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.
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Authors | Moon Hee Jeong, Shang-Jin Kim, Hara Kang, Kye Won Park, Woo Jin Park, Seung Yul Yang, Dong Kwon Yang |
Journal | PloS one
(PLoS One)
Vol. 10
Issue 8
Pg. e0136236
( 2015)
ISSN: 1932-6203 [Electronic] United States |
PMID | 26296085
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- CCN2 protein, rat
- Cardiotonic Agents
- RNA, Small Interfering
- Smad Proteins
- Transforming Growth Factor beta1
- Triterpenes
- Connective Tissue Growth Factor
- Phenylephrine
- Atrial Natriuretic Factor
- Mitogen-Activated Protein Kinases
- Ventricular Myosins
- cucurbitacin I
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Topics |
- Animals
- Animals, Newborn
- Atrial Natriuretic Factor
(genetics, metabolism)
- Cardiotonic Agents
(antagonists & inhibitors, pharmacology)
- Cell Survival
(drug effects)
- Connective Tissue Growth Factor
(antagonists & inhibitors, genetics, metabolism)
- Gene Expression Regulation
- Mitogen-Activated Protein Kinases
(genetics, metabolism)
- Myocytes, Cardiac
(drug effects, metabolism, pathology)
- Phenylephrine
(antagonists & inhibitors, pharmacology)
- Primary Cell Culture
- RNA, Small Interfering
(genetics, metabolism)
- Rats
- Rats, Sprague-Dawley
- Signal Transduction
- Smad Proteins
(genetics, metabolism)
- Transforming Growth Factor beta1
(genetics, metabolism)
- Triterpenes
(pharmacology)
- Ventricular Myosins
(genetics, metabolism)
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