Anwulignan Improves d-Galactose-Induced Learning and Memory Impairment via Regulating P38 MAPK-Nrf2-HO-1 Pathway in Mice

Schisandra sphenanthera has been used as a Chinese traditional medical herb with its restorative and antioxidant functions for hundreds of years. Anwulignan is a monomeric compound isolated from the total lignans of S. sphenanthera. Our previous study showed that anwulignan has a strong antioxidant activity in vitro. However, it is unclear if anwulignan possesses any function in improving learning and memory. In this study, we examined the effect of anwulignan on the learning and memory impairment induced by d-galactose (d-Gal) in mice. By using Morris water maze and step-through test for the observation of behavioral activities, we found that anwulignan significantly reduced the learning and memory impairment induced by d-Gal. Histological and biochemical analyses exhibited the hippocampal morphological damages as well as decreased superoxide dismutase (SOD) and increased malondialdehyde (MDA) in the blood and hippocampus in d-Gal-treated mice, whereas anwulignan could reverse the morphological change and reduce the oxidative damages in mice. Furthermore, the activation of p38 mitogen-activated protein kinase (MAPK) signaling and expression of nuclear factor [erythroid-derived 2]-like 2 (Nrf2) and heme oxygenase 1 (HO-1) were enhanced in anwulignan-treated mice, suggesting that anwulignan improves the learning and memory impairment induced by d-Gal through its antioxidative activity by activating the p38 MAPK-Nrf2-HO-1 pathway in the hippocampus of mice.