Eplerenone

Papapostolou S, et al. JACC: Heart Failure, 2025, 13(7), 102415.

In a double-blind, placebo-controlled clinical study, the antifibrotic efficacy of eplerenone (50 mg daily) was evaluated in 61 patients with nonobstructive hypertrophic cardiomyopathy (HCM) over 12 months. Native T1 mapping on cardiac magnetic resonance imaging (CMR) served as the primary surrogate marker for myocardial fibrosis. Eplerenone treatment significantly reduced native T1 time (1,315 ± 134 ms to 1,259 ± 92 ms; P = 0.041), indicating decreased diffuse fibrosis, while no significant change was observed in the placebo group. Secondary endpoints assessing diastolic function (E/e', mitral E/A) showed no significant improvement. This trial highlights the potential of eplerenone as an antifibrotic agent in early-stage HCM, demonstrating a quantifiable effect on myocardial remodeling using noninvasive CMR techniques.

Refaie MMM, et al. International Immunopharmacology, 2025, 162, 115113.

In a preclinical model of ovarian ischemia/reperfusion (OIR) injury, the pharmacological potential of eplerenone (EPL) was evaluated for its immunomodulatory and cardioprotective effects. Female Wistar albino rats (n = 50) were randomly divided into five experimental groups: control, OIR, OIR + EPL (100 mg/kg), OIR + fenofibrate (300 mg/kg), and OIR + EPL + fenofibrate. OIR was induced via temporary occlusion of ovarian blood flow, followed by reperfusion, simulating a clinical scenario of ovarian torsion.
Administration of eplerenone (100 mg/kg) post-OIR significantly attenuated oxidative stress, as evidenced by reduced malondialdehyde (MDA) and restored antioxidant markers such as total antioxidant capacity (TAC) and reduced glutathione (GSH). Histopathological examination confirmed alleviation of both ovarian and remote cardiac tissue damage. On a molecular level, EPL suppressed upregulation of the TLR4/MYD88/NF-κB/AP1/IL-6 inflammatory axis and cleaved caspase-3, indicating strong anti-inflammatory and anti-apoptotic properties. These effects are attributed to EPL's antagonism of aldosterone receptors, contributing to systemic immune regulation.
Co-treatment with fenofibrate, a PPARα agonist, showed synergistic benefits; however, eplerenone alone demonstrated substantial efficacy in mitigating OIR-induced multi-organ injury. This study highlights eplerenone's experimental application as a therapeutic agent targeting both ovarian and remote cardiac tissue protection through immunological and oxidative stress pathway modulation.

Zhou W, et al. Cellular Signalling, 2024, 122, 111346.

In this study, eplerenone was evaluated in a pregnant rat model of unilateral ureteral obstruction (UUO) to investigate its renoprotective mechanisms. Pregnant Wistar rats were divided into four groups, with or without eplerenone administration. On gestation day 18, urine was collected in metabolic cages, and kidneys were harvested on day 19 for histological, immunohistochemical, and molecular analyses. In vitro, HUVECs were treated with aldosterone, progesterone, estradiol, VEGFA, or bevacizumab to assess proliferation, migration, and tube formation. Eplerenone significantly suppressed UUO-induced upregulation of SGK-1, TGFβ-1/Smad signaling, VEGF-A/VEGFR2, CD34, α-SMA, and collagen I in renal tissue. It also reversed aldosterone-induced endothelial-to-mesenchymal transition in HUVECs. These findings highlight eplerenone's potential in modulating fibrosis and endothelial function in CKD during pregnancy.

Mostafa RE, et al. Life Sciences, 2023, 316, 121405.

In a rat model of knee osteoarthritis induced by intra-articular monosodium iodoacetate (MIA, 3 mg/50 μL), the therapeutic potential of eplerenone was evaluated through its anti-inflammatory activity and modulation of the RANKL/OPG axis. Rats were divided into four groups (n=8), with groups 3 and 4 receiving eplerenone orally (50 or 100 mg/kg/day) for 14 days post-MIA induction. Eplerenone significantly reduced TNF-α, IL-6, and NF-κB levels, and suppressed Akt and ERK gene expression in joint tissues as assessed by qRT-PCR. Histological examination revealed reduced cartilage degradation and improved OARSI scores. Notably, eplerenone decreased RANKL and elevated OPG concentrations, indicating restoration of bone remodeling balance. The study highlights eplerenone's efficacy in modulating key inflammatory and osteolytic pathways, supporting its potential use in osteoarthritis therapy.