Goreisan alleviates cerebral oedema by inhibiting aquaporin 4 function: In vivo study using an established mouse model of cerebral oedema

Abstract Low atmospheric pressure triggers weather-related illnesses, such as headaches. Although many individuals are affected by weather-related illnesses, only a few therapeutic drugs are available. In Japan, Goreisan (GRS) is traditionally used to relieve headaches; however, its mechanism of action is unclear. Therefore, we investigated the mechanism of action of GRS against headaches, focusing on water dynamics in the brain. We used a well-established mouse model of cerebral oedema to evaluate the effects of GRS on related symptoms and brain water content. The mouse model was also subjected to magnetic resonance imaging (MRI) using H 2 17 O to assess water dynamics in the brain. The effect of GRS on water permeability through aquaporin 4 (AQP4) was examined in vitro . GRS inhibited the loss of righting reflex and survival in the mouse model by ameliorating the increase in brain water content. MRI evaluation of water dynamics suggested that GRS inhibited water influx into the brain. Evaluation of water permeability in Xenopus laevis oocytes expressing AQP4 showed that GRS inhibited AQP4 function. These findings provide insights into the alleviating effects of GRS on headaches caused by cerebral oedema. This study could serve as a basis for developing novel therapeutic agents for treating weather-related illnesses.