Qin Gui Huo Luo Oral Liquid Attenuates Blood–Brain Barrier Dysfunction after Cerebral Ischemia–Reperfusion Injury in Mice <i>via</i> the Regulation of the PI3K/AKT/FOXO3A Signaling Pathway

Qin Gui Huo Luo oral liquid (QGHL) is a modern formulation derived from the Traditional Chinese Medicine (TCM) Daqinjiao Decoction. QGHL has been widely adopted in China's clinical settings as a therapeutic agent for microcirculatory dysfunction. However, the mechanistic interplay of QGHL in animal models for ischemic stroke (IS) treatment remains unexplored. This study aimed to investigate the impact of QGHL on blood-brain barrier (BBB) disruption induced by cerebral ischemia-reperfusion (I/R) injury. HPLC analysis was employed to identify the major chemical constituents of QGHL while maintaining stringent quality standards. Male C57BL/6J mice were subjected to 1-h right middle cerebral artery occlusion, followed by 24-h reperfusion to induce I/R injury. Subsequently, QGHL was administered intragastrically at 3 different doses (7.8, 15.6, and 31.2 g kg^-1). QGHL treatment significantly attenuated cerebral I/R injury, as evidenced by reduced infarct volume, improved neurological scores, attenuated cerebral edema, and restored cerebral blood flow. Moreover, QGHL preserved BBB integrity by upregulating zonula occludens-1 (ZO-1) and occludin while suppressing matrix metalloproteinase (MMP)-2/9 expression. Network pharmacology revealed that phosphatidylinositol 3-kinase (PI3K)/AKT/FOXO3A axis served as a major signaling pathway mediating QGHL's therapeutic effects against IS, which was further confirmed by Western blot analysis. QGHL exerts neuroprotection against cerebral I/R injury in mice via modulation of the PI3K/AKT/FOXO3A signaling pathway, suggesting its potential as a novel therapeutic strategy for IS.