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Social isolation (SI) mice exhibit behavioral abnormalities such as impairments of sociability- and attention-like behaviors, offering an animal model of neurodevelopmental disorders such as attention-deficit/hyperactivity disorder (ADHD). This study aimed to identify the effects of Sansoninto (SST; 酸棗仁湯 suān zǎo rén tāng) on the psychiatric symptoms related to ADHD using SI mice. Four-week-old mice were socially isolated during the experimental period, and SST administration (800 or 2400 mg/kg, p.o.) was started at 2 weeks after starting SI. SST ameliorated SI-induced impairments of sociability- and attention-like behaviors in a dose-dependent manner, and tended to ameliorate contextual- and auditory-dependent fear memory deficit. Moreover, the expression level of Egr-1 was down-regulated by SI stress, and was restored by a high dose of SST. These findings suggest that SST is useful for improvement of psychiatric disorders such as ADHD.

In vitro screening methods using cultured Neuro2a cells to examine the activation (phosphorylation) of extracellular signal-regulated kinase (ERK) 1/2 and promotion of neurite outgrowth revealed that the extracts of 5 Kampo (Japanese traditional) formulations have potential as medicines for the treatment of behavioral abnormalities. Since sansoninto (SAT) extract exerted stronger effects than the other candidates tested, we investigated whether its oral administration ameliorates the pathologies of some mouse models of behavioral impairments. The results obtained suggested that SAT extract exerted anti-depression-like effects in the forced swim test, which may be mediated by the up-regulated expression of brain-derived neurotrophic factor (BDNF) in the hippocampus. They may also be mediated by the enhanced phosphorylation of the cAMP response element-binding protein (CREB) via the mitogen-activated protein kinase (MAPK) cascade and Ca/calmodulin-dependent protein kinase II (CaMK II) cascade, a downstream signaling cascade of the N-methyl- d-aspartate (NMDA) receptor. These results indicate that the extract of SAT has potential as a new remedial medicine in the treatment of depression-like behavior. [ABSTRACT FROM AUTHOR]

ABSTRACT Aim Alzheimer's disease ( AD) is associated with a high incidence of sleep disturbance, and several studies have reported that sansoninto ( SNT), a Kampo medicine, ameliorates sleep disturbance. The effects of SNT on sleep disturbance and spatial memory impairment, however, have not been investigated in animal models of AD, therefore the aim of the current study was to carry out these investigations using a rat AD model. Methods Combined cerebral ischemia and intracerebroventricular injections of aggregated beta-amyloid were used to induce a rat model of AD. The quantity and quality of sleep in these rats were determined on electroencephalography and electromyography. Spatial memory impairment was examined using the water maze task. Triazolam, a hypnotic, and donepezil, approved for treating AD, were used as positive controls. Results Compared with sham-operated rats, the AD model rats had decreased total non-rapid eye movement sleep time, more frequent nocturnal awakening in the light phase, and poorer quality of non-rapid eye movement and rapid eye movement sleep on electroencephalography and electromyography. The AD rats also took longer than sham-operated rats to pass the platform area in the water maze retention test. Oral SNT 1000 mg/kg improved those impairments. Conclusion SNT ameliorated not only the abnormal non-rapid eye movement and rapid eye movement sleep structure but also the spatial memory impairment observed in a rat model of AD. [ABSTRACT FROM AUTHOR]

• We developed new automated sleep and rhythm analysis system (AutoCircaS) which can detect the sleep duration analysis of flies (Drosophila) and small fishes (Oryzias latipes). • AutoCircaS showed the caffeine-induced insomnia and the circadian rhythm of close-proximity (CP) for mating behavior in flies. • Japanese traditional herbal medicines, KyushinKannouGan-ki (KKG), NouKassei (NK) as well as Sansoninto, improved the caffeine-induced insomnia in flies. Sleep in Drosophila was defined in the year 2000 by using Drosophila Activity Monitor (DAM) system. But DAM is very small tube space and one fly per tube is very limited to analyze for fly social behavior. To overcome such demerits of DAM system, we developed a novel automated sleep and rhythm analysis system (AutoCircaS) which monitors and records any behaviors like social mating, sleep, and circadian rhythm in flies (Drosophila) and small fishes medaka (Oryzias latipes) in free space using the time-lapse (one frame per 10 sec) imaging. AutoCircaS can detect the caffeine-induced insomnia in flies in light–dark (LD) and constant dark (DD) conditions. Thus, using the AutoCircaS, we discovered that Japanese traditional herbal medicines, KyushinKannouGan-ki (KKG), NouKassei (NK) as well as, and Sansoninto, significantly improved caffeine-induced insomnia in flies. The data suggest that AutoCircaS is useful for sleep analysis of small animals and screening of new sedative-hypnotics from many origins. [ABSTRACT FROM AUTHOR]

A man in his 70s visited our department for dyspnea with pulmonary infiltrate that was unresolved by antibiotics. He had been taking Sansoninto for five years and doubled its dose a month ago. After discontinuing Sansoninto without any additional medications, his symptoms gradually disappeared, and pulmonary infiltration improved. Drug lymphocyte stimulation tests showed a positive result for Sansoninto. We diagnosed this patient with Sansoninto-induced lung injury. Sansoninto is a combination drug that consists of sansonin, bukuryo, senkyo, chimo, and kanzo. This paper reports the first case of Sansoninto-induced lung injury and discusses the mechanism considering its components.

Social isolation (SI) mice exhibit behavioral abnormalities such as impairments of sociability- and attention-like behaviors, offering an animal model of neurodevelopmental disorders such as attention-deficit/hyperactivity disorder (ADHD). This study aimed to identify the effects of Sansoninto (SST; suān zǎo rén tāng) on the psychiatric symptoms related to ADHD using SI mice. Four-week-old mice were socially isolated during the experimental period, and SST administration (800 or 2400 mg/kg, p.o.) was started at 2 weeks after starting SI. SST ameliorated SI-induced impairments of sociability- and attention-like behaviors in a dose-dependent manner, and tended to ameliorate contextual- and auditory-dependent fear memory deficit. Moreover, the expression level of Egr-1 was down-regulated by SI stress, and was restored by a high dose of SST. These findings suggest that SST is useful for improvement of psychiatric disorders such as ADHD.