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.
Highlights
Cardiac hypertrophy is an adaptive response of the heart to various pathological stimuli
Similar results were found for incubation of the cardiomyocytes with 10 μM cucurbitacin I treatment for 48 and 72 h, with cell viability reduced to 72% and 64% of the control value, respectively (Fig 1B, 1C and 1D)
The disorder is initially considered as compensatory for mechanical loading, prolonged cardiac hypertrophy leads to systolic and diastolic dysfunction and the development of heart failure [2]
Summary
Cardiac hypertrophy is an adaptive response of the heart to various pathological stimuli (e.g., hypertension, valvular disease, and myocardial infarction). Cardiac hypertrophy is a major independent risk factor for cardiovascular morbidity and mortality [2]. CTGF is a key mediator and biochemical marker of tissue fibrosis [4]. Numerous studies have demonstrated that CTGF crucially contributes to the pathogenic process of cardiac fibrosis. CTGF is a pro-hypertrophic factor in cardiac myocytes. CTGF activate numerous MAPKs, hypertrophic activators, including ERK1/2, JNK, and p38 kinases [5]. Various kinds of extracellular stimuli (e.g., TGF-β, endothelin-1, and VEGF) upregulate CTGF expression. TGF-β and CTGF have a cooperative interaction to elicit overt cardiac hypertrophy and fibrosis [6]. Activated TGF-β propagates its downstream intracellular pro-hypertrophic signals through the activation of Smad proteins [7]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
