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

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Abstract

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.

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Acknowledgments

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).

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

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Authors and Affiliations

  1. College of Pharmaceutical Sciences, Southwest University, 2 Tiansheng Road, Beibei District, Chongqing, 400716, People’s Republic of China

    Li Li, Ling Nin, Lu Chen, Jie Yu, Zhuyun Jiang, Hongyi Qi & **aoyu Xu

  2. Institute of Laboratory Animals, Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital, Chengdu, 610212, Sichuan, People’s Republic of China

    Na Yang, Zhilong Zhao, Zhendong Zhong & Daiwen Zeng

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  1. Li Li
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  2. Na Yang
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  3. Ling Nin
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  5. Lu Chen
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  6. Jie Yu
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  9. Daiwen Zeng
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  10. Hongyi Qi
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  11. **aoyu Xu
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Correspondence to Hongyi Qi or **aoyu Xu.

Additional information

L. Li and N. Yang contributed equally.

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Li, L., Yang, N., Nin, L. et al. Chinese herbal medicine formula Tao Hong Si Wu decoction protects against cerebral ischemia–reperfusion injury via PI3K/Akt and the Nrf2 signaling pathway . J Nat Med 69, 76–85 (2015). https://doi.org/10.1007/s11418-014-0865-5

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  • DOI: https://doi.org/10.1007/s11418-014-0865-5

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