Oxidative stress is one of the major mechanisms causing neuronal and astroglial cell death in various neurological disorders such as Alzheimer's disease, Parkinson's disease, and brain ischemia. Two diarylheptanoids, (3)-1,7-diphenyl-(4,6)-4,6-heptadien-3-ol (ASPP 049) and (3)-7-(3,4-dihydroxyphenyl)-1-phenyl-(1)-1-hepten-3-ol (ASPP 092), isolated from were investigated for cytoprotective effects on C6 astroglial cells using hydrogen peroxide (HO) exposure as a model of oxidative stress. ASPP 092 demonstrated free radical scavenging activity comparable to that of vitamin C, while ASPP 049 showed no antioxidant activity. Treatment with HO at 400 µM for 12 h caused 79 % C6 astroglial cell death which was significantly reduced to 37 % by pretreatment with ASPP 092 (5 µM). In addition, ASPP 092 attenuated the increase in reactive oxygen species production and the decrease in total glutathione level induced by HO. The mechanism of ASPP 092 protection against HO-induced apoptotic signaling appeared to involve prevention of increase in the level of phosphorylated p53 and the Bax/Bcl-2 ratio as well as cleaved caspase-3. These findings provide new evidence that the diarylheptanoid ASPP 092 from possesses antiapoptotic properties and could be further developed as a potential treatment for oxidative stress-related neuronal diseases.
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