**1. Introduction**

Mild cognitive impairment (MCI) refers to a condition in which one's cognitive function is lower than that of normal peers but not considered dementia [1,2]. However, patients with MCI have an approximately 50% chance of developing Alzheimer's disease within five years [3]. Dementia is not curable. Therefore, it is important to prevent MCI from progressing into dementia. However, there is no established treatment that prevents the progression of MCI to dementia [4].

Animal models are needed to study MCI and develop therapeutics. An appropriate MCI model may have symptoms aggravating with age, but with only subtle memory impairment [5]. Animal models that meet these criteria include middle-aged rodents and transgenic mice that overexpress A β at an early stage before the dementia onset [4]. Spontaneously hypertensive rats (SHRs) appear to be appropriate as MCI models for vascular dementia, since hypertensive astrogliosis, cytoskeleton breakdown, hippocampal atrophy, and cholinergic deficit prematurely appear prematurely in this animal [6–8]. In contrast, drug-induced memory impairment models (such as those using scopolamine, NMDA blockers, and benzodiazepines) are not appropriate because they do not represent the various aspects of MCI [5].

Traumatic brain injury (TBI) is one of the most common brain injuries that causes a progressive decline of memory and cognition [9]. Unlike severe TBI, moderate to minimal TBI tends to be overlooked. However, even mild TBI can cause gradual amnesia, altered executive function, concentration disorders, depression, apathy, and anxiety [8,10,11]. In particular, repetitive head injuries, such as those caused by collision sports or motor vehicle accidents, are known to cause dementia [12]. Animal models of TBI show a decrease in cognitive function that correlates to the extent of injury, the number of impacts, and progressively worsens [13–15]. Therefore, the TBI model is a useful MCI research tool because it is simple, progressive, reproducible, and the severity of cognitive decline is relative to the number of impacts [16].

Chronic mild stress (CMS) is a behavioral model of depression that is caused by sequential exposure to variable mild stressors. CMS is characterized by anhedonia that may be reversed by chronic treatment with antidepressants [17]. However, most depression models show cognitive decline. Also, in the CMS animal model, mild cognitive deficit is accompanied, and antidepressants improve cognitive function in this model [18]. These memory deficits were related to the increased phosphorylation of Tau and APP processing, and the application of stress to wild type mice was suggested as an animal model of sporadic AD (Alzheimer's disease) [19].

Currently, there are many methods on trial to prevent the progression of MCI to dementia. In particular, nonpharmacological methods, such as cognitive leisure activities, education and exercise, and pharmacological methods, such as vitamin E, donepezil, and intranasal insulin, have been tried [20–23]. However, more research is needed to prove their efficacy.

*Angelica gigas* (AG) has been used in traditional medicine to improve circulation, physical weakness, headache, dizziness, joint pain, abdominal pain, constipation, irregular menstruation, and bruises, etc. [24]. Known bioactive components of AG include decursin, decursinol angelate, and nodakenin [24]. It has been shown to improve liver function in rats treated with long-term ethanol. AG also lowered LDL cholesterol and inhibited nicotine sensitization in rats [25,26]. Finally, AG attenuated acetylcholinesterase activity and was neuroprotective against beta-amyloid peptide-induced memory impairment [27]. According to these findings, the AG extract was tested in TBI and CMS models to evaluate whether it would improve memory impairment in MCI.
