Studies on the Neuroprotection of Osthole on Glutamate-Induced Apoptotic Cells and an Alzheimer’s Disease Mouse Model via Modulation Oxidative Stress
In the present study, the neuroprotection of osthole (OST) was confirmed. In l-glutamic acid (l-Glu)-damaged HT22 cells, a 3-h pre-incubation with OST-enhanced cell viability suppressed the apoptosis rate; inhibited the activities of caspase-3, caspase-8, and caspase-9; reduced the over-accumulation of intracellular reactive oxygen species; restored the dissipated mitochondrial membrane potential; and regulated the expression levels of B cell lymphoma-2 (Bcl-2), Bax, cleaved poly (ADP-ribose) polymerase (PARP), NF-E2p45-related factor 2 (Nrf2), and its downstream proteins. In amyloid precursor protein/presenilin 1 (APP/PS1) transgenic mice, an 8-week OST administration improved the pathological behaviors related to memory and cognition, and reduced the expression levels of 4-hydroxynonenal, the deposition of β-amyloid peptides and neuronal fiber tangles formed by the high phosphor-Tau in the brain. OST enhanced the expression levels of Nrf2 and its downstream proteins including superoxide dismutase-1 (SOD-1) and heme oxygenase-1 (HO-1). The present data confirmed the protection of OST against AD-like symptoms via modulating oxidative stress, especially Nrf2 signaling.
KeywordsOsthole Alzheimer’s disease Apoptosis Oxidative stress Nrf2
This work was supported by the Medical Health Project in Jilin Province of P. R. China (Grant No.20191102027YY), “Thirteenth Five-Year” Science and Technology Planning Project of Jilin Province in P. R. China (Grant No. JJKH20190060KJ), and the Science Foundation of Jilin Province in P. R. China (Grant No. 20180101098JC).
Compliance with Ethical Standards
Conflict of Interest
The authors declare that there is no conflict of interest.
The experimental animal protocol was approved by the Animal Ethics Committee of the Second Hospital of Jilin University (20171201).
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