Abstract
The present study aimed to investigate the neuroprotective activity of the black peel pomegranate extract, and silver nanoparticles (AgNPs) biosynthesized using the extract. We pretreated the human neuroblastoma SH-SY5 cells with the extract and AgNPs and evaluated the neuroprotective activity of these agents against methamphetamine (Meth) cytotoxicity. The NPs were spherical with 19 ± 8 nm size, - 28 mV surface charge, and 0.20 PDI. Meth killed the cells by increasing proapoptotic (Bax, PTEN, AKT, PI3K, NF-κB, P53, TNF-α, Cyt C, and Cas 3) and decreasing the antiapoptotic genes (Bcl-2) expression. Exposure to Meth caused DNA fragmentation and increased the intercellular ROS and malondialdehyde (MDA) levels while reducing the mitochondrial membrane potential (MMP). A 4-h pretreatment of the cells with the extract and AgNPs could retain the viability of the cells above 80% by increasing the Bcl-2 expression up to fourfold and inhibiting the cell death pathways. ROS, MDA, and MMP levels in the pretreated cells were close to the control group. The percentage of necrosis in cells pretreated with the extract and AgNPs declined to 32% and 8%, respectively. Our promising findings indicated that AgNPs could reduce Meth-induced oxidative stress and prevent necrotic and apoptotic cell death by regulating related genes' expression.