Triptolide attenuated injury via inhibiting oxidative stress in Amyloid-Beta25-35-treated differentiated PC12 cells.

BACKGROUND: Recently, an abnormal deposition of Amyloid-Beta (Aβ) was considered the primary cause of the pathogenesis of Alzheimer's disease (AD). And how to inhibit the cytotoxicity is considered an important target for the treatment of AD. Triptolide (TP), a purified diterpenoid from the herb Tripterygium wilfordii Hook.f. (TWHF), has potential neuroprotective effects pertinent to disease of the nervous system. However, whether triptolide and its specific mechanisms have protective functions in differentiated PC12 cells treated with Aβ25-35 remain unclear.

AIMS: The purpose is to investigate the protective functions of triptolide in Aβ25-35-stimulated differentiated PC12 cells.

MAIN METHODS: In the study, we use 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, lactate dehydrogenase (LDH) assay, flow cytometry assay, immunohistochemical staining and Western blot to observe the effects of triptolide on cytotoxicity induced by Aβ25-35 and its mechanism of oxidative stress.

KEY FINDINGS: The result of MTT and LDH assay indicates that triptolide protected PC12 cells against Aβ25-35-induced cytotoxicity. The flow cytometry assay shows that triptolide attenuated Aβ25-35-induced apoptosis in differentiated PC12 cells. Meanwhile, the results give a clear indication that triptolide could downregulate generation of reactive oxygen species (ROS), hydrogen peroxide (H2O2) and malondialdehyde (MDA) induced by Aβ25-35. The apoptotic process triggered by triptolide involved the up-regulation of the activity of superoxide dismutase (SOD).

SIGNIFICANCE: The results suggest that triptolide may serve as an important role in the inhibition of the cell apoptosis induced by Aβ and the decreased oxidative stress is a key mechanism in the protective effect of triptolide in AD.