Abstract
Oxidative cell damage contributes to neuronal degeneration in many central nervous system (CNS) diseases such as Parkinson’s disease, Alzheimer’s disease, and ischemia. Inducible heme oxygenase (HO)-1 acts against oxidants that are thought to play a key role in the pathogenesis of neuronal diseases. The stem bark of Acer nikoense Maxim (Aceraceae) is indigenous to Japan; it has been used in folk medicine as a treatment of hepatic disorders and eye diseases. Acerogenin A, a natural compound isolated from Japanese folk medicine A. nikoense, showed neuroprotective effects and reactive oxygen species (ROS) reduction on glutamate-induced neurotoxicity by inducing the expression of HO-1 in mouse hippocampal HT22 cells. Furthermore, acerogenin A caused the nuclear accumulation of nuclear factor-E2-related factor 2 (Nrf2) and the activation of the PI3K/AKT signaling pathways. In this study, we demonstrated that acerogenin A effectively prevents glutamate-induced oxidative damage, and HO-1 induction via PI3K/Akt and Nrf2 pathways appears to play a key role in the protection of HT22 cells. Therefore, this study implies that the Nrf2/HO-1 pathway represents a biological target and that acerogenin A might be a candidate for the prevention of neurodegeneration.
Highlights
The initial factors that cause neuronal death remain unclear
Acerogenin A was isolated from the stem bark of Acer nikoense Maxim, and it has been used in folk medicine as a remedy for hepatic disorders and eyewash
Transient transfection with nuclear factor-E2-related factor 2 (Nrf2) siRNA abolishes induction of heme oxygenase (HO)-1 expression by acerogenin A in both HT22 cells. These results indicated that heme oxygenase-1 (HO-1) induction upon incubation with acerogenin A is related to the Nrf nuclear translocation pathway in HT22 cells
Summary
The initial factors that cause neuronal death remain unclear. Brain tissues are vulnerable to oxidative stress and inflammation that may occur physiologically as a component of aging process or pathologically as a result of neurodegenerative disease [1]. Oxidative stress results in accidental damage to cells, and actively triggers intracellular signaling pathways that lead to cell death [2]. Many neurodegenerative diseases such as ALS, Parkinson’s, Alzheimer’s, and Huntington’s occur as a result of neurodegenerative processes. We isolated acerogenin A and investigated its neuroprotective effects on glutamate-induced oxidative toxicity in mouse hippocampal HT22 cells through nuclear factor E2-related factor 2 (Nrf2)-dependent HO-1 expression via activation of the phosphatidylinositol 3-kinase (PI3K)/AKT pathways
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