Room-temperature super-extraction system (RTSES) optimizes the anxiolytic- and antidepressant-like behavioural effects of traditional Xiao-Yao-San in mice

Abstract

BackgroundXiao-Yao-San (XYS) is a Chinese medicinal formula for treating anxiety and depression. This study aims to evaluate the use of a room-temperature super-extraction system (RTSES) to extract the major active components of XYS and enhance their psycho-pharmacological effects.MethodsThe neuroprotective roles of XYS/RTSES against reserpine-derived neurotoxicity were evaluated using a glial cell injury system (in vitro) and a depression-like C57BL/6 J mouse model (in vivo). The anxiolytic-behavioural effects were measured by the elevated plus-maze (EPM) test and the antidepressant effects were evaluated by the forced swimming test (FST) and tail suspension test (TST). Glucose tolerance and insulin resistance were assayed by ELISA. The expression of 5-HT1A receptors in the prefrontal cortex was examined by western blotting.ResultsXYS/RTSES (300 μg/mL) diminished reserpine-induced glial cell death more effectively than either XYS (300 μg/mL) or fluoxetine (30 μM) at 24 h (P = 0.0481 and P = 0.054, respectively). Oral administration of XYS/RTSES (500 mg/kg/day) for 4 consecutive weeks significantly elevated the ratios of entries (open arms/closed arms; P = 0.0177) and shuttle activity (P = 0.00149) on the EPM test, and reduced the immobility time by 90% on the TST (P = 0.00000538) and FST (P = 0.0000053839). XYS/RTSES also improved the regulation of blood glucose (P = 0.0305) and increased the insulin sensitivity (P = 0.0093). The Western blot results indicated that the activation of cerebral 5-HT1A receptors may be involved in the mechanisms of XYS/RTSES actions.ConclusionThe RTSES could provide a novel method for extracting effective anxiolytic- and antidepressant-like substances. XYS/RTSES improved the regulation of blood glucose and increased the insulin sensitivity in reserpine-induced anxiety and depression. Neuroprotection of glial cells and activation of cerebral 5-HT1A receptors were also involved.

Xiaoyaosan exerts anxiolytic-like effects by down-regulating the TNF-α/JAK2-STAT3 pathway in the rat hippocampus

“…As more people have focused on complementary and alternative medicines (CAM), Xiaoyaosan is gradually being recognized by clinical researchers as a safe and effective prescription for the treatment of depressive and anxious disorders 52 . Recent preclinical findings also have shown the reliable antidepressant and anxiolytic effects of Xiaoyaosan by summarizing its biochemical, neurochemical, and behavioural data 53 , 54 . Furthermore, increasing numbers of researchers have devoted their attention to clarifying the potential validity of the antidepressant and anxiolytic properties of this prescription.…”

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.…”

Nine traditional Chinese herbal formulas for the treatment of depression: an ethnopharmacology, phytochemistry, and pharmacology review

“…Anxiolytic and antidepressant components of “xiaoyaosan” (XYS) can be isolated using a room-temperature superextraction system. 98 XYS treated in this way (300 μg/mL) reduces the reserpine-induced death rate of glial cells more than either untreated XYS (300 μg/mL) or fluoxetine (30 μM) at 24 hours after application. 98 …”

“…XYS ameliorates behavioral changes and ultrastructural damage to the hippocampal CA1 region, and also reverses chronic decreases in GluR2 mRNA and increases in GluR1 mRNA in the CA1 after immobilization stress. 101 It may also act via cerebral 5-HT 1A -receptor activation 98 and the inhibition of locus coeruleus NE neuron activity. XYS decreases serum NE concentrations and protein levels of tyrosine hydroxylase, dopamine-β-hydroxylase, and corticotrophin-releasing factor in the locus coeruleus of rat models of depression.…”