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

Abstract

BackgroundLow 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.MethodsWe 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 subjected to magnetic resonance imaging (MRI) using 17O-labelled water (H217O) to assess water dynamics in the brain. The effect of GRS on water permeability through aquaporin 4 (AQP4) was examined in vitro to elucidate its mechanism of action.ResultsGRS inhibited the loss of righting reflex and survival in the mouse model by ameliorating the increase in brain water content. In the same mouse model, MRI evaluation of water dynamics using H217O-derived signal changes showed that GRS reduced the maximum signal intensity change in the cortex and the areas under the curve in the cortex and lateral ventricle. Evaluation of water permeability in Xenopus laevis oocytes expressing AQP4 showed that GRS inhibited water permeability by suppressing AQP4 function. ConclusionsGRS inhibits cerebral oedema and related symptoms partly by inhibiting AQP4 water permeability. These findings provide insights into the alleviating effects of GRS on headaches caused by cerebral oedema. This study could serve as a basis to develop novel therapeutic agents for treating weather-related illnesses.