Gami-Yukmijihwang-Tang ameliorates scopolamine-induced cognitive impairment by restoring cholinergic function and...

Cholinergic dysfunction is a key pathological feature of cognitive impairment and is closely associated with oxidative stress, neuroinflammation, and dysregulation of neurotrophic signaling in the hippocampus. However, effective therapeutic strategies targeting these interconnected mechanisms remain limited.

Gami-Yukmijihwang-Tang (GMYG), a traditional multi-herbal formulation, was orally administered to C57BL/6 J mice for 14 days. Cognitive impairment was induced by a single intraperitoneal injection of scopolamine (2 mg/kg), and spatial learning and memory were evaluated using the Barnes maze test. Hippocampal tissues were analyzed to assess cholinergic function, oxidative stress, neuroinflammation, and neurotrophic signaling pathways.

GMYG significantly improved spatial learning and memory performance and restored cholinergic function, as evidenced by normalization of acetylcholine-related enzymes (AChE and ChAT). GMYG also attenuated oxidative stress and neuroinflammation, characterized by activation of NRF2/HO-1 signaling and inhibition of TLR4/NF-κB pathways. In addition, GMYG restored the expression of neurotrophic factors, including BDNF, CREB, and NGF, in the hippocampus.

GMYG exerts neuroprotective and cognition-enhancing effects through coordinated regulation of cholinergic, oxidative, inflammatory, and neurotrophic pathways. These findings provide mechanistic evidence supporting the therapeutic potential of GMYG as a multi-target intervention for cognitive impairment associated with neuroinflammation.