Traditional Use of Tao Hong Si Wu Tang Is Proven
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. The researchers 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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