Document Type: Research Paper
Department of Respiratory, Lishui Second Hospital, Lishui, Zhejiang, China
Background: Accumulation of the amyloid beta and hyperphosphorylation of tau proteins is the main pathological feature of Alzheimer disease. Amyloid beta accumulation exerts apoptosis which finally triggers neurons towards death. Natural products have attracted a great interest for neuroprotection in Alzheimer disease.
Objective: The present study explores the molecular mechanism of safranal that provides neuroprotection to SH-SY5Y cells and primary neuronal cells against amyloid beta.
Materials and Methods: SH-SY5Y cells and primary neuronal cells were used in this study. Assessment of neuroprotection by safranal against amyloid beta and cell viability was assessed by MTT assay. Activation of the AMPK pathway and inhibition of mTOR were determined by western blot. Change in intracellular calcium level, reactive oxygen species and mitochondrial membrane potential were assessed by flow cytometer. Student’s t-test was used to compare the data.
Results: In this study, it was confirmed that safranal protects neurons against amyloid beta toxicity. Furthermore, safranal activates AMPK pathway by the activation of calcium/calmodulin-dependent protein kinase (CaMKKβ) to induce autophagy in both cell lines. However, SH-SY5Y and primary neuronal cells were treated with amyloid beta to induce toxicity which was further attenuated by safranal. Morphological analysis of SH-SY5Y and primary neuronal cells depicts health of neuronal which was disrupted by amyloid beta toxicity. Moreover, amyloid beta induced calcium level was significantly decreased by safranal while as reactive oxygen species and mitochondrial membrane potential loss formed by amyloid beta was attenuated by safranal.
Conclusion: These interesting findings led us to the conclusion that safranal protects neurons against amyloid beta by activating AMPK pathway. However, more study should be performed to explore the possibility of safranal as a therapeutic target for Alzheimer disease.