title: Cucurbitacin I Attenuates Cardiomyocyte Hypertrophy via Inhibition of Connective Tissue Growth Factor (CCN2) and TGF- β/Smads Signalings.
abstract: Cucurbitacin I is a naturally occurring triterpenoid derived from Cucurbitaceae family plants that exhibits a number of potentially useful pharmacological and biological activities. However, the therapeutic impact of cucurbitacin I on the heart has not heretofore been reported. To evaluate the functional role of cucurbitacin I in an in vitro model of cardiac hypertrophy, phenylephrine (PE)-stimulated cardiomyocytes were treated with a sub-cytotoxic concentration of the compound, and the effects on cell size and mRNA expression levels of ANF and β-MHC were investigated. Consequently, PE-induced cell enlargement and upregulation of ANF and β-MHC were significantly suppressed by pretreatment of the cardiomyocytes with cucurbitacin I. Notably, cucurbitacin I also impaired connective tissue growth factor (CTGF) and MAPK signaling, pro-hypertrophic factors, as well as TGF-β/Smad signaling, the important contributing factors to fibrosis. The protective impact of cucurbitacin I was significantly blunted in CTGF-silenced or TGF-β1-silenced hypertrophic cardiomyocytes, indicating that the compound exerts its beneficial actions through CTGF. Taken together, these findings signify that cucurbitacin I protects the heart against cardiac hypertrophy via inhibition of CTGF/MAPK, and TGF- β/Smad-facilitated events. Accordingly, the present study provides new insights into the defensive capacity of cucurbitacin I against cardiac hypertrophy, and further suggesting cucurbitacin I's utility as a novel therapeutic agent for the management of heart diseases.
authors: College of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea.
authors: Moon Hee
authors: MH
authors: Jeong
authors: Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Chonbuk National University, Jeonju, Jeonbuk, Republic of Korea.
authors: Shang-Jin
authors: SJ
authors: Kim
authors: Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, Incheon, Republic of Korea.
authors: Hara
authors: H
authors: Kang
authors: Department of Food Science and Biotechnology, College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon, Republic of Korea.
authors: Kye Won
authors: KW
authors: Park
authors: College of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea.
authors: Woo Jin
authors: WJ
authors: Park
authors: Department of Horticulture, Sunchon National University, Sunchon, Jeonnam, Republic of Korea.
authors: Seung Yul
authors: SY
authors: Yang
authors: College of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea.
authors: Dong Kwon
authors: DK
authors: Yang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D009320:Atrial Natriuretic Factor / Q000235:genetics / Q000378:metabolism; D002316:Cardiotonic Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D055513:Connective Tissue Growth Factor / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010656:Phenylephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D061251:Primary Cell Culture; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D051785:Smad Proteins / Q000235:genetics* / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics* / Q000378:metabolism; D014315:Triterpenes / Q000494:pharmacology*; D024723:Ventricular Myosins / Q000235:genetics / Q000378:metabolism
chemical_list: C526316:CCN2 protein, rat; D002316:Cardiotonic Agents; D034741:RNA, Small Interfering; D051785:Smad Proteins; D053773:Transforming Growth Factor beta1; D014315:Triterpenes; D055513:Connective Tissue Growth Factor; D010656:Phenylephrine; D009320:Atrial Natriuretic Factor; D020928:Mitogen-Activated Protein Kinases; D024723:Ventricular Myosins; C038106:cucurbitacin I