Paeoniflorin ameliorates ischemic neuronal damage in vitro via adenosine A1 receptor-mediated transactivation of epidermal growth factor receptor

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 A 1 R (HEK293/A 1 R) 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/A 1 R cells. Both A 1 R antagonist DPCPX and EGFR inhibitor AG1478 not only blocked paeoniflorin-induced phosphorylation of ERK1/2 and Akt in HEK293/A 1 R 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/A 1 R cells. Both Src inhibitor PP2 and MMP-2/MMP-9 inhibitor BiPs not only blocked paeoniflorininduced phosphorylation of ERK1/2 (and Akt) in HEK293/A 1 R 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 A 1 Rmediated transactivation of EGFR.

Hematopoietic Effects of Paeoniflorin and Albiflorin on Radiotherapy‐Induced Myelosuppression Mice

“…There are a lot of major active constituents of P. lactiflora that have been identified, including paeoniflorin (PF), albiflorin (AF), oxypaeoniflorin, paeonilactinone, benzoyloxypaeoniflorin, and lactinolide [ 2 ]. It is well documented that PF possesses remarkable effects for pain [ 3 , 4 ], muscle spasm [ 5 , 6 ], inflammation [ 7 , 8 ], and neurodegenerative disorders [ 9 , 10 ]. However, few pharmacological studies of AF were reported.…”

Astragaloside III activates TACE/ADAM17‐dependent anti‐inflammatory and growth factor signaling in endothelial cells in a p38‐dependent fashion

“…Inhibition of EGFR activity has been considered a potential therapeutic strategy to treat some cardiovascular diseases, including hypertension and cardiac hypertrophy (Forrester et al, ). However, according to several recent studies, EGFR also contributes to protective responses under some conditions, such as chronic isoproterenol stimulation and ischemic/infarction damage (Reichelt, O'Brien, Thomas, & Headrick, ), possibly through activating PI3K/AKT‐ and/or ERK‐dependent antioxidative pathway (Seo et al, ; Zhong, Song, Xu, Ye, & Feng, ). Here, we showed that AS‐III treatment induces TACE activation in bEnd.3 cells, which further causes EGFR transactivation and consequent activation of AKT and ERKs pathways.…”

Adenosine A1 Receptor Agonist Protects Against Hippocampal Neuronal Injury After Lithium Chloride-Pilocarpine- Induced Epilepsy

“…To date, a variety of epilepsy models have been established, such as those induced by chemical agents and electrical stimulation. The epilepsy model induced by intraperitoneal injection of lithium chloride-pilocarpine has unique pathophysiological processes 13 . The changes in EEG of rats during seizures are similar to those in humans.…”