# Neuroprotective Effect of the Mixture of _Gastrodiae elata_ and _Glycyrrhiziae__urlensis_ In Vitro
## 1 Introduction  
Worldwide population aging is emerging as a major long-term problem [1]. As population aging progresses worldwide, the number of people above the age of 65 are expected to steadily increase to two billion by 2050 [2], and the patients with neurodegenerative disease including dementia and cognitive disorder are also expected to increase to over 130 million [3]. Among the numerous age-related diseases, degenerative brain diseases, such as Alzheimer's disease (AD), cause many additional diseases and excessive medical expenses [4]. AD is characterized by cognitive impairment and memory loss [5]. These degenerative brain disorders reduce learning and memory, affecting not only patients, but also their families and social behavior [6]. AD with cognitive function disorders is etiologically characterized by neuroinflammation--mation, causing neuronal loss, amyloid deposition, and nerve fiber entanglement [7]. It is well known that \(\beta\)-amyloid (A\(\beta\)) and oxidative stress are involved in the pathogenesis of cognitive function disorder [8]. The oligomeric form of A\(\beta\) peptide plays a major role in neuronal and glial activation of inflammation. After activation, neuronal cells produce inflammatory agents, including chemokines and cytokines [9]. Itinduces apoptosis and destabilizes calcium homeostasis by A\(\beta\) peptide, ultimately leading to neurotoxicity both in vitro and in vivo [10]. A\(\beta\) peptide is released from amyloid precursor protein (APP) by \(\beta\)-and \(\gamma\)-secretase, which form senile plaques [11]. Therapies that modulate the A\(\beta\) pathway are promising targets for drug development for cognitive function disorders. In connection with this method, approaches are being developed to regulate the A\(\beta\) pathway by inhibition of \(\beta\)- or \(\gamma\)-secretase or anti-A\(\beta\) monoclonal antibodies in cognitive function disorders [12]. Acetylcholine (Ach), a neurotransmitter in the nervous system and brain, plays a key role in memory and learning [13]. General medications might be used for degenerative brain disorders, such as AD and cognitive function disorders, by inhibiting acetylcholinesteraseies (AChE), nicotinic acetylcholine receptors, and muscarinic acetylcholine receptor (mAChR) [14]. The expression of AChE, which breaks down ACh, is activated in patients with cognitive disorders or AD [15]. Generally, in clinical treatment, donepezil,acrine, and rivastigmine are used to inhibit AChE. However, these medicines have side effects, such as somnipathy and nausea, and short half-lives [16]. In the amyloid pathway, \(\beta\)-secretase (BACE-1) is localized in endosomes and cleaved APP [17]. Therapeutically, inhibition of BACE-1 is a better treatment for AD or cognitive function disorders, aimed at suppressing the production of A\(\beta\)[18]. Additionally, A\(\beta\) peptide has been known to inhibit mitochondrial activity and alter intercellular calcium levels and induce cell death through oxidative and inflammatory stimulation [19]. _Gastrodia elata_ (GE), a traditional herbal medicine in South Korea, and its constituents have been used to treat various diseases, such as cardiovascular system disorders [20], convulsions [21], neurotransmitter disorders [22], and cognitive function disorders by regulating APP cleavage [23]. Gastrodin, one of the major constituents of _Gastrodia elata_, has been reported to have beneficial effects on the nervous system, including suppression of microglial activation, anti-inflammation, regulation of oxidative stress, and modulation of neurotransmitters [24]. Furthermore, gastrodin showed a protective effect on the midbrain by increasing the levels of GSH, HO-1, and SOD in MPTP intoxated mice [25]. These results suggest that GE has the potential to treat cognitive function disorders. _Glycythiza alaresis_ (GU), belonging to the _Leguminose_ family [26], has been used as an herbal medicine and a natural sweetener [27].