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<p>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&amp;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.</p>

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Oleuropein attenuates cardiac fibrosis via modulation of TGF-β1/Smad pathway in diabetic cardiomyopathy rat model

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月18日

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  • Lobna M. Abdelrauf,
  • Danira A. Habashy,
  • Nadia M. Sharaf,
  • Asmaa A. El-Shafei,
  • Lobna Kassem,
  • Ragwa M. Abdelghany

摘要

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.