Work

Traditional herbal medicine Ga-Mi Gongjindan improves muscarinic cholinergic dysfunction through regulation of BDNF/CREB signaling pathway using a scopolamine-induced cognitive impairment of mouse model

Year: 2025

Type: article

Abstract: BACKGROUND: Neurodegenerative diseases, such as Alzheimer's disease (AD), are characterized by progressive memory loss and cognitive dysfunction, often linked to cholinergic system deterioration and hippocampal oxidative stress. Current pharmacological treatments offer only modest symptomatic relief and are often accompanied by adverse effects. In traditional Korean medicine, Ga-Mi Gongjindan (GJD), a modified formulation of Gongjindan, has long been used for enhancing cognitive function, but its neuropharmacological basis remains largely unexplored. OBJECTIVE: This study aimed to investigate the neuroprotective potential and underlying mechanisms of GJD in a murine model of scopolamine-induced cognitive impairment, which mimics aspects of muscarinic cholinergic dysfunction observed in Alzheimer's disease (AD). METHODS: C57BL/6 J mice were administered GJD or tacrine (positive control) for 14 days. Cognitive impairment was induced by a single intraperitoneal injection of scopolamine (2 mg/kg), and behavioral analysis was assessed using the Morris Water Maze. Hippocampal tissues were analyzed for markers of oxidative stress, inflammation, cholinergic function, and neurotrophic signaling by focusing on the BDNF/CREB signaling pathway. RESULTS: GJD treatment significantly improved spatial learning and memory performance. It restored cholinergic function by reducing acetylcholinesterase (AChE) activity and increasing choline acetyltransferase (ChAT) levels. GJD also suppressed oxidative stress and neuroinflammation and markedly enhanced hippocampal expression of brain-derived neurotrophic factor (BDNF), cAMP response element-binding protein (CREB), and their receptors (TrkA, TrkB, and M1 mAChR). CONCLUSION: GJD exerted significant neuroprotective effects in a scopolamine-induced model of cognitive dysfunction, potentially via modulation of cholinergic and BDNF/CREB signaling pathways. These findings provide a scientific rationale for the traditional use of GJD in cognitive disorders and support its further development as a candidate for treating neurodegenerative diseases such as AD.

Source: Brain Research Bulletin

DOI: 10.1016/j.brainresbull.2025.111644

Authors: Jong-Kwang Park, Hyeong-Geug Kim, Jong-Suk Lee, Jae-Hong Joo, Ho-Ryong Yoo

Institutions: Daejeon University, Daejeon Oriental Hospital, QPS (United States), Gyeonggido Business and Science Accelerator

Language: English

Topic: Medicinal Plants and Neuroprotection

Subfield: Complementary and alternative medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,280