Protective effect of pterostilbene in a streptozotocin-induced mouse model of Alzheimer's disease by targeting monoamine oxidase B.

Abstract

Alzheimer's disease (AD) is a neurodegenerative disease in elderly population. Pterostilbene (PTS) is a resveratrol analog with neuroprotective activity. However, the biological mechanisms of PTS in AD progression are largely uncertain. An animal model of AD was established using streptozotocin (STZ)-treated C57BL/6J mice. Monoamine oxidase B (MAOB) expression was analyzed by bioinformatics analysis and detected by western blotting assay. The memory impairment was investigated by Morris water maze test. The levels of Tau hyperphosphorylation and death-related proteins were detected by western blotting analysis. The levels of amyloid β (Aβ)1-42 accumulation, oxidative stress-related markers (ROS, MDA, SOD, and GSH), and inflammation-relative markers (TNF-α, IL-1β, IL-6, and p-NF-κB) were measured by ELISA. MAOB expression was increased in hippocampus of AD mice, and it was decreased by PTS. PTS attenuated STZ-induced body weight loss and memory impairment by regulating MAOB. PTS mitigated Aβ1-42 accumulation and Tau hyperphosphorylation by regulating MAOB in STZ-treated mice. PTS attenuated neuronal death by decreasing cleaved caspase-3 and Bax levels and increasing Bcl2 expression in hippocampus by regulating MAOB in STZ-treated mice. PTS weakened STZ-induced oxidative stress in hippocampus by decreasing ROS and MDA levels and increasing SOD and GSH levels by regulating MAOB. PTS protected against STZ-induced neuroinflammation in hippocampus by inhibiting TNF-α, IL-1β, IL-6, and p-NF-κB levels through regulating MAOB. In conclusion, PTS alleviates STZ-induced memory impairment, Aβ1-42 accumulation, Tau hyperphosphorylation, neuronal death, oxidative stress, and inflammation by decreasing MAOB in AD mice, proving anti-AD potential of PTS.