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.
Highlights
According to WHO, depression is one of the serious diseases of the past century, and will cause health burdens in 2030 [1], including the development of tension and mental stress as well as the growing incidence of suicide [2]
Anxiolytic- and antidepressant-like effects In the elevated plus-maze (EPM) test, reserpine (2 mg/kg/day) increased the time spent in the open arms and decreased the time spent in the closed arms after administration for 4 consecutive days, giving smaller ratios of entries onto open arms to closed arms than the control group at 2 weeks (P = 0.00008037) (Figure 2A) and 4 weeks (P = 0.000029) (Figure 2C)
Related studies demonstrated that 1 week of insulin treatment at 0.1 IU/g/day partially antagonized these depressive-like behaviours of streptozotocin-diabetic mice [44], while treatment with insulin at 1.0 IU/kg had a significant enhancing effect on the percentage of open-arm duration in anxious mice [45]. In accordance with these findings, XYS/room-temperature super-extraction system (RTSES) improved the regulation of blood glucose and increased the insulin sensitivity in reserpine-induced glucose intolerance in mice, indicating that the antidepressant effect of XYS/RTSES may be partially caused by improvement of the reserpine-induced glucose intolerance
Summary
According to WHO, depression is one of the serious diseases of the past century, and will cause health burdens in 2030 [1], including the development of tension and mental stress as well as the growing incidence of suicide [2]. Depression is a severe psychotic disorder that includes symptoms of depressed mood, sleep disturbance, and psychomotor and body weight abnormalities, among others [3,4]. The Chinese medicine formula Xiao-Yao-San (XYS) is a mixture of eight crude drugs Kami-Shoyo-San (KSS), a herbal formula commonly prescribed for climacteric symptoms, which is derived from some Chinese herbs and similar in composition to XYS in a Japanese Kampo clinic [7,8]. KSS is commonly used to treat functional dyspepsia, constipation, menopausal symptoms, premenstrual dysphoric disorder, anti-psychotic-induced tardive dyskinesia, panic disorder, parkinsonism, insomnia, and depressive disorders [10,11,12]. Xiao-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
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