Cucurbitacin I Attenuates Cardiomyocyte Hypertrophy via Inhibition of Connective Tissue Growth Factor (CCN2) and TGF- β/Smads Signalings

  • PLoS One. 2015 Aug 21;10(8):e0136236. doi: 10.1371/journal.pone.0136236.
Moon Hee Jeong  1 ,  Shang-Jin Kim  2 ,  Hara Kang  3 ,  Kye Won Park  4 ,  Woo Jin Park  1 ,  Seung Yul Yang  5 ,  Dong Kwon Yang  1
Affiliations
  • 1. College of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea.
  • 2. Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Chonbuk National University, Jeonju, Jeonbuk, Republic of Korea.
  • 3. Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, Incheon, Republic of Korea.
  • 4. Department of Food Science and Biotechnology, College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon, Republic of Korea.
  • 5. Department of Horticulture, Sunchon National University, Sunchon, Jeonnam, Republic of Korea.
PMID: 26296085 DOI: 10.1371/journal.pone.0136236
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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