Arctigenin alleviates myocardial infarction injury through inhibition of the NFAT5-related inflammatory phenotype of cardiac macrophages/monocytes in mice

Ni, Shi-Hao; Sun, Shuning; Zhou, Zheng; Li, Yue; Huang, Yu‐Sheng; Li, Huan; Wang, Jiajia; Xiao, Wei; Xian, Shaoxiang; Yang, Zhong-Qi; Wang, Lingjun; Lu, Lu

doi:10.1038/s41374-019-0340-8

Cited by 12 publications

(9 citation statements)

References 46 publications

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“…Arctigenin is a lignan derived from A. lappa , shown to have anti-inflammatory and cardioprotective effects ( 28 , 98 ). Yang et al ( 28 ) have evaluated the antiarrhythmic and antioxidant effects of ATG in a rat model of I/R injury.…”

Section: Resultsmentioning

confidence: 99%

Mechanism-based targeting of cardiac arrhythmias by phytochemicals and medicinal herbs: A comprehensive review of preclinical and clinical evidence

Soltani

Azizi²,

Rahimi³

et al. 2022

Front. Cardiovasc. Med.

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Cardiac arrhythmias, characterized by an irregular heartbeat, are associated with high mortality and morbidity. Because of the narrow therapeutic window of antiarrhythmic drugs (AADs), the management of arrhythmia is still challenging. Therefore, searching for new safe, and effective therapeutic options is unavoidable. In this study, the antiarrhythmic effects of medicinal plants and their active constituents were systematically reviewed to introduce some possible candidates for mechanism-based targeting of cardiac arrhythmias. PubMed, Embase, and Cochrane library were searched from inception to June 2021 to find the plant extracts, phytochemicals, and multi-component herbal preparations with antiarrhythmic activities. From 7337 identified results, 57 original studies consisting of 49 preclinical and eight clinical studies were finally included. Three plant extracts, eight multi-component herbal preparations, and 26 phytochemicals were found to have antiarrhythmic effects mostly mediated by affecting K+ channels, followed by modulating Ca2+ channels, upstream target pathways, Nav channels, gap junction channels, and autonomic receptors. The most investigated medicinal plants were Rhodiola crenulata and Vitis vinifera. Resveratrol, Oxymatrine, and Curcumin were the most studied phytochemicals found to have multiple mechanisms of antiarrhythmic action. This review emphasized the importance of research on the cardioprotective effect of medicinal plants and their bioactive compounds to guide the future development of new AADs. The most prevalent limitation of the studies was their unqualified methodology. Thus, future well-designed experimental and clinical studies are necessary to provide more reliable evidence.

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Section: Resultsmentioning

confidence: 99%

Mechanism-based targeting of cardiac arrhythmias by phytochemicals and medicinal herbs: A comprehensive review of preclinical and clinical evidence

Soltani

Azizi²,

Rahimi³

et al. 2022

Front. Cardiovasc. Med.

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“…Mouse fibroblasts were isolated from 5-week-old C57BL/6 mice using enzymatic digestion according to our previous protocol 49 . Mouse heart pieces were enzymatically digested with stirring for 10 min, and the supernatant was collected.…”

Section: Cell Isolation and Culturementioning

confidence: 99%

“…For the beta-galactosidase activity of cardiac fibroblasts in vivo, 5-dodecanoylaminofluorescein di-β-D-galactopyranoside (C 12 FDG) was used according to a previous protocol 49 . Briefly, cardiac fibroblasts were isolated using enzymatic digestion and Percoll gradient separation.…”

Section: Beta-galactosidase Activity Assaymentioning

confidence: 99%

G-MDSCs promote aging-related cardiac fibrosis by activating myofibroblasts and preventing senescence

Sun

et al. 2021

Cell Death Dis

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Aging is one of the most prominent risk factors for heart failure. Myeloid-derived suppressor cells (MDSCs) accumulate in aged tissue and have been confirmed to be associated with various aging-related diseases. However, the role of MDSCs in the aging heart remains unknown. Through RNA-seq and biochemical approaches, we found that granulocytic MDSCs (G-MDSCs) accumulated significantly in the aging heart compared with monocytic MDSCs (M-MDSCs). Therefore, we explored the effects of G-MDSCs on the aging heart. We found that the adoptive transfer of G-MDSCs of aging mice to young hearts resulted in cardiac diastolic dysfunction by inducing cardiac fibrosis, similar to that in aging hearts. S100A8/A9 derived from G-MDSCs induced inflammatory phenotypes and increased the osteopontin (OPN) level in fibroblasts. The upregulation of fibroblast growth factor 2 (FGF2) expression in fibroblasts mediated by G-MDSCs promoted antisenescence and antiapoptotic phenotypes of fibroblasts. SOX9 is the downstream gene of FGF2 and is required for FGF2-mediated and G-MDSC-mediated profibrotic effects. Interestingly, both FGF2 levels and SOX9 levels were upregulated in fibroblasts but not in G-MDSCs and were independent of S100A8/9. Therefore, a novel FGF2-SOX9 signaling axis that regulates fibroblast self-renewal and antiapoptotic phenotypes was identified. Our study revealed the mechanism by which G-MDSCs promote cardiac fibrosis via the secretion of S100A8/A9 and the regulation of FGF2-SOX9 signaling in fibroblasts during aging.

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“…On the contrary, NFAT5 can also be detrimental following myocardial infarction. Arctigenin, a cardioprotective compound, was found to inhibit NFAT5 in cardiac macrophages [ 92 ]. More specifically, arctigenin binds the DNA-binding domain of NFAT5, thus inhibiting its ability to facilitate the NFκB signalling pathway and suppressing the conversion of macrophages to an inflammatory phenotype.…”

Section: Nfat5 Signalling In Cardiovascular Dysfunctionmentioning

confidence: 99%

NFAT5-Mediated Signalling Pathways in Viral Infection and Cardiovascular Dysfunction

Zhao

Aghakeshmiri

Chen

et al. 2021

IJMS

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The nuclear factor of activated T cells 5 (NFAT5) is well known for its sensitivity to cellular osmolarity changes, such as in the kidney medulla. Accumulated evidence indicates that NFAT5 is also a sensitive factor to stress signals caused by non-hypertonic stimuli such as heat shock, biomechanical stretch stress, ischaemia, infection, etc. These osmolality-related and -unrelated stimuli can induce NFAT5 upregulation, activation and nuclear accumulation, leading to its protective role against various detrimental effects. However, dysregulation of NFAT5 expression may cause pathological conditions in different tissues, leading to a variety of diseases. These protective or pathogenic effects of NFAT5 are dictated by the regulation of its target gene expression and activation of its signalling pathways. Recent studies have found a number of kinases that participate in the phosphorylation/activation of NFAT5 and related signal proteins. Thus, this review will focus on the NFAT5-mediated signal transduction pathways. As for the stimuli that upregulate NFAT5, in addition to the stresses caused by hyperosmotic and non-hyperosmotic environments, other factors such as miRNA, long non-coding RNA, epigenetic modification and viral infection also play an important role in regulating NFAT5 expression; thus, the discussion in this regard is another focus of this review. As the heart, unlike the kidneys, is not normally exposed to hypertonic environments, studies on NFAT5-mediated cardiovascular diseases are just emerging and rapidly progressing. Therefore, we have also added a review on the progress made in this field of research.

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Arctigenin alleviates myocardial infarction injury through inhibition of the NFAT5-related inflammatory phenotype of cardiac macrophages/monocytes in mice

Cited by 12 publications

References 46 publications

Mechanism-based targeting of cardiac arrhythmias by phytochemicals and medicinal herbs: A comprehensive review of preclinical and clinical evidence

Mechanism-based targeting of cardiac arrhythmias by phytochemicals and medicinal herbs: A comprehensive review of preclinical and clinical evidence

G-MDSCs promote aging-related cardiac fibrosis by activating myofibroblasts and preventing senescence

NFAT5-Mediated Signalling Pathways in Viral Infection and Cardiovascular Dysfunction

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