Scutellarin improves the learning and memory ability of Alzheimer′s rats by stimulating the Sirtuin1/Nrf2/HO-1 signaling pathway

Objective To investigate the effect of scutellarinon on improving the learning and memory ability of Alzheimer's disease(AD) rats by stimulating the sirtuin 1(Sirtuin 1)/nuclear factor E2 related factor 2(Nrf2)/heme oxygenase 1(HO-1) signaling pathway.Methods According to the random number table method, 60 healthy adult male SD rats were divided into six groups(n=10). An AD model was established by intrahippocampal injection of human β-amyloid 1-42(Aβ1-42) in other groups except for the negative control group. The negative control group and the model group were administered with normal saline(1mL·kg^-1) by gavage. The low-dose scutellarin group, the medium-dose scutellarin group and the high-dose scutellarin group were given scutellarin(1 0mg·kg^-1, 20mg·kg^-1 and 40mg·kg^-1) by gavage, respectively. The positive control group was treated with galantamine(3 mg·kg^-1) by gavage, once per day for consecutive 21 days. Then, Morris water maze test was performed. The hippocampal tissue was collected for Hematoxylin-Eosin(HE) staining and TUNEL staining. At the same time, the levels of superoxide dismutase(SOD), glutathione(GSH), and malondialdehyde(MDA) in the hippocampus were detected by enzyme-linked immunosorbent(ELISA). The levels of Sirtuin 1, Nrf2 and HO-1 in hippocampal tissue were detected by Western Blot.Results The negative control group presented normal hippocampal structure, with evenly distributed chromatin, and no neuronal necrosis was seen. The model group showed disordered arrangement of neuron cells in the hippocampus of rats, where the nucleus and cytoplasm were unclear, with a large area of neuronal degeneration and necrosis. Compared with the model group, the scutellarin treatment groups and the positive control group showed repaired hippocampus, with reduction in neuronal degeneration and necrosis. Compared with the negative control group, the other groups showed decreases in the target quadrant swimming time, average swimming speed, and the levels of SOD, GSH, Sirtuin 1, Nrf2 and HO-1, and increases in apoptosis and MDA levels(P<0.05). Compared with the model group, the scutellarin treatment groups and the positive control group presented increases in the target quadrant swimming time, average swimming speed, and the levels of SOD, GSH, Sirtuin 1, Nrf2 and HO-1, and decreases in cell apoptosis and MDA levels, and there was a dose-response relationship among the scutellarin treatment groups(P<0.05). There was no statistical difference in indicators between the positive control group and the high-dose scutellarin group(P>0.05).Conclusions Scutellarin can improve the learning and memory ability of AD rats, which may be related to the activation of the Sirtuin1/Nrf2/HO-1 signaling pathway by scutellarin.