Ginsenoside Rg1 improves Alzheimer's disease by regulating oxidative stress, apoptosis, and neuroinflammation through Wnt/GSK‐3β/β‐catenin signaling pathway

Abstract

Alzheimer's disease (AD) is a chronic neurodegenerative disorder that can cause cognitive impairment. Ginsenoside Rg1 (Rg1) has a significant neuroprotective effect on animals with memory impairment. However, the mechanism of how Rg1 mediates the Wnt signaling pathway and improves cognitive function by regulating oxidative stress, apoptosis, and neuroinflammation is still unclear. In this study, the spatial memory ability of tree shrews was tested by Morris water maze, the expression levels of amyloid protein (Aβ1-42), ionized calcium-binding adapter molecule 1 (iba-1), nitrotyrosine (NT), and 8-hydroxyguanine (8-OHG) were detected by immunohistochemistry. Subsequently, the activity of catalase (CAT) and the glutathione peroxidase (GSH-Px) was, respectively, measured by the ammonium molybdate method and the 5,5′-dithiobis (2-nitrobenzoic acid).Furthermore, the malondialdehyde (MDA) concentration was determined by the thiobarbituric acid test. Finally, the expression levels of Beta-secretase (BACE1), superoxide dismutase (SOD), BCL2-Associated X (Bax), B-cell lymphoma-2 (Bcl-2), caspase-anti-apoptotic factor Cleaved-caspase-3 (Caspase-3), microtubuleassociated proteins 2 (MAP2), Neuronal nuclear antigen (NeuN), as well as the phosphorylation of GSK-3β and βcatenin were detected by Western blot. This study implied that Rg1 reduced the phosphorylation of Tau protein, the deposition of Aβ1-42, and the expression of BACE1. It also showed that Rg1 increased the antioxidant activity of SOD, CAT, GPx, and instead reduced the oxidation products of NT, 8-OHG, and MDA, as wells as the inflammatory factor interleukin-1 and iba-1. It further showed that Rg1 increased the ratio of Bcl-2 to Bax and expression of neuronal markers MAP2 and NeuN, but instead reduced the expression of Caspase-3, GSK-3β, and β-catenin. In conclusion, by regulating the Wnt/GSK-3β/β-catenin signaling pathway, Rg1 of moderate and high dose could alleviate oxidative stress damage, improve neuroinflammation, protect neurons,

Ginsenoside and Its Therapeutic Potential for Cognitive Impairment

“…Moreover, in aging rats induced by isoflurane anesthesia, an inhalation anesthetic frequently used in clinics, which can impair cognition [ 171 ], Rg1 was found to improve CI via increasing the levels of PI3K, AKT, and GSK-3β in the hippocampus [ 154 ]. Otherwise, Rg1 improved the tau hyperphosphorylation, reduced the deposition of Aβ 1–42 , and improved the cognitive deficit of the AD tree shrew via regulating the GSK-3β signaling pathway [ 172 ]. mTOR is confirmed to exert a significant effect on synaptic plasticity and β-amyloid clearance via regulating autophagy [ 173 ].…”

New Therapeutic Approaches to and Mechanisms of Ginsenoside Rg1 against Neurological Diseases

“…Recent research showed that Rg1 alleviates cadmium-induced neurotoxicity in vitro and in vivo by attenuating oxidative stress and inflammation [ 74 ]. Rg1 improved oxidative stress, apoptosis, and neuroinflammation in AD [ 75 ] ( Figure 6 ). Therefore, Rg1 can inhibit oxidative stress by acting on neuronal cells in vitro.…”

Ginsenoside Rg1 and Re alleviates inflammatory responses and oxidative stress of broiler chicks challenged by lipopolysaccharide

“…Ginsenoside Re and Rg1 are tetracyclic triterpenoid derivatives extracted from the roots of Panax ginseng C. A. Meyer. Both of them have anti-inflammatory, antioxidant, and hepatoprotective effect ( Li et al, 2016 ; Zhao et al, 2021a ; Mao et al, 2022 ; Yang et al, 2022 ). Our previous study showed that treatment with ginsenoside Rg1 (Rg1) and ginsenoside Re (Re) can reverse growth inhibition ( Bi et al, 2022a ).…”