Goreisan alleviates cerebral edema: Possibility of its involvement in inhibiting aquaporin-4 function

Aim: In Japan, goreisan (GRS) is used to alleviate cerebral edema and relieve headaches. Although improvement of water maldistribution in the brain may be one of the mechanisms of action of GRS for cerebral edema and headache, scientific evidence is limited. Here, we aimed to investigate the action mechanism of GRS against cerebral edema and headaches, focusing on water dynamics in the brain.Methods: We used a well-established mouse model of cerebral edema to evaluate the effects of GRS on related symptoms and brain water content. The mouse model was subjected to magnetic resonance imaging (MRI) using (H2O)-O-17 to assess water dynamics in the brain. The effect of GRS on water permeability through aquaporin-4 (AQP4) was also examined in vitro.Results: GRS inhibited the loss of righting reflex and improved survival in the mouse model by ameliorating the increase in brain water content. The MRI evaluation of water dynamics suggested that GRS inhibited water influx into the brain. Evaluation of water permeability via AQP4 in Xenopus laevis oocytes and HEK293 cells showed that GRS inhibited AQP4 function.Conclusion: GRS suppressed the ubiquity of water in the brain in a mouse model of cerebral edema, suggesting inhibition of AQP4 function (not AQP4 expression) as one of the action mechanisms of GRS. Our findings provide fundamental evidence for the clinical efficacy of GRS against cerebral edema and headaches.