Revealing the Acetylcholinesterase Inhibitory Potential ofPhyllanthus amarusand Its Phytoconstituents: In Vitro and in Silico Approach

Abstract

The inhibition of acetylcholinesterase plays a vital role in the treatment of Alzheimer disease. This study aimed to explore the acetylcholinesterase inhibition potential of Phyllanthus amarus and its phytoconstituents through an in vitro and in silico approach. The in vitro acetylcholinesterase inhibitory activity of P amarus was carried out, followed by the molecular docking studies of its phytoconstituents. The top-ranked molecules identified through molecular docking were subjected to molecular dynamics simulation (MDS) and density functional theory (DFT) studies. The results obtained revealed the methanolic extract of P amarus as a potent acetylcholinesterase inhibitor, while amarosterol A, hinokinin, β-sitosterol, stigmasterol and ellagic acid were identified as potential acetylcholinesterase inhibitors. The MDS and DFT results are in agreement with those obtained from the docking studies. Our findings suggest further studies on the hit molecules.

Analysis of the anti-Alzheimer potential of bioactive compounds from Citrus hystrix DC. peel, leaf, and essential oil by network pharmacology

“…Owing to its several bioactive compounds proven to have anti-Alzheimer activities (mediating Aβ-toxicity, inhibiting related targets e.g. acetylcholinesterase), such as sitosterol [ 21 , [27] , [28] , [29] ]. Recent research has also shown that KL peel extract exhibits a neuroprotective effect against oxidative stress [ 64 ] and improves spatial memory [ 65 ] in mice in vivo studies.…”

“…Moreover, bioactive compounds of KL, such as sitosterol, are known to exhibit anti-AD properties. Sitoserol is reported to be a good inhibitor of cholinesterase (AChE), capable of preventing glutamate and Aβ toxicity, and possesses antioxidant activity [ 21 , [27] , [28] , [29] ].…”

Alzheimer's disease: A role of biomarkers in early diagnosis and evidences from African ethnomedicinal knowledge

“…Around the world, scientists are working to discover new medications along with their current understanding of several competing hypothesis and notions regarding the AD, which is highly complex and remains largely unexplained, and thus effective preventative and treatment strategies are lacking. Among the various treatment regimens, cholinergic transmission is the most successful medication target for AD therapy; however, additional treatments such as antiparkinsonian agents, antidepressants, β‐blockers, anxiolytics and anti‐epileptic therapies have been utilised to treat its secondary symptoms (Faloye et al, 2022). Focussing on early interventions, biomarkers are becoming more and more critical to the development of AD drugs, and most of the biomarkers are associated with the cerebrospinal fluid (CSF) levels of tau, phosphorylated tau (p‐tau) and amyloid beta protein (Aβ).…”