Mulberry fruit improves memory in scopolamine-treated mice: role of cholinergic function, antioxidant system, and TrkB/Akt signaling

ABSTRACT

Objectives: Although mulberry fruit possesses some biological activities, it is not known how it protects neuronal cells in neurodegenerative diseases. Here, we examined whether mulberry fruit extract (MFE) protected neuronal cells against oxidative stress-induced neurodegeneration.

Methods: In this experiments, glutamate challenged hippocampal neuronal HT-22 cell lines as an in vitro model and scopolamine-induced memoty-impairment mice model were used.

Results: MFE improved cell viability and glutathione level as well as reducing reactive oxygen species level in glutamate-treated HT-22 cells. Additionally, MFE suppressed apoptotic bodies and mitochondrial depolarization through regulating expression of apoptosis-related proteins. Furthermore, MFE elevated expression of p-TrkB, p-Akt, p-CREB, BDNF, and antioxidant enzymes as well as nuclear translocation of Nrf2. In contrast, the inclusion of K252a, a TrkB inhibitor, or MK-2206, an Akt selective inhibitor, neutralized the neuroprotective actions of MFE. Separately, MFE attenuated scopolamine-induced amnesia via regulating the activities of enzymes related with cholinergic function and the antioxidant system in mice. Additionally, MFE protected neuronal cells in the hippocampal CA1 and CA3 regions in brain of mice.

Conclusions: MFE protects neuronal cells against oxidative stress-induced apoptosis through upregulating the expression of BDNF and antioxidant enzymes by stabilizing the activation of the TrkB/Akt pathway. Such an effect of MFE, which includes rich polyphenols, may provide information for its application as a food supplement for the prevention and treatment of neurodegenerative diseases.

KEYWORDS:

• Akt
• antioxidant enzymes
• apoptosis
• brain-derived neurotrophic factor
• hippocampal neuronal cells
• memory impairment
• mulberry fruit
• tropomyosin-related kinase receptor B

Acknowledgements

S.K.S. performed most in vitro experiments, and participated in the experimental design. J.M.Y. participated in the experimental design, analyzed the data, and drafted the manuscript. F.Y.L. performed in vivo studies. S.Y.B. performed some in vitro experiments, and participated in the preparation and interpretation of some data. M.R.K. provided the study idea, designed the experiments, interpreted data, supervised all the experiments, and revised the manuscript. All authors read and approved the final manuscript. The study was approved by the Committee of Animal Care and Experiment of Chungnam National University (Daejeon, Korea) with a reference number (CNU-01061) on June 8, 2018.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education [grant number 2017R1D1A3B03027867].

Notes on contributors

Suk Kyung Shin

Suk Kyung Shin is a researcher at Ohjeong Agricultural Products Inspection Office, Division of Food and Drug Research, Institute of Health and Environment in Daejeon currently.

Jae-Myung Yoo

Jae-Myung Yoo is a researcher at Korean Medicine R&D Team 1, National Institute for Korean Medicine Development (NIKOM) currently.

Fu Yi Li

Fu Yi Li is a Master student at Chungnam National University.

Seong Yeon Baek

Seong Yeon Baek is a PhD. student at Chungnam National University.

Mee Ree Kim

Mee Ree Kim is a Professor at Chungnam National University.