Xiao Xu Ming Decoction attenuates cerebral ischemia-reperfusion injury by promoting remyelination and reducing white matter injury.

Xiao Xu Ming Decoction (XXMD), a classical Chinese herbal formula documented in the 'Beiji Qianjin Yaofang', is traditionally used for stroke management. Although XXMD has been shown to promote neurological functional recovery after cerebral ischemia through various pharmacological activities, the precise mechanisms underlying its therapeutic effects have yet to be fully elucidated. This study aims to elucidate the mechanism by which XXMD confers protection against cerebral ischemia-reperfusion injury, focusing on its effects in promoting remyelination and attenuating white matter injury (WMI). Liquid chromatography-mass spectrometry (LC-MS) was employed for comprehensive chemical profiling and quality assessment of XXMD. A transient middle cerebral artery occlusion (tMCAO) mouse model was established using the suture method. Neurobehavioral tests were conducted to evaluate the effects of XXMD on neurological dysfunction, motor disability, and cognitive deficits. Furthermore, immunoblotting, luxol fast blue staining, and immunofluorescence assays were performed to elucidate the mechanism by which XXMD attenuates WMI. Our study demonstrated that continuous intragastric administration of XXMD (60 and 120 g/kg, i.g.) for 42 days significantly reduced the neurological deficit score, reversed the shortening of rotarod duration, decreased the number of right turns in the turning test, reduced the gait abnormality coefficient, improved discriminative memory in the novel object recognition test, and enhanced spatial learning ability in the Morris water maze test in tMCAO mice. Furthermore, treatment with XXMD (60 and 120 g/kg, i.g.) for 28 days significantly reversed the decrease in myelin density in the corpus callosum and striatum, ameliorated myelin fiber disorganization, restored the expression of myelin basic protein (MBP) and neurofilament-200 (NF200) in the striatum, and attenuated microglial activation in tMCAO mice. XXMD significantly ameliorates neurological dysfunction, motor disability, and cognitive decline in a mouse model of cerebral ischemia-reperfusion injury induced by tMCAO. The underlying mechanism may involve the promotion of remyelination and the subsequent mitigation of white matter injury (WMI).