Xiao Yao San Improves Depressive‐Like Behaviors in Rats with Chronic Immobilization Stress through Modulation of Locus Coeruleus‐Norepinephrine System

Abstract

Most research focuses on the hypothalamic-pituitary-adrenal (HPA) axis, hypothalamus-pituitary-thyroid (HPT) axis, and hypothalamus-pituitary-gonadal (HPGA) axis systems of abnormalities of emotions and behaviors induced by stress, while no studies of Chinese herbal medicine such as Xiao Yao San (XYS) on the mechanisms of locus coeruleus-norepinephrine (LC-NE) system have been reported. Therefore, experiments were carried out to observe mechanism of LC-NE system in response to chronic immobilization stress (CIS) and explore the antidepressant effect of XYS. Rat model was established by CIS. LC morphology in rat was conducted. The serum norepinephrine (NE) concentrations and NE biosynthesis such as tyrosine hydroxylase (TH), dopamine-β-hydroxylase (DBH), and corticotrophin-releasing-factor (CRF) in LC were determined. Results showed that there were no discernible alterations in LC in rats. The serum NE concentrations, positive neurons, mean optical density (MOD), and protein levels of TH, DBH, and CRF in model group were significantly increased compared to the control group. But XYS-treated group displayed a significantly decreased in NE levels and expressions of TH, DBH, and CRF compared to the model group. In conclusion, CIS can activate LC-NE system to release NE and then result in a significant decrease in rats. XYS treatment can effectively improve depressive-like behaviors in rats through inhibition of LC-NE neurons activity.

Anti-depressant-like effect of atractylenolide I in a mouse model of depression induced by chronic unpredictable mild stress

“…Of note, AT-I treatment significantly reduced these changes, as evidenced by increased sucrose preference as well as shortened immobility time in FST and TST. Of note, plenty of studies have confirmed that Xiaoyao San, a well-known traditional Chinese formula containing Rhizoma Atractylodis macrocephalae exerted anti-depressant-like effects in an animal model of CUMS-induced depression (21,22) and perimenopausal women with depression (23). In addition, a study by Zhou et al (16) identified that AT-I may be the component of Xiaoyao San responsible for its anti-depressant effects.…”

Xiao Yao San Improves the Anxiety-Like Behaviors of Rats Induced by Chronic Immobilization Stress: The Involvement of the JNK Signaling Pathway in the Hippocampus

“…33) Moreover, the mechanism may be related to the mediation of neurosteroid synthesis, 34) the modulation of the locus coeruleus-norepinephrine system, 35) and the serum levels of 5-HT, brain derived neurotrophic factor (BDNF), CORT and interleukin-6.…”

Modified Xiaoyaosan reverses aberrant brain regional homogeneity to exert antidepressive effects in mice

“…Accumulated evidence has shown that Xiaoyaosan, a traditional Chinese herbal formula, exerts antidepressant effects via improving the core symptoms of behavioral despair and anhedonia . Xiaoyaosan has been prescribed to treat mental disorders for thousands of years in China and was originally recorded in Taiping Huimin Heji Jufang , the first official compilation of materia medica around the world during the Song Dynasty in China (960–1127 AD).…”

“…4,5 Accumulated evidence has shown that Xiaoyaosan, a traditional Chinese herbal formula, exerts antidepressant effects via improving the core symptoms of behavioral despair and anhedonia. [6][7][8][9] Xiaoyaosan has been prescribed to treat mental disorders for thousands of years in China 6,10 and was originally recorded in Taiping Huimin Heji Jufang, the first official compilation of materia medica around the world during the Song Dynasty in China (960-1127 AD). In our previous studies, we discovered that Xiaoyaosan and its modified formulas might ameliorate hypothalamic-pituitary-adrenal hyperactivity, reverse neurotrophic abnormalities, and maintain the internal homeostasis of the kynurenine/serotonin pathway.…”