DA-9801, a standardized Dioscorea extract, improves memory function via the activation of nerve growth factor-mediated signaling

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.

KEYWORDS:

• DA-9801
• Dioscorea japonica
• Dioscorea nipponica
• memory function
• memory enhancement
• nerve growth factor
• ERK/CREB signaling
• cell differentiation

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This study was performed using research funds from Kyung Hee University [20190736]. Ethics approval The experimental protocol was approved by the Principle of Laboratory Animal Care (NIH publication No. 85-23, revised 1985) and the Animal Care and Use Guidelines of Kyung Hee University, Seoul, Korea.

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.