Frontiers in Cardiovascular Medicine (Nov 2020)

Hispidulin Attenuates Cardiac Hypertrophy by Improving Mitochondrial Dysfunction

  • Yan Wang,
  • Yan Wang,
  • Yan Wang,
  • Yan Wang,
  • Zengshuo Xie,
  • Zengshuo Xie,
  • Zengshuo Xie,
  • Nan Jiang,
  • Zexuan Wu,
  • Zexuan Wu,
  • Ruicong Xue,
  • Ruicong Xue,
  • Bin Dong,
  • Bin Dong,
  • Wendong Fan,
  • Wendong Fan,
  • Gang Dai,
  • Gang Dai,
  • Chen Chen,
  • Chen Chen,
  • Jiayong Li,
  • Jiayong Li,
  • Hao Chen,
  • Hao Chen,
  • Zi Ye,
  • Rong Fang,
  • Rong Fang,
  • Manting Choy,
  • Manting Choy,
  • Jingjing Zhao,
  • Jingjing Zhao,
  • Yugang Dong,
  • Yugang Dong,
  • Yugang Dong,
  • Chen Liu,
  • Chen Liu,
  • Chen Liu

DOI
https://doi.org/10.3389/fcvm.2020.582890
Journal volume & issue
Vol. 7

Abstract

Read online

Cardiac hypertrophy is a pathophysiological response to harmful stimuli. The continued presence of cardiac hypertrophy will ultimately develop into heart failure. The mitochondrion is the primary organelle of energy production, and its dysfunction plays a crucial role in the progressive development of heart failure from cardiac hypertrophy. Hispidulin, a natural flavonoid, has been substantiated to improve energy metabolism and inhibit oxidative stress. However, how hispidulin regulates cardiac hypertrophy and its underlying mechanism remains unknown. We found that hispidulin significantly inhibited pressure overload-induced cardiac hypertrophy and improved cardiac function in vivo and blocked phenylephrine (PE)-induced cardiomyocyte hypertrophy in vitro. We further proved that hispidulin remarkably improved mitochondrial function, manifested by increased electron transport chain (ETC) subunits expression, elevated ATP production, increased oxygen consumption rates (OCR), normalized mitochondrial morphology, and reduced oxidative stress. Furthermore, we discovered that Sirt1, a well-recognized regulator of mitochondrial function, might be a target of hispidulin, as evidenced by its upregulation after hispidulin treatment. Cotreatment with EX527 (a Sirt1-specific inhibitor) and hispidulin nearly completely abolished the antihypertrophic and protective effects of hispidulin on mitochondrial function, providing further evidence that Sirt1 could be the pivotal downstream effector of hispidulin in regulating cardiac hypertrophy.

Keywords