漢方薬の基礎的研究～加味帰脾湯の研究より～

抄録

Oxytocin is a well–known neuropeptide that induces uterine contractions and milk ejection as a posterior pituitary hormone. Recently, its central effects, including anti–stress and anxiolytic properties, have gained attention. However, oxytocin poorly crosses the blood–brain barrier (BBB), limiting its central effects when administered peripherally. This study aimed to investigate whether the traditional Japanese herbal medicine Kamikihito (KKT) could enhance endogenous oxytocin secretion and exert anti–stress and anxiolytic effects.

Wistar male rats were orally administered KKT for seven days, but plasma levels of adrenocorticotropic hormone (ACTH), corticosterone (CORT), and oxytocin showed no significant changes compared to the control group. In contrast, in a 90–minute restraint stress model, KKT–treated rats exhibited a significant reduction in defecation, an effect partially reversed by an oxytocin receptor antagonist. Plasma ACTH and CORT levels were significantly elevated, suggesting an adaptive activation of the hypothalamic–pituitary–adrenal (HPA) axis, while plasma oxytocin levels remained unchanged.

To assess central oxytocin dynamics, cerebrospinal fluid (CSF) was collected using microdialysis. In the KKT–treated group, CSF oxytocin levels significantly increased during restraint stress and remained elevated for 30 to 60 minutes after stress cessation. Furthermore, in the open field test (OFT), KKT–treated rats showed less reduction in locomotor activity following stress, and this effect was attenuated by an oxytocin receptor antagonist.

These findings suggest that KKT enhances stress resilience and recovery, potentially through the promotion of oxytocin secretion. This study highlights the possibility of developing new anti–stress and anxiolytic therapies targeting the oxytocin system.