## 1 Introduction  
Dementia can be caused by a wide variety of conditions and a chronic disease with a significant emotional and physical burden [1]. Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disorder associated with memory deficits and loss of comprehension, language, attention, and judgment [2]. It is the most common cause of dementia affecting people over 65 years of age and is estimated to have up to 75 million cases by 2030 [3]. Despite decades of research and considerable pharmaceutical industry efforts to develop treatments for AD, there are currently no effective treatments for AD [4].  
[PERSON]'s disease is characterized by the accumulation of insoluble \(\beta\)-amyloid plaques formed due to an improper cleavage of amyloid precursor protein (APP) in addition to the formation of neurofibrillary tangles formed due to the hyper-phosphorylation of micro-tubulin protein tau [5, 6]. Both of them are involved in neuronal cell death, a prominent feature of AD [7]. Several different signaling pathways were found to be involved in cell survival, and the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) is one of them. P13K/Akt signaling is generally involved in cell survival, growth, proliferation, and migration. Recent studies demonstrated that inhibition of P13K/Akt by the \(\beta\)-amyloid could cause oxidative stress and neuronal cell death [8, 9].  
Glycogen synthase kinase-3 (GSK-3) is a protein kinase that phosphorylates various substrates in cellular metabolism [10, 11]. It has two isoforms: GSK-3\(\alpha\) and GSK-3\(\beta\)[12]. The GSK-3\(\beta\) was found to involved informing the integral component of neurofibrillary tangles (NFT) [13]. The phosphorylation of GSK-3\(\beta\) inhibits the GSK-3\(\beta\), which is reversibly associated with MAPK signaling [14]. Moreover, p38-MAPK is known to produce neuroinflammatory responses, as well as causing neuronal cell death [15]. Also, recently reportedstudies indicated the role of GSK-3 and MAPK in hyperphosphorylation of tau [16; 17]. Therefore, targeting these signaling pathways could be serving as a therapeutic agent in AD.  
Ginseng (_Panax ginseng_) is a perennial herb belonging to the family Arialaceae that has been used for medicinal purposes since ancient times [18]. Depending on the processing method used, ginseng can be categorized into fresh and white ginseng, red ginseng, and black ginseng [19; 20]. It is a natural substance that has been used for more than 2000 years in Korea, East Asia, China, and Japan [21]. Ginseng contains ginseng, phenolic compounds, polyacetylenes, alkaloids, polysaccharides, peptides, amino acids, fatty acids, and vitamins [19]. The main ingredient, ginseng, is a saponin component that can be active in the cell nucleus, inside the cell, and in the cell membrane [22]. It is also known to improve cognitive ability [23] and memory [24], as well as have anti-aging [25], anti-cancer [26], anti-inflammatory [27], and anti-diabetic [28] effects. It is classified as a protopanaxadiol (PPD) and protopanaxatriol (PPT) according to its structural characteristics [29]. PPD saponins include ginseng-Rb1, -Rb2, -Rc, -Rd, and -Rg3. PPT saponins have ginseng-Re, -Rg1, -Rg2, and -Rb1. Ginsenoside-Rg2, -Rg3, -Rh1, and -Rh2 are the only ingredients in red ginseng [30]. One of these ginseng saponins, ginseng Rh1, is a metabolite of ginseng Rg1 caused by bacteria [31; 32]. Rg1 has been found to have anti-cancer [33; 34], anti-oxidant [35], anti-inflammatory [18], and anti-obesity [36] effects. However, only a few studies have been conducted on the effects of ginseng on dementia. The aim of our study was to investigate the neuroprotective effects of ginseng Rh1, together with finding out the mechanism through which it could inhibit A\(\beta\)-induced oxidative stress and neuronal cell death.