Involvement of heme oxygenase-1 in neuroprotection by sanguinarine against glutamate-triggered apoptosis in HT22 neuronal cells

• Sanguinarine reduced glutamate-induced cell death.
• Sanguinarine reduced glutamate-induced loss of MMP.
• Sanguinarine reduced glutamate-induced intracellular ROS and calcium levels.
• Neuroprotective effects of sanguinarine via Nrf-2-HO-1 pathway.

Sanguinarine is a natural compound isolated from the roots of Macleaya cordata and M. microcarpa, has been reported to possess several biological activities such as anti-inflammatory and anti-oxidant effects. In the present study, we demonstrated that sanguinarine markedly induces the expression of HO-1 which leads to a neuroprotective response in mouse hippocampus-derived neuronal HT22 cells from apoptotic cell death induced by glutamate. Sanguinarine significantly attenuated the loss of mitochondrial function and membrane integrity associated with glutamate-induced neurotoxicity. Sanguinarine protected against glutamate-induced neurotoxicity through inhibition of HT22 cell apoptosis. JC-1 staining, which is a well-established measure of mitochondrial damage, was decreased after treatment with sanguinarine in glutamate-challenged HT22cells. In addition, sanguinarine diminished the intracellular accumulation of ROS and Ca2+. Sanguinarine also induced HO-1, NQO-1 expression via activation of Nrf2. Additionally, we found that si RNA mediated knock-down of Nrf2 or HO-1 significantly inhibited sanguinarine-induced neuroprotective response. These findings revealed the therapeutic potential of sanguinarine in preventing the neurodegenerative diseases.