Centella asiatica Protects d-Galactose/AlCl3 Mediated Alzheimer’s Disease-Like Rats via PP2A/GSK-3β Signaling Pathway in Their Hippocampus

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder more prevalent among the elderly population. AD is characterised clinically by a progressive decline in cognitive functions and pathologically by the presence of neurofibrillary tangles (NFTs), deposition of beta-amyloid (Aβ) plaque and synaptic dysfunction in the brain. Centella asiatica (CA) is a valuable herb being used widely in African, Ayurvedic, and Chinese traditional medicine to reverse cognitive impairment and to enhance cognitive functions. This study aimed to evaluate the effectiveness of CA in preventing d-galactose/aluminium chloride (d-gal/AlCl3) induced AD-like pathologies and the underlying mechanisms of action were further investigated for the first time. Results showed that co-administration of CA to d-gal/AlCl3 induced AD-like rat models significantly increased the levels of protein phosphatase 2 (PP2A) and decreased the levels of glycogen synthase kinase-3 beta (GSK-3β). It was further observed that, CA increased the expression of mRNA of Bcl-2, while there was minimal effect on the expression of caspase 3 mRNA. The results also showed that, CA prevented morphological aberrations in the connus ammonis 3 (CA 3) sub-region of the rat’s hippocampus. The results clearly demonstrated for the first time that CA could alleviate d-gal/AlCl3 induced AD-like pathologies in rats via inhibition of hyperphosphorylated tau (P-tau) bio-synthetic proteins, anti-apoptosis and maintenance of cytoarchitecture.

A Systematic Screening of Traditional Chinese Medicine Identifies Two Novel Inhibitors Against the Cytotoxic Aggregation of Amyloid Beta

“…They are mainly used to treat memory decline in the elderly ( Howes et al, 2017 ; Yang et al, 2017 ; Ong et al, 2018 ). In the perspective of modern medicine, TCM extracts and their active ingredients have been proved to exhibit anti-AD effects through improving acetylcholine level and decreasing acetyl cholinesterase activity ( Wang et al, 2018 ), suppressing abnormal phosphorylation of Tau protein ( Ma et al, 2015 ), inhibiting neuronal apoptosis ( Ji et al, 2020 ), anti-oxidation ( Xu et al, 2017 ), anti-inflammation ( Liu et al, 2014 ), and inhibiting Aβ deposition ( Chiroma et al, 2019 ) in different studies. Because the toxic aggregation of Aβ may occur in the early stages of AD and induce further apoptosis, inflammation, and neurodegeneration, inhibiting the generation or aggregation of Aβ has been regarded as the preferred therapeutic approach for AD ( Takahashi and Mihara, 2008 ; Liu et al, 2017 ; Xiong et al, 2017 ).…”

Cepharanthine promotes the effect of dexmedetomidine on the deposition of β-amyloid in the old age of the senile dementia rat model by regulating inflammasome expression

“…The aged animal model of AD resembles the pathophysiology and morphological characteristics of human AD [19]. Chronic D-gal administration produces cognitive dysfunction and neurodegeneration similar to that in aged rats and thus has a well proved AD rat model [4]. Moreover, AD was characterized histopathologically by formation of Aβ plaques in the brain tissue and intracerebroventricular administration of Aβ in rats produces AD or dementia [12].…”

Glucagon‐like peptide‐1 analog improves neuronal and behavioral impairment and promotes neuroprotection in a rat model of aluminum‐induced dementia

“…The cell count was performed on an area of 19,259.17 μ 2 using 400× magnification for the pyramidal cells in the mid‐portion of the CA3 field and CA1 field in all the studied groups. The percentage of neuronal loss calculated as the mean number of neurons in control sections minus the mean number of neurons in the treated group sections divided by the mean number of neurons in control sections multiplied by 100 as described by (Chiroma et al., 2019).…”