Kamikihito rescued depressive-like behaviors and hippocampus neurogenesis in chronic restraint stress rats

Naoki Adachi; Fatma Zahra Sakhri; Hideshi Ikemoto; Yusuke Ohashi; Mami Kato; Tatsuki Inoue; Tadashi Hisamitsu; Masataka Sunagawa

doi:10.1016/j.jtcme.2021.08.001

Kamikihito rescued depressive-like behaviors and hippocampus neurogenesis in chronic restraint stress rats

J Tradit Complement Med. 2021 Aug 2;12(2):172-179. doi: 10.1016/j.jtcme.2021.08.001. eCollection 2022 Mar.

Authors

Naoki Adachi¹, Fatma Zahra Sakhri^{1

2}, Hideshi Ikemoto¹, Yusuke Ohashi¹, Mami Kato¹, Tatsuki Inoue¹, Tadashi Hisamitsu¹, Masataka Sunagawa¹

Affiliations

¹ Department of Physiology, School of Medicine, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan.
² Department of Animal Biology, University of Freres Mentouri Constantine-Algeria, 25000, Constantine, Algeria.

Abstract

Background and aim: Substantial evidence suggests the effectiveness of plant-based medicine in stress-related diseases. Kamikihito (KKT), a Japanese traditional herbal medicine (Kampo), has been used for anemia, insomnia, and anxiety. Recent studies revealed its ameliorating effect on cognitive and memory dysfunction in several animal models. We, therefore, determined whether daily supplementation of KKT has an antidepressant-like effect on the stress-induced behavioral and neurological changes in rats.

Experimental procedure: The effect of KKT against the stress-induced changes in anxiety- and depressive-like behaviors and hippocampal neurogenesis were determined using a rat model of chronic restraint stress (CRS). KKT was orally administered daily at 300 or 1000 mg/kg during 21 consecutive days of CRS (6 h/day). The effect of CRS and KKT on physiological parameters, including body weight gain, food/water consumptions, plasma corticosterone (CORT) levels, and percentage of adrenal gland weight to body weight, were firstly measured. Anxiety- and depressive-like behaviors in rats were assessed in the open field test (OFT), sucrose preference test (SPT), and forced swimming test (FST). Hippocampal neurogenesis was determined by immunohistochemistry.

Results and conclusion: CRS for 21 days caused a significant decrease in body weight gain and increase in plasma CORT levels and percentage of adrenal gland weight to body weight, which were rescued by KKT treatment. KKT also suppressed the CRS-induced anxiety- and depressive-like behaviors and impairment of hippocampal neurogenesis. These results suggest that daily treatment of KKT has a protective effect against physiological, neurological, and behavioral changes in a rat model of depression.

Keywords: Antidepressant-like effect; BDNF, brain-derived neurotrophic factor; CORT, corticosterone; CRS, chronic restraint stress; Chronic restraint stress; DCX, doublecortin; DG, dentate gyrus; DNA, methyltransferase; FST, forced swimming test; HPA, hypothalamus-pituitary-adrenal; Hippocampal neurogenesis; KKT, Kamikihito; Kamikihito (加味帰脾湯); MAO, monoamine oxidase; MDD, major depressive disorder; Major depressive disorder; NSPCs, neural progenitor/stem cells; OFT, open field test; ROS, reactive oxygen species; SPT, sucrose preference test.