Kihito prevents corticosterone-induced brain dysfunctions in mice

Ryota Araki; Hayato Tachioka; Ayami Kita; Hironori Fujiwara; Kazufumi Toume; Kinzo Matsumoto; Takeshi Yabe

doi:10.1016/j.jtcme.2021.05.002

Kihito prevents corticosterone-induced brain dysfunctions in mice

J Tradit Complement Med. 2021 May 15;11(6):513-519. doi: 10.1016/j.jtcme.2021.05.002. eCollection 2021 Nov.

Authors

Ryota Araki¹, Hayato Tachioka¹, Ayami Kita¹, Hironori Fujiwara², Kazufumi Toume³, Kinzo Matsumoto², Takeshi Yabe¹

Affiliations

¹ Laboratory of Functional Biomolecules and Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Setsunan University, 45-1 Nagaotoge-cho, Hirakata, Osaka, 573-0101, Japan.
² Division of Medicinal Pharmacology, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
³ Division of Pharmacognosy, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.

Abstract

Kihito (KIT; Gui Pi Tang) is a traditional herbal medicine that is used for treatment of neuropsychiatric disorders such as depression, anxiety, neurosis and insomnia in China and Japan. Recently, it has also been shown that KIT improves cognitive dysfunction in patients with Alzheimer's disease. In this study, to investigate the mechanisms underlying the effects of KIT on stress-induced brain dysfunctions such as a depressed state and memory impairment, we examined whether KIT prevents behavioral and neurophysiological abnormalities in mice treated chronically with corticosterone (CORT). CORT (40 mg/kg/day, s.c.) and KIT (1000 mg/kg/day, p.o.) were given to 7-week-old male ddY mice for 14 days. Twenty-four hours after the last treatment, depression-like behavior in the forced swim test, spatial memory in the Barnes maze test, cell survival and the number of new-born immature neurons, dendritic spine density and expression levels of mRNA for neurotrophic factors were analyzed. Depression-like behavior and spatial memory impairment were observed in CORT-treated mice without KIT treatment. Hippocampal cell survival, the number of hippocampal new-born immature neurons, hippocampal and accumbal dendritic spine density and mRNA levels for neurotrophic factors such as glial cell line-derived neurotrophic factor (GDNF) were decreased in CORT-treated mice without KIT treatment. KIT prevented CORT-induced depression-like behavior, spatial memory impairment, and decreases in hippocampal cell survival, the number of hippocampal new-born immature neurons, accumbal dendritic spine density and GDNF mRNA. KIT may ameliorate stress-induced brain dysfunctions via prevention of adverse effects of CORT on cell survival, new-born immature neurons, spine density and neurotrophic factors.

Keywords: Corticosterone; Depression; Kihito; Spatial memory; Stress.