title: Cucurbitacin B Protects Against Pressure Overload Induced Cardiac Hypertrophy.
abstract: Lack of effective anti-cardiac hypertrophy drugs creates a major cause for the increasing prevalence of heart failure. In the present study, we determined the anti-hypertrophy and anti-fibrosis potential of a natural plant triterpenoid, Cucurbitacin B both in vitro and in vivo. Aortic banding (AB) was performed to induce cardiac hypertrophy. After 1 week of surgery, mice were receive cucurbitacin B treatment (Gavage, 0.2 mg/kg body weight/2 day). After 4 weeks of AB, cucurbitacin B demonstrated a strong anti-hypertrophy and -fibrosis ability as evidenced by decreased of heart weight, myocardial cell cross-sectional area and interstitial fibrosis, ameliorated of systolic and diastolic abnormalities, normalized in gene expression of hypertrophic and fibrotic markers, reserved microvascular density in pressure overload induced hypertrophic mice. Cucurbitacin B also showed significant hypertrophy inhibitory effect in phenylephrine stimulated cardiomyocytes. The Cucurbitacin B-mediated mitigated cardiac hypertrophy was attributable to the increasing level of autophagy, which was associated with the blockade of Akt/mTOR/FoxO3a signal pathway, validated by SC79, MK2206, and 3-MA, the Akt agonist, inhibitor and autophagy inhibitor in vitro. The overexpression of constitutively active Akt completely abolished the Cucurbitacin B-mediated protection of cardiac hypertrophy in human cardiomyocytes AC16. Collectively, our findings suggest that cucurbitacin B protects against cardiac hypertrophy through increasing the autophagy level in cardiomyocytes, which is associated with the inhibition of Akt/mTOR/FoxO3a signal axis. J. Cell. Biochem. 118: 3899-3910, 2017. © 2017 Wiley Periodicals, Inc.
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, PR China.|Cardiovascular Research Institute, Wuhan University, Wuhan, 430060, PR China.|Hubei Key Laboratory of Cardiology, Wuhan, 430060, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, PR China.|Cardiovascular Research Institute, Wuhan University, Wuhan, 430060, PR China.|Hubei Key Laboratory of Cardiology, Wuhan, 430060, PR China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, PR China.|Cardiovascular Research Institute, Wuhan University, Wuhan, 430060, PR China.|Hubei Key Laboratory of Cardiology, Wuhan, 430060, PR China.
authors.forename: Qing-Qing
authors.initials: QQ
authors.lastname: Wu
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, PR China.|Cardiovascular Research Institute, Wuhan University, Wuhan, 430060, PR China.|Hubei Key Laboratory of Cardiology, Wuhan, 430060, PR China.
authors.forename: Xiao-Han
authors.initials: XH
authors.lastname: Jiang
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, PR China.|Cardiovascular Research Institute, Wuhan University, Wuhan, 430060, PR China.|Hubei Key Laboratory of Cardiology, Wuhan, 430060, PR China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, PR China.|Cardiovascular Research Institute, Wuhan University, Wuhan, 430060, PR China.|Hubei Key Laboratory of Cardiology, Wuhan, 430060, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chang
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, PR China.|Cardiovascular Research Institute, Wuhan University, Wuhan, 430060, PR China.|Hubei Key Laboratory of Cardiology, Wuhan, 430060, PR China.
authors.forename: Zhou Yan
authors.initials: ZY
authors.lastname: Bian
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, PR China.|Cardiovascular Research Institute, Wuhan University, Wuhan, 430060, PR China.|Hubei Key Laboratory of Cardiology, Wuhan, 430060, PR China.
authors.forename: Jin Xiu
authors.initials: JX
authors.lastname: Zhu
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, PR China.|Cardiovascular Research Institute, Wuhan University, Wuhan, 430060, PR China.|Hubei Key Laboratory of Cardiology, Wuhan, 430060, PR China.
authors.forename: Qi-Zhu
authors.identifier: 0000-0003-0119-5578
authors.initials: QZ
authors.lastname: Tang
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects*; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: D014315:Triterpenes; C041246:cucurbitacin B
keywords: AKT; AUTOPHAGY; CARDIAC HYPERTROPHY; CUCURBITACIN B