Evidence map›Paper›PMID 40383837›Full record

ArticlePflugers Archiv : European journal of physiology2025

Targeting NLRP3 inflammasome attenuates cardiac pyroptosis and fibrosis in estrogen-deficient diabetic rats.

Sukanya Phungphong, Phichaya Suthivanich, Worakan Boonhoh, Chuchard Punsawad, Zhaokang Cheng, Tepmanas Bupha-Intr

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Article in Pflugers Archiv : European journal of physiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

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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

4 citing papers in PubMed.

  1. Article
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4 · The record

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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

6 authors.

Sukanya PhungphongDepartment of Medical Science, School of Medicine, Walailak University, Nakhon Si Thammarat, 80160, Thailand. Sukanya.pu@wu.ac.th.
Phichaya SuthivanichDoctor of Philosophy Program in Physiology, Graduate School, Chulalongkorn University, Bangkok, 10330, Thailand.
Worakan BoonhohAkkhraratchakumari Veterinary College, Walailak University, Nakhon Si Thammarat, 80160, Thailand.
Chuchard PunsawadDepartment of Medical Science, School of Medicine, Walailak University, Nakhon Si Thammarat, 80160, Thailand.
Zhaokang ChengDepartment of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Washington State University, Spokane, WA, 99202-2131, USA.
Tepmanas Bupha-IntrDepartment of Physiology, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand.

Funding

National Research Council of Thailand N42A660830
6 · The paper itself

Abstract

Cardiac diastolic dysfunction is a hallmark of diabetic cardiomyopathy (DCM), particularly in postmenopausal women where estrogen deficiency exacerbates cardiac remodeling. This study investigated the roles of NLRP3 inflammasome activation and cardiac mast cell (CMC) behavior in diabetic ovariectomized (OVX) rat models. Female Wistar rats were divided into five groups: sham-operated, OVX, diabetic (Sham-DM), OVX-diabetic (OVX-DM), and OVX-DM treated with the NLRP3 inhibitor MCC950. Diabetes was induced using a high-calorie quick fat diet (13.8% crude fat, 24.35% crude protein, 25% sucrose; 406.80 kcal/100 g) followed by a single intraperitoneal injection of streptozotocin (30 mg/kg). MCC950 (10 mg/kg BW, intraperitoneally) was administered daily for 4 weeks. Echocardiography revealed significant diastolic dysfunction in OVX-DM rats, with increased left ventricular internal diameter (LVIDd) and reduced mitral valve E/A ratio, while MCC950 treatment partially restored diastolic function (p < 0.05). Masson's trichrome staining showed increased myocardial fibrosis in OVX-DM rats (2.59 ± 0.20%) compared to Sham-DM (1.94 ± 0.16%, p < 0.05), which was reduced with MCC950 treatment (0.88 ± 0.13%, p < 0.05). Western blot analysis demonstrated elevated expression of NLRP3, cleaved caspase-1, IL-1β, and GSDMD-N in OVX-DM hearts. MCC950 significantly reduced cleaved caspase-1, IL-1β, and GSDMD-N expression without altering NLRP3 protein levels. Additionally, mast cell degranulation was markedly increased in OVX-DM rats (62.14%) compared to controls (P < 0.05) and was attenuated by MCC950 (31.06%, P < 0.05). These findings suggest that NLRP3 inflammasome activation under conditions of estrogen deficiency and diabetes contributes to myocardial pyroptosis and mast cell degranulation, driving cardiac remodeling in postmenopausal DCM. Targeting NLRP3 pathways may provide an effective therapeutic strategy to mitigate diastolic dysfunction, fibrosis, and inflammation in diabetic hearts.

Indexed as

Diabetes Mellitus, ExperimentalDiabetic CardiomyopathiesEstrogensInflammasomesMyocardiumNLR Family, Pyrin Domain-Containing 3 ProteinPyroptosisAnimalsFemaleFibrosisFuransIndenesMast CellsRatsRats, WistarSulfonamidesEstrogensFuransIndenesInflammasomesN-(1,2,3,5,6,7-hexahydro-S-indacen-4-ylcarbamoyl)-4-(2-hydroxy-2-propanyl)-2-furansulfonamideNLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, ratSulfonamidesSulfonesCardiac inflammationCardiac mast cellDiabetic heart diseaseNLRP3 inflammasomePostmenopausal

Identifiers

PMID40383837

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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.