Advertisement

Molecular and Cellular Biochemistry

, Volume 359, Issue 1–2, pp 9–16 | Cite as

Gastrodin protects against cardiac hypertrophy and fibrosis

  • Chunming Shu
  • Changgui Chen
  • Da-Ping Zhang
  • Haipeng Guo
  • Heng Zhou
  • Jing Zong
  • Zhouyan Bian
  • Xuan Dong
  • Jia Dai
  • Yan Zhang
  • Qizhu TangEmail author
Article

Abstract

Phenolic glucoside gastrodin (Gas), which is a main component extracted from the Chinese herbs Gastrodia elata Bl, is a well-known natural calcium antagonist with antioxidant and anti-inflammatory functions. It has long been used clinically for treatment of cardiovascular and cerebrovascular diseases. Previous studies have shown that gastrodin possesses comprehensive pharmacological functions. However, very little is known about whether gastrodin has protective role on cardiac hypertrophy. The aim of this study was to determine whether gastrodin attenuates pressure overload-induced cardiac hypertrophy in mice and to clarify the underlying molecular mechanisms. Our data demonstrated that gastrodin prevented cardiac hypertrophy induced by aortic banding (AB), as assessed by heart weight/body weight and lung weight/body weight ratios, echocardiographic parameters, and gene expression of hypertrophic markers. The inhibitory effect of gastrodin on cardiac hypertrophy is mediated by ERK1/2 signaling and GATA-4 activation. Further studies showed that gastrodin attenuated fibrosis and collagen synthesis through abrogating ERK1/2 signaling pathway. Therefore, these findings indicated that gastrodin, which is a potentially safe and inexpensive therapy for clinical use, has protective potential in targeting cardiac hypertrophy and fibrosis through suppression of ERK1/2 signaling.

Keywords

Gastrodin Cardiac hypertrophy Fibrosis ERK1/2 

Notes

Acknowledgments

This research was supported by the National Natural Science Foundation of China (No. 30900524, No. 30972954, and No. 81000036) and by the Excellent Doctoral Dissertation Foundation of Wuhan University (No. 20080029).

References

  1. 1.
    Berk BC, Fujiwara K, Lehoux S (2007) ECM remodeling in hypertensive heart disease. J Clin Invest 117:568–575PubMedCrossRefGoogle Scholar
  2. 2.
    Oka T, Komuro I (2008) Molecular mechanisms underlying the transition of cardiac hypertrophy to heart failure. Circ J 72:13–16CrossRefGoogle Scholar
  3. 3.
    Wang Q, Chen G, Zeng S (2007) Pharmacokinetics of gastrodin in rat plasma and CSF after i.n. and i.v. Int J Pharm 341:20–25PubMedCrossRefGoogle Scholar
  4. 4.
    Zhang Q, Yang YM, Yu GY (2008) Effects of gastrodin injection on blood pressure and vasoactive substances in treatment of old patients with refractory hypertension: a randomized controlled trial. J Chin Integr Med 6:695–699CrossRefGoogle Scholar
  5. 5.
    Hsieh CL, Chiang SY, Cheng KS, Lin YH, Tang NY, Lee CJ, Pon CZ, Hsieh CT (2001) Anticonvulsive and free radical scavenging activities of Gastrodia elata Bl. in kainic acid-treated rats. Am J Chin Med 29:331–341PubMedCrossRefGoogle Scholar
  6. 6.
    Zeng X, Zhang Y, Zhang S, Zheng X (2007) A microdialysis study of effects of gastrodin on neurochemical changes in the ischemic/reperfused rat cerebral hippocampus. Biol Pharm Bull 30:801–804PubMedCrossRefGoogle Scholar
  7. 7.
    Xu X, Lu Y, Bie X (2007) Protective effects of gastrodin on hypoxia-induced toxicity in primary cultures of rat cortical neurons. Planta Med 73:650–654PubMedCrossRefGoogle Scholar
  8. 8.
    Zeng X, Zhang S, Zhang L, Zhang K, Zheng X (2006) A study of the neuroprotective effect of the phenolic glucoside gastrodin during cerebral ischemia in vivo and in vitro. Planta Med 72:1359–1365PubMedCrossRefGoogle Scholar
  9. 9.
    Liu Y, Tang X, Pei J, Zhang L, Liu F, Li K (2006) Gastrodin interaction with human fibrinogen: anticoagulant effects and binding studies. Chemistry 12:7807–7815PubMedCrossRefGoogle Scholar
  10. 10.
    Yong W, Xing TR, Wang S, Chen L, Hu P, Li CC, Wang HL, Wang M, Chen JT, Ruan DY (2009) Protective effects of gastrodin on lead-induced synaptic plasticity deficits in rat hippocampus. Planta Med 75:1112–1117PubMedCrossRefGoogle Scholar
  11. 11.
    Song YT, Tang YP, Hong QT (2004) Protection of traditional Chinese medicine Kangdai I against cerebral cortex neuron jury induced by simulated brain ischemia and reperfusion in vitro. Chin J Clin Rehabil 8:1375–1377Google Scholar
  12. 12.
    Yu SJ, Kim JR, Lee CK, Han JE, Lee JH, Kim HS, Hong JH, Kang SG (2005) Gastrodia elata Blume and an active component, p-hydroxybenzyl alcohol reduce focal ischemic brain injury through antioxidant related gene expressions. Biol Pharm Bull 28:1016–1020PubMedCrossRefGoogle Scholar
  13. 13.
    Ahn EK, Jeon HJ, Lim EJ, Jung HJ, Park EH (2007) Anti-inflammatory and anti-angiogenic activities of Gastrodia elata Blume. J Ethnopharmacol 110:476–482PubMedCrossRefGoogle Scholar
  14. 14.
    Shen DF, Tang QZ, Yan L, Zhang Y, Zhu LH, Wang L, Liu C, Bian ZY, Li H (2010) Tetrandrine blocks cardiac hypertrophy by disrupting reactive oxygen species-dependent ERK1/2 signalling. Br J Pharmacol 159:970–981PubMedCrossRefGoogle Scholar
  15. 15.
    Eghbali M, Weber KT (1990) Collagen and the myocardium: fibrillar structure, biosynthesis and degradation in relation to hypertrophy and its regression. Mol Cell Biochem 96:1–14PubMedCrossRefGoogle Scholar
  16. 16.
    Finckenberg P, Mervaala E (2010) Novel regulators and drug targets of cardiac hypertrophy. J Hypertens 28:S33–S38PubMedCrossRefGoogle Scholar
  17. 17.
    Liang Q, Wiese RJ, Bueno OF, Dai YS, Markham BE, Molkentin JD (2001) The transcription actor GATA4 is activated by extracellular signal-regulated kinase 1- and 2-mediated phosphorylation of serine 105 in cardiomyocytes. Mol Cell Biol 21:7460–7469PubMedCrossRefGoogle Scholar
  18. 18.
    Takeishi Y, Huang Q, Abe J, Glassman M, Che W, Lee JD, Kawakatsu H, Lawrence EG, Hoit BD, Berk BC, Walsh RA (2001) Src and multiple MAP kinase activation in cardiac hypertrophy and congestive heart failure under chronic pressure-overload: comparison with acute mechanical stretch. J Mol Cell Cardiol 33:1637–1648PubMedCrossRefGoogle Scholar
  19. 19.
    Bisping E, Ikeda S, Kong SW, Tarnavski O, Bodyak N, McMullen JR, Rajagopal S, Son JK, Ma Q, Springer Z, Kang PM, Izumo S, Pu WT (2006) Gata4 is required for maintenance of postnatal cardiac function and protection from pressure overload-induced heart failure. Proc Natl Acad Sci USA 103:14471–14476PubMedCrossRefGoogle Scholar
  20. 20.
    Shahbazian D, Roux PP, Mieulet V, Cohen MS, Raught B, Taunton J, Hershey JW, Blenis J, Pende M, Sonenberg N (2006) The mTOR/PI3 K and MAPK pathways converge on eIF4B to control its phosphorylation and activity. EMBO J 25:2781–2791PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • Chunming Shu
    • 1
    • 2
  • Changgui Chen
    • 1
    • 2
  • Da-Ping Zhang
    • 1
    • 2
  • Haipeng Guo
    • 1
    • 2
  • Heng Zhou
    • 1
    • 2
  • Jing Zong
    • 1
    • 2
  • Zhouyan Bian
    • 1
    • 2
  • Xuan Dong
    • 2
  • Jia Dai
    • 1
    • 2
  • Yan Zhang
    • 1
    • 2
  • Qizhu Tang
    • 1
    • 2
    Email author
  1. 1.Department of CardiologyRenmin Hospital of Wuhan UniversityWuhanPeople’s Republic of China
  2. 2.Cardiovascular Research Institute of Wuhan UniversityWuhanPeople’s Republic of China

Personalised recommendations