Department of Orthopaedics, Tangdu Hospital, The Fourth Military Medical University, Xi'an 710032, China.
Department of Neurology, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China.
Life Sci. 2017 Jan 1;168:16-23. doi: 10.1016/j.lfs.2016.11.002. Epub 2016 Nov 4.
Previous study demonstrated that Ginsenoside Rd. (GS-Rd) could improve cognitive and memory function in animal model of Alzheimer's disease. This study was aimed to investigate whether GS-Rd could improve non-amyloidogenic pathway by activating estrogen receptor (ER).
10mg/kg GS-Rd in ovariectomy (OVX)+GS-Rd group and equivalent volume of saline in sham operated group and OVX group were administrated intraperitoneally for two months, respectively. The Morris Water Maze was used to examine cognitive function of rats, with sAPPα and Aβ levels in the hippocampi measured. The culture medium of HT22 hippocampal neuronal cells were incubated with GS-Rd, ER antagonist ICI182.780, MAPK inhibitor PD98059, or PI3Kinhibitor LY294002, respectively. sAPPα levels was measured, and expression of α-secretase, sAPPα, β-secretase, Aβ, phosphorylation form of AKT (p-AKT), total AKT, p-ERK, total ERK, p-ERα, total ERα, p-ERβ and total ERβ were examined by Western blot to explore the estrogenic-like activity of GS-Rd.
GS-Rd attenuate cognitive and memory impairment, increased levels of sAPPα and reduced extracellular Aβ of OVX rats. In HT22, GS-Rd could upregulate sAPPα level, which can be inhibited by inhibitor of MAPK and PI3K pathway. In addition, inhibitor of estrogen receptor prevented GS-Rd triggered release of sAPPα and activation of MAPK and PI3K pathways. GS-Rd could increase expression of α-secretase and sAPPα, while decrease expression of β-secretase and Aβ. Besides, GS-Rd promoted phosphorylation of estrogen receptor alpha at Ser118 residue.
Our findings show that GS-Rd enhances learning and memory function of OVX rats by activating estrogen-like activity.
先前的研究表明，人参皂苷 Rd（GS-Rd）可改善阿尔茨海默病动物模型的认知和记忆功能。本研究旨在探讨 GS-Rd 是否可以通过激活雌激素受体（ER）来改善非淀粉样蛋白生成途径。
分别给卵巢切除（OVX）+GS-Rd 组 10mg/kg GS-Rd 和假手术组及 OVX 组等容量生理盐水，腹腔内给药 2 个月。采用 Morris 水迷宫检测大鼠认知功能，检测海马 sAPPα 和 Aβ 水平。将 HT22 海马神经元细胞的培养基分别与 GS-Rd、ER 拮抗剂 ICI182.780、MAPK 抑制剂 PD98059 和 PI3K 抑制剂 LY294002 孵育，检测 sAPPα 水平，并通过 Western blot 检测 α-分泌酶、sAPPα、β-分泌酶、Aβ、AKT（p-AKT）、总 AKT、p-ERK、总 ERK、p-ERα、总 ERα、p-ERβ 和总 ERβ 的表达，以探讨 GS-Rd 的雌激素样活性。
GS-Rd 可减轻 OVX 大鼠的认知和记忆障碍，增加 sAPPα 水平，减少细胞外 Aβ。在 HT22 中，GS-Rd 可上调 sAPPα 水平，MAPK 和 PI3K 通路抑制剂可抑制其作用。此外，雌激素受体抑制剂可阻止 GS-Rd 触发的 sAPPα 释放和 MAPK 和 PI3K 通路的激活。GS-Rd 可增加 α-分泌酶和 sAPPα 的表达，减少 β-分泌酶和 Aβ 的表达。此外，GS-Rd 促进 ERα 丝氨酸 118 残基磷酸化。
我们的研究结果表明，GS-Rd 通过激活雌激素样活性增强 OVX 大鼠的学习和记忆功能。
