Abstract
Ginsenoside Rh2 (Rh2) is an active principal ingredient contained in ginseng (Panax ginseng Meyer), a medicinal herb used to enhance health worldwide. The present study is designed to investigate the effect of Rh2 on myocardial fibrosis in diabetic rats. In a streptozotocin-induced model of type-1 diabetic rats (STZ-diabetic rats), the increased fasting blood glucose levels and heart weight/body weight (HW/BW) ratio were substantially alleviated by Rh2. Moreover, Rh2 improved cardiac performance in STZ-diabetic rats. Histological results from Masson staining showed that Rh2 attenuated cardiac fibrosis in STZ-diabetic rats. The effects of Rh2 were reversed by GSK0660 at a dose sufficient to inhibit peroxisome proliferator-activated receptor δ (PPARδ) in STZ-diabetic rats. The role of PPARδ was subsequently investigated in vitro. Rh2 restored the decreased PPARδ expression level in high glucose-cultured cardiomyocytes. Moreover, increased protein levels of fibrotic signals, including signal transducer and activator of transcription 3 (STAT3), connective tissue growth factor (CCN2) and fibronectin, were reduced by Rh2 in high glucose-cultured cardiomyocytes. These effects of Rh2 were reversed by GSK0660 or siRNA specific for PPARδ Taken together, PPARδ activation may inhibit STAT3 activation to reduce CCN2 and fibronectin expression in diabetic rats with cardiac fibrosis. Moreover, Rh2 improves cardiac function and fibrosis by increasing PPARδ signaling. Therefore, Rh2 is suitable to develop as an alternative remedy for cardiac fibrosis.
Highlights
Cardiovascular complications have been described as an important cause of death in patients with diabetes [1]
We investigated the effects of Rh2 on cardiac fibrosis induced by hyperglycemia in both rats and cultured cardiomyocytes
The body weights and heart weights of the rats in the STZ-diabetic group were substantially lower than those in the normal control group, whereas the blood glucose level was significantly increased in the STZ-diabetic group
Summary
Cardiovascular complications have been described as an important cause of death in patients with diabetes [1]. Diabetic patients develop heart failure [2]. The development of novel therapeutics, including phytotherapy, is extremely important. Hyperglycemia, a central condition in the pathogenesis of diabetes, induces the activation of the signal transducer and activator of transcription 3 (STAT3) signaling pathway, which is integral to various types of tissue damage, including myocardial dysfunctions [6]. CCN2 is introduced to mediate the occurrence and development of DCM [8]. Fibronectin is another extracellular matrix, and the fibronectin extra domain-A (ED-A) is crucial in myofibrosis [9].
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