Hippophae rhamnoides L.leaves extract enhances cell proliferation and neuroblast differentiation through upregulation of intrinsic factors in the dentate gyrus of the aged gerbil

Background Hippophae rhamnoides L.(HL) exerts antioxidant activities against various oxidative stress conditions. In this study, we investigated effects of extract from HL leaves(HLE) on cell proliferation and neuroblast differentiation in the subgranular zone(SGZ) of the dentate gyrus(DG) of aged gerbils.Methods Aged gerbils(24 months) were divided into vehicle(saline)-treated- and HLE-treated-groups. The vehicle and HLE were orally administered with 200 mg/kg once a day for 20 days before sacrifice. Cell proliferation and neuroblast differentiation were examined in the DG using Ki67 and doublecortin(DCX), respectively. We also observed changes in immunoreactivities of superoxide dismutase 1(SOD1) and superoxide dismutase 2(SOD2), brain-derived neurotrophic factor(BDNF), and phospho-glycogen synthase kinase-3-beta(p-GSK-3β) to examine their relation with neurogenesis using immunohistochemistry.Results The administration of HLE significantly increased the number of Ki67-positive cells and DCX-positive neuroblasts with well-developed processes in the SGZ of the DG of the HLE-treated-group. In addition, immunoreactivities of SOD1, SOD2, BDNF, and p-GSK-3β were significantly increased in granule and polymorphic cells of the DG in the HLE-treatedgroup compared with those in the vehicle-treated-group.Conclusions HLE treatment significantly increased cell proliferation and neuroblast differentiation, showing that immunoreactivities of SOD1, SOD2, BDNF, and p-GSK-3β were significantly increased in the DG. These indicate that increased neuroblast differentiation neurogenesis may be closely related to upregulation of SOD1, SOD2, BDNF, and p-GSK-3β in aged gerbils.