Abstract

Centella asiatica (C. asiatica) is one of the medicinal plants that has been reported to exert comprehensive neuroprotection in vitro and in vivo. In view of this, the present study was performed to investigate the effect of ethanolic extract of C. asiatica, designated as raw-extract of C. asiatica (RECA) in reducing the acetylcholinesterase (AChE), inflammations, and oxidative stress activities via both in vitro (SH-SY5Y and RAW 264.7 cells) and in vivo (Sprague Dawley rats). Quantitative high-performance liquid chromatography analysis reveals that RECA contains a significantly high proportion of glycosides than the aglycones with madecassoside as the highest component, followed by asiaticoside. Treatment of SH-SY5Y cells with RECA significantly reduced the AChE activity in a concentration-dependent manner with an IC50 value of 31.09 ± 10.07 µg/mL. Furthermore, the anti-inflammatory and antioxidant effects of RECA were evaluated by lipopolysaccharides (LPS)-stimulated RAW 264.7 cells. Our results elucidated that treatment with RECA significantly suppressed the level of pro-inflammatory cytokine/mediators and oxidative stress released in a concentration-dependent manner. Interestingly, these patterns of inhibition were consistent as observed in the LPS-induced neuroinflammation Sprague Dawley rats’ model. The highest concentration used in the two models presented the most significant results. Herein, our findings strongly suggest that RECA may offer therapeutic potential for the treatment of Alzheimer’s disease through inhibiting the AChE, inflammation, and oxidative stress activities.

Highlights

  • Alzheimer’s disease (AD), which is associated with progressive memory loss and impairment in cognitive and behavioral functions, is the most common neurodegenerative disease worldwide [1].Molecules 2020, 25, 892; doi:10.3390/molecules25040892 www.mdpi.com/journal/moleculesThe etiopathogenesis of this disease is multifactorial and recent pieces of evidence have demonstrated that the deficits in central cholinergic neurotransmission in the brain, inflammatory injury, and induction of oxidative stress are interrelated in the onset and progression of AD [2,3,4]

  • The present study reports the capability of ethanolic extract of C. asiatica (RECA) in inhibiting acetylcholinesterase (AChE) activity and its possible association in suppressing the elevated expression acetylcholinesterase (AChE) activity and its possible association in suppressing the elevated of pro-inflammatory cytokine/mediators and oxidative stress via in vitro and in vivo models of expression of pro-inflammatory cytokine/mediators and oxidative stress via in vitro and in vivo

  • Even though AD is manifested by the accumulation of neurofibrillary tangles and amyloid plaques, Even though AD is manifested by the accumulation of neurofibrillary tangles and amyloid several pieces of evidence suggest the involvement of AChE in the pathogenesis of AD [3,32,33]

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Summary

Introduction

The etiopathogenesis of this disease is multifactorial and recent pieces of evidence have demonstrated that the deficits in central cholinergic neurotransmission in the brain, inflammatory injury, and induction of oxidative stress are interrelated in the onset and progression of AD [2,3,4]. Suppressing the acetylcholinesterase activity in the brain is one of the most popular targets for AD treatment to ameliorate cognitive ability. This enzyme, when in excess, could further lead to depletion of the acetylcholine concentration that will eventually result in deficit neurotransmission within the synaptic region [5]. Inhibition of the inflammatory response is crucial in restricting the development of this disease

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