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 neurobiast 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-treated-group 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.

Inhibitory Mechanisms of Water Extract of Oplopanax elatus on Lipopolysaccharide-lnduced Inflammatory Responses in RAW 264.7 Murine Macrophage Cells

Objective:To study the anti-inflammatory action and cellular mechanism of Oplopanax elatus.Methods:A hot water extract of OE(WOE)was prepared and a major constituent,syringin,was successfully isolated.Its content in WOE was found to be 214.0 p.g/g dried plant(w/w).Their anti-inflammatory activities were examined using RAW 264.7 macrophages and a mouse model of croton oil-induced ear edema.Results:In lipopolysaccharide(LPS)-treated RAW 264.7 cells,a mouse macrophage cell line,WOE was found to significantly and strongly inhibit cyclooxygenase-2(COX-2)-induced prostaglandin E2(PGE2)production[half maximal inhibitory concentration(IC50)=135.2μg/mL]and inducible nitric oxide synthase(iNOS)-induced NO production(IC50=242.9μg/mL).In the same condition,WOE was revealed to inhibit NO production by downregulating iNOS expression,mainly by interrupting mitogen activated protein kinases(MAPKs)/activator protein-1(AP-1)pathway.The activation of all three major MAPKs,p38 MAPK,extracellular signal-regulated kinase(ERK),and c-Jun N-terminal kinase,was inhibited by WOE(50-300μg/mL).On the other hand,WOE reduced PGE2 production by inhibiting COX-2 enzyme activity,but did not affect COX-2 expression levels.In addition,WOE inhibited the production of proinflammatory cytokines such as interleukin-6 and tumor necrosis factor-α.In croton oil-induced ear edema in mice,oral administration of WOE(50-300 mg/kg)dose-dependently inhibited edematic inflammation.Conclusion:Water extract of OE exhibited multiple anti-inflammatory action mechanisms and may have potential for treating inflammatory disorders.