Neuroprotective Effects of Apocynin and Galantamine During the Chronic Administration of Scopolamine in an Alzheimer’s Disease Model

Joseph, Eliezer; Villalobos-Acosta, Daniel Miguel Ángel; Torres-Ramos, Mónica; Farfán‐García, Eunice D.; Gómez-López, Modesto; Miliar-García, Ángel; Fragoso-Vázquez, Manuel Jonathan; García-Marín, Iohanan Daniel; Correa‐Basurto, José; Rosales‐Hernández, Martha Cecilia

doi:10.1007/s12031-019-01426-5

Cited by 23 publications

(8 citation statements)

References 62 publications

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“…SCOP has been widely used in models of learning and memory impairment mainly including AD, and is able to induce the release of Aβ ( Hernandez-Rodriguez et al, 2020 ; Ning et al, 2021 ). Treatment with SCOP may better model the increase in Aβ production that is observed during AD ( Joseph et al, 2020 ). Therefore, in this study, the AD model was established by intraperitoneal injection of SCOP, and the treatment of CK was found to improve the learning memory ability of AD model mice.…”

Section: Discussionmentioning

confidence: 99%

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

Pang²,

Zhang³

et al. 2023

Front. Pharmacol.

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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.

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Section: Discussionmentioning

confidence: 99%

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

Pang²,

Zhang³

et al. 2023

Front. Pharmacol.

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“…The study further confirmed the findings by Liu (Liu et al, 2020) on PSCE and SB inhibiting AChE activity in vitro. Then, the disorder of oxidative stress in the brain neurons is significant in the pathogenesis of AD (Joseph et al, 2020), and dysfunction related to oxidative levels has also been reported in AD patients (Mahdi et al, 2021). CAT and SOD are necessary antioxidant enzymes in the brain, and GSH is an essential antioxidant substrate.…”

Section: Discussionmentioning

confidence: 99%

Integrating network pharmacology analysis and pharmacodynamic evaluation for exploring the active components and molecular mechanism of moutan seed coat extract to improve cognitive impairment

Wang

Yang

et al. 2022

Front. Pharmacol.

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Paeonia suffruticosa (Moutan) is a traditional medicinal plant in China. Its seed coat is rich in resveratrol oligomer, especially suffruticosol B (SB). Previous studies had shown that the seed coat extracts of Paeonia suffruticosa (PSCE) had good cholinesterase inhibitory activity and neuroprotective effect, but the effective dose range was unknown, and the pharmacodynamic components and molecular mechanism of PSCE had not been discussed. The current study aimed to screen the pharmacodynamic components in PSCE and investigate the improvement effect of PSCE and the selected SB on scopolamine-induced cognitive dysfunction in mice and its mechanism. The results of high-throughput sequencing and bioinformatics analysis showed that suffruticosol B (SB) and trans-gnetin H (GH) might be the main active components of PSCE; PSCE might improve cognitive dysfunction through p53, HIF-1, MAPK, and PI3K-Akt signaling pathways, while SB and GH might improve cognitive dysfunction through HIF-1 signaling pathway. SB and GH had good molecular docking activity with the target of HIF-1 signaling pathway. The pharmacodynamic activities of PSCE and SB were further verified by behavioral experiments. PSCE and SB could improve the recognition ability of familiar and new objects and shorten the escape latency in the Morris Water Maze test (PSCE 120 mg∙kg-1, p < 0.05; SB 60 mg∙kg-1, p < 0.01); PSCE and SB could increase Ach and GSH levels, enhance the activities of ChAT, SOD and CAT, decrease the levels of IL-1β, IL-6, and TNF-α, and decrease the activity of AChE. In conclusion, the results indicated that PSCE might exert pharmacodynamic activity through multiple components, targets, and pathways, and SB and GH might be the main active components of PSCE. PSCE and SB might improve cognitive dysfunction by regulating cholinergic, antioxidant, and anti-inflammatory effects. These results indicated that PSCE and SB might be potential anti-AD drug candidates, providing a scientific basis for the development and utilization of Moutan bark.

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“…To evaluate the potential of BCCs for exerting ameliorative therapeutic effects in AD, experimental assessment was conducted in an murine model of AD, with cognitive deficit induced by hormonal diminishing after gonadectomy [ 54 , 65 ]. The evaluation was in agreement with Mexican National Research Council specifications for the production, care, and use of laboratory animals and the use of some species inside the laboratory; the protocol was approved by the Institutional Committee for the Care of Animals in the Laboratory (CICUAL-01/23-01-2019-1.0).…”

Section: Methodsmentioning

confidence: 99%

Synthesis, In Silico, and Biological Evaluation of a Borinic Tryptophan-Derivative That Induces Melatonin-like Amelioration of Cognitive Deficit in Male Rat

Barrón-González

Rosales‐Hernández

Abad-García

et al. 2022

IJMS

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Preclinical and clinical evidence supports melatonin and its analogues as potential treatment for diseases involving cognitive deficit such as Alzheimer’s disease. In this work, we evaluated by in silico studies a set of boron-containing melatonin analogues on MT1 and MT2 receptors. Then, we synthesized a compound (borolatonin) identified as potent agonist. After chemical characterization, its evaluation in a rat model with cognitive deficit showed that it induced ameliorative effects such as those induced by equimolar administration of melatonin in behavioral tests and in neuronal immunohistochemistry assays. Our results suggest the observed effects are by means of action on the melatonin system. Further studies are required to clarify the mechanism(s) of action, as the beneficial effects on disturbed memory by gonadectomy in male rats are attractive.

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Neuroprotective Effects of Apocynin and Galantamine During the Chronic Administration of Scopolamine in an Alzheimer’s Disease Model

Cited by 23 publications

References 62 publications

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

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

Integrating network pharmacology analysis and pharmacodynamic evaluation for exploring the active components and molecular mechanism of moutan seed coat extract to improve cognitive impairment

Synthesis, In Silico, and Biological Evaluation of a Borinic Tryptophan-Derivative That Induces Melatonin-like Amelioration of Cognitive Deficit in Male Rat

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