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Fulltext Combining In Silico and In Vitro Studies to Evaluate the Acetylcholinesterase Inhibitory Profile of Different Accessions and the Biomarker Triterpenes of Centella asiatica

Jusril NA, Muhamad Juhari ANN, Abu Bakar SI, Md Saad WM, Adenan MI

Molecules, 2020 Jul 24;25(15).
PMID: 32721993 DOI: 10.3390/molecules25153353

Alzheimer's disease (AD) is a neurodegenerative disease and the most cause of dementia in elderly adults. Acetylcholinesterase (AChE) is an important beneficial target for AD to control cholinergic signaling deficit. Centella asiatica (CA) has proven to be rich with active ingredients for memory enhancement. In the present study, the chemical profiling of three accession extracts of CA namely SECA-K017, SECA-K018, and, SECA-K019 were performed using high-performance liquid chromatography (HPLC). Four biomarker triterpene compounds were detected in all CA accessions. Quantitative analysis reveals that madecassoside was the highest triterpene in all the CA accessions. The biomarker compounds and the ethanolic extracts of three accessions were investigated for their acetylcholinesterase (AChE) inhibitory activity using Ellman's spectrophotometer method. The inhibitory activity of the triterpenes and accession extracts was compared with the standard AChE inhibitor eserine. The results from the in vitro study showed that the triterpene compounds exhibited an AChE inhibitory activity with the half-maximal inhibitory concentration (IC50) values between 15.05 ± 0.05 and 59.13 ± 0.18 µg/mL. Asiatic acid was found to possess strong AChE inhibitory activity followed by madecassic acid. Among the CA accession extracts, SECA-K017 and SECA-K018 demonstrated a moderate AChE inhibitory activity with an IC50 value of 481.5 ± 0.13 and 763.5 ± 0.16 µg/mL, respectively from the in silico docking studies, it is observed that asiatic acid and madecassic acid showed very good interactions with the active sites and fulfilled docking parameters against AChE. The present study suggested that asiatic acid and madecassic acid in the CA accessions could be responsible for the AChE inhibitory action and could be used as markers to guide further studies on CA as potential natural products for the treatment of AD.
Nanoemulsion of Ethanolic Extract of Centella asiatica (NanoSECA) Ameliorates Learning and Memory Performance by Enhancing Cholinergic Activities, Increasing Antioxidative Levels, and Attenuating oxidative stress markers in adult rats

Jusril NA, Mukhtar SM, Abu Bakar SI, Md Saad WM, Wen NK, Adenan MI

Pharm Nanotechnol, 2023 Aug 31.
PMID: 37653639 DOI: 10.2174/2211738511666230831122844

BACKGROUND: Centella asiatica (C. asiatica) has long been traditionally used as a memory enhancer. Nanoemulsion of ethanolic extract C. asiatica (NanoSECA) has been developed to improve brain functions. However, the effect of NanoSECA on enhancing memory and cognitive functions remains unexplored.
OBJECTIVES: This research aimed to investigate the potential of NanoSECA on cognitive tasks and memory enhancement pathways in a normal adult rat model.
METHODS: Thirty male Sprague Dawley rats (7-8 weeks old) were randomly subjected to five groups (n=six per group). Treatment groups were supplemented with NanoSECA and ethanolic extract of C. asiatica (SECA) for 28 days by oral gavages. Different brain sections were isolated, homogenized, and tested for acetylcholinesterase, antioxidants (glutathione and malondialdehyde), and anti-inflammatory agents (nitric oxide, tumour necrosis factor-α, and prostaglandin E2).
RESULT: NanoSECA supplementation markedly enhanced the acetylcholine, glutathione levels and reduced a distinct diminution in plasma activities of acetylcholinesterase, malondialdehyde, nitric oxide, prostaglandin E, and tumor necrosis factor-α levels.
CONCLUSION: NanoSECA can be used as a memory enhancer through enhanced cholinergic activity, increased antioxidant level, and reduced oxidative stress.

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