi:10.1016/j.sjbs.2021.02.007

Cited by 26 publications

(14 citation statements)

References 49 publications

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“…Among these bioactive components (Figure 3), some were dedicated to pain relief or cancer treatment (Gao et al, 1994;Xu et al, 2012;Chen et al, 2016;Wang et al, 2016;Wang et al, 2019), while berberine, coptisine, THP, palmatine, and quercetin were reported to be cardioprotective (Kim et al, 2009;Guo et al, 2013;Zhu et al, 2020;Albadrani et al, 2021). In this study, we conducted molecular docking of the 5 components with AKT1, the core target related to the PI3K/Akt pathway.…”

Section: Results Of Molecular Docking Analysismentioning

confidence: 99%

Uncovering the Effect and Mechanism of Rhizoma Corydalis on Myocardial Infarction Through an Integrated Network Pharmacology Approach and Experimental Verification

Huang

et al. 2022

Front. Pharmacol.

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Background: Myocardial infarction (MI), characterized by reduced blood flow to the heart, is a coronary artery disorder with the highest morbidity and mortality among cardiovascular diseases. Consequently, there is an urgent need to identify effective drugs to treat MI. Rhizoma Corydalis (RC) is the dry tuber of Corydalis yanhusuo W.T. Wang, and is extensively applied in treating MI clinically in China. Its underlying pharmacological mechanism remains unknown. This study aims to clarify the molecular mechanism of RC on MI by utilizing network pharmacology and experimental verification.Methods: Based on network pharmacology, the potential targets of the RC ingredients and MI-related targets were collected from the databases. Furthermore, core targets of RC on MI were identified by the protein-protein interaction (PPI) network and analyzed with Gene Ontology (GO) analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Molecular docking was used to validate the binding affinity between the core targets and the bioactive components. Oxygen-glucose deprivation (OGD) was performed on H9c2 cells to mimic MI in vitro. A Cell Counting Kit-8 assay was used to assess the cardioprotective effect of the active ingredient against OGD. Western blot analysis and RT-qPCR were used to measure the cell apoptosis and inflammation level of H9c2 cells.Results: The network pharmacology obtained 60 bioactive components of RC, 431 potential targets, and 1131 MI-related targets. In total, 126 core targets were screened according to topological analysis. KEGG results showed that RC was closely related to the phosphatidylinositol 3-kinase (PI3K)/Protein kinase B (PKB, also called Akt) signaling pathway. The experimental validation data showed that tetrahydropalmatine (THP) pretreatment preserved cell viability after OGD exposure. THP suppressed cardiomyocyte apoptosis and inflammation induced by OGD, while LY294002 blocked the inhibition effect of THP on OGD-induced H9c2 cell injury. Moreover, the molecular docking results indicated that THP had the strongest binding affinity with Akt over berberine, coptisine, palmatine, and quercetin.Conclusion: THP, the active ingredient of RC, can suppress OGD-induced H9c2 cell injury by activating the PI3K/Akt pathway, which in turn provides a scientific basis for a novel strategy for MI therapy and RC application.

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Section: Results Of Molecular Docking Analysismentioning

confidence: 99%

Uncovering the Effect and Mechanism of Rhizoma Corydalis on Myocardial Infarction Through an Integrated Network Pharmacology Approach and Experimental Verification

Huang

et al. 2022

Front. Pharmacol.

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“…Quercetin has been reported to have protective effects on the heart because of its antioxidant, anti-inflammatory, and other biological properties ( 35 ). Albadrani et al revealed that quercetin upregulates Smad7 and has an anti-fibrosis effect ( 36 ). Quercetin is contained in TSF herbs, such as rhubarb root and rhizome, notoginseng root, cornus fruit, burning bush twig, and astragalus root, so the TSF regulation of Smad7 is dependent on quercetin.…”

Section: Discussionmentioning

confidence: 99%

Tangshen Formula Improves Diabetes-Associated Myocardial Fibrosis by Inhibiting TGF-β/Smads and Wnt/β-Catenin Pathways

Wang

Wan

et al. 2021

Front. Med.

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Cardiovascular disease has become the main cause of death among complications of diabetes. Myocardial fibrosis is a crucial pathological change of cardiovascular disease. Tangshen Formula (TSF) shows a good clinical effect in the treatment of diabetic kidney disease (DKD). However, whether TSF alleviates diabetes-associated myocardial fibrosis is still unknown. In the present research, we studied the effect and mechanism of TSF in the treatment of myocardial fibrosis in vivo and in vitro. We found that TSF treatment significantly downregulates myocardial fibrosis-related markers, including collagens I and III, and α-SMA. TSF also protects primary mouse cardiac fibroblast (CF) from transforming growth factor-β1- (TGF-β1-) induced damage. Moreover, TSF decreased the expression levels of TGF-β/Smad-related genes (α-SMA, collagens I and III, TGF-β1, and pSmad2/3), and increased Smad7 gene expression. Finally, TSF decreased the expressions of wnt1, active-β-catenin, FN, and MMP7 to regulate the Wnt/β-catenin pathway. Taken together, TSF seems to attenuate myocardial fibrosis in KKAy mice by inhibiting TGF-β/Smad2/3 and Wnt/β-catenin signaling pathways.

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“…Quercetin has a significant therapeutic effect on ventricular remodeling model rats after AMI, which is mainly reflected by reducing myocardial injury and myocardial fibrosis, inhibiting the production of ROS, increasing the levels of SOD and GSH, and reducing NF‐κB. The mechanism is related to its scavenging ROS and inhibiting the NF‐κB signaling pathway (Albadrani et al, 2021). Pretreatment with quercetin could reduce the infarct size, improve the left ventricular (LV) functions, and reduce circulatory levels of lactate dehydrogenase (LDH) and creatinine‐kinase MB (CKMB) in AMI rats.…”

Section: Introductionmentioning

confidence: 99%

Flavonoids in Lu’an GuaPian tea as potential inhibitors of TMA‐lyase in acute myocardial infarction

Fang

Zhou

Bao

et al. 2022

Journal of Food Biochemistry

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Acute myocardial infarction (AMI) is caused by a sudden blockage of the coronary artery, resulting in ischemic necrosis of the local myocardium due to the interruption of blood supply to the associated arteries, which is currently one of the leading causes of death and disability worldwide and requires adequate attention (Shoaib et al., 2021). Pathological studies show that most AMI is caused by plaque rupture and subsequent thrombosis and is also caused by plaque erosion (Vandermolen et al., 2016;Zhang et al., 2021). Therefore, it is very important to distinguish whether patients are plaque rupture or plaque erosion for determining the individualized

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Quercetin prevents myocardial infarction adverse remodeling in rats by attenuating TGF-β1/Smad3 signaling: Different mechanisms of action

Cited by 26 publications

References 49 publications

Uncovering the Effect and Mechanism of Rhizoma Corydalis on Myocardial Infarction Through an Integrated Network Pharmacology Approach and Experimental Verification

Uncovering the Effect and Mechanism of Rhizoma Corydalis on Myocardial Infarction Through an Integrated Network Pharmacology Approach and Experimental Verification

Tangshen Formula Improves Diabetes-Associated Myocardial Fibrosis by Inhibiting TGF-β/Smads and Wnt/β-Catenin Pathways

Flavonoids in Lu’an GuaPian tea as potential inhibitors of TMA‐lyase in acute myocardial infarction

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