Journal of Natural Medicines

, Volume 69, Issue 1, pp 76–85 | Cite as

Chinese herbal medicine formula Tao Hong Si Wu decoction protects against cerebral ischemia–reperfusion injury via PI3K/Akt and the Nrf2 signaling pathway

  • Li Li
  • Na Yang
  • Ling Nin
  • Zhilong Zhao
  • Lu Chen
  • Jie Yu
  • Zhuyun Jiang
  • Zhendong Zhong
  • Daiwen Zeng
  • Hongyi QiEmail author
  • Xiaoyu XuEmail author
Original Paper


The Chinese herbal medicine formula Tao Hong Si Wu decoction (THSWD) is traditionally used for the prevention and treatment of ischemic stroke. Transcription factor NF-E2-related factor 2 (Nrf2) regulates a battery of phase II enzymes and is known as the major mechanism of cellular defense against oxidative stress. The present study aimed to explore the potential effect of THSWD on the Nrf2 signaling pathway and the consequent effect during cerebral ischemia−reperfusion (I/R) injury. We found that THSWD reduced infarct volume and improved neurological function in a rat stroke model induced by middle cerebral artery occlusion (MCAO). Additionally, heme oxygenase 1 (HO-1), a key endogenous antioxidant enzyme regulated by Nrf2, was significantly further induced by THSWD in this in vivo model. In neuronal-like PC12 cells, THSWD remarkably up-regulated HO-1 expression and promoted Nrf2 nuclear translocation. Furthermore, phosphatidylinositol 3-kinase (PI3K)/Akt kinase was found to be involved in the upstream of Nrf2 regulation. In an in vitro oxygen−glucose deprivation/reperfusion (OGD-Rep) model, THSWD treatment significantly reduced cell death induced by OGD-Rep insult. Importantly, the protective action was attenuated while PI3K activity was inhibited by a specific inhibitor, LY294002, and the Nrf2 signaling pathway was blocked by antioxidant response element (ARE) decoy oligonucleotides. Collectively, these results demonstrated that THSWD exhibited notable neuroprotective properties in vitro and in vivo and activation of PI3K/Akt and the Nrf2 signaling pathway may be, at least in part, responsible for the protection. This study provides a better understanding of the molecular mechanism underlying the traditional use of the Chinese herbal medicine formula THSWD.


Tao Hong Si Wu decoction NF-E2-related factor 2 Phosphatidylinositol 3-kinase/Akt Neuroprotection Ischemia−reperfusion 



This work was supported by the NSFC Projects (No. 81202946), TCM Scientific Program Grant (2012-2-87) from Chongqing Municipal Health Bureau Grant, Doctoral Fund Program grant (swu11107) from Southwest University and Basic Scientific Research Program of Scientific Research Institutes for Public Welfare (to Na Yang).

Conflict of interests

There is no conflict of interest to be declared by the authors.

Supplementary material

11418_2014_865_MOESM1_ESM.docx (94 kb)
Supplementary material 1 (DOCX 94 kb)


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Copyright information

© The Japanese Society of Pharmacognosy and Springer Japan 2014

Authors and Affiliations

  • Li Li
    • 1
  • Na Yang
    • 2
  • Ling Nin
    • 1
  • Zhilong Zhao
    • 2
  • Lu Chen
    • 1
  • Jie Yu
    • 1
  • Zhuyun Jiang
    • 1
  • Zhendong Zhong
    • 2
  • Daiwen Zeng
    • 2
  • Hongyi Qi
    • 1
    Email author
  • Xiaoyu Xu
    • 1
    Email author
  1. 1.College of Pharmaceutical SciencesSouthwest UniversityChongqingPeople’s Republic of China
  2. 2.Institute of Laboratory AnimalsSichuan Academy of Medical Sciences and Sichuan Provincial People’s HospitalChengduPeople’s Republic of China

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