Evidence map›Paper›PMID 40828375›Full record

ArticleJournal of molecular medicine (Berlin, Germany)2025

4-Hydroxychalcone alleviated Angiotensin II-induced atrial fibrillation via immunoproteasome-IKK-NF-κB signaling pathway modulation.

Yun-Long Zhang, Ze-Yan Xu, Yan Sun, Qian-Qiu Zhu, Sheng-Xing Tang, Qing-Hua Zhong, Xiao Han

Abstract read
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In one paragraph

Article in Journal of molecular medicine (Berlin, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Yun-Long Zhang *Department of Cardiology, Yijishan Hospital of Wannan Medical College, No. 2, Zheshan West Road, Wuhu, 241000, China.
Ze-Yan Xu *Department of Cardiology, Nanyang Central Hospital, No.312, Gongnong Road, Nanyang, 473000, China.
Yan SunDepartment of Cardiology, Longgang Central Hospital of Shenzhen, No.6802, Longgang Road, Longgang District, Shenzhen, 518000, China.
Qian-Qiu ZhuDepartment of Cardiology, Yijishan Hospital of Wannan Medical College, No. 2, Zheshan West Road, Wuhu, 241000, China.
Sheng-Xing TangDepartment of Cardiology, Yijishan Hospital of Wannan Medical College, No. 2, Zheshan West Road, Wuhu, 241000, China. Tsx1964@vip.163.com.
Qing-Hua ZhongDepartment of Cardiology, Longgang Central Hospital of Shenzhen, No.6802, Longgang Road, Longgang District, Shenzhen, 518000, China. zqh9701417@163.com.
Xiao HanInstitute of Cardio-Cerebrovascular Medicine, Central Hospital of Dalian University of Technology, No.826, South West Road, Shahekou District, Dalian, 116089, China. hx9935@126.com.

Funding

Anhui Provincial Department of Education 2023AH030103Anhui Provincial Department of Education 2023AH040258National Natural Science Foundation of China 82000398Natural Science Foundation of Anhui Province 2408085Y046Natural Science Foundation of Liaoning Province 2024-BS-333
6 · The paper itself

Abstract

Atrial Fibrillation (AF) is the most common type of cardiac arrhythmia and a significant contributor to stroke occurrence. Although 4-Hydroxychalcone (4HCH) has notable anti-inflammatory and antioxidant properties, playing critical therapeutic roles in hypertensive nephropathy and cardiac remodeling, its effects on AF are somewhat unclear, thus forming the basis of this study. Herein, AF was induced in mice via continuous infusion of Angiotensin II (Ang II) at a dose of 2000 ng/kg/min for three weeks. The atrial diameter was assessed through echocardiography, while pathological staining was employed to evaluate atrial inflammation, Oxidative Stress (OS), and fibrosis. Compared to vehicle-treated controls, treatment with 4HCH significantly lowered both the incidence and duration of Ang II-induced AF, while also mitigating atrial dilation, inflammation, OS, and fibrosis. Mechanistically, 4HCH suppressed Ang II-induced immunoproteasome activity, including that of its catalytic subunits (β1i, β2i, and β5i), thus blocking the inflammatory IKKα/β-NF-κB signaling pathway. This inhibition downregulated the TGF-β1/Smad2/3 pathway and the potassium ion channel protein Kir 2.1, while upregulating connexin 40 (Cx40) and Cx43, thus mitigating atrial fibrosis and fibrillation. Conversely, the proteasome activator MK-886 increased both immunoproteasome expression and activity, triggering the IKKα/β-NF-κB pathway and leading to atrial inflammation, thus negating 4HCH's protective effects against Ang II-induced atrial remodeling and fibrillation. Overall, 4HCH may confer protective effects against AF, highlighting its potential as a therapeutic candidate for preventing the condition. KEY MESSAGES: 4-Hydroxychalcone (4HCH) confers protection against atrial fibrillation (AF) induced by angiotensin II. 4HCH attenuates the expression and activity of immunosubunits, resulting in the inhibition of IKK-NF-κB signaling and its downstream pathways. Increased activity of the immunoproteasome diminishes the beneficial effects of 4HCH on atrial remodeling and the prevention of AF.

Indexed as

Angiotensin IIAtrial FibrillationChalconesI-kappa B KinaseNF-kappa BProteasome Endopeptidase ComplexSignal TransductionAnimalsAtrial RemodelingDisease Models, AnimalHeart AtriaMaleMiceMice, Inbred C57BLOxidative StressAngiotensin IIChalconesI-kappa B KinaseNF-kappa BProteasome Endopeptidase Complex4-HydroxychalconeAngiotensin IIAtrial FibrillationFibrosisInflammationOxidative Stress

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.