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In the present study, we determined the anti\u2010hypertrophy and anti\u2010fibrosis 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\u2009mg\/kg body weight\/2 day). After 4 weeks of AB, cucurbitacin B demonstrated a strong anti\u2010hypertrophy and \u2010fibrosis ability as evidenced by decreased of heart weight, myocardial cell cross\u2010sectional 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\u2010mediated 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\u2010MA, the Akt agonist, inhibitor and autophagy inhibitor in vitro. The overexpression of constitutively active Akt completely abolished the Cucurbitacin B\u2010mediated 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\u20133910, 2017. \u00a9 2017 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcb.26041","type":"journal-article","created":{"date-parts":[[2017,4,8]],"date-time":"2017-04-08T13:43:23Z","timestamp":1491659003000},"page":"3899-3910","source":"Crossref","is-referenced-by-count":52,"title":["Cucurbitacin B Protects Against Pressure Overload Induced Cardiac Hypertrophy"],"prefix":"10.1002","volume":"118","author":[{"given":"Yang","family":"Xiao","sequence":"first","affiliation":[{"name":"Department of Cardiology Renmin Hospital of Wuhan University Wuhan 430060 PR China"},{"name":"Cardiovascular Research Institute Wuhan University Wuhan 430060 PR China"},{"name":"Hubei Key Laboratory of Cardiology Wuhan 430060 PR China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zheng","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Cardiology Renmin Hospital of Wuhan University Wuhan 430060 PR 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