Osthole attenuated cytotoxicity induced by 6-OHDA in SH-SY5Y cells through inhibition of JAK/STAT and MAPK pathways

Autor: Samira Barangi, Parisa Hosseinizadeh, Gholamreza Karimi, Zahra Tayarani‑Najaran, Soghra Mehri
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Iranian Journal of Basic Medical Sciences, Vol 26, Iss 8, Pp 953-959 (2023)
Druh dokumentu: article
ISSN: 2008-3866
2008-3874
DOI: 10.22038/ijbms.2023.68292.14905
Popis: 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-SY5Y cells from the cytotoxicity of 6-hydroxydopamine (6-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 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), and caspase-3 activation levels were examined using western blotting.Results: In SH-SY5Y cells, the results showed that a 24-hour exposure to 6-OHDA (200 µM) lowered cell viability but markedly elevated ROS, p-JAK/JAK, p-STAT/STAT, p-ERK/ERK, p-JNK/JNK ratio, and caspase-3 levels. Interestingly, osthole (100 µM) pretreatment of cells for 24 hr prevented 6-OHDA-induced cytotoxicity by undoing all effects of 6-OHDA. Conclusion: In summary, our data showed that osthole protects SH-SY5Y cells against 6-OHDA-induced cytotoxicity by inhibiting ROS generation and reducing the activity of the JAK/STAT, MAPK, and apoptotic pathways.
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