Jangwon-hwan Improves Memory Performance in Mice with Enhanced Cholinergic Signaling and Synaptic Plasticity

Background/Objectives: Jangwon-hwan (JH), known as Zhuangyuan-wan in Chinese medicine, has traditionally been used for forgetfulness and poor memory, often accompanied by palpitations and insomnia. However, the pharmacological mechanisms underlying its traditional use for memory-related symptoms remain unclear. This study aimed to evaluate the effects of JH on memory function and to elucidate the underlying mechanisms, thereby providing scientific evidence for its use. Methods: JH (30 or 100 mg/kg) was orally administered for 28 days in normal mice and for 14 days in scopolamine-induced memory-impaired mice. Memory performance was assessed behaviorally, with molecular and histological analyses of brain tissue. Results: JH improved passive avoidance memory and increased hippocampal synaptophysin and postsynaptic density protein 95 in normal mice. JH also enhanced medial septal cholinergic neuronal activation and increased hippocampal acetylcholine levels. It further increased muscarinic acetylcholine receptor M1 and metabotropic glutamate receptor 5 expression, upregulated synaptic plasticity-related genes, and enhanced hippocampal neuronal activation. Consistent with its effects on cholinergic signaling, JH attenuated scopolamine-induced memory impairment and preserved hippocampal phosphorylation of calcium/calmodulin-dependent protein kinase II, extracellular signal-regulated kinase, and cAMP response element-binding protein. Conclusions: Collectively, these findings indicate that the memory-enhancing effects of JH are associated with enhanced cholinergic signaling, synaptic plasticity, and hippocampal neuronal activation, providing molecular evidence supporting its traditional use for forgetfulness and poor memory.