According to WHO, depression is one of the serious diseases of the past century, and will cause health burdens in 2030 , including the development of tension and mental stress as well as the growing incidence of suicide . Depression is a severe psychotic disorder that includes symptoms of depressed mood, sleep disturbance, and psychomotor and body weight abnormalities, among others [3, 4]. Recent studies have shown metabolic syndrome abnormalities (obesity, glucose intolerance, hypertension, and hyperlipidemia), that may also be associated features of depression [5, 6].
The Chinese medicine formula Xiao-Yao-San (XYS) is a mixture of eight crude drugs (Bupleurum falcatum, Angelica sinensis, Paeonia lactiflora, Atractylodes lancea, Wolfiporia cocos, Zingiber officinale, Mentha arvensis, and Glycyrrhiza uralensis. 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]. It has been suggested that KSS is a safe and efficacious therapy for relief of climacteric symptoms in postmenopausal women . 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 [10–12].
Treatments with XYS had analgesic and antipyretic effects, increased motor activity with a hedonic effect, caused significant reversal of stress-induced deficits in learning and memory in a spatial memory task, and produced anxiolytic-like effects on the elevated plus-maze (EPM) test [13, 14]. Accordingly, treatments with KSS significantly lowered the immobility time on the forced swimming test (FST), improved neurogenesis in the hippocampus, and induced antidepressant climbing behaviour, suggesting that XYS and KSS might be effective antidepressant agents [15, 16]. KSS increased the plasma tumour necrosis factor-alpha levels in depressed menopausal patients and decreased the interleukin-6 concentrations in women with psychological symptoms [10–12]. It also decreased the homocysteine levels and did not affect the total cholesterol levels in ovariectomized rats . The social interaction test indicated that KSS caused its anxiolytic effect through neurosteroid synthesis followed by gamma-aminobutyric acid/benzodiazepine receptor stimulations in male mice.
Interestingly, clinical examination of patients with depression revealed a rising prevalence of impaired glucose tolerance including high fasting blood glucose and abnormal oral glucose tolerance test (OGTT) curve, suggesting that the frequency of impaired glucose tolerance increases with abnormal glycometabolism in patients with depression .
Chinese herbal medicine compositions are very complex, and the traditional methods for extracting effective components have many disadvantages, such as long cycle processes, insufficient extraction rates and residual organic solvents [18, 19]. To increase the extraction rate, several novel extraction methods, including cold-soaked extraction, percolation extraction, reflux extraction, shattering extraction, continuous-reflux extraction, ultrahigh-pressure extraction, ultrasonic extraction, and microwave extraction have been used for effective extraction of the bioactive components and major ingredients from Chinese medicinal plants and Chinese herbal prescriptions [20, 21]. The room-temperature super-extraction system (RTSES) is a novel, organic, solvent-free extraction technology for ultrasonic extraction of molecules from solid particles . The system contains an ultrasound-producing element that produces concentrated ultrasonic waves, and acoustic cavities that crush the particles in the fluid. As a result, large molecules in the extract retain their activities, and no organic waste and contaminants are present in the extract or during the extraction course . In particular, the RTSES has a higher extraction yield, lower extraction temperature, and shorter extraction time, involves less power consumption, and preserves the extracts’ bioactivities, making it suitable for the extraction of Chinese medicine components.
It was reported that fluoxetine reduced locomotion in the C57BL/6 J and 129SvEv mouse strains, but not in the BALB/c and DBA/2 mouse strains . In the FST, treatment with fluoxetine (10 and 18 mg/kg/day) increased swimming and reduced immobility . Later research showed that the use of inbred C57BL/6 J mice in a pathological condition and chronic fluoxetine treatment was more accurate for estimating antidepressant efficiency .
The emotional impacts of XYS (conventional water extraction) and XYS/RTSES (XYS extracted by the RTSES) were assessed for reserpine-induced anxiety- or depressive-like behaviours compared with fluoxetine. In this study, we used the C6 glial cell line, which was cloned from a rat glioma as a model system, to examine the neuroprotective roles of XYS/RTSES treatments against reserpine-mediated injury (in vitro). The anxiolytic and antidepressant effects of these treatments in C57BL/6 J mice were investigated through the EPM, and the FST and tail-suspension test (TST), respectively. The oral glucose tolerance and insulin resistance were assessed to evaluate the influences of the plasma glucose level and variable insulin sensitivity in reserpine-induced performance. The expression of 5-hydroxytryptamine 1A (5-HT1A) receptors in the prefrontal cortex of mice was measured by western blotting to compare the efficacies of conventional XYS and XYS/RTSES.
This study aims to investigate the RTSES for extracting anxiolytic- and antidepressant-like substances from XYS and to compare the extraction efficacy of the RTSES with those of other methods.