Red Ginseng Attenuates Aβ-Induced Mitochondrial Dysfunction and Aβ-mediated Pathology in an Animal Model of Alzheimer’s Disease

Abstract

Alzheimer’s disease (AD) is the most common neurodegenerative disease and is characterized by neurodegeneration and cognitive deficits. Amyloid beta (Aβ) peptide is known to be a major cause of AD pathogenesis. However, recent studies have clarified that mitochondrial deficiency is also a mediator or trigger for AD development. Interestingly, red ginseng (RG) has been demonstrated to have beneficial effects on AD pathology. However, there is no evidence showing whether RG extract (RGE) can inhibit the mitochondrial deficit-mediated pathology in the experimental models of AD. The effects of RGE on Aβ-mediated mitochondrial deficiency were investigated in both HT22 mouse hippocampal neuronal cells and the brains of 5XFAD Aβ-overexpressing transgenic mice. To examine whether RGE can affect mitochondria-related pathology, we used immunohistostaining to study the effects of RGE on Aβ accumulation, neuroinflammation, neurodegeneration, and impaired adult hippocampal neurogenesis in hippocampal formation of 5XFAD mice. In vitro and in vivo findings indicated that RGE significantly improves Aβ-induced mitochondrial pathology. In addition, RGE significantly ameliorated AD-related pathology, such as Aβ deposition, gliosis, and neuronal loss, and deficits in adult hippocampal neurogenesis in brains with AD. Our results suggest that RGE may be a mitochondria-targeting agent for the treatment of AD.

Korean Red Ginseng Inhibits Amyloid-β-Induced Apoptosis and Nucling Expression in Human Neuronal Cells

“…These studies suggest that RG might serve as a preventive and therapeutic agent for ischemic brain injury and Aβ-induced brain damage. In addition, the present preventive effect of RG on Aβ -induced mitochondrial dysfunction was supported by the study of Shin et al [37] demonstrating that RG increases mitochondrial basal respiration, ATP-linked respiration and maximal respiration in Aβ-treated mouse hippocampal neuronal HT22 cells.…”

“…In a recent study carried out using the 5XFAD transgenic mouse model of AD, it was shown that RG treatment significantly reduces Aβ deposition and attenuates neuroinflammation and neuronal cell death [37]. One of the main mechanisms that deposition of Aβ leads to neuronal cell death is apoptosis [38].…”

“…Previous studies have shown the Aβ deposits induce neuronal cell death by inducing apoptosis [37]. To investigate Aβ induction of neuronal cell death, SH-SY5Y cells were incubated with increasing concentrations of Aβ (1, 2, and 5 µmol/L) for 24 h and then analyzed for cell viability using the MTT assay.…”

Red Ginseng Inhibits Tau Aggregation and Promotes Tau Dissociation In Vitro

“…In the previous study, the commercial KRGE was freeze-dried and ground into a fine powder [36]. The KRGE for SF, NSF, and NFP ( Figure S1) was supplied by the Korea Ginseng Corporation (Buyeo, Republic of Korea) according to the reported method [32].…”

“…In addition, ginseng has been used as a medicinal herb that can treat various diseases such as cancer, diabetes, and cardiovascular diseases [33][34][35]. Moreover, RG has been reported to mitigate ADrelated pathology in animal models of AD and patients with AD [36][37][38][39][40]. Furthermore, ginsenosides have been shown to ameliorate AD-related pathology, potentially by modulating amyloid-β (Aβ) processing, phosphorylated tau (p-tau) expression, and choline acetyltransferase expression [41,42].…”