Noscapine Modulates Neuronal Response to Oxygen-glucose Deprivation/Reperfusion Injury Via Activation of Sigma-1 Receptor in Primary Cortical Cultures

• Published in: Iranian journal of pharmaceutical research : IJPR 2020-01, Vol.19 (1), p.331-342
• Main Authors: Vahabzadeh, Gelareh, Rahbar-Roshandel, Nahid, Ebrahimi, Soltan-Ahmad
• Format: Article
• Language: English
• Subjects: Original
• ISSN: 1735-0328; 1726-6890
• DOI: 10.22037/ijpr.2019.112317.13683

In the present study, we investigated the effects of noscapine (0.5-2 µM), an alkaloid from the opium poppy ( Papaver somniferum ), on primary murine cortical neurons exposed to 60 min oxygen–glucose deprivation (OGD) in the presence of 5 µM BD-1047, a selective sigma-1 receptor antagonist. The experiments were performed on cortical neurons after 11–16 days of culture. To initiate oxygen–glucose deprivation, the culture medium was transferred to glucose-free DMEM, and placed in a humidified incubation chamber containing a mixture of 95% N 2 and 5% CO 2 at 37 °C for 60 min. In order to explore the effect on neurons under oxygen–glucose deprivation in this condition, some cultures were pretreated with noscapine and BD1047 together, 24 h prior to OGD followed by 24 h recovery. Cell viability, nitric oxide (NO) production and intracellular calcium concentration ([Ca 2+ ]i) levels were evaluated by MTT assay, the modified Griess method, and Fura-2, respectively. Pretreatment of the cultures with noscapine in the presence of BD1047 significantly increased cell viability and decreased NO generation in a dose-dependent manner compared to BD1047 alone. Pretreatment with 2 μM noscapine and BD-1047 was shown to decrease the rise in [Ca 2+ ]i induced by sodium azide (NaN3) and glucose deprivation. We concluded that noscapine in the presence of BD1047 could protect primary cortical neurons after oxygen–glucose deprivation-induced cell injury but this effect was not complete. Our results indicate that neuroprotective effects of noscapine could be mediated partially through activation of sigma-1 receptor and by decreasing NO production and [Ca 2+ ]i levels.