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Neuroprotective Effect of Ginkgetin in Experimental Cerebral ischemia/reperfusion via Apoptosis Inhibition and PI3K/Akt/mTOR Signaling Pathway Activation

Neuroprotective Effect of Ginkgetin in Experimental Cerebral ischemia/reperfusion via Apoptosis Inhibition and PI3K/Akt/mTOR Signaling Pathway Activation

Zhaohua Tian, Congyao Tang, Zhigang Wang

J Cell Biochem. 2019 Oct;120(10):18487-18495.

PMID: 31265179

Abstract:

Background:
Ginkgetin, extracted from Ginkgo biloba L leaves, has been demonstrated to have potential anti-inflammatory and immune-suppressive properties. But the neuroprotective effect and potential mechanisms of ginkgetin on cerebral ischemia/reperfusion (IR) injury remain unclear.
Methods:
In this research, we studied the neuroprotective effect of ginkgetin in the middle part of the middle cerebral artery occlusion/reperfusion rat model, by analyzing the apoptosis of brain tissues harvested from treatment groups and control groups using the terminal deoxynucleotidyl transferase dUTP nick-end labeling and apoptosis assays. In addition, we detected the association of the neuroprotective effect of ginkgetin with apoptosis inhibition via the activation of the phosphatidylinositol-3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway using Western blot analysis.
Results:
Our results showed that administration of ginkgetin remarkably reduced brain infarction volumes and neurologic deficits; in addition, reducing apoptotic cell numbers, downregulating the levels of cleaved caspase-3 and Bax, and upregulating the level of Bcl-2 in rats subjected to IR injury in a dose-dependent manner. Moreover, high-dose ginkgetin treatment (100 mg/kg) significantly increased the phosphorylations of Akt and mTOR. Blocking of PI3K by LY294002 clearly decreased its antiapoptotic effect and reduced both Akt and mTOR phosphorylation levels.
Conclusions:
Taken together, these results for the first time suggest that ginkgetin antagonizes cerebral IR-induced injury by inhibiting apoptosis in rats, and this effect was attenuated by the activation of PI3K/Akt/mTOR signaling pathway.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP481469	Ginkgetin		481-46-9	Price

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