The memory ameliorating effects of INM-176, an ethanolic extract of Angelica gigas, against scopolamine- or Aβ_1-42-induced cognitive dysfunction in mice

Ethnopharmacological relevance: Alzheimer's disease is a neurodegenerative disorder associated with cognitive impairment and cholinergic neuronal death. INM-176 is a standardized ethanolic extract of Angelica gigas Nakai that has been traditionally used in herbal medicine in China, Japan, and Korea to treat anemia or as a sedative. We investigated whether INM-176 exhibits anti-amnesic effects. Materials and methods: Memory impairment was induced by scopolamine, a cholinergic muscarinic receptor antagonist, or amyloid β_1-42 (Aβ_1-42) protein. Anti-amnesic effects of INM-176 were measured by the passive avoidance and the Morris water maze tasks in mice. We also examined the effect of INM-176 on the acetylcholinesterase activity, as well as Aβ_1-42 protein-induced astrogliosis or cholinergic neuronal loss in the brain. Results: Scopolamine-induced cognitive dysfunction was significantly attenuated by a single or sub-chronic administration of INM-176 in the passive avoidance and the Morris water maze tasks. A single or sub-chronic administration of INM-176 also ameliorated memory impairments induced by Aβ_1-42 protein. INM-176 inhibited acetylcholinesterase activity in the hippocampal tissue in vitro and ex vivo. In addition, INM-176 attenuated the Aβ_1-42 protein-induced astrocyte activation in the hippocampus as well as cholinergic neuronal damage in the CA3 region of the hippocampus and the nucleus basalis of Meynert. Conclusion: These results suggest that the memory ameliorating effects of INM-176 on scopolamine- or Aβ_1-42 protein-induced memory impairment are mediated, in part, via acetylcholinesterase inhibition and neuroprotective activities.