Inhibitory Effects of Momordicine I on High-Glucose-Induced Cell Proliferation and Collagen Synthesis in Rat Cardiac Fibroblasts

• Published in: Oxidative medicine and cellular longevity 2018, Vol.2018 (2018), p.1-11
• Main Authors: Liu, Ju-Chi, Chen, Chun-Chao, Hao, Wen-Rui, Shih, Neng-Lang, Chen, Po-Yuan, Sung, Li-Chin
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants; Antioxidants - pharmacology; Biochemistry; Bone morphogenetic proteins; Cardiomyopathy; Cell growth; Cell Proliferation - drug effects; Collagen; Collagen - biosynthesis; Dextrose; Diabetes; Fibroblasts; Fibroblasts - drug effects; Fibroblasts - metabolism; Fibroblasts - pathology; Gene expression; Glucose; Glucose - toxicity; Growth factors; Heart; Hyperglycemia; Immunoglobulins; Laboratory animals; Models, Biological; Myocardium - pathology; NF-E2-Related Factor 2 - metabolism; Oxidative stress; Pharmacology; Phosphorylation - drug effects; Physiology; Quassins - pharmacology; Rats, Sprague-Dawley; Reactive oxygen species; Reactive Oxygen Species - metabolism; RNA, Small Interfering - metabolism; Signal transduction; Signal Transduction - drug effects; Smad Proteins - metabolism; Sterols - chemistry; Sterols - pharmacology; Studies; Transforming Growth Factor beta1 - metabolism; Transforming growth factors
• ISSN: 1942-0900; 1942-0994
• DOI: 10.1155/2018/3939714

Diabetes-associated cardiac fibrosis is a severe cardiovascular complication. Momordicine I, a bioactive triterpenoid isolated from bitter melon, has been demonstrated to have antidiabetic properties. This study investigated the effects of momordicine I on high-glucose-induced cardiac fibroblast activation. Rat cardiac fibroblasts were cultured in a high-glucose (25 mM) medium in the absence or presence of momordicine I, and the changes in collagen synthesis, transforming growth factor-β1 (TGF-β1) production, and related signaling molecules were assessed. Increased oxidative stress plays a critical role in the development of high-glucose-induced cardiac fibrosis; we further explored momordicine I’s antioxidant activity and its effect on fibroblasts. Our data revealed that a high-glucose condition promoted fibroblast proliferation and collagen synthesis and these effects were abolished by momordicine I (0.3 and 1 μM) pretreatment. Furthermore, the inhibitory effect of momordicine I on high-glucose-induced fibroblast activation may be associated with its activation of nuclear factor erythroid 2-related factor 2 (Nrf2) and the inhibition of reactive oxygen species formation, TGF-β1 production, and Smad2/3 phosphorylation. The addition of brusatol (a selective inhibitor of Nrf2) or Nrf2 siRNA significantly abolished the inhibitory effect of momordicine I on fibroblast activation. Our findings revealed that the antifibrotic effect of momordicine I was mediated, at least partially, by the inhibition of the TGF-β1/Smad pathway, fibroblast proliferation, and collagen synthesis through Nrf2 activation. Thus, this work provides crucial insights into the molecular pathways for the clinical application of momordicine I for treating diabetes-associated cardiac fibrosis.