Protective Effects of Centella asiatica on Cognitive Deficits Induced by D-gal/AlCl₃ via Inhibition of Oxidative Stress and Attenuation of Acetylcholinesterase Level.

Samaila Chiroma,Zulkhairi Amom,Mohamad Baharuldin,Mohamad Moklas,Onesimus Mahdi,Saravanan Jagadeesan,Che Mat Taib,Mohd Ilham Adenan

doi:10.3390/toxics7020019

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with cholinergic dysfunctions and impaired redox homeostasis. The plant Centella asiatica (CA) is renowned for its nutritional benefits and herbal formulas for promoting health, enhancing cognition, and its neuroprotective effects. The present study aims to investigate the protective role of CA on D-gal/AlCl3-induced cognitive deficits in rats. The rats were divided into six groups and administered with donepezil 1 mg/kg/day, CA (200, 400, and 800 mg/kg/day) and D-gal 60 mg/kg/day + AlCl3 200 mg/kg/day for 10 weeks. The ethology of the rats was evaluated by the Morris water maze test. The levels of acetylcholinesterase (AChE), phosphorylated tau (P-tau), malondialdehyde (MDA) and activities of superoxide dismutase (SOD), in the hippocampus and cerebral cortex were estimated by enzyme-linked immunosorbent assay (ELISA). Additionally, the ultrastructure of the prefrontal cortex of the rats’ was observed using transmission electron microscopy (TEM). Rats administered with D-gal/AlCl3 exhibited cognitive deficits, decreased activities of SOD, and marked increase in AChE and MDA levels. Further, prominent alterations in the ultrastructure of the prefrontal cortex were observed. Conversely, co-administration of CA with D-gal/AlCl3 improved cognitive impairment, decreased AChE levels, attenuated the oxidative stress in hippocampus and cerebral cortex, and prevented ultrastructural alteration of neurons in the prefrontal cortex. Irrespective of the dose of CA administered, the protective effects were comparable to donepezil. In conclusion, this study suggests that CA attenuated the cognitive deficits in rats by restoring cholinergic function, attenuating oxidative stress, and preventing the morphological aberrations.

Highlights

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder associated with cholinergic dysfunction and impaired redox homeostasis in the brain [1]
The two-way ANOVA showed a significant interaction between the effect of treatment and the days of treatment, [F(5, 30) 7.180, p = 0.0002] on the average distance covered by the rat groups in search of the escape platform
A similar trend was observed on day five of the test where a statistically significant increase was observed in the distance covered by rats of the model group when compared to the control, donepezil, and Centella asiatica (CA)

Summary

Introduction

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder associated with cholinergic dysfunction and impaired redox homeostasis in the brain [1]. ACh into inactive metabolites choline and acetate, and the increased activity of this enzyme can result in a deficiency of ACh. Drugs (AChE inhibitors) that were able to restore the appropriate levels of ACh were developed on the rationale of cholinergic hypothesis of AD, wherein these drugs act by inhibiting the action of AChE [3]. AChE inhibitors are still the mainstay of AD treatment though they do not cure the disease, but play a significant role in palliative management of AD [4]. Another pathological hallmark of AD is the neurofibrillary tangles in the brain which are formed by hyperphosphorylation and abnormal aggregation of tau protein [5]. The current drugs that are based on amyloid beta (Aβ) have not yielded the desired results, prompting clinicians and researchers to look for alternatives drugs, including phosphorylated tau (P-tau) based therapeutics [5,9]

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