Protective Effects of a Propolis– <i>Petasites japonicus</i> Mixture on Scopolamine-Induced Memory Impairment in Mice

mixture (PPJM) against scopolamine-induced memory impairment in mice and explored its underlying mechanisms. Male C57BL/6 mice were pretreated with PPJM prior to scopolamine administration. Spatial learning and memory were evaluated using the Morris water maze. Hippocampal cholinergic function was assessed by measuring acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) activities. Molecular mechanisms were examined by Western blot analysis of neuroplasticity-related signaling (BDNF-TrkB-AKT-CREB), phosphorylated Tau (p-Tau), MAPK activation, and neuroinflammatory markers. Immunohistochemical staining for TrkB and p-Tau, along with histological analysis, was performed to assess hippocampal alterations. PPJM pretreatment significantly ameliorated scopolamine-induced deficits in spatial learning and memory, as indicated by reduced escape latency and increased time spent in the target quadrant. PPJM partially restored cholinergic function by reducing AChE activity and increasing ChAT activity in the hippocampus. In addition, PPJM was associated with increased BDNF-TrkB-AKT-CREB signaling, along with reduced p-Tau and attenuation of JNK/p38 MAPK activation. Neuroinflammatory responses, including NF-κB activation and the expression of COX-2, TNF-α, and IL-6, were also reduced following PPJM pretreatment. Histological analyses further indicated preservation of neuronal architecture and modulation of TrkB and p-Tau expression in the hippocampus. These findings suggest that PPJM exerts protective effects against scopolamine-induced memory impairment, accompanied by modulation of cholinergic function, neuroplasticity-related signaling, and neuroinflammatory responses. However, further studies are required to validate these effects in chronic and translational models.