Curcumin, novel application in reversing myocardial fibrosis in the treatment for atrial fibrillation from the perspective of transcriptomics in rat model

Yue, Honghua; Zhao, Xueshan; Liang, Weitao; Qin, Xiaoli; Bian, Longrong; He, Kang; Wu, Zhong

doi:10.1016/j.biopha.2021.112522

Cited by 17 publications

(11 citation statements)

References 44 publications

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“…These agents can modulate a myriad of molecular mechanisms relevant to AF, including intracellular calcium kinetics, pro-inflammatory cytokine profiles, and the PI3K/Akt/eNOS signaling cascade, as well as modify the expression of certain microRNA levels, resulting in reduced incidence and severity of AF in both preclinical and clinical studies [85][86][87][88][89][90][91]. On the other hand, retinoids, such as fenretinide and tretinoin, have less evidence in the context of AF.…”

Section: Discussionmentioning

confidence: 99%

The Transcriptional Landscape of Atrial Fibrillation: A Systematic Review and Meta-analysis

Gómez-Ochoa,

Möhn,

Malz

et al. 2023

Preprint

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Background and AimsDespite advances in understanding atrial fibrillation (AF) pathophysiology through the lens of transcriptomics, marked differences in the key AF genes between studies remain, while drugs targeting preserved dysregulated pathways are limited. This systematic review and meta-analysis aimed to provide a consensus transcriptional signature of AF and use it to identify potentially repurposable drugs.MethodsBibliographic databases and data repositories were systematically searched for studies reporting gene expression patterns in atrial heart auricle tissue from patients with AF and controls in sinus rhythm. A qualitative synthesis and a transcriptomics meta-analysis were performed. We calculated the pooled differences in individual gene expression to create a consensus signature (CS), from which we identified differentially regulated pathways and estimated transcription factors activity. We also created a protein-protein interaction network to identify drug interactions with highly interconnected genes (hub genes) from the AF-CS.ResultsThirty-four observational studies were assessed in the qualitative synthesis, while fourteen, comprising 511 samples (338 AF and 173 SR), were included in the meta-analysis. Despite the heterogeneity observed across individual studies, the AF-CS in both chambers were consistent and robust, showing a better performance in classifying AF status than individual studies. The functional analysis revealed commonality in the dysregulated cellular processes across the atria, including extracellular matrix remodeling, downregulation of cardiac conduction pathways, metabolic derangements, and innate immune system activity processes. Finally, drug-gene analyses highlighted several compounds as repurposing drug candidates for AF, highlighting lipid-lowering agents, antioxidants, and retinoids, among others.ConclusionsDespite variability in individual studies, this meta-analysis elucidated conserved molecular pathways involved in AF pathophysiology across its phenotypes, offering robust and potentially generalizable diagnostic biomarkers. From this AF-CS, we identified potential compounds targeting these dysregulated pathways, thereby addressing an extant gap in AF-specific pharmacotherapy.Key QuestionCan a meta-analytically derived consensus transcriptional signature effectively capture the core molecular mechanisms underlying AF and serve as a basis for identifying novel drug candidates targeting these conserved pathways?Key FindingsExtracellular matrix remodeling, downregulation of cardiac conduction pathways, and modulation of innate immune system activity emerged as conserved molecular hallmarks across the AF spectrum. Drug-gene interaction analyses highlighted the repurposing potential of lipid-lowering agents, antioxidants, and retinoids, among other compounds, for targeted intervention in these dysregulated pathways.Take Home MessageDespite AF’s complexity, a transcriptional signature derived through a meta-analysis can pinpoint conserved molecular pathways across AF phenotypes. These insights provide a foundation for identifying and repurposing drugs targeting the core dysregulated processes in the disease, offering new avenues for targeted, mechanism-based treatment of AF.GRAPHICAL ABSTRACT

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Section: Discussionmentioning

confidence: 99%

The Transcriptional Landscape of Atrial Fibrillation: A Systematic Review and Meta-analysis

Gómez-Ochoa,

Möhn,

Malz

et al. 2023

Preprint

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“…Some of the herbal ingredients identified herein reportedly alleviate tissue fibrosis by modulating the TGF-β/Smad signaling pathway; for example, curcumin has been reported to attenuate pulmonary, hepatic, and renal interstitial fibrosis ( Saidi et al, 2019 ; Wang Z. et al, 2020 ; Kong et al, 2020 ). Moreover, curcumin has been found to be effective for treating cardiovascular diseases, such as heart failure, myocardial infarction, atherosclerosis ( Li H. et al, 2020 ), and and it can significantly inhibit the duration of atrial fibrillation episodes, attenuate cardiac fibrosis ( Yue et al, 2021 ). However, there are fewer studies on curcumin’s anti-fibrotic effects through its action on TGFBR1.…”

Section: Discussionmentioning

confidence: 99%

Prediction of herbal medicines based on immune cell infiltration and immune- and ferroptosis-related gene expression levels to treat valvular atrial fibrillation

Jiang

Zhang

et al. 2022

Front. Genet.

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Inflammatory immune response is apparently one of the determinants of progressive exacerbation of valvular atrial fibrillation(VAF). Ferroptosis, an iron-dependent modality of regulated cell death, is involved in the immune regulation of cardiovascular disease. However, the relevant regulatory mechanisms of immune infiltration and ferroptosis in VAF have been less studied. In the current study, a highly efficient system for screening immunity- and ferroptosis-related biomarkers and immunomodulatory ability of herbal ingredients has been developed with the integration of intelligent data acquisition, data mining, network pharmacology, and computer-assisted target fishing. VAF patients showed higher infiltration of neutrophils and resting stage dendritic cells, while VSR patients showed higher infiltration of follicular helper T cells. In addition, six (e.g., PCSK2) and 47 (e.g., TGFBR1) ImmDEGs and one (SLC38A1) and four (TGFBR1, HMGB1, CAV1, and CD44) FerDEGs were highly expressed in patients with valvular sinus rhythm (VSR) and VAF, respectively. We further identified a core subnetwork containing 34 hub genes, which were intersected with ImmDEGs and FerDEGs to obtain the key gene TGFBR1. Based on TGFBR1, 14 herbs (e.g., Fructus zizyphi jujubae, Semen Juglandis, and Polygonum cuspidatum) and six herbal ingredients (curcumin, curcumine, D-glucose, hexose, oleovitamin A, and resveratrol) were predicted. Finally, TGFBR1 was found to dock well with curcumin and resveratrol, and it was further verified that curcumin and resveratrol could significantly reduce myocardial fibrosis. We believe that herbs rich in curcumin and resveratrol such as Rhizoma curcumae longae and Curcuma kwangsiensis, mitigate myocardial fibrosis to improve VAF by modulating the TGFβ/Smad signaling pathway. This strategy provides a prospective approach systemically characterizing phenotype-target-herbs relationships based on the tissue-specific biological functions in VAF and brings us new insights into the searching lead compounds from Chinese herbs.

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“…It also acts as a substrate of lipoxygenase and as an inhibitor of cyclo-oxygenase (COX)-1 and COX-2 enzymes, and is also an inducer of hemoxigenase 23 in vascular endothelial cells, 24,25 rheumatoid arthritis, 26 and works against cardiovascular problems. 27,28 Mainly it has been shown to have anticancer efficacy. 29 Curcumin is an immunogenic inducer of cell death and can potentially be used to induce anti-tumour immune responses; 30 through in vivo experiments, it was found that low doses of a curcumin derivative (ST03) are effective against tumour growth with no apparent systemic toxicity.…”

Section: Therapeutic Properties and Bioavailability Of Curcuminmentioning

confidence: 99%

“…Even at high concentrations of superoxides, curcumin can inhibit the activity of these compounds. It also acts as a substrate of lipoxygenase and as an inhibitor of cyclo‐oxygenase (COX)‐1 and COX‐2 enzymes, and is also an inducer of hemoxigenase 23 in vascular endothelial cells, 24,25 rheumatoid arthritis, 26 and works against cardiovascular problems 27,28 . Mainly it has been shown to have anticancer efficacy 29 .…”

Section: Bioactive Compounds With Potential Biological Activity In Admentioning

confidence: 99%

Curcumin and omega‐3 polyunsaturated fatty acids as bioactive food components with synergistic effects on Alzheimer's disease

Velasco‐Rodríguez,

García,

Rascón‐Díaz

2024

Psychogeriatrics

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Curcumin and omega‐3 polyunsaturated fatty acids (ω‐3 PUFA) are multifunctional compounds which play an important role in Alzheimer's disease (AD) and little has been addressed about the role of these two compounds together in the progression of the disease. There is evidence of the beneficial effect of combined administration of ω‐3 PUFA and other dietary supplements such as vitamins and polyphenols in the prevention of AD, although much remains to be understood about their possible complementary or synergistic activity. Therefore, the objective of this work is to review the research focused on studying the effect and mechanisms of action of curcumin, ω‐3 PUFA, and the combination of these nutraceutical compounds, particularly on AD, and to integrate the possible ways in which these compounds can potentiate their effect. The most important pathophysiologies that manifest in AD will be addressed, in order to have a better understanding of the mechanisms of action through which these bioactive compounds exert a neuroprotective effect.

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Curcumin, novel application in reversing myocardial fibrosis in the treatment for atrial fibrillation from the perspective of transcriptomics in rat model

Cited by 17 publications

References 44 publications

The Transcriptional Landscape of Atrial Fibrillation: A Systematic Review and Meta-analysis

The Transcriptional Landscape of Atrial Fibrillation: A Systematic Review and Meta-analysis

Prediction of herbal medicines based on immune cell infiltration and immune- and ferroptosis-related gene expression levels to treat valvular atrial fibrillation

Curcumin and omega‐3 polyunsaturated fatty acids as bioactive food components with synergistic effects on Alzheimer's disease

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