Suppressive effect of Yokukansan on excessive release of glutamate and aspartate in the hippocampus of zinc-deficient rats

Abstract

Yokukansan (TJ-54), a herbal medicine, has been used as a cure for insomnia and irritability in children. Yokukansan also improves behavioral and psychological symptoms such as agitation, aggression and irritability in patients with dementia including Alzheimer's disease, in which the glutamatergic neurotransmitter system is perturbed. However, the action of Yokukansan in synaptic neurotransmission is unknown. In the present study, the action of Yokukansan in the glutamatergic neurotransmitter system was examined in zinc-deficient rats, a neurological disease model, in which the glutamatergic neurotransmitter system is perturbed. Administration of Yokukansan significantly suppressed the increase in extracellular concentrations of glutamate and aspartate in the hippocampus after stimulation with 100 mM KCl, but not the increase in extracellular concentrations of glycine and taurine, suggesting that Yokukansan is involved in modulation of excitatory neurotransmitter systems. The present study demonstrates that Yokukansan is a possible medicine for prevention or cure of neurological diseases associated with excitotoxicity.

Yokukansan inhibits morphine tolerance and physical dependence in mice: The role of α2A-adrenoceptor

“…Although the mechanisms underlying the inhibition of morphine tolerance by YKS have not been determined, the role of the noradrenergic system in the development of morphine tolerance appears to be minimal (Dossin et al, 1996;Ö zdog˘an et al, 2004). Although we cannot fully exclude the possibility that a 2 -AR is involved in the attenuation of morphine tolerance by YKS, we consider that other mechanisms, such as the modulation of glutamatergic system by YKS (Trujillo and Akil, 1991;Takeda et al, 2008;Kawakami et al, 2009Kawakami et al, , 2011Suzuki et al, 2012), may be involved instead.…”

Ameliorative effects of yokukansan, a traditional Japanese medicine, on learning and non-cognitive disturbances in the Tg2576 mouse model of Alzheimer's disease

“…Therefore, TJ-54 may be instrumental in the amelioration of dysfunctions of various neuronal systems caused by A␤. In fact, recently, TJ-54 was demonstrated to suppress the excessive release of glutamate and aspartate in the hippocampus of zinc-deficient rats (Takeda et al, 2008) and to decrease expression of 5-hydroxytryptamine (5-HT) receptors in the prefrontal cortex of rats (Egashira et al, 2008). Yokukansan-ka-chimpi-hange has been reported to increase both choline acetyltransferase activity and the acetylcholine level in experimental animals (Yabe et al, 1995;Ito, 1997).…”

Efficacy and Tolerability of Risperidone, Yokukansan, and Fluvoxamine for the Treatment of Behavioral and Psychological Symptoms of Dementia

“…34 In rats with elevated glutamate levels, yokukansan significantly suppressed the increase in extracellular concentrations of glutamate in the hippocampus. 35 Furthermore, yokukansan improved glutamate uptake and inhibited glutamate-induced neuronal death in a dose-dependent manner, thereby exerting a neuroprotective effect by improvement of the dysfunction of astrocytes. 36 It seems that protection of the neuronal cells by glutamate uptake may be involved in the mechanisms of yokukansan.…”