Neuroprotective Effects of Pycnogenol Against Oxygen-Glucose Deprivation/Reoxygenation-Induced Injury in Primary Rat Astrocytes via NF-κB and ERK1/2 MAPK Pathways

Abstract

Backgrounds/aims: Pycnogenol (PYC) is a patented mix of bioflavonoids with potent anti-oxidant and anti-inflammatory properties. In this study, we investigated the effects of PYC on oxygen-glucose deprivation/reoxygenation (OGD/R)-induced injury in primary rat astrocytes.

Methods: The primary rat astrocytes were randomly divided into 6 groups, blank control, OGD/R, OGD/R+PYC (10, 20, 40, and 60 µg/mL). The cell activity were detected by MTT and LDH assays, then the levels of oxidant products [malondialdehyde (MDA) and reactive oxygen species (ROS)] , antioxidants [superoxide dismutase (SOD)], mitochondrial membrane potential (MMP) and inflammatory cytokines were detected. In addition, the expression levels of apoptosis-related proteins (Bax, Bcl-2 and Cleaved caspase 3), proinflammatory factors (NF-κB p65), and p-ERK1/2 were measured by Western blot analysis.

Results: The results showed that PYC incubation dose-dependently attenuated cell viability loss, LDH leakage, oxidative stress, inflammatory cytokines accumulation and cell apoptosis caused by OGD/R. Furthermore, PYC pretreatment dose-dependently suppressed OGD/R-induced NF-κB p65 nuclear translocation, NF-κB activity and ERK1/2 phosphorylation. Similarly to PYC, NF-κB inhibitor PDTC and ERK1/2 inhibitor PD098059 dramatically inhibited OGD/R-induced NF-κB activation, ERK1/2 phosphorylation, and ROS production, as well as TNF-α secretion.

Conclusions: These findings revealed that PYC has neuroprotective effects against OGD/R-induced injury via NF-κB and ERK1/2 pathways in primary rat astrocytes.

Keywords: Astrocytes; Inflammatory response; Oxidative stress; Oxygen-glucose deprivation/reoxygenation; Pycnogenol.