Ginsenoside compound K reduces neuronal damage and improves neuronal synaptic dysfunction by targeting Aβ

Abstract

Background: Alzheimer’s disease (AD) is the most common neurodegenerative condition worldwide, with amyloid ß (Aβ) fibrils presenting as its main pathological feature. This study investigated whether Ginsenoside Compound K (CK) has activity against Aβ and its mechanism in reducing synaptic damage and cognitive impairment.Methods: The binding capacity of CK to Aβ42 and Nrf2/Keap1 was determined using molecular docking. Transmission electron microscopy was used to monitor CK-mediated degradation of Aβ fibrils. The effect of CK on the survival of Aβ42-damaged HT22 cells was determined using a CCK-8 assay. The therapeutic efficacy of CK in a scopoletin hydrobromide (SCOP) induced cognitive dysfunction mouse model was measured using a step-down passive avoidance test. GO enrichment analysis of mouse brain tissue was peformed using Genechip. Hydroxyl radical scavenging and reactive oxygen species assays were performed to verify the antioxidant activity of CK. The effects of CK on the expression of Aβ42, the Nrf2/Keap1 signaling pathway, and other proteins were determined by western blotting, immunofluorescence, and immunohistochemistry.Results: Molecular docking results showed that CK interacts with Lys16 and Glu3 of Aβ42. CK reduced the aggregation of Aβ42 as observed using transmission electron microscopy. CK increased the level of insulin-degrading enzyme and decreased the levels ß-secretase and γ-secretase; therefore, it can potentially inhibit the accumulation of Aβ in neuronal extracellular space in vivo. CK improved cognitive impairment and increased postsynaptic density protein 95 and synaptophysin expression levels in mice with SCOP-induced cognitive dysfunction. Further, CK inhibited the expression of cytochrome C, Caspase-3, and cleaved Caspase-3. Based on Genechip data, CK was found to regulate molecular functions such as oxygen binding, peroxidase activity, hemoglobin binding, and oxidoreductase activity, thus affecting the production of oxidative free radicals in neurons. Further, CK regulated the expression of the Nrf2/Keap1 signaling pathway through its interaction with the Nrf2/Keap1 complex.Conclusion: Our findings show that CK regulates the balance between Aβ monomers production and clearance, CK binds to Aβ monomer to inhibits the accumulation of Aβ, increases the level of Nrf2 in neuronal nuclei, reduces oxidative damage of neurons, improves synaptic function, thus ultimately protecting neurons.

7,8‑Dihydroxyflavone functions as an antioxidant through the inhibition of Kelch‑like ECH‑associated protein 1: Molecular docking and an in vivo approach in a rat model of ischemia‑reperfusion brain injury

“…As aforementioned, the Keap1/Nrf2 complex plays a critical role in stroke-ischemic situations by regulating cellular defense against oxidative stress and promoting the activation of genes involved in antioxidant and detoxification pathways, such as superoxide dismutase (SOD), catalase (CAT) and glutathione or GST (37,38). Under conditions of oxidative stress, BDNF is also modulated by activated Nrf2 (39).…”

Integrating Network Pharmacology and Metabolomics to Explore the Potential Mechanism of Pinolenic Acid against Atherosclerosis

“…Immunofuorescence assays were performed as previously described [23]. In brief, after the cells were fxed and permeabilized, they were incubated with the p-NRF2 antibody overnight at 4 °C, followed by incubation with fuorescently-labeled secondary antibodies for 1 h at 37 °C and DAPI for 5 min at 37 °C to stain the nuclei.…”

Ginseng Extract Improves the Sub-health Status in Young Population: An Observational Study

“…2 Increasing studies in the past few years have illustrated that its active ingredient ginsenosides can effectively relieve chronic fatigue, and protect the cardiovascular system and cerebral function, thus maintaining body homeostasis. [3][4][5] Recently, a high-grade dietary ginseng supplement called Renshen Yuanqi (RSYQ) Drink has been launched by China Medico Corporation, Tianjin, China, which would theoretically tonify the primordial qi, replenish the qi of the spleen and lung, and tranquilize the mind, promoting harmonization of the entire body's qi and blood, leading to the natural elimination of the symptoms of sub-health. However, the efficacy and safety of RSYQ Drink are based exclusively on conventional theories and speculative hypotheses, which remain under-researched.…”