Samira Barangi - Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
Parisa Hosseinizadeh - Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
Gholamreza Karimi - Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
Zahra Tayarani‑Najaran - Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
Soghra Mehri - Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

Objective(s): Natural coumarin called osthole is regarded as a medicinal herb with widespread applications in Traditional Chinese Medicine. It has various pharmacological properties, including antioxidant, anti-inflammatory, and anti-apoptotic effects. In some neurodegenerative diseases, osthole also shows neuroprotective properties. In this study, we explored how osthole protects human neuroblastoma SH-SY۵Y cells from the cytotoxicity of ۶-hydroxydopamine (۶-OHDA). Materials and Methods: Using the MTT assay and DCFH-DA methods, respectively, the viability of the cells and the quantity of intracellular reactive oxygen species (ROS) were evaluated. Signal Transducers and Activators of Transcription (STAT), Janus Kinase (JAK), extracellular signal-regulated kinase ۱/۲ (ERK۱/۲), c-Jun N-terminal kinase (JNK), and caspase-۳ activation levels were examined using western blotting.Results: In SH-SY۵Y cells, the results showed that a ۲۴-hour exposure to ۶-OHDA (۲۰۰ µM) lowered cell viability but markedly elevated ROS, p-JAK/JAK, p-STAT/STAT, p-ERK/ERK, p-JNK/JNK ratio, and caspase-۳ levels. Interestingly, osthole (۱۰۰ µM) pretreatment of cells for ۲۴ hr prevented ۶-OHDA-induced cytotoxicity by undoing all effects of ۶-OHDA. Conclusion: In summary, our data showed that osthole protects SH-SY۵Y cells against ۶-OHDA-induced cytotoxicity by inhibiting ROS generation and reducing the activity of the JAK/STAT, MAPK, and apoptotic pathways.

۶-OHDA, Apoptosis, JAK Kinases, Mitogen-activated protein-kinase, Osthole, STAT۳