HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

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.
AuthorsMoon Hee Jeong, Shang-Jin Kim, Hara Kang, Kye Won Park, Woo Jin Park, Seung Yul Yang, Dong Kwon Yang
JournalPloS one (PLoS One) Vol. 10 Issue 8 Pg. e0136236 ( 2015) ISSN: 1932-6203 [Electronic] United States
PMID26296085 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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
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)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: