Similarly, the classic formula Wuling Powder has been shown in mice to reduce brain water content after ischemic stroke by suppressing AQP4, a mechanism that involves Mn2+ and Zn2+ ions and is consistent with its observed inhibition of AQP4-dependent permeability in MLE-12 cells (Nakano et al., 2018). Here, AQP4 is linked to ischemic stroke.