ABSTRACT
Objectives
Nerve growth factor (NGF) is a neurotrophin that plays a critical role in mammalian learning and memory functions. NGF also regulates neuronal cell differentiation and neurite outgrowth by activating ERK/CREB signaling. This present study examined the effects of a standardized Dioscorea extract (DA-9801), which is composed of Dioscorea japonica Thunb and Dioscorea nipponica Makino on memory function via its NGF-potentiating activities using an in vitro and in vivo paradigm.
Methods
Cells were incubated with or without different concentrations of DA-9801 (10, 25, and 50 μg/ml) extract for 24 h. The cultured conditioned medium from C6 glioma cells was used for NGF production assay, and neurite length in N2a cells was measured after every 2 h. Mice were orally treated with DA-9801 (10 and 100 mg/kg/day) once daily for 7 days. They were subjected to passive avoidance test to evaluate memory functions. The question of whether DA-9801 induced NGF synthesis was assessed by measuring the levels of NGF in the mouse cortical and hippocampal tissues. Hippocampal cell differentiation and NGF-mediated ERK/CREB signaling were evaluated by performing immunohistochemical analysis using BrdU, ki67, DCX, phosphorylated ERK and CREB in the mouse hippocampus.
Results
DA-9801 treatment increased the NGF contents and neurite length, respectively. Mice with DA-9801 administration showed memory enhancement in the passive avoidance test. DA-9801 also increased newborn cell differentiation, neurite length, NGF secretion, and ERK/CREB phosphorylation in the mouse hippocampus.
Discussion
These results suggest that DA-9801 treatment could improve memory function by inducing hippocampal NGF synthesis and ERK/CREB signaling.
Disclosure statement
No potential conflict of interest was reported by the author(s).
Additional information
Funding
Notes on contributors
Jin Gyu Choi
Jin Gyu Choi: Research professor (Ph.D.), College of Pharmacy and Kyung Hee East-West Pharmaceutical Research Institute, Kyung Hee University, Republic of Korea.
Zahra Khan
Zahra Khan: Master degree, College of Pharmacy and Gachon Institute of Pharmaceutical Science, Gachon University, Republic of Korea.
Sang-Zin Choi
Sang-Zin Choi: Chief Technology Officer (Ph.D.), NeuroBo Co., Ltd, Republic of Korea.
Myung Sook Oh
Myung Sook Oh: Professor (Ph.D.), College of Pharmacy and Kyung Hee East-West Pharmaceutical Research Institute, Kyung Hee University, Republic of Korea.