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Paeoniflorin Ameliorates Ischemic Neuronal Damage in Vitro via Adenosine A1 Receptor-Mediated Transactivation of Epidermal Growth Factor Receptor

Paeoniflorin Ameliorates Ischemic Neuronal Damage in Vitro via Adenosine A1 Receptor-Mediated Transactivation of Epidermal Growth Factor Receptor

Min Zhong, Wan-ling Song, Ye-chun Xu, Yang Ye, Lin-yin Feng

Acta Pharmacol Sin. 2015 Mar;36(3):298-310.

PMID: 25661317

Abstract:

Aim:
Paeoniflorin from Chinese herb Paeoniae Radix has been shown to ameliorate middle cerebral artery occlusion-induced ischemia in rats. The aim of this study was to investigate the mechanisms underlying the neuroprotective action of PF in cultured rat cortical neurons.
Methods:
Primary cultured cortical neurons of rats were subjected to oxygen-glucose deprivation and reoxygenation (OGD/R) insult. Cell survival was determined using MTT assay. HEK293 cells stably transfected with A1R (HEK293/A1R) were used for detailed analysis. Phosphorylation of the signaling proteins was evaluated by Western blot or immunoprecipitation. Receptor interactions were identified using co-immunoprecipitation and immunofluorescence staining.
Results:
Paeoniflorin (10 nmol/L to 1 μmol/L) increased the survival of neurons subjected to OGD/R. Furthermore, paeoniflorin increased the phosphorylation of Akt and ERK1/2 in these neurons. These effects were blocked by PI3K inhibitor wortmannin or MEK inhibitor U0126. Paeoniflorin also increased the phosphorylation of Akt and ERK1/2 in HEK293/A1R cells. Both A1R antagonist DPCPX and EGFR inhibitor AG1478 not only blocked paeoniflorin-induced phosphorylation of ERK1/2 and Akt in HEK293/A1R cells, but also paeoniflorin-increased survival of neurons subjected to OGD/R. In addition, paeoniflorin increased the phosphorylation of Src kinase and activation of MMP-2 in HEK293/A1R cells. Both Src inhibitor PP2 and MMP-2/MMP-9 inhibitor BiPs not only blocked paeoniflorin-induced phosphorylation of ERK1/2 (and Akt) in HEK293/A1R cells, but also paeoniflorin-increased survival of neurons subjected to OGD/R.
Conclusion:
Paeoniflorin promotes the survival of cultured cortical neurons by increasing Akt and ERK1/2 phosphorylation via A1R-mediated transactivation of EGFR.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP193807588	MMP-2/MMP-9 Inhibitor I - CAS 193807-58-8		193807-58-8	Price

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