Oleuropein significantly reduced myocardial collagen accumulation by a mean difference of 50.05% compared to untreated diabetic rats, attenuating cardiac fibrosis.
Does Oleuropein attenuate cardiac fibrosis and improve cardiac function in a rat model of diabetic cardiomyopathy?
Oleuropein demonstrates anti-fibrotic and cardioprotective effects in a rat model of diabetic cardiomyopathy, likely via modulation of the TGF-β1/Smad signaling pathway.
Effect estimate: MD -50.05% (95% CI -63.07 to -37.03)
p-value: p=<0.001
Abstract Cardiac fibrosis is a key pathological feature of diabetic cardiomyopathy (DCM), contributing to progressive cardiac dysfunction. Transforming growth factor beta-1 (TGF-β1), via Smad2/3 signaling pathway, promotes fibrotic gene expression. Oleuropein (OL), a major phenolic constituent of olive products, exhibits significant antioxidant properties and contributes to cardiovascular protection. This study aimed to investigate the anti-fibrotic effects of OL in a rat model of DCM and its modulation of the TGF-β1/Smad signaling pathway, using Losartan as a positive control. Thirty-two male Wistar rats were randomly assigned to four groups: control, DCM, DCM + OL (40 mg/kg), and DCM + Losartan (10 mg/kg). DCM was induced via high-fat diet (HFD) and a single low-dose streptozotocin (STZ) injection (40 mg/kg). Cardiac function was assessed by echocardiography. Histological evaluation included hematoxylin–eosin (H&E) and Masson trichrome staining. Cardiac biomarkers, oxidative stress markers, and fibrosis-related markers were analyzed using RT-qPCR, immunohistochemistry, and western blotting. DCM rats exhibited cardiac dysfunction and fibrosis. OL treatment significantly improved cardiac function, reduced collagen and fibronectin (FN) deposition, and downregulated TGF-β1, Smad2/3, α-smooth muscle actin (α-SMA), collagen types I/III, matrix metalloproteinases-2/9 (MMPs), and tissue inhibitor of metalloproteinases-1 (TIMP-1), while enhancing Smad7 expression. Besides, OL demonstrated notable antioxidant and antidiabetic effects. In conclusion, OL alleviates cardiac fibrosis and dysfunction in DCM, potentially through modulation of the TGF-β1/Smad signaling, highlighting its therapeutic promise in diabetic cardiac complications.
Abdelrauf et al. (2026) studied Diabetic cardiomyopathy (n=32). Oleuropein vs. Untreated diabetic cardiomyopathy (DCM) was evaluated on Collagen accumulation (percentage of fibrotic area) (MD -50.05%, 95% CI -63.07 to -37.03, p=<0.001). Oleuropein significantly reduced myocardial collagen accumulation by a mean difference of 50.05% compared to untreated diabetic rats, attenuating cardiac fibrosis.