Resveratrol Targets AKT1 to Inhibit Inflammasome Activation in Cardiomyocytes Under Acute Sympathetic Stress

Wang, Rui; Wang, Yanming; Wu, Jimin; Guo, Yanli; Xiao, Han; Zhang, Youyi; Ma, Ketao

doi:10.3389/fphar.2022.818127

Cited by 11 publications

(9 citation statements)

References 34 publications

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“…Resveratrol formed four hydrogen bonds with Asn54 and Thr82 in the PH domain and Gln203 and Ser205 in the kinase domain. Likewise, a previous study reported that resveratrol could bind to Akt-1 with an allosteric site [ 18 ]. RD2 formed four hydrogen bonds with Asn54, Gln79 (2 bonds) in the PH domain, and Ser205 in the kinase domain.…”

Section: Resultsmentioning

confidence: 99%

Akt/mTOR Targeting Activity of Resveratrol Derivatives in Non-Small Lung Cancer

et al. 2022

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The Akt-mTOR signal is important for the survival and proliferation of cancer cells and has become an interesting drug target. In this study, five resveratrol derivatives were evaluated for anticancer activity and Akt/mTOR targeting activity in non-small lung cancer cell lines. The effects of resveratrol derivatives on cell proliferation were assessed by 2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, nucleus staining, and colony formation assay. Furthermore, the effect of resveratrol derivatives on proliferation-related protein expression was analyzed by immunofluorescence and Western blotting. For the structure–activity relationship (SAR), results reveal that two derivatives of resveratrol which are 4,4′-(ethane-1,2-diyl) bis(2-methoxyphenol) (RD2) and the 4-(3-hydroxy-4-methoxyphenethyl)-2-methoxyphenol (RD3) had very similar structures but exerted different cytotoxicity. The IC50 of RD2 and RD3 were 108.6 ± 10.82 and more than 200 µM in the A549 cell line and 103.5 ± 6.08 and more than 200 µM in H23 cells, respectively. RD2 inhibited cell proliferation and induced apoptosis when compared with the control, while RD3 caused minimal effects. Cells treated with RD2 exhibited apoptotic nuclei in a concomitant with the reduction of cellular p-Akt and p-mTOR. RD3 had minimal effects on such proteins. According to these results, molecular docking analysis revealed a high-affinity interaction between RD2 and an Akt molecule at the ATP-binding and the allosteric sites, indicating this RD2 as a potential Akt inhibitor. This study provides useful information of resveratrol derivatives RD2 for treating lung cancer via Akt/mTOR inhibition.

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Section: Resultsmentioning

confidence: 99%

Akt/mTOR Targeting Activity of Resveratrol Derivatives in Non-Small Lung Cancer

et al. 2022

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“…AKT1 may inhibit activation of NLRP3 inflammatory corpuscles in myocardial cells and is an important target for intervention in inflammation activation and initiation. [46] TP53 may inhibit the transcription of vascular endothelial growth factor, and therefore, prevent AS. [47] Several studies show that heat shock protein 90 (HSP90) was the target of anti-AS and could resist inflammation, [48][49][50][51] oxidative stress, and smooth muscle proliferation, and regulate the endothelial function by inhibiting the expression of HSP90.…”

Section: Discussionmentioning

confidence: 99%

Mechanism of Yiqi Huoxue Huatan recipe in the treatment of coronary atherosclerotic disease through network pharmacology and experiments

Huang

Xu³

et al. 2023

Medicine

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In recent years, with population aging and economic development, morbidity and mortality of atherosclerotic cardiovascular disease associated with atherosclerosis (AS) have gradually increased. In this study, a combination of network pharmacology and experimental verification was used to systematically explore the action mechanism of Yiqi Huoxue Huatan Recipe (YHHR) in the treatment of coronary atherosclerotic heart disease (CAD). We searched and screened the active ingredients of Coptis chinensis, Astragalus membranaceus, Salvia miltiorrhiza, and Hirudo. We also searched multiple databases for related target genes corresponding to the compounds and CAD. STRING was used to construct the protein-protein interaction (PPI) network of genes. Metascape was used to perform gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis for common targets to analyze the main pathways, and finally, the molecular docking and main possible pathways were verified by experimental studies. Firstly, a total of 1480 predicted target points were obtained through the Swiss Target Prediction database. After screening, merging, and deleting duplicate values, a total of 768 targets were obtained. Secondly, “Coronary atherosclerotic heart disease” was searched in databases such as the OMIM, GeneCards, and TTD. 1844 disease-related targets were obtained. Among PPI network diagram of YHHR-CAD, SRC had the highest degree value, followed by AKT1, TP53, hsp90aa1 and mapk3. The KEGG pathway bubble diagram was drawn using Chiplot, the Signal pathways such as NF kappa B signaling pathway, Lipid and AS, and Apelin signaling pathway are closely related to the occurrence of CAD. The PCR and Western blot methods were used to detect the expression of NF-κB p65. When compared with that in the model group, the expression of NF-κB p65mRNA decreased in the low-concentration YHHR group, with P < .05, while the expression of NF-κB p65mRNA decreased significantly in the high-concentration YHHR group, with P < .01. On the other hand, when compared with that in the model group, the expression of NF-κB p65 decreased in the low-concentration YHHR group, but was not statistically significant, while the expression of NF-κB p65 was significant in the high-concentration YHHR group, and has statistical significance with P < .05. YHHR has been shown to resist inflammation and AS through the SRC/NF-κB signaling pathway.

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“…A study showed that resveratrol targeting AKT1 inhibited inflammatory vesicle activation in cardiomyocytes under sympathetic stress, inhibited β-adrenergic receptor-mediated NLRP3 inflammatory vesicle activation in cardiomyocytes and mouse hearts, and the resulting cardiac inflammation. [ 41 ] IL-6 and VEGFA are closely related to the progression of cardiac hypertrophy and coronary artery disease, while VEGFA is widely distributed in the brain, VEGFA is widely distributed in the brain, heart, and other tissue cells, and has an important regulatory role in angiogenesis and atherosclerosis. [ 42 ] Studies have shown that MSCs can reduce inflammation in the heart and lungs through TNF signaling.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Mechanism of Datura metel on sinus bradycardia based on network pharmacology and molecular docking

et al. 2022

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Objective: To investigate the mechanism of action of Datura metel in the treatment of sinus bradycardia based on network pharmacology and molecular docking. Methods: The active ingredients and targets of Datura metel were collected by TCMSP database, and the Cytoscape software was used to map to show the interrelationship. Use 5 databases: GeneCards, PharmGKB, OMIM, DisGeNET, and Drugbank to obtain targets related to sinus bradycardia; establish a protein-to-protein interaction network with the help of the STRING platform; GO and Kyoto Encyclopedia of Genes and Genomes analysis of the selected core targets using the Metascape platform; Finally, the AutoDock platform was used for molecular docking and the results were displayed through Pymol. Results: 27 kinds of active ingredients of the drug were screened, including 10 kinds of main ingredients; 198 drug targets and 1059 disease targets. There are 54 targets of action in the treatment of sinus bradycardia, of which 19 targets such as AKT1, IL6, TNF, and VEGFA are the core targets of Datura metel in the treatment of sinus bradycardia. Kyoto Encyclopedia of Genes and Genomes obtained 18 results suggesting that AGE-RAGE, hepatitis C, relaxin, and JAK-STAT may be key signaling pathways. Molecular docking shows that most components of the drug have good docking ability with the core target, indicating that the prediction results have certain reliability. Conclusion: This study preliminarily explores the potential active ingredients and possible mechanisms of action of Datura metel in the treatment of sinus bradycardia and provides a basis for in-depth investigation of its medicinal material basis and mechanism of action.

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Resveratrol Targets AKT1 to Inhibit Inflammasome Activation in Cardiomyocytes Under Acute Sympathetic Stress

Cited by 11 publications

References 34 publications

Akt/mTOR Targeting Activity of Resveratrol Derivatives in Non-Small Lung Cancer

Akt/mTOR Targeting Activity of Resveratrol Derivatives in Non-Small Lung Cancer

Mechanism of Yiqi Huoxue Huatan recipe in the treatment of coronary atherosclerotic disease through network pharmacology and experiments

Mechanism of Datura metel on sinus bradycardia based on network pharmacology and molecular docking

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